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Background: While prior research on the SPC (second primary cancer) risk among pharyngeal carcinoma (PC) patients has been conducted in other regions, the European perspective is underrepresented. Our register-based cohort study aims to assess the subsite-specific risk of SPC among individuals initially diagnosed with a pharyngeal index tumour., Methods: Standardized incidence ratios (SIR) of SPC were calculated relative to the general population for all patients diagnosed with a primary oropharyngeal, nasopharyngeal, and hypopharyngeal carcinoma (OPC, NPC, and HPC) in Finland during 1953-2021., Results: A total of 4701 PC patients - 3320 men (71%) and 1381 women (29%) - were identified. The average and median follow-up times were 5.7 and 2.8 years, respectively. A SPC was diagnosed in 561 patients (11.9%): in 12.3% of men (n = 410) and 10.9% of women (n = 151). For male PC patients, the overall SIR for an SPC at any primary site was 1.83 (95% CI: 1.65-2.01). For female patients, the corresponding SIR was 1.89 (95% CI: 1.60-2.22). OPC and HPC showed increased risks for SPCs of the mouth/pharynx (SIR 4.41 and 6.91, respectively) and respiratory organs (SIR 3.51 and 4.80). OPC patients also had an increased risk in digestive organs (SIR 1.83). Male NPC patients exhibited increased risks for oral/pharyngeal, brain, and haematolymphoid SPCs (SIRs 5.14, 6.60, and 3.05, respectively)., Conclusion: PC patients face an 80% higher SPC risk, which persists decades after treatment. Healthcare professionals must be aware of this, providing counselling and encouraging a healthy lifestyle, including smoking cessation, while monitoring symptoms., Competing Interests: Declarations Ethics approval and consent to participate The current study was based on data from existing registries and did not include any human intervention. Study participants were not contacted during the execution of the study. All methods were carried out in accordance with relevant guidelines and regulations. All analysed results are anonymous, rendering the recognition of an individual study subject unfeasible. Approval from any institutional review board or ethics committee was not required for this research, as Finnish law does not require any ethical board review for register-based research, as long as the study does not involve direct contact with the individuals whose data are included in the register. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Transitioning to adulthood often involves achieving independence from the parental home. We assessed whether the likelihood of leaving the parental home, cohabitation, and marriage was similar between patients who experienced a hematologic malignancy at a young age and their peers., Methods: We identified 11,575 patients diagnosed with a hematologic malignancy under the age of 20 years between 1971 and 2011 in Denmark, Finland, and Sweden, 57,727 country-, age-, and sex-matched population comparisons and 11,803 sibling comparisons and obtained annual information on family and marital status by linking to the statistical institute databases. Hazard ratios (HR) for leaving the parental home, cohabitation and marriage were estimated using Cox proportional hazards modeling., Results: Young adults with a history of a hematologic malignancy were slightly less likely to leave the parental home (HR 0.89; 95% confidence interval [CI] 0.86-0.92; HR 0.87 [95% CI 0.82-0.92]), cohabit with a nonmarital partner (HR 0.83 [95%CI 0.78-0.87]; HR 0.84 [95% CI 0.77-0.92]) and be married (HR 0.87 [95% CI 0.82-0.91]; HR 0.86 [95% CI 0.79-0.93]), compared with population comparisons and siblings, respectively., Conclusions: Our findings provide reassurance that young adults with a history of a hematologic malignancy show only a slight decrease in their likelihood of gaining independence from their childhood family and forming close interpersonal relationships compared to peers. While most patients are coping well in the long term, integrating structured psychosocial support into long-term follow-up is recommended to facilitate a timely and adequate transition into adulthood., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: The occurrence of a second primary cancer (SPC) after primary esophageal carcinoma (EC) or gastric cardia carcinoma(GCC) is well acknowledged. However, previous research on the risk of SPC among these patients has been predominantly conducted in Asian countries. Yet, notable population-dependent variation in histological types and risk profiles exists. This register-based study assesses the histology-specific risk of SPC among individuals initially diagnosed with a first primary EC or GCC., Patients and Methods: We obtained data on 7197 patients diagnosed with EC/GCC in Finland between 1980 and 2022 from the Finnish Cancer Registry. Standardized incidence ratios (SIR) of SPC were subsequently calculated relatively to the cancer risk of the general population., Results: The average and median follow-up times were 2.8 years and 10.5 months. Adenocarcinomas and squamous cell carcinomas comprised 57.8% (n = 4165) and 36.6% (n = 2631) of all cases, respectively. An increased SIR was noted among EC/GCC patients after 15-20 years of follow-up (SIR 1.49, 95% CI: 1.01-2.11). Among adenocarcinoma patients, an increased SIR for SPCs of the digestive organs was seen in the 40-54-year-old group (SIR 9.86, 95% CI: 3.62-21.45). Squamous cell carcinoma patients displayed increased SIRs for cancer of the mouth/pharynx (SIR 3.20, 95% CI: 1.17-6.95) and respiratory organs (1.77, 1.07-2.76)., Conclusion: Healthcare professionals should be aware of the increased risk of SPCs occurring in the mouth/pharynx, respiratory and digestive organs in survivors of EC/GCC. Patients should be advised about this risk and remain alert for symptoms, even beyond the standard 5-year follow-up period., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Nikkilä et al.)

Background: Survivors of childhood cancer may face difficulties at school. We investigated whether childhood cancer affects attainment of upper secondary education, in a register-based cohort study from Denmark, Finland, and Sweden, where we limit bias from selection and participation., Methods: From the national cancer registers, we identified all long-term survivors of childhood cancer diagnosed aged 0-14 years in 1971-2005 (n = 7629), compared them to matched population comparisons (n = 35,411) and siblings (n = 6114), using odds ratios (OR) and 95% confidence intervals (CI)., Results: Overall, 6127 survivors (80%) had attained upper secondary education by age 25, compared to 84% among comparison groups. Elevated OR for not attaining this level were mainly confined to survivors of central nervous system (CNS) tumours (OR Surv_PopComp 2.05, 95%CI: 1.83-2.29). Other risk groups were survivors who had spent more time in hospital around cancer diagnosis and those who had hospital contacts in early adulthood, particularly psychiatric. Survivors of all cancer types were less likely to have attained upper secondary education without delay., Conclusions: Although survivors of childhood cancer experienced delays in their education, many had caught up by age 25. Except for survivors of CNS tumours, survivors attained upper secondary education to almost the same extent as their peers., (© 2023. The Author(s).)

Background: Evidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe., Methods: Patients diagnosed with primary LSCC from 1953-2018 were retrieved from the Finnish Cancer Registry. A total of 6241 LSCC patients were identified adding to 49,393 person-years (PY) of follow-up until the end of 2019. Only one patient emigrated and was lost to follow-up. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population. Only non-laryngeal SPCs diagnosed six months after diagnosis of primary LSCC were included., Results: A SPC was diagnosed in 1244 LSCC patients (20% of all LSCC patients) over the 65-year period, predominantly in men (92%, n  = 1170). Out of all SPCs, 34% were diagnosed within 0.5 to 5 years and 66% after 5 years from primary LSCC. Among male patients, the overall SIR for SPC at any location was 1.61 (95% CI: 1.52-1.71), corresponding to 9.49 excess SPCs per 1000 PYR (95% CI: 8.19-11). The corresponding SIR for women was 1.47 (95% CI: 1.15-1.84), yielding 4.82 excess SPCs per 1000 PYR (95% CI: 2.36-9.84). The risk remained significant even after 20 years of follow-up (SIR for all 1.73, 95% CI: 1.49-2.01 and EAR 16.8 per 1000 PY, 11.88-23.75). The risk for SPC was also significantly elevated in all age groups, except <40. The highest SIRs were for SPCs arising in the mouth/pharynx (SIR for all 3.08, 95% CI: 2.36-3.95 and EAR 0.80 per 1000 PY, 0.55-1.15) and lungs (3.02, 2.75-3.30 and 5.90 per 1000, 5.13-6.78)., Conclusion: Patients with LSCC as primary cancer have a 60% excess risk for an SPC, especially for tobacco-associated cancers, remaining significantly elevated even decades after treatment.

Background: Cervical, liver and stomach cancers are the most common infection-associated malignancies and the leading cause of morbidity in non-Western regions. We compared the incidence and mortality of these cancers between non-Western immigrant and non-immigrant Nordic female populations. We also analysed the effect of age at immigration, duration of residence and education on cancer burden., Material and Methods: Study population consisted of women residents in Denmark, Finland, Iceland and Norway in 1973-2020. Non-Western women contributed 3.1% of the total 260 million person-years at risk. All women were followed from their 20th birthday, or from the date of immigration if after, until the date of their first primary cancer diagnosis, death, emigration, or the end of the country-specific study period. All data were adjusted for 10-year age groups and calendar periods, and immigrant data was further broken down by region of birth, age at immigration and education level. Country-specific estimates were produced by multivariable Poisson regression and pooled in Finland with a random effects model., Results: Altogether, there were 60 982 cases of cervical, liver and stomach cancer in the study population, causing 36 582 deaths. The immigrant women had significantly higher liver (rate ratio [RR] 1.78, 95% confidence interval (CI) 1.03-3.06) and stomach cancer incidence (RR 1.68, CI 1.29-2.18), and stomach cancer mortality (RR 1.49, CI 1.17-1.92) than non-immigrant women. In the immigrant population, high education was related to lower incidence and mortality of studied cancers. The rate ratio of cervical cancer decreased with duration of residence and increased with rising age at immigration., Conclusion: Due to the increased incidence and mortality of infection-related cancers and changes in cancer patterns by age at immigration and duration of residence, attention should be paid to targeted health care services for immigrants. Special efforts should be given to women who have spent their youth in high-risk areas.

Background: Childhood cancer survivors face various adverse consequences. This Nordic register-based cohort study aimed to assess whether survivors of childhood cancer are more likely to have low income than their peers., Methods: We identified 17,392 childhood cancer survivors diagnosed at ages 0 to 19 between 1971 and 2009 with 83,221 age-, sex-, and country-matched population comparisons. Annual disposable income at ages 20 to 50 years was retrieved from statistical offices (for 1990-2017) and categorized into low income and middle/high income. The number of transitions between income categories were assessed using binomial regression analyses., Results: The prevalence of annual low income among childhood cancer survivors was 18.1% and 15.6% among population comparisons (risk ratio [RR] 1.17; 95% confidence interval [CI] 1.16-1.18). Compared to population comparisons, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to transition from low to middle/high income and 12% (10%-15%) more likely to transition from middle/high to low income during follow-up. Among those initially in the low income category, survivors were 7% (95% CI 3%-11%) more likely to remain in the low income category. If the initial category was middle/high income, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to remain in the middle/high income and 45% (37%-53%) more likely to transition to the low income category permanently., Conclusions: Childhood cancer survivors are at higher risk for low income in adulthood than their peers. These disparities might be reduced by continued career counseling along with support in managing within the social security system., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Cancer risk varies geographically, and migrants are influenced by different risk factors before, during and after migration. Increased migration from non-Western countries to the Nordic countries calls for a better understanding of the migrants' cancer risk and the change in risk patterns over time. The aim of this study was to compare the incidence and mortality of breast, colorectal and lung cancer between non-Western immigrant and the native female population in Denmark, Finland, Iceland, and Norway., Material and Methods: Data from national registries were processed and pre-analysed in each country. Multivariate Poisson regression models were used to model the relative differences in incidence and mortality as rate ratios (RR). The country-specific estimates and summary statistics were pooled together using a random effects model., Results: Non-Western immigrant women had significantly lower breast (RR 0.71, 0.65-0.78), colorectal (RR 0.72, 0.57-0.92) and lung (RR 0.55, 0.42-0.72) cancer incidence rates than native women, and the risk of these cancers among immigrant women increased with duration of residence. Differences were parallel in breast, colorectal and lung cancer mortality (RR 0.64, 0.55-0.74; RR 0.66, 0.48-0.92; RR 0.51, 0.34-0.79). Among immigrant women, higher education increased the risk for breast cancer and decreased it for lung cancer., Conclusion: The results significantly complement and add to the previous findings of cancer burden and cancer burden transition among migrants and provide evidence of a prolonged cancer risk advantage among non-Western immigrant women. However, the findings show an increasing risk of lifestyle-related cancers with increasing duration of residence in the host country. Further studies are needed to discover underlying reasons for this phenomenon., (© 2023. The Author(s).)

Background: Colorectal cancer (CRC) patient pathways focus typically on periods after confirmed diagnosis and only limited data are available on pathways prior to cancer diagnosis. The aim of the study was to describe the use of health services (HS) one year before diagnosis among CRC patients in Finland. We also studied the role of sex, age, stage, and university hospital district in relation to the use of HS during the pre-diagnostic phase. This information is expected to bring light on the question why CRC is often not found in its early stages., Methods: Incident CRC cases (N = 3115) concerning year 2015 were retrieved from the Finnish Cancer Registry and linked with data from the Finnish Institute for Health and Welfare on primary or specialised care outpatient visits or inpatient episodes over one year prior to CRC diagnosis. We modelled the average number of HS events per patient using Poisson regression model with log-link. Change points for monthly HS event rates and 95% CIs one year before diagnosis were evaluated using Poisson broken line regression models., Results: Around 10% of patients diagnosed in 2015 had no events prior to cancer leaving 2816 CRCs in the study. Of all pre-diagnostic events (N = 23268), 86% were outpatient events and 14% inpatient episodes. More than half of the inpatient episodes (65%) started as urgent admissions. The use of HS started to increase 3-4 months before diagnosis. The average number of pre-diagnostic HS events per patient varied by sex, age, stage and university hospital district. Overall, men had more events per patient than women and older patients had more events than younger patients., Conclusions: The amount of inpatient episodes starting as urgent admissions indicate potential bottlenecks in the access to health services. An increase in service use only 3-4 months prior to diagnosis reflects a need for advice both for health care professionals and the general population in recognising symptoms of CRC., (© 2023. The Author(s).)

Introduction: Limited data exist regarding head and neck cancer (HNC) burden among immigrants who may have distinct characteristics, and hence different incidence rates from the general population. Variations in behavioral habits, cultural lifestyle, or diet may cause variations across different subgroups., Methods: The whole immigrant population of Finnish residents born abroad, and their children were retrieved for the years 1970-2017. First-generation immigrants are defined as individuals born abroad, excluding their children (even if born abroad). The study comprised 0.5 million first-generation immigrants and 0.3 million children, contributing to 6 million and 5 million person-years of follow-up, respectively. Standardized incidence ratios (SIR) and excess absolute risk (EAR) per 100,000 person-years at risk were calculated to quantify the risk of HNC among immigrants relative to the general Finnish population., Results: The overall risk of any HNC was not increased among first-generation male immigrants (SIR 1.00, 95% CI: 0.88-1.15), but significantly elevated for cancer of the pharynx (SIR 1.56, 95% CI: 1.22-1.95), and larynx (SIR 1.38, 95% CI: 1.02-1.83) and decreased for lip (SIR 0.38, 95% CI: 0.20-0.67). The increased risk of pharyngeal cancer was highest among male immigrants from Asia Pacific (SIR 4.21, 95% CI: 2.02-7.75). First-generation immigrant women had a significantly reduced risk of any HNC (SIR 0.45, 95% CI: 0.37-0.55), which remained even after stratification by site. We observed no increased risk of any HNC among the children of first-generation immigrants., Conclusion: Healthcare professionals need to recognize the groups at higher HNC risk. Efforts to address the main etiological risk factors, such as smoking, are needed among the selected immigrant populations, that haven't yet reached similar decreasing trends, as in for example smoking, as the main population.NOVELTY AND IMPACTCurrently, globally, over 280 million people live outside their country of birth. Limited data exist regarding head and neck cancer (HNC) burden among immigrants who may have distinct characteristics and hence different incidence rates from the general population. Immigrant studies can provide novel data by shedding light on risk alterations and the pace of acculturation of different populations.

Background: Central nervous system (CNS) tumors are a heterogeneous group of tumors that include several aggressive malignancies with a high mortality rate. This study aimed to evaluate the familial relative risk of CNS tumors in family members of early-onset index cases (probands) in and between diffuse glioma, non-diffuse glioma, meningioma, and other CNS tumors., Methods: We retrieved tumor data from the Finnish cancer registry and familial relationships data from the population information system. We ascertained 5408 probands diagnosed with primary CNS tumors (age ≤40 years) between 1970 and 2012 in Finland. We report the standardized incidence ratios as a measure of familial aggregation using Poisson regression., Results: The risk of early-onset diffuse glioma increased among siblings of probands with the same tumor [SIR 3.85, 95% confidence interval (CI): 1.66-7.59], with association mainly returning to grade 2-3 diffuse gliomas. Early-onset other CNS tumors were associated with an increased risk of other CNS tumors, early-onset meningioma, and late-onset diffuse glioma in 1st-degree relatives. The elevated risk of other CNS tumors was largely caused by schwannomas (SIR 59.44, 95% CI: 27.18-112.84 for 1st-degree relatives) and associated with neurofibromatosis. No tumor syndrome was associated with an increased risk of diffuse gliomas., Conclusions: The early onset of grade 2-3 diffuse gliomas is associated with an increased risk of similar tumor entities. Early-onset schwannomas dramatically increase CNS tumor risk with a broader tumor-type profile. In future studies, it would be important to identify the underlying shared hereditary factors that contribute to the development of familial diffuse gliomas., Competing Interests: No conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Adolescents with chronic diseases are shown to be vulnerable for risky sexual behavior. Childhood cancer patients seem to engage in risky health behaviors as frequently as general population, but little is known about sexual issues in this group of patients., Material and Methods: We characterized the risk for sexually transmitted diseases (STD) in a Finnish population-based cohort of over 6,000 childhood cancer patients diagnosed with cancer under the age of 20 years between 1971 and 2009, compared with over 30,000 age- and sex -matched population comparisons. The data were constructed through linkage between national cancer, population, infectious diseases, and hospital discharge registries. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression modeling with attained age as the underlying time scale., Results: Childhood cancer patients had a decreased risk for having an infection with chlamydia, the most common STD in our cohort, when comparing with population comparisons (HR 0.77, 95% CI 0.69-0.86). The risk was lowest among male patients (HR 0.64, 95% CI 0.53-0.79) and patients with central nervous system (CNS) tumors (HR 0.46, 95% CI 0.33-0.63). The overall risk for cervical dysplasia was slightly increased among female cancer patients when compared with their population comparisons (HR 1.28, 95% CI 1.02-1.60). Greatest risk elevation was found among patients diagnosed with cancer in ages 10-14 years (HR 2.31, 95% CI 1.46-3.65) and patients with lymphoma (HR 1.95, 95% CI 1.20-3.16). The risk for all explored outcomes seemed to be decreased among patients with CNS tumors., Conclusions: Our findings highlight the importance of integrating sexual issues as a part of psychosocial support and having a systematic transition program in the follow-up care of childhood cancer patients.

Background: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population., Methods: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer., Findings: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3-16·5) for childhood cancer survivors, 14·0% (13·5-14·5) for siblings, and 12·7% (12·4-12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31-1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28-1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals., Interpretation: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors., Funding: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Hospitalised patients are at risk of temporary or permanent loss of functioning which impacts their future independence. Implementation of a rehabilitative approach in everyday nursing in the acute care setting may produce good therapeutic results and promote independent daily living of patients. Thus, the aim of the study was to explore and understand the patterns of a rehabilitative approach in acute hospital wards from the perspective of interdisciplinary team members. Specifically, our aim was to identify the factors promoting and preventing a rehabilitative approach., Method: We conducted four focus group interviews with 21 participants, including multidisciplinary team members from acute hospital wards. Data were analysed with conventional inductive content analysis., Results: The findings highlighted that the rehabilitative approach, as a personal way of working and personal working attitude, was a part of comprehensive nursing. The main goals of the rehabilitative approach were to support the physical functioning of the patients and their independent initiative and individuality during clinical care in hospital ward. The promoting and preventing factors that influenced the development of the rehabilitative approach consisted of personal factors, organisational factors and the physical settings of the hospital wards., Conclusion: The findings of this study indicate that the rehabilitative approach in nursing focused on supporting the physical functioning, independence and self-confidence of the patient. The staff highlighted that interdisciplinary teamwork was one feature of the rehabilitative approach. The rehabilitative approach in nursing should be established as a part of everyday activity in clinical practice., (© 2021 Nordic College of Caring Science.)

Background: A childhood cancer diagnosis and late effects of treatment may affect survivors' possibilities of employment or highly skilled occupations later in life. In this study, we compared the employment and occupational status of childhood cancer survivors with population comparisons and siblings., Methods: In a cohort study based on Nordic registers, we identified 10 461 survivors of childhood cancer diagnosed before age 20 years in Denmark, Finland and Sweden since 1971. Survivors were compared with 48 928 population comparisons matched to survivors by age, sex and geographical region and 12 605 siblings of survivors. Annual outcome information on employment, unemployment, health-related unemployment and occupational position was obtained from the statistical institutes between 1980-2017 and assessed in multivariate logistic regression analyses from age 30 onwards., Findings: By 30 years of age, 9.2% (95% CI, 8.6-9.9%) of survivors were unemployed for health reasons. Childhood cancer survivors had considerably higher odds of health-related unemployment at ages 30, 40 and 50 than population comparisons (OR age30 , 2.57; 95% CI, 2.35-2.81) and siblings (OR age30 , 2.50; 95% CI, 2.15-2.90). We observed no large difference in unemployment unrelated to health or in occupational position. Health-related unemployment was particularly pronounced among survivors of central nervous system tumours and survivors diagnosed below 15 years of age., Interpretation: Survivors at risk of health-related unemployment should be offered comprehensive survivorship care and interventions for obtaining and maintaining suitable employment., Funding: NordForsk [76111], the Danish Childhood Cancer Foundation [2016-0293], Aarhus University [43239402], the Swedish Childhood Cancer Foundation [PR2020-0130] and [OB2019-0003], Tømrermester Jørgen Holm og Hustru Elisa F. Hansens Mindelegat [20088] and the Swiss National Science Foundation to LM [P2LUP3&#95;175288]., Competing Interests: The authors report no conflicts of interest., (© 2021 The Author(s).)

Introduction: The growing number of survivors of childhood cancer, with many years of life ahead, demonstrates the increasing clinical and public health relevance of investigating the risks of social and socioeconomic impairment after a childhood cancer diagnosis and the life-saving treatment. To enrich understanding of the mental, social and socioeconomic difficulties that childhood cancer survivors may face during their life-course, identify particularly vulnerable survivors and overcome the limitations of previous research, we initiated the Socioeconomic Consequences in Adult Life after Childhood Cancer in Scandinavia (SALiCCS) research programme., Methods: This Nordic cross-border research programme is a collaboration between the Danish Cancer Society, the Finnish Cancer Registry and Karolinska Institutet to investigate a broad range of mental, social and socioeconomic conditions in long-term childhood cancer survivors in Denmark, Finland and Sweden. SALiCCS is based on a registry-based matched cohort design, comprising five-year survivors of cancer diagnosed at ages 0-19 years (1971-2008 in Denmark, 1971-2009 in Finland, 1971-2011 in Sweden), age-, sex- and country-matched population comparisons and sibling comparisons who were followed over time. Outcomes of interest included mental disorders, educational achievements, employment and profession, family life and the need of social security benefits. Individual-level data linkage among various national registries provided the data for the research programme., Results: The SALiCCS core population comprises 21,292 five-year survivors, 103,303 population comparisons and 29,644 siblings as a second comparison group. The most common diagnoses in survivors were central nervous system tumours, leukaemias and lymphomas., Discussion: SALiCCS is the largest, most comprehensive population-based research initiative in this field, based on high-quality registry data with minimal risk of bias. The findings will be informative for evidence-based survivorship care targeting not only somatic late effects but also psychosocial impairments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Erdmann, Frederiksen, Mogensen, Pedersen, Mader, Talbäck, Bautz, Hirvonen, Kyrönlahti, Korhonen, Hasle, Malila, Madanat-Harjuoja, Feychting and Winther.)

Introduction: Smoking cessation is essential part of a successful treatment in many chronic diseases. Our aim was to analyse how actively clinicians discuss and document patients' smoking status into electronic health records (EHR) and deliver smoking cessation assistance., Methods: We analysed the results using a combination of rule and deep learning-based algorithms. Narrative reports of all adult patients, whose treatment started between years 2010 and 2016 for one of seven common chronic diseases, were followed for two years. Smoking related sentences were first extracted with a rule-based algorithm. Subsequently, pre-trained ULMFiT-based algorithm classified each patient's smoking status as a current smoker, ex-smoker, or never smoker. A rule-based algorithm was then again used to analyse the physician-patient discussions on smoking cessation among current smokers., Results: A total of 35,650 patients were studied. Of all patients, 60% were found to have a smoking status in EHR and the documentation improved over time. Smoking status was documented more actively among COPD (86%) and sleep apnoea (83%) patients compared to patients with asthma, type 1&2 diabetes, cerebral infarction and ischemic heart disease (range 44-61%). Of the current smokers (N=7,105), 49% had discussed smoking cessation with their physician. The performance of ULMFiT-based classifier was good with F-scores 79-92., Conclusion: Ee found that smoking status was documented in 60% of patients with chronic disease and that the clinician had discussed smoking cessation in 49% of patients who were current smokers. ULMFiT-based classifier showed good/excellent performance and allowed us to efficiently study a large number of patients' medical narratives., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Study Question: Does the probability of a live birth after fresh IVF/ICSI cycles with autologous oocytes differ in early onset female cancer survivors compared to their siblings?, Summary Answer: The probability of a live birth was similar in female cancer survivors and siblings after four fresh IVF/ICSI cycles., What Is Known Already: Fertility preservation strategies are rapidly being developed to help female cancer patients who wish to have children later. However, there are only a few studies available on fertility treatments and following live births in female cancer survivors before fertility preservation strategies became available. In one of them, the probability of a live birth was reduced after assisted reproductive technology with autologous oocytes in cancer survivors compared to siblings., Study Design, Size, Duration: In this retrospective, register-based study, data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8944 female cancer survivors (diagnosed with cancer between 1953 and 2012 at the age of 0-40 years) and 9848 female siblings of survivors eligible for IVF/ICSI treatments between January 1993 and December 2012., Participants/materials, Setting, Methods: Fresh IVF/ICSI cycles and following live birth rates (LBRs) within 22-48 weeks in cancer survivors and siblings at the age of 20-41 years were identified. A binomial regression model with log-link function was used to calculate risk ratio (RR) for live births after fresh IVF/ICSI cycles in survivors compared to siblings, adjusting for attained age and calendar time. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for an IVF/ICSI treatment, as well as overall live births, including both pregnancies after fertility treatments and spontaneous pregnancies, in survivors compared to siblings., Main Results and the Role of Chance: We observed an overall decreased LBR, irrespective of IVF/ICSI treatments, in cancer survivors compared to siblings (IRR 0.68, 95% CI 0.64-0.71). All in all, 179 (2.0%) survivors and 230 (2.3%) siblings were prescribed fertility drugs for IVF/ICSI treatments (IRR 0.72, 95% CI 0.62-0.84). For the first fresh IVF/ICSI cycle, the LBR was 17.2% among survivors and 15.7% among siblings (RR 1.13, 95% CI 0.72-1.87). The mean LBR after four fresh IVF/ICSI cycles was not statistically different in survivors compared to siblings., Limitations, Reasons for Caution: In this study, only IVF/ICSI treatments with autologous oocytes were included. The probability of a live birth after a frozen embryo transfer or oocyte donation could not be evaluated in this study. Information on miscarriages, extrauterine pregnancies or termination of pregnancies was not available., Wider Implications of the Findings: For those early onset cancer survivors, who received IVF/ICSI treatments, the probability of live birth was not different from siblings who received IVF/ICSI treatments. However, an overall decreased LBR, irrespective of IVF/ICSI treatments, was observed in cancer survivors compared to siblings, indicating that cancer survivors receiving IVF/ICSI treatments in our study consisted of a selected group with at least a moderate ovarian reserve., Study Funding/competing Interest(s): This study was supported by a grant from the Cancer Foundation (Finland) (grant number 130079) and by a grant from LähiTapiola. The authors have no potential conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The prevalence of asthma has been growing among working age people over the last decades. In this study, we examine the development of Work Ability Score (WAS) among middle-aged asthmatics in a longitudinal setting, in order to find risk factors for poor development., Methods: We followed the development of WAS trends during 10 years in a cohort of 529 middle-aged asthmatics, who were active in working life. Follow-up questionnaires were mailed in years 1, 2, 4, 6, 8, and 10. To study the development of WAS over time, we computed the discrete Frechet distance, which describes the similarity between the shapes of WAS curves., Results: Sixty-eight percent of the patients' WAS remained good or excellent throughout the follow-up period, while 24% of the patients WAS trend remained moderate. However, in 8%, the WAS was poor already in baseline and decreased further throughout the study. Using logistic regression, the moderate/poor development was associated significantly with high body mass index (BMI), pack years, adult onset asthma, physically strenuous work, number of co-morbidities, especially in psychiatric conditions, hypertension, and gastroesophageal reflux disease(GERD). When the model was adjusted for age and gender, adulthood onset of asthma and pack years lost their significance. Based on medication (high dose of inhaled corticosteroids (ICS) and second controller in use), 8% of the patients had severe asthma., Conclusion: In the great majority of middle-aged asthma patients WAS remained stable throughout the follow-up period. However, 8% of the patients, who had more severe asthma and multiple co-morbidities, showed significantly poorer outcomes.

Population-based studies on familial aggregation of haematological malignancies (HM) have rarely focused specifically on early-onset HMs. We estimated standardized incidence ratios (SIR) and cumulative risks of relatives with Hodgkin lymphoma (HL), non-Hodgkin lymphomas (NHL), acute lymphoblastic leukaemia/lymphoma (ALL/LBL) and acute myeloid leukaemia (AML) when index persons and relatives were diagnosed with early-onset HM. A total of 8791 patients aged ≤40 years and diagnosed with primary HM in Finland from 1970 to 2012 were identified from the Finnish Cancer Registry and their 75 774 family members were retrieved from the population registry. SIRs for concordant HMs were elevated among first-degree relatives in all of the most common HMs of children and adolescents and young adults (AYA). The risk was highest among siblings with HL (SIR 9·09, 95% confidence interval 5·55-14·04) and AML (8·29, 1·00-29·96). HL also had the highest cumulative risk for siblings at ≤40 years of age (0·92% vs. 0·11% in the population). In conclusion, significantly elevated SIRs indicate a role of shared aetiological factors in some families, which should be noted in the clinical setting when caring for patients with early-onset HMs., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Testicular cancer (TC) is the most common form of cancer in men aged 15-35 years. Familial risk for TC is among highest of all cancers., Material and Methods: A prospective observational cohort of 9111 relatives in 2,188 families of early-onset TC patients, called probands, diagnosed at age ≤40 years in Finland between 1970 and 2012. Standardized incidence ratios (SIR) were used as measures of familial aggregation for early-onset (≤40 years) TC. Follow-up ended at diagnosis of TC, death or 31 December 2014 whichever earliest., Results: Among first-degree relatives of early-onset TCs, in all 12 early-onset TC cases (0.24%) were diagnosed over the follow-up; the SIR for any first-degree relative was 4.59 (95% confidence interval (CI): 2.37-8.01) and for brothers the SIR was 6.51 (95% CI 3.12-11.96)., Discussion: Familial aggregation of TC shows substantial risk for early-onset TC among first-degree relatives of early-onset TC patients in Finland. This is important to acknowledge to avoid diagnostic delay especially of TC., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An association between maternal diabetes, its medication and childhood cancer has not been previously explored in a registry-based setting. With a case-control design, we aimed to explore whether maternal diabetes is associated with an increased risk of childhood cancer in the offspring. Combining data from population-based registries, we analyzed a total of 2,029 cases, that is, persons with childhood cancer diagnosed under the age of 20 years between years 1996-2014 and a total of 10,103 matched population controls. The mothers of the cases/controls and their diagnoses of diabetes (DM) before/during pregnancy as well as their insulin/metformin prescriptions during pregnancy were identified. Conditional logistic regression modeling was used to analyze the risk of childhood cancer. The OR for childhood cancer among those exposed to any maternal diabetes was 1.32 (95% CI 1.14-1.54) compared to the offspring of the nondiabetic mothers. The effect of maternal diabetes on the risk of childhood cancer remained elevated even after adjusting for maternal age, parity and smoking. Our data suggest that maternal diabetes medication may reduce the risk for childhood cancer (adjusted OR 0.83, 95% CI 0.36-1.94), especially in gestational diabetes (adjusted OR 0.26, 95% CI 0.05-1.25), compared to the diabetic mothers without medication. The risk of childhood leukemia was significantly higher among children exposed to any maternal diabetes (OR 1.36, CI 1.04-1.77) compared to the unexposed. Maternal diabetes appears to be associated with an increased risk of childhood cancer in the offspring. The possible risk-reducing effect of an exposure to diabetes medication on offspring cancer risk warrants further investigation., (© 2019 UICC.)

Background: Linked population-based registries provide a unique source for identification of new family cancer syndromes and for elucidating risk of early-onset cancer in close relatives of cancer patients., Methods: Using the Finnish Cancer Registry, we identified 9078 probands who had been diagnosed with cancer at <21 years of age between 1970 and 2012. Siblings, offspring, parents, nephews, and nieces of probands were identified from the Population Registry. Childhood and young adult (ChYA) cancer diagnoses (age 0-39 years) in relatives were identified by linking to the Finnish Cancer Registry. The relative risk of ChYA cancer in family members of probands was estimated using standardized incidence ratios (SIRs)., Results: Among 58,010 family members of the 9078 probands, 363 ChYA cancers were diagnosed, 324 of which were expected (SIR, 1.12; 95% CI, 1.01-1.24). The risk of ChYA cancer was elevated both in offspring (SIR, 2.25; 95% CI, 1.51-3.24) and in siblings (SIR, 1.17; 95% CI, 1.01-1.36). Offspring of probands with retinoblastoma were at highest risk (SIR, 75.85; 95% CI, 32.75-149.45); risks were also elevated for siblings of probands with lymphoma (SIR, 1.62; 95% CI, 1.14-2.25). Known cancer predisposition syndromes were observed in 29 (66%) of 44 sibling pairs with cancers diagnosed at <21 years of age and in 20% of the 135 families with a childhood cancer proband whose sibling was diagnosed with a young adult malignancy., Conclusion: Linked population-based registry data indicate a modestly increased risk of ChYA in relatives of children with cancer. Some of the observed cancer clusters in the cohort suggest novel patterns and familial cancer syndromes., (© 2020 American Cancer Society.)

Introduction & Objectives: There are conflicting reports on the association of vasectomy and the risk of prostate cancer (PCa). Our objective was to evaluate the association between vasectomy and PCa from a nationwide cohort in Finland., Materials & Methods: Sterilization registry of Finland and the Finnish Cancer Registry data were utilized to identify all men who underwent vasectomy between years 1987-2014 in Finland. Standard incidence ratio (SIR) for PCa as well as all-cause standardized mortality ratios (SMR) were calculated., Results: We identified 38,124 men with vasectomy with a total of 429,937 person-years follow-up data. The median age at vasectomy was 39.7 years (interquartile range [IQR] 35.9-44.0), after vasectomy PCa was diagnosed in 413 men (122 cases 0-10 years, 219 cases 10-20 years and 72 cases >20 years from vasectomy). SIR for PCa for the vasectomy cohort was 1.15 (95% CI: 1.04-1.27). By the end of follow-up, 19 men had died from PCa, while the expected number was 20.5 (SMR 0.93 [95%CI: 0.56-1.44]). The overall mortality was decreased (SMR 0.54 [95%CI: 0.51-0.58]) among men with vasectomy., Conclusion: We found a small statistically significant increase in PCa incidence after vasectomy, but in contrast the mortality of vasectomized men was significantly reduced. This may be due to higher likelihood of vasectomized men to undergo prostate-specific antigen testing, having healthier general lifestyle and other biological factors e.g. high reproductive fitness., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Advances in multimodality cancer treatments have increased the risk of long-term complications in early-onset cancer survivors. For female cancer survivors, these include diminished reproductive function, often resulting in a narrowed fertile window. The aim of our study was to evaluate the use of fertility treatments in cancer survivors (aged 0-39 years at diagnosis) compared to siblings. Data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8,929 survivors and 9,495 siblings without previous deliveries. Fertility drug purchases from 1993 to 2012 at the age of 16-41 years were included. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for the use of fertility drugs, adjusting for age and calendar time at fertility drug purchase. Fertility treatments were more common in survivors compared to siblings, as 6.1% of survivors compared to 3.8% of siblings had bought fertility drugs (IRR 1.43, 95% confidence interval [CI] 1.25-1.65). A subclassification of fertility treatments into ovulation inductions and assisted reproductive technology (ART), showed increased use of ART (IRR 2.41, 95% CI 1.97-2.96), whereas the use of ovulation induction was similar in survivors and siblings. Analyses by calendar time periods showed the use of ART to be significantly higher in the most recent decade, from 2003 onwards. We conclude that cancer survivors have an increased risk for subfertility, which is why fertility counseling is important. However, our results mirror a more active approach among clinicians towards fertility treatments in cancer survivors during the most recent years., (© 2019 UICC.)

Introduction : Smoking has a significant impact on the development and progression of asthma and chronic obstructive pulmonary disease (COPD). Self-reported questionnaires and structured interviews are usually the only way to study patients' smoking history. In this study, we aim to examine the consistency of the responses of asthma and COPD patients to repeated standardised questions on their smoking habits over the period of 10 years. Methods : The study population consisted of 1329 asthma and 959 COPD patients, who enrolled in the study during years 2005-2007. A follow-up questionnaire was mailed to the participants 1, 2, 4, 6, 8, and 10 years after the recruitment. Results : Among the participants who returned three or more questionnaires ( N = 1454), 78.5 % of the patients reported unchanged smoking status (never smoker, ex-smoker or current smoker) across the time. In 4.5% of the answers, the reported smoking statuses were considered unreliable/conflicting (first never smoker and, later, smoker or ex-smoker). The remainder of the patients changed their status from current smoker to ex-smoker and vice versa at least once, most likely due to struggling with quitting. COPD patients were more frequently heavy ex- or current smokers compared to the asthma group. The intraclass coefficient correlations between self-reported starting (0.85) and stopping (0.94) years as well as the consumption of cigarettes (0.74) over time showed good reliability among both asthma and COPD patients. Conclusion : Self-reported smoking data among elderly asthma and COPD patients over a 10-year follow-up is reliable. Pack years can be considered a rough estimate for their comprehensive consumption of tobacco products over time. We also observed that the questionnaire we used was not designed for dynamic changes in smoking which are rather common among heavy smokers especially when the follow-up time is several years, as in our study.

Viruses are a significant threat to both human health and the economy, and there is an urgent need for novel anti-viral drugs and vaccines. High-resolution viral structures inform our understanding of the virosphere, and inspire novel therapies. Here we present a method of obtaining such structural information that avoids potentially disruptive handling, by collecting diffraction data from intact infected cells. We identify a suitable combination of cell type and virus to accumulate particles in the cells, establish a suitable time point where most cells contain virus condensates and use electron microscopy to demonstrate that these are ordered crystalline arrays of empty capsids. We then use an X-ray free electron laser to provide extremely bright illumination of sub-micron intracellular condensates of bacteriophage phiX174 inside living Escherichia coli at room temperature. We have been able to collect low resolution diffraction data. Despite the limited resolution and completeness of these initial data, due to a far from optimal experimental setup, we have used novel methodology to determine a putative space group, unit cell dimensions, particle packing and likely maturation state of the particles.

A 45-year-old man needed emergency tracheostomy and cranioplasty. He was intubated with a cuffed oral polyvinylchloride endotracheal tube and ventilated with 100% oxygen before tracheal incision. During opening of the trachea using diathermy, a popping sound was heard and flames originating from the tracheal incision were observed. The endotracheal tube was charred and its lumen had melted. Immediately after the incident, bronchofibroscopic examination revealed inhalation injury. After remaining for 8 weeks in hospital, the patient was transferred to a health care centre, where he was found dead in his bed.

Background: Although supplemental oxygen has been shown to be as effective as ondansetron in the prevention of post-operative nausea and vomiting (PONV) in one study in abdominal surgery patients, the antiemetic efficacy of supplemental oxygen is controversial on the basis of studies with other patients. We compared the efficacy of 80% and 30% oxygen in decreasing PONV in breast surgery. Ondansetron was used as an active control., Methods: Ninety patients were given a standardized sevoflurane anesthetic. They were randomly assigned to three groups: 30% oxygen in nitrogen and saline 2 ml intravenously (i.v.) at the end of surgery (group 30); 80% oxygen in nitrogen and saline 2 ml (group 80); and 30% oxygen in nitrogen and ondansetron 4 mg (group O). Oxygen was administered during surgery and up to 2 h after surgery., Results: The incidence of total response (no retching or vomiting, no nausea) during the first 24 post-operative hours was not different between group 80 (17%) and group 30 (11%) but was higher in group O (43%) than in group 30 (P<0.05). Compared with group O, patients in group 80 experienced more vomiting during the study period 0-24 h (66% vs. 32%; P<0.05) and more nausea during the period 6-24 h (72% vs. 39%; P<0.05). There was no difference between the groups in their risk for PONV, pain scores, opioid consumption, or patient satisfaction., Conclusions: In this study, supplemental 80% oxygen administration failed to decrease PONV in breast surgery.

A 53- year-old woman without a previous history of thyroid disease was scheduled for mastectomy. On arrival in the operating theatre unpremedicated she appeared restless and tachycardic. Midazolam and fentanyl was administered intravenously. Concomitantly, sinus tachycardia developed and a flush reaction was observed in the skin of the thoracic region and neck. The blood pressure increased to 265/160 mmHg and the patient lost consciousness and became apnoeic. Unconsciousness and apnoea lasted for approximately 25 min and the operation was postponed. Further investigations revealed an elevated serum free thyroxine level and suppressed serum thyrotropin diagnostic of hyperthyroidism. The serum TSH receptor antibody concentration was elevated, indicating that the patient was suffering from Graves' disease. We present a case of a previously unknown hyperthyroid patient, with breast cancer, presenting as a thyroid crisis on induction of anaesthesia. Although being quite a rare occurrence, unsuspected thyroid disease should be borne in mind when an agitated patient enters the operating theatre.

Objective: This randomized, double-blind, multicenter study was planned to compare the efficacy and tolerance of a novel oral regimen containing estradiol (2.0 mg) sequentially combined with trimegestone, at a daily dose of either 0.25 mg or 0.5 mg, with a standard hormone replacement therapy containing estradiol and norethisterone acetate (E2 + NETA) in the treatment of climacteric symptoms., Methods: The study was conducted over 13 cycles, each of 28 days, and involved 487 subjects, of whom 349 completed the study., Results: All three treatments were equally effective in alleviating hot flushes and showed a progressive and significant reduction in the value of the Kupperman index. The treatments diminished equally effectively urogenital signs and symptoms. All treatments were well tolerated and the incidences of adverse events associated with each treatment were similar across the treatment groups. The duration of expected withdrawal bleeding was shorter in the estradiol + trimegestone 0.5 mg group than in the estradiol + trimegestone 0.25 mg or E2 + NETA group., Conclusion: All treatments were effective and well tolerated, providing significant relief from climacteric symptoms. Treatment with estradiol + trimegestone 0.5 mg provided the most favorable bleeding pattern.

Objective: To assess the acceptability, efficacy and endometrial safety of transdermal estradiol gel (Divigel/Sandrena) combined with monthly or quarterly oral progestogen (medroxyprogesterone acetate)., Methods: This 12-month, multicenter, open-label study was carried out at 12 study centers in Finland and Sweden. A total of 395 postmenopausal women received 1 mg estradiol in 1 g gel, daily, with oral medroxyprogesterone acetate 10 mg for the first 12 days every month (groups I and III) or every 3 months (group II). The main outcome measures were relief of climacteric symptoms, bleeding patterns and endometrial safety., Results: All regimens reduced the severity of hot flushes, sweating episodes and vaginal dryness. In groups I and III, approximately 80% and 70% of women, respectively, had regular monthly withdrawal bleeding (excepting the first cycle), with irregular bleeding in 8.3% and 5.3% of treatment months. In group II, approximately 94% of women had regular tri-monthly withdrawal bleeding, with irregular bleeding in 10.7% of the treatment months. Endometrial hyperplasia was observed in 0.3% of women. More than 87% of subjects completed the study, and 97% of these rated the gel as acceptable or convenient., Conclusions: Both the 1- and 3-month regimens were equally effective in controlling climacteric symptoms and protecting against endometrial hyperstimulation. The bleeding patterns were comparable between groups and were similar to those reported for oral estrogens. Estradiol gel was highly acceptable to the majority of women.

Background: The increased intra-abdominal pressure during pneumoperitoneum, together with the head-up tilt used in upper abdominal laparoscopies, would be expected to decrease venous return to the heart. The goal of our study was to determine whether laparoscopy impairs cardiac performance when preventive measures to improve venous return are taken, and to analyze the effects of positioning, anesthesia, and increased intra-abdominal pressure., Methods: Using invasive monitoring, hemodynamic changes were investigated in 15 ASA class I or II patients under isoflurane-fentanyl anesthesia during laparoscopic cholecystectomy. Before laparoscopy, the patients received an intravenous (IV) infusion of colloid solution if cardiac filling pressures were low, and their legs were wrapped from toes to groin with elastic bandages. Measurements were taken while the patients were awake in the supine (baseline) and head-up tilt (15-20 degrees) positions, and after the induction of anesthesia in the same positions. Measurements were repeated at regular intervals during laparoscopy (intra-abdominal pressure at 13-16 mm Hg), after deflation of the gas, and in the recovery room., Results: With the passive head-up tilt in awake and anesthetized patients, the cardiac index (CI), stroke index (SI), central venous pressure (CVP), and pulmonary capillary wedge pressure (PCWP) decreased, and systemic vascular resistance increased. With the patient under anesthesia, SI decreased, but CI did not change significantly as a result of the compensatory increase in heart rate. Carbon dioxide (CO2) insufflation at the start of laparoscopy produced increases in CVP and PCWP as well as mean systemic and mean pulmonary arterial pressures without changes in CI or SI. Toward the end of the laparoscopy, CI decreased by 15%. The hemodynamic values returned to nearly prelaparoscopic levels after deflation of the gas, and CI was elevated during the recovery period, whereas systemic vascular resistance was decreased in comparison with the baseline., Conclusions: By correcting relative dehydration and preventing the pooling of blood, CI decreased less than 20% during pneumoperitoneum as compared with the baseline awake level. The head-up positioning accounts for many of the adverse effects in hemodynamics during laparoscopic cholecystectomy.

In this prospective randomized clinical trial, two long-term contraceptive implants were studied with respect to hemostasis and liver function in 86 healthy young women. The two implants used were Implanon, containing the progestagen etonogestrel (the biologically active metabolite of desogestrel) and Norplant, the implant containing the progestagen levonorgestrel. The results of the trial showed that both implants had similar small effects on the hemostatic system that are not suggestive of a tendency towards thrombosis. The effect on liver function was characterized by increases in total bilirubin and gamma-glutamyl transferase and decreases in alanine aminotransferase and aspartate aminotransferase.

Objectives: A retrospective, subset analysis of the prospective Menopause Study Group data was performed to determine the effects of four conjugated estrogens (CE) + medroxyprogesterone acetate (MPA) regimens and one unopposed CE regimen on the lipid profiles of women with abnormal lipid levels (n = 525). Previously unpublished data on the entire study population were also reviewed to determine the effects of these hormone replacement regimens on blood pressure and weight (n = 1368, 1374, respectively)., Methods: During a 1-year, prospective trial, all patients took CE. Groups A and B also took continuous MPA 2.5 and 5 mg, respectively, C and D took MPA 5 and 10 mg for the last 14 cycle days of each 28-day cycle, and E took matching placebo tablets to replace MPA., Results: After 1 year, all five regimens were directly associated with significant elevations in high density lipoprotein-2 (HDL2) cholesterol and significant reductions in low density lipoprotein (LDL) cholesterol (p < 0.05), although unopposed estrogen produced the greatest increase in HDL2 cholesterol. The CE + MPA regimens were also associated with significant decreases in total cholesterol. Triglyceride levels did not change significantly from baseline in any treatment group (baseline values > 1.808 mmol/l (> 160 mg/dl)), although the CE + MPA regimens were associated with a mean triglyceride decrease and CE-only women (n = 8) had a mean triglyceride increase. No regimen produced significant weight or blood pressure changes., Conclusions: This analysis suggests that hormone replacement therapy (CE + MPA), used in appropriate dosages, may alter the HDL2 cholesterol and LDL cholesterol lipoproteins in postmenopausal women with borderline lipid levels (a higher-risk population) in a cardioprotective manner.

Objective: To compare two doses of a transdermal oestradiol gel (Divigel/Sandrena) plus oral sequential medroxyprogesterone acetate (MPA) with oral oestradiol valerate plus oral sequential MPA (Divina/Dilena)., Design: Two year, randomised, open-label, comparative study., Setting: Menopausal outpatient clinic in Helsinki., Subjects: Postmenopausal women with climacteric complaints or already using HRT., Interventions: (1) One gram gel containing 1 mg oestradiol for 3 months plus 20 mg oral MPA during the last 14 days; (2) 2 g gel containing 2 mg oestradiol for 21 days plus 10 mg oral MPA during the last 14 days; (3) 2 mg oestradiol valerate tablets for 3 weeks plus 10 mg oral MPA during the last 10 days. In all groups, each treatment period was followed by a 7-day medication-free interval., Main Outcome Measures: Climacteric complaints, bleeding control, bone mineral density, biomarkers of bone metabolism, lipid profile, tolerability and safety., Results: With each preparation, climacteric complaints were significantly reduced and good bleeding control was obtained. In addition, maintenance of bone mineral density as well as a reduction of bone turnover was achieved in all groups. Lipid parameters showed no unfavourable changes. Continuation rates were similar in all groups with overall 74% of patients completing the first year, whereas 94% of patients who elected to continue completed the second year. Tolerability of the gel was good: only 1.7% of patients discontinued treatment due to skin irritation., Conclusions: Transdermal oestradiol gel and oral oestradiol valerate tablets, used in combination with oral sequential MPA, are effective regimens of HRT in postmenopausal women. Transdermal oestradiol gel is an efficient, well-tolerated form of HRT.

Objective: To compare the efficacy, safety and tolerability of an oestradiol gel (1.0 mg of oestradiol daily, Divigel/Sandrena) with those of an oestradiol delivering patch (delivering 50 micrograms oestradiol/24 h, Estraderm TTS) in hormone replacement therapy of postmenopausal women. Dydrogesterone tablets (Terolut), 10 mg daily for the first 12 days of every month, were used as the progestogen component of the therapy., Main Outcome Measures: The effect of treatment on clinical symptoms and on endometrium, total body bone mineral density and lipid metabolism as well as the tolerability of the treatments with special emphasis on skin irritation and compliance were evaluated., Design: An open, randomised, controlled, parallel-group trial of 12 months' duration., Setting: The Medical Clinic of Kalevankatu, Helsinki, Finland., Participants: One hundred twenty postmenopausal women were treated with transdermal oestradiol combined with dydrogesterone. In addition, 25 women without HRT served as a reference group for the bone mineral density measurements., Results: Both treatment regimens were equally effective in alleviating climacteric symptoms, preserving bone mineral density and were equally safe. A trend towards heavier bleeding was detected in patients treated with the oestradiol delivering patch. A statistically nonsignificant decrease of total cholesterol and triglyceride concentrations but no change in high-density lipoprotein cholesterol concentration was observed in both groups. The acceptability of the treatment was higher in the gel group (96.4%) than in the patch group (90.7%). Only two (3.3%) women using the oestradiol gel complained of skin irritation whereas 28 patients (46.7%, P < 0.001) using the oestradiol delivering patch reported this adverse effect., Conclusions: Both the oestradiol gel and the oestradiol delivering patch are equally effective in hormone replacement therapy but the gel preparation is less irritative to the skin.

This study was designed to assess the sexuality of young women surviving acute leukaemia in childhood or early adolescence. Thirty of 31 survivors were compared with 50 healthy age matched controls. Three methods were used: a self report questionnaire, a face to face interview conducted by a psychiatrist, and a projective psychological test. The age at initiation of dating and sexual activity, the frequency of sexual intercourse, and opinions on sexual behaviour were similar in the two groups. With regard to inner sexuality, however, the survivors differed significantly from the healthy controls. Their images of sexuality were more restrictive, and their attitudes, especially those concerning sexual pleasure, were more negative than those of the controls. Sexual identity among the survivors was less often feminine and more often infantile as compared with the controls. The findings obtained with the three methods of assessment were concordant.

In order to determine if there are differences in stress responses, as reflected in neuroendocrine activation, we have compared data from two groups of patients undergoing laparoscopic surgery either in the head-up position for cholecystectomy or in the head-down position for hysterectomy. Arterial blood samples were obtained for measurement of serum concentrations of cortisol, catecholamines, renin activity and atrial natriuretic peptide (measured as N-terminal peptide of proANP), and haemodynamic data (pulmonary capillary wedge pressure, PCWP) were collected at the following times: in awake patients, supine at rest (baseline); in awake patients in the position used during surgery; during laparoscopy; and 2 h after surgery. The same anaesthetic technique and normocapnic mechanical ventilation were used in both groups. There were no significant differences between groups in cortisol or adrenaline concentrations, or in renin activity. There was, however, a three-fold increase in cortisol towards the recovery period in both groups. Noradrenaline concentrations increased more in the head-up group suggesting increased sympathetic nervous activity. In awake patients, plasma NT-proANP concentrations were significantly higher in the head-down tilt compared with the head-up position, and NT-proANP correlated well with PCWP. During pneumoperitoneum, however, NT-proANP concentrations remained low in spite of increased PCWP suggesting that inflation of the abdomen interferes with venous return. In conclusion, abdominal surgical laparoscopy in both the head-up and head-down positions caused marked activation of neuroendocrine responses. The two surgical positions, however, differed in their effect on the circulation. In awake patients, head-down tilt was associated with increased concentrations of plasma NT-proANP, indicating increased venous return and atrial stretch.

The purpose of this study was to assess the body image of young female survivors of leukemia. Young female survivors of leukemia (n = 42) were compared with healthy age-matched control subjects (n = 69). The study included a semistructured face-to-face interview and a psychological test. The data were separated into three distinct evaluations of each subject's body image: 1) the subject's self-assessment, 2) evaluation by a psychiatrist, and 3) the Rorschach test. The body images of the survivors were inferior to those of the control subjects in all three evaluations (P < 0.001). The preceding leukemia was assessed still as extremely threatening in 26% of the survivors.

This study was designed to compare the efficacy and safety of two sizes of Lyrelle, a new matrix design transdermal oestrogen patch, with Estraderm TTS 50, a reservoir system. Three hundred and ninety-four (394) hysterectomised postmenopausal women between 30 and 65 years of age participated in this open-label, randomised, multicentre clinical trial. The main efficacy criterion was the reduction in the mean number of hot flushes per day at six months. Secondary efficacy end points included other climacteric symptoms as well as various psychofunctional and genitourinary disorders. A significant decrease from baseline in the mean number of hot flushes/day was observed in all three groups from the end of cycle 1, reaching 90% at the end of cycle 7. there was no statistically significant difference between Lyrelle 50 and Estraderm at any time point for any parameter; however, between-group differences between Lyrelle 80 and Estraderm for various parameters were seen in the first three cycles in favour of Lyrelle 80. A similar impact on blood lipid levels was observed in all three groups, without significant between-group differences. We conclude that the new Lyrelle patch is a highly effective system for transdermal oestrogen replacement therapy that may enhance long-term patient compliance.

The history of progesterone and hormone replacement therapy goes back to 1934 when Butenandt obtained crystalline progesterone and Kaufmann started to treat ovariectomized women with both estrogens and progesterone (Table 1). Today synthetic perorally active 19-nortestosterone and 17-alpha-hydroxyprogesterone derivatives are used in addition to contraception and hormone replacement therapy in a variety of gynecological disorders. In hormone replacement therapy progestin is added only to prevent development of hyperplasia of the endometrium and its consequences. However, because progestins may cause both subjective and metabolic adverse effects minimum effective antiproliferative doses are recommended. The duration of the progestin phase cannot be shortened to less than 10 days whereas the frequency of administration apparently can be reduced without increased risk of hyperplasia. Development of new modes of administration may further help in reduction of the doses.

Objectives: The aim of this study was to compare a new estradiol-desogestrel (E2-DG) regimen with an E2-norethisterone acetate (NETA) combination (Trisekvens) regarding the treatment of menopausal complaints, bleeding pattern, histology of the endometrium and the occurrence of adverse experiences., Methods: A total of 310 peri-/postmenopausal women with climacteric symptoms were randomly allocated to oral sequential treatment with either the E2-DG combination (1.5 mg E2 for 24 days with 0.15 mg DG for the last 12 days followed by 1 placebo tablet for 4 days) or with the E2-NETA combination (Trisekvens, 2 mg E2 for 22 days with 1 mg NETA for the last 10 days followed by 1 mg E2 for 6 days). Treatments were administered double-blind for 12 cycles of 28 days., Results: One hundred and four women, 48 in the E2-DG group and 56 in the E2-NETA group, discontinued the study due to bleeding irregularities and various adverse effects. Both treatments reduced menopausal symptoms and complaints effectively and almost equally. The alleviation of perspirations and the improvement of general fitness were more apparent (P = 0.009) during cycle 1 with the E2-NETA treatment but were greater (P < 0.02) during the last 9/10-12 cycles of E2-DG treatment compared to E2-NETA. Regular withdrawal bleeding appeared in 93% and 90% of the women during treatment with E2-DG and E2-NETA, respectively. Intermenstrual bleeding occurred in 8% of women receiving E2-DG and in 13% of women treated with E2-NETA. The corresponding figures for intermenstrual bleeding-spotting were 21% and 22%. Secretory endometrium was detected in 65% and 54% of the samples taken at the end of treatment with E2-DG and E2-NETA, respectively. No hyperplasia or atypia was found. No serious adverse events related to treatment occurred., Conclusions: Both regimens alleviated effectively menopausal complaints and did not induce hyperplasia of endometrium. The minor differences recorded between the two regimens were probably due to the differences in their composition concerning the amount of estradiol and its distribution along the cycle, the amount and type of progestin and the length of estradiol/progestin combination phase.

More prolonged gynecological laparoscopic operations are being performed in recent years, and a steeper head-down position is required. The early reports of hemodynamic changes during gynecologic laparoscopy are conflicting, and the effects of anesthesia, head-down tilt and pneumoperitoneum have not been clearly separated. Invasive hemodynamic monitoring was carried out in 20 female ASA Class I-II patients who underwent laparoscopic hysterectomy. Baseline measurements were made in the supine, supine-lithotomy and Trendelenburg (25-30 degrees) positions in awake patients. Measurements were repeated in the supine-lithotomy and Trendelenburg positions after induction of anesthesia, during laparoscopy 5 minutes after the beginning of peritoneal CO2-insufflation (intra-abdominal pressure 13-16 mmHg) and at 15-minute intervals thereafter, after laparoscopy in the Trendelenburg and supine positions, after extubation and in the recovery room at 30-minute intervals. Patients received balanced general anesthesia with isoflurane in 35% O2 in an oxygen/air mixture. End tidal PCO2 was maintained between 4.5-4.8 kPa (33-36 mmHg) by changing the minute volume of controlled ventilation. The Trendelenburg position in awake and anesthetized patients increased pulmonary arterial pressures (PAP), central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP). These pressures increased further at the start of CO2-insufflation, decreased towards the end of the laparoscopy and reached pre-insufflation levels after deflation of pneumoperitoneum. The mean arterial pressure (MAP) increased at the beginning of laparoscopy in comparison with the pre-laparoscopic values. Heart rate (HR) was quite stable during laparoscopy. The cardiac index (CI) decreased with anesthesia from 3.8 to 3.2 1.min-1.m-2 and further during laparoscopy to 2.7 1.min-1.m-2, returning to pre-insufflation values soon after deflation. The stroke index (SI) changed in concert with the CI changes. The right ventricular stroke work index decreased during laparoscopy more than the left ventricular stroke work index. The right atrial pressure (CVP) exceeded the PCWP more often during laparoscopy than during any other phase of the procedure. Anesthesia and the Trendelenburg position increased the CVP, PCWP and pulmonary arterial pressures and decreased cardiac output. Pneumoperitoneum increased these pressures further mostly in the beginning of the laparoscopy, and cardiac output decreased towards the end of the laparoscopy. The risk of systemic CO2-embolus was increased during laparoscopy.

We evaluated the ventilatory effects and blood gas changes of prolonged CO2-pneumoperitoneum in nor-moventilated patients and examined the respiratory and gas exchange consequences of head-down positioning (25-30 degrees) and CO2 insufflation into the peritoneal cavity in 20 patients without major cardiorespiratory disorders in various phases of laparoscopic hysterectomy. The patients received general anesthesia with isoflurane, fentanyl, and vecuronium, and minute ventilation (MV) was adjusted to maintain the PETCO2 at 33-36 mm Hg throughout the entire procedure, either by increasing the tidal volume (TV) and keeping the respiratory rate (RR) at 12/min (10 patients) or by changing the RR and maintaining the TV at 8 mL/kg (10 patients). Arterial and mixed venous blood samples were collected simultaneously for blood gas analysis and for measurements of oxygen consumption, and respiratory mechanics and gases were recorded by an anesthetic gas analyzer and side stream spirometry device. Oxygen consumption decreased with anesthesia, remained stable to the end of the laparoscopy, increased soon after deflation of the pneumoperitoneum, and reached preanesthetic values during recovery. The MV requirement increased by approximately 30% after the start of CO2 insufflation, then increased somewhat further toward the end of the laparoscopy, reaching the highest level a few minutes after deflation of the intraabdominal gas. The compliance decreased by 20% with the head-down position and by an additional 30% with the increased intraabdominal pressure. PaCO2 and mixed venous PCO2 increased with CO2 insufflation, and the arterial to end-tidal PCO2 (a-etPCO2) gradient increased by 1.5 mm Hg during laparoscopy. A mild metabolic acidosis developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aim of the Study: To examine intracranial blood flow during major laparoscopic gynecologic operation and the effects of a deep Trendelenburg position and pneumoperitoneum on the flow., Material: Fifteen patients scheduled for laparoscopic hysterectomy., Methods: Trans-cranial Doppler examination of blood flow velocity waveforms in the middle cerebral artery during operation., Results: Trendelenburg position and pneumoperitoneum were followed by a decrease in cardiac output and an increase of central venous pressure and pulmonary capillary wedge pressure. No significant changes in the pulsatility index or maximal or mean blood flow velocities in the middle cerebral artery occurred during operations. A negative correlation between percentual changes in the pulsatility index and mean arterial pressure existed., Conclusions: Uncomplicated laparoscopic hysterectomy is not associated with harmful changes in intracranial circulation in spite of a Trendelenburg position, pneumoperitoneum and changes in the patient's extracranial hemodynamics.

We evaluated whether a progestin, added for 14 days every 3 months to estrogen replacement therapy, is capable of preventing the development of endometrial hyperplasia in postmenopausal women during a treatment period of 2 years. Postmenopausal women (263) in 10 hospitals and medical centers in Finland participated in this non-randomized prospective multicenter trial. The women received estradiol valerate 2 mg daily for 84 days and 20 mg of medroxyprogesterone acetate daily for days 71-84 followed by seven drug-free tablets. This regimen was repeated four times per year. The first year of treatment was completed by 227 (86%) women and the second year by 143 out of 146 women. The incidence of unscheduled and heavy bleedings was higher in women who were postmenopausal for less than 3 years. Endometrial biopsies demonstrated progestational response in 64% at 12 and 24 months, respectively. The 3 month regimen prevented development of endometrial hyperplasia but was not able to restore a hyperplastic endometrium to normal.

An open multicenter trial was performed in six centers in Finland to study the efficacy, safety and acceptability of a new biphasic oral contraceptive pill containing natural estradiol and cyproterone acetate. The participants were 288 women with a mean age of 39.3 +/- 3.4 years (range 30-49) who were willing to use the new pill as their only contraceptive method. In total, 23% of the women were smokers. The cumulative experience was 2800 treatment cycles during the first year. The net 12-month continuation rate was 63%. One pregnancy occurred in a woman who lost 5 tablets in the second treatment cycle, which gives a 12-month cumulative pregnancy rate of 0.4%. Serum progesterone values, determined twice during the third treatment cycle, showed ovulation inhibition in 95% of women. There were no serious side effects. Intermenstrual bleeding was recorded by 35.5% and 24.5% of women at 3 and 12 months, respectively. The bleedings became scantier in most women and dysmenorrhoea disappeared. No changes were observed in total and high density lipoprotein cholesterol concentrations after 1 year. With the exception of intermenstrual spotting, the efficacy, safety and acceptability of the new pill was almost as good as that of the modern low dose oral contraceptives. This is the first pill containing natural estradiol that has gained clinical acceptance and which can also be prescribed for smokers over 35 years old until the climacteric.