Risk of hospital-treated injury in children with cerebral palsy: a population-based cohort study

Aim To study whether cerebral palsy (CP) increases the risk of hospital-treated injuries in children up to 13 years of age. Methods A Finnish population-based cohort (n=328 903) of children born during 2001 to 2006 was followed up for hospital-treated injuries until the end of 2014 via linkage of nation-wide registers. The rate of first injury was compared in children with and without CP. The effect of CP type, gender, severe comorbidities (intellectual disability, epilepsy, hearing or visual impairment), and the type of injury was evaluated. Results Children with CP had an increased risk of injury compared with children without CP (unadjusted HR: 1.2, 95% CI: 1.0 - 1.4, p=0.40). Girls with CP (n=191) had a higher risk of injury compared with girls without CP (29% vs 22%, HR: 1.4, 95% CI: 1.1 to 1.8, p = 0.01). Any comorbidity increased the risk of injury (HR: 1.5, 95% CI: 1.1 to 2.2, p = 0.015) among children with CP. Children with CP had a higher risk of traumatic brain injury (HR: 1.7, 95% CI 1.2 to 2.4, p = 0.002) than children without CP. Conclusion Girls with CP had the highest risk of hospital-treated injury. Children with CP are particularly prone to traumatic brain injuries.Peer reviewe

Is Symptomatic Long QT Syndrome Associated with Depression in Women and Men?

We examined whether long QT syndrome (LQTS) mutation carrier status or symptomatic LQTS are associated with depression, and whether there are sex differences in these potential relationships. The sample comprised 782 participants (252 men). Of the 369 genetically defined LQTS mutation carriers, 169 were symptomatic and 200 were asymptomatic. The control group consisted of 413 unaffected relatives. Depression was assessed using the Beck Depression Inventory-II (BDI-II). No association was found for LQTS mutation carrier status with depression. The multinomial logistic regression showed that LQTS mutation carrier men with arrhythmic events scored higher on depression compared with the control group, even when adjusting for age, beta-blockers, antidepressants, and social support (OR = 1.09, 95 % CI [1.02, 1.15], p = .007). The binary logistic regression comparing symptomatic and asymptomatic LQTS mutation carriers showed that symptomatic LQTS was associated with depression in men (OR = 1.10, 95 % CI [1.03, 1.19], p = .009). The results were unchanged when additionally adjusted for education. These findings suggest that symptomatic LQTS is associated with depression in men but not in women. Overall, however, depression is more frequent in women than men. Thus, regular screening for depression in LQTS mutation carriers and their unaffected family members can be important.Peer reviewe

Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC.

background: We derived estimates of overdiagnosis by polygenic risk groups and examined whether polygenic risk-stratified screening for prostate cancer reduces overdiagnosis. methods: We calculated the polygenic risk score based on genotypes of 66 known prostate cancer loci for 4967 men from the Finnish section of the European Randomised Study of Screening for Prostate Cancer. We stratified the 72 072 men in the trial into those with polygenic risk below and above the median. Using a maximum likelihood method based on interval cancers, we estimated the mean sojourn time (MST) and episode sensitivity. For each polygenic risk group, we estimated the proportion of screen-detected cancers that are likely to be overdiagnosed from the difference between the observed and expected number of screen-detected cancers. results: Of the prostate cancers, 74% occurred among men with polygenic risk above population median. The sensitivity was 0.55 (95% confidence interval (CI) 0.45–0.65) and MST 6.3 (95% CI 4.2–8.3) years. The overall overdiagnosis was 42% (95% CI 37–52) of the screen-detected cancers, with 58% (95% CI 54–65) in men with the lower and 37% (95% CI 31–47) in those with higher polygenic risk. conclusion: Targeting screening to men at higher polygenic risk could reduce the proportion of cancers overdiagnosed

Diffusion tensor imaging is associated with motor outcomes of very preterm born children at 11 years of age

Aim Very preterm children born Methods A cohort of 37 very preterm infants (mean gestational age 29 4/7, SD 2 0/7) born in 2004-2006 in Turku University Hospital underwent diffusion tensor imaging at term. A region of interest analysis of fractional anisotropy and mean diffusivity was performed. Motor outcomes at 11 years of age were measured with the Movement Assessment Battery for Children - Second Edition. Results The diffusion metrics of the corpus callosum (genu P = .005, splenium P = .049), the left corona radiata (P = .035) and the right optic radiation (P = .017) were related to later motor performance. Mean diffusivity decreased and fractional anisotropy increased in proportion to the improving performance. Conclusion The diffusion metrics of the genu and splenium of the corpus callosum, the left corona radiata and the right optic radiation at term were associated with motor skills at 11 years of age. Diffusion tensor imaging should be further studied as a potential tool in recognising children at risk for motor impairment.</div

Performans of the Finnish Prostate Cancer Screening Trial Based on Process Indicators

Sairauksien seulontaa on kuvattu oireettoman taudin toteamiseksi suhteellisen yksinkertaisella testillä. Syöpäseulonnan tavoitteena on alentaa kuolleisuutta tai sairastuvuutta ja parantaa elämänlaatua. Väestöön kohdistuvan seulonnan kohteena tulee olla tauti, joka on väestössä yleinen ja jolla on kansanterveydellistä merkitystä. Seulottavalla taudilla tulee myös olla oireeton vaihe, jolloin se voidaan todeta ja hoitaa ja myös saavuttaa hoidolla hyvä paranemisennuste. Lisäksi käytettävissä on oltava seulontamenetelmä, jonka herkkyys (testin kyky tunnistaa sairaat) ja tarkkuus (testin kyky tunnistaa terveet) ovat hyväksyttävällä tasolla. Seulontamenetelmä ei myöskään saa aiheuttaa tarpeetonta vahinkoa seulontaan osallistuville. Seulontatestin tulee olla väestön hyväksymä ja seulonnan kustannuksien tasapainossa terveydenhuollon kokonaiskustannukset huomioiden. Eturauhassyöpä on tällä hetkellä Suomessa miesten yleisin syöpä ja yli 5300 miehellä tauti todetaan vuosittain ja noin 800 kuolee vuosittain eturauhassyöpään. Eturauhasen erittämän syövän merkkiaineen (PSA) on todettu kohoavan eturauhassyöpäpotilailla 5-10 vuotta ennen kuin tauti todetaan oireiden perusteella. PSA testin käyttämistä eturauhassyövän seulontatestiksi on suositeltu, mutta seulonnan vaikutuksesta kuolleisuuteen ei ole tutkittua tietoa. European Randomized Study of Screening for Prostate Cancer (ERSPC) eurooppalainen yhteistutkimus, jossa on mukana kahdeksan maata ja yhteensä mukaan satunnaistettu 205,000 miestä. Suomen aineisto on tutkimuksen suurin noin 80,000 miestä. Vuosina 1996 -1999 satunnaistettiin pääkaupunkiseudulla ja Tampereella sekä ympäristökunnissa 55 - 67-vuotiaat miehet. Kolmannes heistä kutsuttiin PSA-seulontaan neljän vuoden välein. Tämä väitöskirjatutkimus käsittelee ensimmäisen seulontakierroksen tuloksia. Osallistuminen oli vilkkaampaa Tampereen alueella 76 % kuin pääkaupunkiseudulla 66 %. Seerumin PSA pitoisuus ylitti seulontaraja-arvon 9 % osallistuneista ja neljäsosalla näistä miehistä todettiin syöpä. Testin herkkyys oli 85 % ja tarkkuus 94 %. Seulonnalla todetuista syövistä 86 % oli paikallisia ja 80 % oli hitaasti kasvavia ja siten hyväennusteisia. Seulonnan edellytyksistä voi tämän ensimmäisen seulontakierroksen tuloksien perusteella todeta, että seulonta testi on väestön hyväksymä, testin herkkyys ja tarkkuus ovat hyväksyttävällä tasolla ja löydetyt syövät ovat paikallisia ja siis hoidettavissa. Johtopäätökseksi jää, että tutkimusta voidaan jatkaa. Seulonnan taloudellisista vaikutuksista, vaikutuksista elämänlatuun ja mikä tärkeintä vaikutusta kuolleisuuteen ei voida tämän tiedon perusteella arvioida. Näiden tulosten perusteella on mahdollista, että myös kuolleisuus tulee muuttumaan seulotuilla ja tulee olemaan pienempi kuin verrokkimiehillä.The aim of cancer screening is to reduce mortality and improve quality of life. Evaluation of this effectiveness ultimately requires extensive follow-up. Therefore, intermediate or process indicators are used as necessary, but not sufficient, early evidence with the potential to predict the mortality effect. For prostate cancer, the effectiveness of screening is unknown and two large-scale trials are being carried out. The Finnish prostate cancer screening trial is the largest component of the European Randomized Study of Screening for Prostate Cancer. The purpose of this thesis is to assess the Finnish prostate cancer screening trial with PSA, using intermediate endpoints, i.e., participation, PSA distribution, detection rate, sensitivity, specificity, predictive values and prognostic factors of screen-detected cancers. Altogether 30,197 men were invited and 20,793 (69%) attended. Among attenders 1,826 (9%) were screen-positives with PSA > 4.0 ng/ml and additional 1,075 men were referred for diagnostic examination based on DRE or free to total PSA ratio among men with moderately increased level of PSA (3.0­3.9 ng/ml). Altogether 542 cancers were detected with detection rate of 2.6%. The positive predictive value of the PSA test at cut-off level of 4.0 ng/ml was 28%. The sensitivity by age of the PSA test at PSA 4.0 ng/ml and with ancillary tests of TRUS and free to total PSA ratio determination was 85% during the 4-year screening interval. Specificity at the cut-off limits of the PSA test at PSA 3.0 ng/ml and with ancillary tests of DRE, TRUS and free to total PSA ratio was 94%. The clinical stage distribution of the screen-detected cancers was favourable (T1-T2 M0) in 86% and only 3% of the cancers had distant metastases (M1). Of the screen-detected cancers, 6% were aggressive (Gleason 8­10). The Finnish prostate cancer screening trial is acceptable to the target population, the test is capable of identifying a small proportion of men with a high risk of prostate cancer. Detection of aggressive, potentially lethal cancer implies that PSA testing does not detect only indolent cancers. The results on the process indicators justify the continuation of the Finnish prostate cancer screening trial for estimation of the ultimate effectiveness in terms of mortality reduction

Performans of the Finnish Prostate Cancer Screening Trial Based on Process Indicators

Sairauksien seulontaa on kuvattu oireettoman taudin toteamiseksi suhteellisen yksinkertaisella testillä. Syöpäseulonnan tavoitteena on alentaa kuolleisuutta tai sairastuvuutta ja parantaa elämänlaatua. Väestöön kohdistuvan seulonnan kohteena tulee olla tauti, joka on väestössä yleinen ja jolla on kansanterveydellistä merkitystä. Seulottavalla taudilla tulee myös olla oireeton vaihe, jolloin se voidaan todeta ja hoitaa ja myös saavuttaa hoidolla hyvä paranemisennuste. Lisäksi käytettävissä on oltava seulontamenetelmä, jonka herkkyys (testin kyky tunnistaa sairaat) ja tarkkuus (testin kyky tunnistaa terveet) ovat hyväksyttävällä tasolla. Seulontamenetelmä ei myöskään saa aiheuttaa tarpeetonta vahinkoa seulontaan osallistuville. Seulontatestin tulee olla väestön hyväksymä ja seulonnan kustannuksien tasapainossa terveydenhuollon kokonaiskustannukset huomioiden. Eturauhassyöpä on tällä hetkellä Suomessa miesten yleisin syöpä ja yli 5300 miehellä tauti todetaan vuosittain ja noin 800 kuolee vuosittain eturauhassyöpään. Eturauhasen erittämän syövän merkkiaineen (PSA) on todettu kohoavan eturauhassyöpäpotilailla 5-10 vuotta ennen kuin tauti todetaan oireiden perusteella. PSA testin käyttämistä eturauhassyövän seulontatestiksi on suositeltu, mutta seulonnan vaikutuksesta kuolleisuuteen ei ole tutkittua tietoa. European Randomized Study of Screening for Prostate Cancer (ERSPC) eurooppalainen yhteistutkimus, jossa on mukana kahdeksan maata ja yhteensä mukaan satunnaistettu 205,000 miestä. Suomen aineisto on tutkimuksen suurin noin 80,000 miestä. Vuosina 1996 -1999 satunnaistettiin pääkaupunkiseudulla ja Tampereella sekä ympäristökunnissa 55 - 67-vuotiaat miehet. Kolmannes heistä kutsuttiin PSA-seulontaan neljän vuoden välein. Tämä väitöskirjatutkimus käsittelee ensimmäisen seulontakierroksen tuloksia. Osallistuminen oli vilkkaampaa Tampereen alueella 76 % kuin pääkaupunkiseudulla 66 %. Seerumin PSA pitoisuus ylitti seulontaraja-arvon 9 % osallistuneista ja neljäsosalla näistä miehistä todettiin syöpä. Testin herkkyys oli 85 % ja tarkkuus 94 %. Seulonnalla todetuista syövistä 86 % oli paikallisia ja 80 % oli hitaasti kasvavia ja siten hyväennusteisia. Seulonnan edellytyksistä voi tämän ensimmäisen seulontakierroksen tuloksien perusteella todeta, että seulonta testi on väestön hyväksymä, testin herkkyys ja tarkkuus ovat hyväksyttävällä tasolla ja löydetyt syövät ovat paikallisia ja siis hoidettavissa. Johtopäätökseksi jää, että tutkimusta voidaan jatkaa. Seulonnan taloudellisista vaikutuksista, vaikutuksista elämänlatuun ja mikä tärkeintä vaikutusta kuolleisuuteen ei voida tämän tiedon perusteella arvioida. Näiden tulosten perusteella on mahdollista, että myös kuolleisuus tulee muuttumaan seulotuilla ja tulee olemaan pienempi kuin verrokkimiehillä.The aim of cancer screening is to reduce mortality and improve quality of life. Evaluation of this effectiveness ultimately requires extensive follow-up. Therefore, intermediate or process indicators are used as necessary, but not sufficient, early evidence with the potential to predict the mortality effect. For prostate cancer, the effectiveness of screening is unknown and two large-scale trials are being carried out. The Finnish prostate cancer screening trial is the largest component of the European Randomized Study of Screening for Prostate Cancer. The purpose of this thesis is to assess the Finnish prostate cancer screening trial with PSA, using intermediate endpoints, i.e., participation, PSA distribution, detection rate, sensitivity, specificity, predictive values and prognostic factors of screen-detected cancers. Altogether 30,197 men were invited and 20,793 (69%) attended. Among attenders 1,826 (9%) were screen-positives with PSA > 4.0 ng/ml and additional 1,075 men were referred for diagnostic examination based on DRE or free to total PSA ratio among men with moderately increased level of PSA (3.0­3.9 ng/ml). Altogether 542 cancers were detected with detection rate of 2.6%. The positive predictive value of the PSA test at cut-off level of 4.0 ng/ml was 28%. The sensitivity by age of the PSA test at PSA 4.0 ng/ml and with ancillary tests of TRUS and free to total PSA ratio determination was 85% during the 4-year screening interval. Specificity at the cut-off limits of the PSA test at PSA 3.0 ng/ml and with ancillary tests of DRE, TRUS and free to total PSA ratio was 94%. The clinical stage distribution of the screen-detected cancers was favourable (T1-T2 M0) in 86% and only 3% of the cancers had distant metastases (M1). Of the screen-detected cancers, 6% were aggressive (Gleason 8­10). The Finnish prostate cancer screening trial is acceptable to the target population, the test is capable of identifying a small proportion of men with a high risk of prostate cancer. Detection of aggressive, potentially lethal cancer implies that PSA testing does not detect only indolent cancers. The results on the process indicators justify the continuation of the Finnish prostate cancer screening trial for estimation of the ultimate effectiveness in terms of mortality reduction

Stressful Work Involvement and Inherited Long QT-Syndrome

Aims: The long QT syndrome (LQTS) is an inherited cardiac disorder which predisposes the mutation carrier to ventricular arrhythmias that can lead to sudden death. The objective of the study was to study whether stressful work involvement (i.e. worrying about work and job dissatisfaction) is related to arrhythmic risk in LQTS. Study design: Cross-sectional study. Place and Duration of Study: The study took place in Finland in 2006 for the LQTS mutation carriers and 2007 for the general Finnish population. Methodology: The study subjects included 164 symptomatic and 229 asymptomatic LQTS mutation carriers from the Finnish LQTS registry and 1368 comparison subjects randomly derived from the population-based sample, Young Finns Study (YFS). Stressful work involvement was measured with questions derived from the Framingham type A scale. Results: Upon assessment of the stressful work involvement, symptomatic LQTS mutation carriers scored higher than asymptomatic LQTS mutation carriers (1.51 vs. 1.40, p=0.003, η²=0.022) and the general Finnish population (1.51 vs. 1.39, p<0.001, η²=0.012), while asymptomatic LQTS mutation carriers did not differ from the general Finnish population in the corresponding scores (1.40 vs. 1.39, p=0.374, η²<0.001). Conclusion: The results confirm the suggestion that perceived stress, in terms of stressful work involvement, may increase the likelihood of arrhythmic events in LQTS mutation carriers. Thus, individual stress proneness may be a risk factor for LQT symptoms, which should be taken into account in counseling LQTS patients. There is previous evidence that stress proneness can be modified by behavioral therapy

Under the thin skin of narcissus : facial muscle activity reveals amplified emotional responses to negative social evaluation in individuals with grandiose narcissistic traits

Individuals with grandiose narcissism exhibit enhanced antagonism and a defensive pattern of discordance between their emotional and physiological reactions to self-threatening evaluations. Although theoretical perspectives link narcissistic defensiveness to negative emotions, empirical evidence linking grandiose narcissism to emotional reactivity remains mixed. The current study used self-reported affect, electrocardiography, and facial electromyography (fEMG) to examine whether people scoring high in grandiose narcissism show amplified physiological and self-reported emotional reactivity to negative social evaluation. Following two challenging cognitive tasks, participants received negative and neutral feedback in a face-to-face evaluation situation. Receiving negative feedback decreased self-reported positive affect and dominance, slowed heart rate, and amplified fEMG activity related to frowning and eye constriction. Although self-reported emotional reactions were unrelated to grandiose narcissism, fEMG activity associated with negative affect was significantly enhanced by grandiose narcissism. In conclusion, individuals with higher levels of grandiose narcissism may not be willing to report overt emotional reactivity to self-threatening feedback, but physiological responses “beneath their thin skin” reveal amplified threat-related facial muscle activity suggestive of a negative emotional state.Individuals with grandiose narcissism exhibit enhanced antagonism and a defen- sive pattern of discordance between their emotional and physiological reactions to self- threatening evaluations. Although theoretical perspectives link narcissistic defensiveness to negative emotions, empirical evidence linking grandiose narcissism to emotional reactivity remains mixed. The current study used self-reported affect, electrocardiography, and facial electromyography (fEMG) to examine whether people scoring high in grandiose narcissism show amplified physiological and self-reported emotional reactivity to negative social evaluation. Following two challenging cognitive tasks, participants received negative and neutral feedback in a face-to-face evaluation situation. Receiving negative feedback decreased self- reported positive affect and dominance, slowed heart rate, and amplified fEMG activity related to frowning and eye constriction. Although self-reported emotional reactions were unrelated to grandiose narcissism, fEMG activity associated with negative affect was significantly enhanced by grandiose narcissism. In conclusion, individuals with higher levels of grandiose narcissism may not be willing to report overt emotional reactivity to self-threatening feedback, but physiological responses “beneath their thin skin” reveal amplified threat-related facial muscle activity suggestive of a negative emotional state.Peer reviewe

Screening and prostate-cancer mortality in a randomized European study

BACKGROUND: The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer. METHODS: We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006. RESULTS: In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P=0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90). CONCLUSIONS: PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.