Decision aids to assist Icelandic men with PSA testing and prostate cancer treatment decision-making

Prostate cancer (PC) is the second most common cancer among men globally and the most common cancer among Icelandic men. Early detection of PC is possible with a prostate-specific antigen (PSA) test. Before making a decision about PSA testing and before deciding which treatment to choose for localized PC, shared decision-making (SDM) is encouraged as many uncertainties are associated with those decisions and it is important that patients understand the pros and cons of all options before making a decision. Decision aids (DAs) have been found to enhance SDM by, for example, affecting patient involvement and patient-physician communication. While it is known that Icelandic men, newly diagnosed with PC, lack information about the pros and cons of different treatment options, no study to date has examined how much information Icelandic men receive about the pros and cons of PSA testing prior to undergoing PSA testing. Furthermore, DAs for PSA testing decision and PC treatment decision are not available in Icelandic. To address these limitations, the aims of the current Thesis were to; 1) establish the need for an Icelandic PSA testing DA, 2) translate and culturally adapt a pre-existing PSA testing DA for Icelandic men, and 3) develop, culturally adapt and extend an interactive DA to assist men, diagnosed with localized PC, to make a treatment decision. In Paper I, all Icelandic men diagnosed with PC from 2015 to 2020 were invited to participate in a quantitative study evaluating how much information men receive about the pros and cons of PSA testing prior to undergoing a PSA test. Participants were 471 men aged 51 to 95 (M = 71.9, SD = 7.3). In Paper II, a pre-existing DA for PSA testing decision was translated and culturally adapted, and usability was tested in a mixed-methods study, first in a qualitative study and then in a quantitative study. Ten men, aged 51 to 66 (M = 59.9, SD = 5.6) participated in the qualitative study using a semi-structured interview and a questionnaire. Minor modifications were made to the DA following the qualitative study, whereafter, a quantitative study was conducted among 135 men aged 50 to 70 years (M = 59.7, SD = 5.2) to evaluate the final version of the DA. In Paper III, a DA for localized PC treatment decision was culturally adapted, modified and extended. The usability of the DA was evaluated in a mixed-methods study, first in a qualitative study and then in a quantitative study. The qualitative study included semi-structured interviews and a usability scale and participants were 12 men, aged 58 to 80 years (M = 70.66, SD=6.58), diagnosed with PC. A thematic analysis of the interviews led to minor revisions of the DA. Then a quantitative evaluation of the usability of the final version of the DA was conducted among 11 newly diagnosed men with PC, aged 60 to 74 (M = 66.18, SD = 4.79). Findings from Paper I underscored the need for an Icelandic PSA testing DA as Icelandic men lack information before making a PSA testing decision. Half of the participants received information about the pros and cons of PSA testing, a third did not receive any information and 22.2% did not even know they were being tested. Additionally, more than 80% of the men reported none or little knowledge of PSA testing. The findings of Paper II demonstrated that participants found the translation and cultural adaptation of the DA for PSA testing decision to be successful, as they found the DA helpful and comprehensible and almost all participants said they would recommend it to others. The results of Paper III demonstrated that the DA for treatment decision for localized PC was well received by participants. Participants were satisfied with the DA and the realistic information on side effects that was presented. They found the information about the pros and cons of treatment options helpful, and all noted they would recommend the DA to others facing the same decision. Currently, a randomized clinical trial is being conducted to evaluate the effectiveness of the DA for localized PC treatment decision. The main results from the overall Thesis were that men do not receive adequate information about the pros and cons of PSA testing and that the DAs for PSA testing and localized PC treatment decisions were successfully modified. DAs have been shown to enhance SDM, be cost-effective, and have a minimal burden on the healthcare system. Therefore, the usage of DAs is likely to benefit both patients and healthcare providers of the Icelandic healthcare system.Blöðruhálskirtilskrabbamein (BHKK) er annað algengasta krabbamein meðal karlmanna á heimsvísu og algengasta krabbameinið meðal íslenskra karlmanna. Mikilvægt er að skilja kosti og galla PSA (prostate-specific antigen) prófs, sem getur greint BHKK á frumstigi, og einnig kosti og galla mögulegra meðferðarúrræða við staðbundnu BHKK áður en ákvörðun er tekin þar sem ýmsir óvissuþættir fylgja þessum ákvörðunum. Ákvörðunartæki geta stuðlað að sameiginlegri ákvörðunartöku sjúklings og heilbrigðisstarfsfólks en slík ákvörðunartaka hefur jákvæð áhrif á þátttöku sjúklings í ákvörðuninni sem og á samskipti sjúklings og heilbrigðisstarfsfólks. Rannsóknir sýna að íslenska menn sem nýgreindir eru með BHKK, skortir upplýsingar um kosti og galla þeirra meðferðaleiða sem í boði eru. Hinsvegar hefur ekki verið rannsakað hvort íslenskir menn fái nægar upplýsingar um kosti og galla PSA prófs áður en þeir fara í slíkt próf. Hvorki ákvörðunartæki sem aðstoðar menn við að taka ákvörðun varðandi PSA próf né ákvörðunartæki sem aðstoðar menn við að taka ákvörðun um meðferðarleið fyrir BHKK eru í boði á íslensku. Því var markmið þessarar doktorsrannsóknar að 1) sýna fram á að það væri þörf fyrir íslenskt ákvörðunartæki sem aðstoðar menn áður en þeir taka ákvörðun varðandi PSA próf, 2) þýða yfir á íslensku og staðfæra ákvörðunartæki sem aðstoðar við ákvarðanatöku varðandi PSA próf, 3) þróa og staðfæra gagnvirkt ákvörðunartæki til að aðstoða menn, sem hafa greinst með staðbundið BHKK, við að taka ákvörðun um hvaða meðferðarúrræði henti þeim best. Fyrsta rannsóknin var megindleg rannsókn þar sem kannað var hversu miklar upplýsingar menn fengu um PSA próf áður en þeir fóru í slíkt próf. Þátttakendur voru íslenskir menn, 471 talsins, á aldrinum 51 til 95 ára (M = 71.9, SD = 7.3) sem höfðu greinst með BHKK á árunum 2015 til 2020. Í næstu rannsókn var ákvörðunartæki, sem aðstoðar menn við ákvörðunartöku varðandi PSA próf, þýtt og staðfært. Síðan var blandaðri aðferð beitt til að kanna notagildi ákvörðunartækisins, fyrst í eigindlegri rannsókn og síðan megindlegri. Samtals tóku 10 menn á aldrinum 51 til 66 ára (M = 59.9, SD = 5.6) þátt í eigindlegu rannsókninni þar sem notuð voru hálfstöðluð viðtöl og spurningalistar til að meta upplifun þátttakenda af ákvörðunartækinu. Niðurstöður eigindlegu rannsóknarinnar leiddu til smávægilegra breytinga á ákvörðunartækinu sem síðan var notendaprófað í megindlegri rannsókn meðal 135 manna á aldrinum 50 til 70 ára (M = 59.7, SD = 5.2). Í þriðju rannsókninni var ákvörðunartæki fyrir meðferðarákvörðun fyrir staðbundið BHKK staðfært og umfang þess aukið. Samtals tóku 12 menn á aldrinum 58 til 80 ára (M = 70.66, SD=6.58) þátt og allir höfðu þeir verið greindir með BHKK. Notendaprófun var gerð með hálfstöðluðum viðtölum og þátttakendur beðnir um að svara kvarða sem metur notandaupplifun. Þemagreining á viðtölunum leiddi í ljós að gera þurfti minniháttar breytingar á ákvörðunartækinu. Lokaútgáfa ákvörðunartækisins var síðan notendaprófuð í megindlegri rannsókn meðal 11 manna á aldrinum 60 til 74 ára (M = 66.18, SD = 4.79) sem voru nýgreindir með BHKK. Niðurstöður fyrstu rannsóknarinnar leiddu í ljós að íslenskir menn fá ekki nægar upplýsingar áður en þeir fara í PSA próf og þar af leiðandi er þörf fyrir íslenskt ákvörðunartæki sem aðstoðar menn með ákvörðun varðandi PSA próf. Um helmingur þátttakenda fékk upplýsingar um kosti og galla PSA prófs áður en þeir fóru í prófið, þriðjungur fékk engar upplýsingar og 22.2% þátttakenda vissu ekki fyrirfram að það væri verið að mæla PSA gildin þeirra. Þar að auki greindu 80% þátttakenda frá að þeir hefðu litla eða enga þekkingu haft á kostum og göllum PSA prófs áður PSA gildið þeirra var mælt. Niðurstöður annarar rannsóknarinnar, á ákvörðunartæki fyrir PSA ákvörðun leiddi í ljós að bæði þýðing og staðfærsla ákvörðunartækisins að íslenskum aðstæðum tókst vel. Þátttakendum fannst ákvörðunartækið hjálplegt og auðskiljanlegt og nánast allir þátttakendur sögðust myndu mæla með því við aðra í sömu sporum. Niðurstöður þriðju rannsóknarinnar, á ákvörðunartæki fyrir meðferðarákvörðun fyrir staðbundið BHKK sýndi sömuleiðis fram á að þátttakendur voru ánægðir með tækið og þær upplýsingar sem þar var að fá. Sérstaklega voru þeir ánægðir með þær raunsæju upplýsingar um aukaverkanir sem voru gefnar í tækinu og þeim fannst einnig upplýsingar um kosti og galla hverrar meðferðar gagnlegar. Að auki sögðu allir þátttakendur að þeir myndu mæla með ákvörðunartækinu við aðra í sömu sporum. Nú fer fram slembiröðuð klínísk rannsókn til að meta virkni ákvörðunartækisins fyrir meðferðarúrræði við staðbundnu BHKK. Á heildina litið eru niðurstöður doktorsrannsóknarinnar þær að íslenska karlmenn fá ekki nægar upplýsingar áður en þeir fara í PSA próf og að þátttakendur voru ánægðir með bæði ákvörðunartækin. Niðurstöður benda til þess að ákvörðunartækin geti komið að góðum notum fyrir menn sem standa frammi fyrir þessum ákvörðunum. Rannsóknir hafa sýnt að ákvörðunartæki auka þátttöku sjúklinga í ákvörðunartöku, eru hagkvæm og auka ekki álag innan heilbrigðiskerfisins. Ákvörðunartæki ættu því að nýtast vel innan íslenska heilbrigðiskerfisins bæði fyrir sjúklinga og heilbrigðisstarfsfólk en jafnframt fyrir heilbriðiskerfið allt

How Much Information Do Icelandic Men Receive on Pros and Cons of Prostate-Specific Antigen Testing Prior to Undergoing Testing?

Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Traditional Chinese Medical Science and Technology Project of Zhejiang Province (Grant No. 2022ZB130), and the National Famous Old Chinese Medicine Experts SONG Xinwei Inheritance Studio Project (G.TCM.R.J.H.[2018]134). Funding Information: The authors acknowledge the important work done at the Icelandic Cancer Registry that made this study possible and thank their staff for invaluable guidance. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Icelandic Center for Research (grant no. 141490) and the Research Fund of the Icelandic Cancer Society (grant no. 2017-05). Publisher Copyright: © The Author(s) 2022.Prostate-specific antigen (PSA) testing for asymptomatic men is neither encouraged nor discouraged in most countries; however, shared decision-making is emphasized prior to PSA testing. The objective of this study was to examine to what extent Icelandic men receive information about the pros and cons of PSA testing. Furthermore, to explore if patient–provider communication about pros and cons of PSA testing has improved in the last decade during which time more emphasis has been placed on shared decision-making. All Icelandic men diagnosed with prostate cancer in the years 2015 to 2020 were invited to participate, and a total of 471 out of 1002 men participated (response rate 47.0%). Participants’ age ranged from 51 to 95 years (M = 71.9, SD = 7.3). Only half of the men received information about the pros and cons of PSA testing, a third did not receive any information prior to testing and, alarmingly, 22.2% of the men did not even know that they were being tested. A majority of the participants lacked knowledge about the testing with half of the men reporting that they had no knowledge about pros and cons of PSA testing prior to testing. The findings have major public health relevance as they indicate that information provided prior to PSA testing continue to be deficient and that there is a pressing need for interventions that educate men about the benefits and limitations of PSA testing before men undergo medical procedures that can seriously affect their quality of life.Peer reviewe

MAP1B mutations cause intellectual disability and extensive white matter deficit

Publisher's version (útgefin grein). Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Discovery of coding variants in genes that confer risk of neurodevelopmental disorders is an important step towards understanding the pathophysiology of these disorders. Wholegenome sequencing of 31,463 Icelanders uncovers a frameshift variant (E712KfsTer10) in microtubule-associated protein 1B (MAP1B) that associates with ID/low IQ in a large pedigree (genome-wide corrected P = 0.022). Additional stop-gain variants in MAP1B (E1032Ter and R1664Ter) validate the association with ID and IQ. Carriers have 24% less white matter (WM) volume (β = −2.1SD, P = 5.1 × 10−8), 47% less corpus callosum (CC) volume (β = −2.4SD, P = 5.5 × 10−10) and lower brain-wide fractional anisotropy (P = 6.7 × 10−4). In summary, we show that loss of MAP1B function affects general cognitive ability through a profound, brain-wide WM deficit with likely disordered or compromised axons.We are grateful to the participants and we thank the psychologists, nurses and staff, in particular Berglind Eiriksdottir, at the Research Recruitment Center and technicians and staff at Röntgen Domus. We also thank the staff at deCODE genetics core facilities and all our colleagues for their important contribution to this work. L.J. received support from the Swedish Society of Medicine, the Swedish Brain Foundation and Swedish Society for Medical Research. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreements’ no. 115008 (NEWMEDS) and no. 115300 (EUAIMS) of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (EU-FP7/2007-2013), EU-FP7 funded grant no. 602450 (IMAGEMEND) and EU funded FP7-People-2011-IAPP grant agreement no. 286213 (PsychDPC).Peer Reviewe

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study

© 2023. The Author(s).BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.Peer reviewe

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

An Adaptation, Extension and Pre-Testing of an Interactive Decision Aid for Men Diagnosed with Localized Prostate Cancer in Iceland: A Mixed-Method Study.

To access publisher's full text version of this article click on the hyperlink belowIn this study an interactive decision aid (DA) for men diagnosed with localized prostate cancer was adapted, extended and pre-tested. The DA's prototype was based on a literature review and other empirically tested DAs. Semi-structured interviews with 12 men (age 65-80) diagnosed with localized prostate cancer were conducted to get feedback on content, usability, and the DA's layout. The interviews were analyzed using thematic analysis and themes were identified using deductive and inductive coding. Participants found the accessibility of the information and the explicit values clarification tool helpful. Four themes were identified: (1) usability and design, (2) content and knowledge, (3) deciding factors of decision-making, and (4) social support. Participants valued receiving extensive and realistic information on surgery/radiation therapy side effects and getting unbiased presentations of treatment options. Following the thematic analysis, the DA was revised and tested in a survey among 11 newly diagnosed prostate cancer patients (age 60-74). The participants valued the DA and found it helpful when making a treatment decision, and all reported that they would recommend it to others making a prostate cancer treatment decision. The DA is currently being tested in a randomized clinical trial (RCT). This is the first DA developed for prostate cancer patients in Iceland and if the results of the RCT show that it is more effective than standard care in assisting newly diagnosed patients with their treatment decision, the DA can be easily translated and adapted to cultures similar to Iceland such as the Nordic countries. Keywords: decision aid; explicit values clarification; localized prostate cancer; treatment options.Icelandic Center for Research 141490 Research Fund of the Icelandic Cancer Societ