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Oral drug administration to pediatric patients is characterized by a lack of age-appropriate drug products and the off-label use of medicines. However, drug administration practices at hospital wards is a scarcely studied subject. The aim of this study was to explore the oral drug administration practices at pediatric hospital wards, with a focus on experiences and challenges faced, methods used to mitigate existing problems, drug manipulation habits, perceptions about oral dosage forms and future needs of oral dosage forms for children. This was a qualitative study consisting of focus group discussions with physicians, nurses and clinical pharmacists in a tertiary university hospital with the objective of bringing forward a holistic view on this research topic. These healthcare professionals recognized different administration challenges that were classified as either dosage form-related or patient-related ones. A lack of depot formulations developed especially for children as well as oral pediatric dosage forms of drug substances currently available as intravenous dosage forms was recognized. The preferred oral dosage forms were oral liquids and orodispersible tablets. Patient-centered drug administration practices including factors facilitating drug administration both at hospital wards and at home after patient discharge were identified. Among all healthcare professionals, the efficient cooperation in drug prescribing and administration as well as in educating the child&rsquo, s caregivers in correct administration techniques before discharge and improving the overall discharge process of patients was emphasized. This study complements the prevalent understanding that new dosage forms for children of varying ages and stages of development are still needed. It also brings a holistic view on different aspects of oral drug administration to pediatric patients and overall patient-centered drug administration practices.

Mitochondrial acyl-coenzyme A species are emerging as important sources of protein modification and damage. Succinyl-CoA ligase (SCL) deficiency causes a mitochondrial encephalomyopathy of unknown pathomechanism. Here, we show that succinyl-CoA accumulates in cells derived from patients with recessive mutations in the tricarboxylic acid cycle (TCA) gene succinyl-CoA ligase subunit-β (SUCLA2), causing global protein hyper-succinylation. Using mass spectrometry, we quantify nearly 1,000 protein succinylation sites on 366 proteins from patient-derived fibroblasts and myotubes. Interestingly, hyper-succinylated proteins are distributed across cellular compartments, and many are known targets of the (NAD+)-dependent desuccinylase SIRT5. To test the contribution of hyper-succinylation to disease progression, we develop a zebrafish model of the SCL deficiency and find that SIRT5 gain-of-function reduces global protein succinylation and improves survival. Thus, increased succinyl-CoA levels contribute to the pathology of SCL deficiency through post-translational modifications., The pathomechanism of succinyl-CoA ligase (SCL) deficiency, a hereditary mitochondrial disease, is not fully understood. Here, the authors show that increased succinyl-CoA levels contribute to SCL pathology by causing global protein hyper-succinylation.

Background Lumbar disc herniation is often managed conservatively; nevertheless, surgical intervention can be required. Majority of patients experience a drastic relief of symptoms after surgery, but previous studies have reported that their health-related quality of life remains inferior compared to the general population for several years. There may be a major cumulative loss of health-related quality of life for young patients as they have long expected life ahead of them. Methods A total of 526 eligible adult patients under the age of 40 underwent surgery for lumbar disc herniation from 1990 to 2005. Patients’ baseline characteristics were acquired by chart review to confirm eligibility to the study. Follow-up quality of life data was acquired by sending patients EQ-5D questionnaire at median 18 years after index surgery, and those 316 patients responding to the questionnaire (60%) were included in the study. Propensity score matching was utilized to match every study patient with two general population sample participants from a large Finnish population health study. Primary objective was to compare the quality of life to that of the control population. Secondary objective was to explore which patient characteristics lead to inferior outcome. Results The mean EQ-index for the patient cohort was 0.86, while it was 0.84 for the age and gender–matched general population sample (difference 0.02, 95% CI − 0.0004 to 0.049). Within the patient cohort, an increasing number of lifetime lumbar surgeries was associated with progressively deteriorating EQ-index scores (p = 0.049) and longer duration of symptoms prior to the surgery correlated with lower score (p = 0.013). Conclusion Patients who underwent surgery for lumbar disc herniation nearly two decades ago reported quality of life comparable to the age and gender–matched general population. However, patients who had undergone numerous lumbar surgeries had significantly worse outcome. Therefore, possible ways to prevent cumulation of lumbar surgeries could improve long-term health-related quality of life.

Objectives: The COVID-19 pandemic has globally affected healthcare workers’ (HCWs) health and wellbeing. Most studies on COVID-19 have focused on tertiary healthcare. The aim of this study was to increase the knowledge on the effects of the pandemic on working conditions in tertiary and primary healthcare. Material and Methods: The comparative cross-sectional study consisted of an online questionnaire sent to HCWs of the City of Helsinki (primary healthcare) and Helsinki University Hospital (tertiary healthcare). Altogether 1580 HCWs with direct patient contact participated in the study: 895 from tertiary and 685 from primary healthcare. Statistical analysis used SPSS 25 from IBM. The tests used were the χ2 test, Fisher’s exact test, and binary logistic regression analysis. Results: Primary HCWs were less likely to treat COVID-19 patients (OR = 0.45, 95% CI: 0.37–0.56). However, both groups reported a similar number of COVID-19 infections, primary HCWs 4.9% and tertiary HCWs 5.0%, and work-related quarantine was significantly more prevalent (OR = 1.96, 95% CI: 1.38–2.79) among primary HCWs. In addition, work-related wellbeing was poorer among primary HCWs than tertiary HCWs in terms of feeling more stressed at work (OR = 3.20, 95% CI: 2.55–4.02), not recovering from work (OR = 0.49, 95% CI: 0.39–0.62), reported mental wellbeing below normal levels (OR: 1.59, 95% CI: 1.26–2.00), and increased working hours (OR = 1.63, 95% CI: 1.25–2.12). Conclusions: The study demonstrates how the pandemic has affected the wellbeing and working conditions of not only tertiary but also less studied primary HCWs. The authors’ findings suggest that the challenges identified during the COVID-19 pandemic in the health and wellbeing of healthcare workers are even greater in primary care than in tertiary care.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that obstructs the bile ducts and causes liver cirrhosis and cholangiocarcinoma. Efficient surrogate markers are required to measure disease progression. The cytokeratin 7 (K7) load in a liver specimen is an independent prognostic indicator that can be measured from digitalized slides using artificial intelligence (AI)-based models.A K7-AI model 2.0 was built to measure the hepatocellular K7 load area of the parenchyma, portal tracts, and biliary epithelium. K7-stained PSC liver biopsy specimens (n = 295) were analyzed. A compound endpoint (liver transplantation, liver-related death, and cholangiocarcinoma) was applied in Kaplan-Meier survival analysis to measure AUC values and positive likelihood ratios for each histological variable detected by the model.The K7-AI model 2.0 was a better prognostic tool than plasma alkaline phosphatase-ALP, fibrosis stage evaluated by Nakanuma classification, or K7 score evaluated by a pathologist based on the AUC values of measured variables. A combination of parameters, such as portal tract volume and area of K7-positive hepatocytes analyzed by the model, produced an AUC of 0.81 for predicting the compound endpoint. Portal tract volume measured by the model correlated with the histological fibrosis stage.The K7-staining of histological liver specimens in PSC provides significant information on disease outcomes through objective and reproducible data, including variables that cannot be measured by a human pathologist. The K7-AI model 2.0 could serve as a prognostic tool for clinical endpoints and as a surrogate marker in drug trials. This article is protected by copyright. All rights reserved.

Introduction: Alcohol, tobacco and coffee are commonly used substances and use in adolescence has previously been linked to mood disorders. However, few large prospective studies have investigated adolescent use in relation to mental health outcomes in adulthood. The main aim of this study was to examine the prospective associations between alcohol use, cigarette smoking and coffee consumption at age 16 and subsequent mood disorders up to 33 years of age. Methods: Data from The Northern Finland Birth Cohort 1986 Study were used and a total of 7660 participants (49.9% male) were included. Associations between alcohol use, cigarette smoking and coffee consumption at age 16 and later diagnoses of major depression and bipolar disorder were examined using multinomial logistic regression analyses. Results: Mean number of cigarettes/day (OR, 1.23 [95% CI 1.01–1.50]) and mean volume of alcohol consumption (OR, 1.22 [95% CI 1.01–1.47]), but not frequency of excessive drinking, in adolescence were associated with increased risk for subsequent bipolar disorder after adjustment for sex, parental psychiatric disorders, family structure, illicit substance use, and emotional and behavioral problems at age 16. An association between cigarette smoking and major depression attenuated to statistically non-significant when adjusted for emotional and behavioral problems. No associations were observed between adolescent coffee consumption and subsequent mood disorders. Conclusions: This is the first study to report an association of adolescent cigarette smoking and subsequent bipolar disorder diagnosis providing grounds for further research and pointing to a place for preventive measures among adolescents. publishedVersion

Background Admission computed tomography (CT) scoring systems can be used to objectively quantify the severity of traumatic brain injury (TBI) and aid in outcome prediction. We aimed to externally validate the NeuroImaging Radiological Interpretation System (NIRIS) and the Helsinki CT score. In addition, we compared the prognostic performance of the NIRIS and the Helsinki CT score to the Marshall CT classification and to a clinical model. Methods We conducted a retrospective multicenter observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted in four university hospital ICUs during 2003–2013. We analyzed the CT scans using the NIRIS and the Helsinki CT score and compared the results to 6-month mortality as the primary outcome. In addition, we created a clinical model (age, Glasgow Coma Scale score, Simplified Acute Physiology Score II, presence of severe comorbidity) and combined clinical and CT models to see the added predictive impact of radiological data to conventional clinical information. We measured model performance using area under curve (AUC), Nagelkerke’s R2 statistics, and the integrated discrimination improvement (IDI). Results A total of 3031 patients were included in the analysis. The 6-month mortality was 710 patients (23.4%). Of the CT models, the Helsinki CT displayed best discrimination (AUC 0.73 vs. 0.70 for NIRIS) and explanatory variation (Nagelkerke’s R2 0.20 vs. 0.15). The clinical model displayed an AUC of 0.86 (95% CI 0.84–0.87). All CT models increased the AUC of the clinical model by + 0.01 to 0.87 (95% CI 0.85–0.88) and the IDI by 0.01–0.03. Conclusion In patients with TBI treated in the ICU, the Helsinki CT score outperformed the NIRIS for 6-month mortality prediction. In isolation, CT models offered only moderate accuracy for outcome prediction and clinical variables outweighing the CT-based predictors in terms of predictive performance.

Comorbidity with various health conditions is common in environmental intolerances (EIs), which restricts understanding for what symptoms that are associated with the intolerance per se. The present objectives were to study (i) prevalence of a broad range of specific symptoms in chemical, building-related, electromagnetic field-(EMF) related, and sound EI, irrespective of comorbidity, (ii) prevalence of symptoms in body systems in exclusive EIs, and (iii) increased risk of symptoms in body systems in exclusive EIs that cannot be referred to functional somatic syndromes, inflammatory diseases or mental disorders. Cross-sectional data (n = 4941) were used from two combined population-based surveys, the Va center dot sterbotten (Sweden) and center dot Osterbotten (Finland) Environmental Health Studies. Categorization of EI cases and controls were based on self-reports. Symptoms were assessed with the Environmental Hypersensitivity Symptom Inventory, and these were converted to 27 symptoms of the International Classification of Primary Care, 2nd edition, in eight chapters of body systems. The results showed, with few exceptions, that all assessed specific symptoms were significantly more prevalent in all four EIs than in referents. Although a large overlap between EIs, characteristic body system symptoms were eye and respiratory symptoms in chemical and building-related intolerance, skin symptoms in EMF-related intoler-ance, and general and unspecified, digestive, eye, cardiovascular, neurological, and psychological symptoms in sound intolerance. After controlling for various comorbidities, all studied body system symptoms were positively associated with chemical intolerance, fewer with sound intolerance, only one with building-related intolerance, and none with EMF-related EI. In conclusion, a broad range of symptoms are reported in all four EIs implying common mechanisms, but symptoms of certain body systems are more likely to be reported in a certain EI that cannot be explained by comorbidity.

Radiosumins are a structurally diverse family of low molecular weight natural products that are produced by cyanobacteria and exhibit potent serine protease inhibition. Members of this family are dipeptides characterized by the presence of two similar non-proteinogenic amino acids. Here we used a comparative bioinformatic analysis to identify radiosumin biosynthetic gene clusters from the genomes of 13 filamentous cyanobacteria. We used direct pathway cloning to capture and express the entire 16.8 kb radiosumin biosynthetic gene cluster from Dolichospermum planctonicum UHCC 0167 in Escherichia coli. Bioinformatic analysis demonstrates that radiosumins represent a new group of chorismate-derived non-aromatic secondary metabolites. High-resolution liquid chromatography-mass spectrometry, nuclear magnetic resonance spectroscopy and chemical degradation analysis revealed that cyanobacteria produce a cocktail of novel radiosumins. We report the chemical structure of radiosumin D, an N-methyl dipeptide, containing a special Aayp (2-amino-3-(4-amino-2-cyclohexen-1-ylidene) propionic acid) with R configuration that differs from radiosumin A-C, an N-Me derivative of Aayp (Amyp) and two acetyl groups. Radiosumin C inhibits all three human trypsin isoforms at micromolar concentrations with preference for trypsin-1 and -3 (IC50 values from 1.7 mu M to >7.2 mu M). These results provide a biosynthetic logic to explore the genetic and chemical diversity of the radiosumin family and suggest that these natural products may be a source of drug leads for selective human serine proteases inhibitors.

Genome-wide association studies (GWAS) have successfully identified associations for cervical cancer, but the underlying mechanisms of cervical biology and pathology remain uncharacterised. Our GWAS meta-analyses fill this gap, as we characterise the genetic architecture of cervical phenotypes, including cervical ectropion, cervicitis, cervical dysplasia, as well as up to 9229 cases and 490 304 controls for cervical cancer from diverse ancestries. Leveraging the latest computational methods and gene expression data, we refine the association signals for cervical cancer and propose potential causal variants and genes at each locus. We prioritise PAX8/PAX8-AS1, LINC00339, CDC42, CLPTM1L, HLA-DRB1 and GSDMB as the most likely candidate genes for cervical cancer signals, providing insights into cervical cancer pathogenesis and supporting the involvement of reproductive tract development, immune response and cellular proliferation/apoptosis. We construct a genetic risk score (GRS) that is associated with cervical cancer [hazard ratios (HR) = 3.1 (1.7-5.6) for the top 15% vs lowest 15% of individuals], and with other HPV- and immune-system-related diagnoses in a phenome-wide association study analysis. Our results propose valuable leads for further functional studies and present a GRS for cervical cancer that allows additional risk stratification and could potentially be used to personalise the conventional screening strategies for groups more susceptible to cervical cancer.

Introduction The sixth angstrom land Islands Conference on von Willebrand disease (VWD) on the angstrom land Islands, Finland, was held from 20 to 22 September 2018. Aim The meeting brought together experts in the field of VWD from around the world to share the latest advances and knowledge in VWD. Results and discussion The topics covered both clinical aspects of disease management, and biochemical and laboratory insights into the disease. The clinical topics discussed included epidemiology, diagnosis and treatment of VWD in different countries, management of children with VWD, bleeding control during surgery, specific considerations for the management of type 3 VWD and bleeding control in women with VWD. Current approaches to the management of acquired von Willebrand syndrome were also discussed. Despite significant advances in the understanding and therapeutic options for VWD, there remain many challenges to be overcome in order to optimise patient care. In comparison with haemophilia A, there are very few registries of VWD patients, which would be a valuable source of data on the condition and its management. VWD is still underdiagnosed, and many patients suffer recurrent or severe bleeding that could be prevented. Awareness of VWD among healthcare practitioners, including non-haematologists, should be improved to allow timely diagnosis and intervention. Diagnosis remains challenging, and the development of fast, simple assays may help to facilitate accurate and rapid diagnosis of VWD.

We report a case of pyruvate dehydrogenase E1 alpha subunit deficiency associated with a novel hemizygous PDHA1 variant presenting prenatally as multiple structural brain abnormalities in a male fetus. A healthy Finnish couple was initially referred to the Fetomaternal Medical Center because of suspected fetal choroid plexus cyst at 11 + 2 weeks of pregnancy. At 20 + 0 weeks, multiple abnormalities were observed with ultrasound including narrow thorax, slightly enlarged heart, hypoplastic cerebellum, absent cerebellar vermis and ventriculomegaly. Autopsy and genetic analyses were performed after the termination of pregnancy. The findings of macroscopic examination included cleft palate, abnormally overlapping position of fingers and toes and dysmorphic facial features. Neuropathological examination confirmed the absence of corpus callosum, cerebellar hypoplasia and ventriculomegaly. Nodular neuronal heterotopia was also observed. Trio exome sequencing revealed a novel hemizygous de novo variant c.1144C>T p.(Gln382*) in the PDHA1 gene, classified as likely pathogenic. We suggest that inherited metabolic disorders should be kept in mind as differential diagnoses in fetuses with structural brain abnormalities.

Background Doping is a well-recognized risk factor for several potentially severe health effects. Scientific literature concerning the need for medical treatment for such adversities is still sparse. This is especially true for women, due to lower doping use prevalence compared to men. Our study explored the nature of medical contacts and deviance in red blood cell parameters of female patients with doping use in Finnish specialized health care. Methods This was a retrospective register study. The study sample was gathered from the Hospital District of Helsinki and Uusimaa, Finland (HUS) Datalake. An exhaustive search for doping related terms was performed to find patients with doping use documentation within free-text patient records. Medical record data was supplemented with laboratory data and medical diagnoses covering a total observation time of two decades. Statistical analysis included Fisher's Exact Test and one-way ANOVA. Results We found 39 female patients with history of doping use and specialized health care contacts in the HUS-area between 2002–2020. At initial contact (i.e., the first documentation of doping use), the mean age of these patients was 33.6 years (min 18.1, max 63.5, SD 10.6). The most frequently used doping agents were anabolic androgenic steroids (AAS). The initial contacts were significantly more often acute in nature among patients with active doping use than among patients with only previous use (no use within one year; p = 0.002). Psychiatric and substance use disorder (SUD) morbidity was high (46.2% and 30.8%, respectively). Eight patients (20.5%) had received specialized health care for acute poisoning with alcohol or drugs, and nine (23.1%) for bacterial skin infections. Less than 45% of patients with active AAS use presented with off-range red blood cell parameters. Conclusions Our findings suggest that female patients with a history of doping use encountered in specialized health care may exhibit high psychiatric and SUD related morbidity. Also, majority of patients with AAS use had red blood cell parameters within-range. Further studies are required to assess the generalizability of these findings to patients within primary health care services, and to determine the usefulness of hematological parameters as indicators of AAS use in female patients.

Background: Poor medication management may negatively impact the health and functional capacity of older adults. This cross-sectional study aimed to identify medication-related risk factors in home-dwelling residents using a validated self-assessment as part of comprehensive health screening. Methods: The data were derived from comprehensive health screening (PORI75) for older adults of 75 years living in Western Finland in 2020 and 2021. One of 30 validated measures in health screening focused on identifying medication-related risk factors (LOTTA Checklist). The Checklist items were divided into (1) systemic risk factors (10 items) and (2) potentially drug-induced symptoms (10 items). Polypharmacy was categorized according to the number of used drugs: (1) no polypharmacy (5 drugs, that is, having polypharmacy. Of the systemic risk factors most common was that the resident had more than one physician responsible for the treatment (48% of the residents), followed by missing drug list (43%), missing regular monitoring (35%), and unclear durations of the medication (35%). The most experienced potentially drug-induced symptoms were self-reported constipation (21%), urinating problems (20%), and unusual tiredness (17%). An increasing number of drugs in use, particularly excessive polypharmacy, was associated with various medication-related risk factors. Conclusion: As a part of comprehensive health screening the LOTTA Checklist provides useful information to prevent medication-related risk factors in home-dwelling older adults. The Checklist could be used to guide planning and implementing health services in the future. publishedVersion

AimThe aim of this review was to synthesize the instruments that assess nurse educators' competence. DesignA scoping review was conducted with the five-stage process informed by Arksey and O'Malley. Review MethodsThe predetermined search strategy was used including an additional hand search. The studies were selected according to inclusion and exclusion criteria to answer the research questions followed: (1) "What instruments are used to assess nurse educators' competence?", (2) "How are the psychometric properties of nurse educators' competence instruments reported in the literature?". The thematic synthesis was used. Data SourcesThe literature search was conducted in January 2021 using the CINAHL, MEDLINE and ERIC databases from January 2000 to December 2020. ResultsOf the 1,567 articles searched through, 25 met the inclusion criteria. A total of 19 instruments with 10 areas of competence were identified. Typical competence areas were pedagogical and nursing competence. In addition, leadership in managerial competence was included in several instruments. However, the theoretical backgrounds of the instruments varied and the psychometric properties were reported in varied ways in reviewed studies. Implications for the ProfessionThis study provides evidence about the valid and comprehensive assessment of nurse educators' competence, as competent nurse educators promote excellence in nursing education. To assess a nurse educators' competence comprehensively, a variety of theoretical backgrounds of this competence and more than one instrument for the measurement need to be considered. The selection of the instruments to assess nurse educators' competence should be based on the selected theoretical background and use of valid measurements. Reporting MethodThis study was reported by following the reporting recommendations of the PRISMA extension for Scoping Reviews (PRISMA-ScR). Patient or Public ContributionNo Patient or Public Contribution was applied, since research design was a scoping review.

Publisher Copyright: © 2023 International Federation of Clinical Neurophysiology Objective: To study if interictal epileptiform discharges (IEDs) are associated with language performance or pre-/perinatal factors in children with developmental language disorder (DLD). Methods: We recorded routine EEG in wake and sleep in 205 children aged 2.9–7.1 years with DLD, without neurologic diseases or intellectual disability. We examined the language performance of the children and collected data on pre-/perinatal factors. Results: Interictal epileptiform discharges were not associated with lower language performance. Children with so-called “rolandic”, i.e. centrotemporoparietal, IEDs had better language skills, but age explained this association. Most pre-/perinatal factors evaluated did not increase the risk of rolandic IEDs, except for maternal smoking (OR 4.4, 95% CI 1.4–14). We did not find electrical status epilepticus during slow-wave sleep (ESES)/spike-and-wave activation in sleep (SWAS) in any children. Conclusions: Interictal epileptiform discharges are not associated with lower language performance, and ESES/SWAS is not common in children with DLD. Significance: Routine EEGs do not bring additional information about language performance in children with DLD who do not have any neurologic diseases, seizures, intellectual disability, or regression of language development.

Non

Background Pressure injures are a common adverse event in a hospital, and they are one of the most important quality indicators of patient care. Risk assessment is recommended as the first step in the prevention of pressure injuries. A Prevent Pressure Injury Risk Assessment Tool is a new tool for risk assessment that was developed by the Helsinki University Hospital. Aim The aim of this study was to evaluate the predictive validity and the concurrent validity of the Prevent Pressure Injury Risk Assessment Tool in acute care. Method The prospective observational study was conducted in 19 in-patient wards representing internal medicine, neurology, and surgery during 2017–2018. The participants’ inclusion criteria were: age ≥18 years old, no pressure injury on admission to the hospital and consenting to participate. The data collected by physical assessment of patients was combined with data from electronic patient records. Each patient was assessed by two different nurses with the Prevent Pressure Injury Risk Assessment Tool and the Braden Scale at patient admission. Furthermore, skin condition was observed throughout the hospital stay. Results Of the 637 patients accepted for the study, 10 (1.6%) developed a pressure injury during the hospital stay. Poisson regression analysis showed that pressure injuries were more likely in high–risk patients compared to those with low-risk. The sensitivity of the Prevent Pressure Injury Risk Assessment Tool was adequate (75%), while specificity was poor (40%). A moderate correlation was found between the Prevent Pressure Injury Risk Assessment Tool and the Braden Scale. Conclusions The Prevent Pressure Injury Risk Assessment Tool may be useful for identifying the adult pressure injury risk patients in acute care. Further research is needed to evaluate interrater reliability, and usability and validity with different patient populations.

Oral health and declining cognition may have a bi-directional association. We characterized the subgingival microbiota composition of subjects from normal cognition to severe cognitive decline in two cohorts. Memory and Periodontitis (MINOPAR) include 202 home-living participants (50-80 years) in Sweden. Finnish Oral Health Studies in Older Adults (FINORAL) include 174 participants (>= 65 years) living in long-term care in Finland. We performed oral examination and assessed the cognitive level with Mini Mental State Examination (MMSE). We sequenced the 16S-rRNA gene (V3-V4 regions) to analyse the subgingival bacterial compositions. The microbial diversities only tended to differ between the MMSE categories, and the strongest determinants were increased probing pocket depth (PPD) and presence of caries. However, abundances of 101 taxa were associated with the MMSE score. After adjusting for age, sex, medications, PPD, and caries, only eight taxa retained the significance in the meta-analyses of the two cohorts. Especially Lachnospiraceae [XIV] at the family, genus, and species level increased with decreasing MMSE. Cognitive decline is associated with obvious changes in the composition of the oral microbiota. Impaired cognition is accompanied with poor oral health status and the appearance of major taxa of the gut microbiota in the oral cavity. Good oral health-care practices require special deliberations among older adults.

Background Adaptations in lipid metabolism are essential to meet the physiological demands of pregnancy and any aberration may result in adverse outcomes for both mother and offspring. However, there is a lack of population-level studies to define the longitudinal changes of maternal circulating lipids from preconception to postpartum in relation to cardiometabolic risk factors. Methods LC-MS/MS-based quantification of 689 lipid species was performed on 1595 plasma samples collected at three time points in a preconception and longitudinal cohort, Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). We mapped maternal plasma lipidomic profiles at preconception (N = 976), 26–28 weeks’ pregnancy (N = 337) and 3 months postpartum (N = 282) to study longitudinal lipid changes and their associations with cardiometabolic risk factors including pre-pregnancy body mass index, body weight changes and glycaemic traits. Results Around 56% of the lipids increased and 24% decreased in concentration in pregnancy before returning to the preconception concentration at postpartum, whereas around 11% of the lipids went through significant changes in pregnancy and their concentrations did not revert to the preconception concentrations. We observed a significant association of body weight changes with lipid changes across different physiological states, and lower circulating concentrations of phospholipids and sphingomyelins in pregnant mothers with higher pre-pregnancy BMI. Fasting plasma glucose and glycated haemoglobin (HbA1c) concentrations were lower whereas the homeostatic model assessment of insulin resistance (HOMA-IR), 2-h post-load glucose and fasting insulin concentrations were higher in pregnancy as compared to both preconception and postpartum. Association studies of lipidomic profiles with these glycaemic traits revealed their respective lipid signatures at three physiological states. Assessment of glycaemic traits in relation to the circulating lipids at preconception with a large sample size (n = 936) provided an integrated view of the effects of hyperglycaemia on plasma lipidomic profiles. We observed a distinct relationship of lipidomic profiles with different measures, with the highest percentage of significant lipids associated with HOMA-IR (58.9%), followed by fasting insulin concentration (56.9%), 2-h post-load glucose concentration (41.8%), HbA1c (36.7%), impaired glucose tolerance status (31.6%) and fasting glucose concentration (30.8%). Conclusions We describe the longitudinal landscape of maternal circulating lipids from preconception to postpartum, and a comprehensive view of trends and magnitude of pregnancy-induced changes in lipidomic profiles. We identified lipid signatures linked with cardiometabolic risk traits with potential implications both in pregnancy and postpartum life. Our findings provide insights into the metabolic adaptations and potential biomarkers of modifiable risk factors in childbearing women that may help in better assessment of cardiometabolic health, and early intervention at the preconception period. Trial registration ClinicalTrials.gov, NCT03531658.

Background Various indexes have been developed to estimate the risk for mortality, institutionalization, and other adverse outcomes for older people. Most indexes are based on a large number of clinical or laboratory parameters. An index based on only a few parameters would be more practical to use in every-day clinical practice. Our aim was to create an index to predict the risk for mortality and institutionalization with as few parameters as possible without compromising their predictive ability. Methods A prospective study with a 10-year follow-up period. Thirty-six clinical and fourteen laboratory parameters were combined to form an index. Cox regression model was used to analyze the association of the index with institutionalization and mortality. A backward statistical method was used to reduce the number of parameters to form an easy-to-use index for predicting institutionalization and mortality. Results The mean age of the participants (n = 1172) was 73.1 (SD 6.6, range 64‒97) years. Altogether, 149 (14%) subjects were institutionalized, and 413 (35%) subjects deceased during the follow-up. Institutionalization and mortality rates increased as index scores increased both for the large 50-parameter combined index and for the reduced indexes. After a backward variable selection in the Cox regression model, three clinical parameters remained in the index to predict institutionalization and six clinical and three laboratory parameters in the index to predict mortality. The reduced indexes showed a slightly better predictive value for both institutionalization and mortality compared to the full index. Conclusions A large index with fifty parameters included many unimportant parameters that did not increase its predictive value, and therefore could be replaced with a reduced index with only a few carefully chosen parameters, that were individually associated with institutionalization or death.

Background Voriconazole, a first-line antifungal drug, exhibits nonlinear pharmacokinetics (PK), together with large interindividual variability but a narrow therapeutic range, and markedly inhibits cytochrome P450 (CYP) 3A4 in vivo. This causes difficulties in selecting appropriate dosing regimens of voriconazole and coadministered CYP3A4 substrates. Objective This study aimed to investigate the metabolism of voriconazole in detail to better understand dose- and time-dependent alterations in the PK of the drug, to provide the model basis for safe and effective use according to CYP2C19 genotype, and to assess the potential of voriconazole to cause drug-drug interactions (DDIs) with CYP3A4 substrates in more detail. Methods In vitro assays were carried out to explore time-dependent inhibition (TDI) of CYP3A4 by voriconazole. These results were combined with 93 published concentration-time datasets of voriconazole from clinical trials in healthy volunteers to develop a whole-body physiologically based PK (PBPK) model in PK-Sim(R). The model was evaluated quantitatively with the predicted/observed ratio of the area under the plasma concentration-time curve (AUC), maximum concentration (C-max), and trough concentrations for multiple dosings (C-trough), the geometric mean fold error, as well as visually with the comparison of predicted with observed concentration-time datasets over the full range of recommended intravenous and oral dosing regimens. Results The result of the half maximal inhibitory concentration (IC50) shift assay indicated that voriconazole causes TDI of CYP3A4. The PBPK model evaluation demonstrated a good performance of the model, with 71% of predicted/observed aggregate AUC ratios and all aggregateC(max)ratios from 28 evaluation datasets being within a 0.5- to 2-fold range. For those studies reporting CYP2C19 genotype, 89% of aggregate AUC ratios and all aggregateC(max)ratios were inside a 0.5- to 2-fold range of 44 test datasets. The results of model-based simulations showed that the standard oral maintenance dose of voriconazole 200 mg twice daily would be sufficient for CYP2C19 intermediate metabolizers (IMs; *1/*2, *1/*3, *2/*17, and *2/*2/*17) to reach the tentative therapeutic range of > 1-2 mg/L to

To evaluate the association between the exposure of particulate matter with an aerodynamic diameter of ≤ 2.5μm (PMAll Finnish primiparous women without previously diagnosed diabetes who delivered between 2009 and 2015 in the city of Vantaa, Finland, composed the study cohort (N = 6189). Diagnosis of GDM was based on a standard 75 g 2-hour oral glucose tolerance test. The average daily concentration of PMNo association was observed between the average daily concentrations of PMEven globally low PM

IntroductionPersistent physical symptoms (PPS) refer to symptoms that cannot be fully explained by structural bodily pathology or by environmental factors. Their impact on daily functioning varies from mild to severe disability. So far, evidence-based treatments for PPS have resulted in only small to moderate effects. Treatment protocols with a stronger orientation toward personalized approaches are needed to improve the efficacy and applicability of treatment. In this study, we aim to assess the effect of an online individual case conceptualization with web-based program for PPS. This study is conducted among two focus groups: patients with indoor air-related symptoms and patients with chronic fatigue syndrome.Methods and analysesUsing a randomized controlled design (RCT) with two parallel groups in a 1:1 ratio, we will compare individual video-based case conceptualization with a web-based program based on Acceptance and Commitment Therapy (ACT), combined with treatment as usual, with treatment as usual only. The web-based program consists of ten modules, each lasting 1 week and including training. The planned sample size is 124 eligible patients without attrition. The primary outcome will be the health-related quality of life as measured by the 15D questionnaire. The secondary outcome measures will include questionnaires on psychiatric and physical symptoms, illness perceptions, psychological flexibility, and work ability. We will also use national registers to obtain information on the use of healthcare and social benefits to complete patient-reported outcomes. Data collection began in August 2020 and will continue until 2023.DiscussionThis trial will provide information on the effects and usefulness of an online administrated individual case conceptualization and an ACT-based web-program on PPS.Ethics and disseminationThe Ethics Committee of the Hospital District of Helsinki and Uusimaa, Finland, has granted approval for the study. The results will be published in peer-reviewed journals.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT04532827 preresults.

ObjectiveTo explore predictive factors of postoperative outcome of frontal sinus balloon dilation. Study DesignRetrospective questionnaire study. SettingDepartment of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Finland. MethodsWe reviewed electronic records of all patients who underwent frontal sinus balloon dilatation (successful or attempted) in our clinic from 2008 to 2019. We documented patient characteristics, preoperative imaging results, intraoperative factors, possible complications, and reoperations. Those who underwent frontal sinus balloon sinuplasty were sent a questionnaire regarding their current symptoms and long-term satisfaction with surgery. ResultsIn total, 258 operations (404 frontal sinuses) were reviewed, with a technical success rate of 93.6% (n = 378). The revision rate was 15.7% (n = 38). Previous sinonasal surgery predicted a higher revision rate (p = .004, odds ratio [OR] = 3.03, 95% confidence interval [CI] 1.40-6.56). Patients with hybrid surgery had significantly fewer reoperations compared to the balloon only group (p = .002, OR = 0.33, 95% CI 0.16-0.67). The response rate of the questionnaire was 64.5% (n = 156), of which 88.5% (n = 138) reported a long-term benefit from the balloon sinuplasty. Patient satisfaction was higher (p = .02, OR = 8.26, 95% CI 1.06-64.24) among patients using nasal corticosteroids. ConclusionTechnical success rate and patient satisfaction after frontal sinus balloon sinuplasty are high. Balloon sinuplasty seems insufficient in reoperations. A hybrid approach appears to result in fewer reoperations than a balloon only approach.

Introduction Acute appendicitis is a common surgical emergency, and the standard approach to diagnosis and management has been codified in several practice guidelines. Adherence to these guidelines provides insight into independent surgical practice patterns and institutional resource constraints as impediments to best practice. We explored data from the recent ESTES SnapAppy observational cohort study to determine guideline compliance in contemporary practice to identify opportunities to close evidence-to-practice gaps. Methods We undertook a preplanned analysis of the ESTES SnapAppy observational cohort study, identifying, at a patient level, congruence with, or deviation from WSES Jerusalem guidelines for the diagnosis and management of acute appendicitis and the Surviving Sepsis Campaign in our cohort. Compliance was then correlated with the incidence of postoperative complications. Results Four thousand six hundred and thirteen (4613) consecutive adult and adolescent patients with acute appendicitis were followed from date of admission (November 1, 2020, and May 28, 2021) for 90 days. Patient-level compliance with guideline elements allowed patients to be grouped into those with full compliance (all 5 elements: 13%), partial compliance (1–4 elements: 87%) or noncompliance (0 elements: 0.2%). We identified an excess postoperative complication rate in patients who received noncompliant and partially compliant care, compared with those who received fully guideline-compliant care (36% and 16%, versus 7.3%, p Conclusions The observed diagnostic and treatment practices of the participating institutions displayed variability in compliance with key recommendations from existing guidelines. In general, practice was congruent with recommendations for preoperative antibiotic surgical site infection prophylaxis administration, time to surgery, and operative approach. However, there remains opportunities for improvement in the choice of diagnostic imaging modality, postoperative antibiotic stewardship to timely discontinue prophylactic antibiotics, and the implementation of ambulatory treatment pathways for uncomplicated appendicitis in the healthy young adult.

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency 1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P –11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of

Background Spontaneous angiogram-negative subarachnoid hemorrhage (SAH) is considered a benign illness with little of the aneurysmal SAH-related complications. We describe the clinical course, SAH-related complications, and outcome of patients with angiogram-negative SAH. Methods We retrospectively reviewed all adult patients admitted to a neurosurgical intensive care unit during 2004–2018 due to spontaneous angiogram-negative SAH. Our primary outcome was a dichotomized Glasgow Outcome Scale (GOS) at 3 months. We assessed factors that associated with outcome using multivariable logistic regression analysis. Results Of the 108 patients included, 84% had a favorable outcome (GOS 4–5), and mortality was 5% within 1 year. The median age was 58 years, 51% were female, and 93% had a low-grade SAH (World Federation of Neurosurgical Societies grading I–III). The median number of angiograms performed per patient was two. Thirty percent of patients showed radiological signs of acute hydrocephalus, 28% were acutely treated with an external ventricular drain, 13% received active vasospasm treatment and 17% received a permanent shunt. In the multivariable logistic regression model, only acute hydrocephalus associated with unfavorable outcome (odds ratio = 4.05, 95% confidence interval = 1.05–15.73). Two patients had a new bleeding episode. Conclusion SAH-related complications such as hydrocephalus and vasospasm are common after angiogram-negative SAH. Still, most patients had a favorable outcome. Only acute hydrocephalus was associated with unfavorable outcome. The high rate of SAH-related complications highlights the need for neurosurgical care in these patients.

Background Little is known on the landscape of viruses that have taken residence within our cells, nor on the interplay with the host imperative for their persistence. However, a lifetime of interactions conceivably have an imprint on our physiology and immune phenotype. Importantly, current metagenomics-insights on the healthy human virome are derived from bodily fluids, which are only a proxy of the true prevalence of human eukaryotic viruses within tissues. Most significantly, the virome’s systemic composition across the different organs of an individual has thus far remained uncharted. Results In this work, we revealed the genetic make-up of the eukaryotic human DNA virome in the body and showed that each organ (colon, liver, lung, heart, brain, kidney, skin, blood, hair) has unique viral compositions. By integration of quantitative (qPCR) and qualitative (hybrid-capture sequencing) analysis, we identified the DNAs of 17 viruses, primarily herpes-, parvo-, papilloma- and anello-viruses (>80% prevalence), typically persisting in low copies (mean 540 copies/ million cells). The within-sample diversities (a-diversity) were highest in the lung, liver, colon, and kidney. We assembled in total 70 viral genomes (>90% breadth coverage), distinct in each of the individuals, and identified high sequence homology across the organs. Moreover, we detected variations in virome composition and distribution in two individuals with underlying malignant conditions. Conclusions Our findings reveal unprecedented prevalences of viral DNAs in human organs. We showed that bodily fluids, although accessible to sampling, fail to deliver a comprehensive view of the numerous intracellular viruses colonizing our tissues. Our data demonstrate how a multi-organ approach is essential for analyzing differing virome compositions in various disease states. This atlas provides a fundamental ground for the studies of correlates to disease, and for the interpretation of next-generation sequencing data in clinical virology. Ultimately, our findings call for investigation of the crosstalk between human DNA viruses, the host, and other microbes, as it predictably has a significant impact on our health.

Background Emergency Medical Services (EMS) is, by its nature, a challenging context that may create risks for both patients and employees. It is also known that an organisation’s safety culture has an influence on both patient and employee safety. Finnish EMS organisations lack knowledge of how their safety culture is perceived by their employees. Aim This study aims to test the psychometric properties of the Emergency Medical Services Safety Attitudes Questionnaire (EMS-SAQ) in a Finnish EMS setting. We also explore the connections between individual- and organisation-based characteristics and safety attitudes in the Finnish EMS. Methods A cross-sectional survey study design was used. The EMS-SAQ was used to collect data via social media. The instrument measures six domains of workplace safety culture: safety climate, teamwork climate, perceptions of management, job satisfaction, working conditions and stress recognition. The 5-point Likert scale was converted to a 100-point scale and mean ≥ 75 was dichotomized as a positive. Confirmatory factor analysis (CFA) was carried out to validate the EMS-SAQ in a Finnish setting. Other results were analysed by using non-parametric tests. Results 327 responses were included in the analysis. CFA showed that the total EMS-SAQ model had acceptable goodness-of-fit values in the Finnish EMS setting. Total mean scores for each safety culture domain were identified non-positively (mean score p Conclusions The EMS-SAQ is a valid tool to evaluate safety culture among the Finnish EMS organisations; it offers a novel method to evaluate safety and patient safety within the Finnish EMS organisations. According to the findings, the organisation-based characteristics more likely had an impact on safety attitudes than did the individual-based characteristics. Therefore, it is suggested that the Finnish EMS organisations undertake safety culture development at the organisational level.

The trends in incidence of lung cancer in never smokers are unclear as well as the significance of risk factors. We studied time trends in the incidence and risk factors of lung cancer in never smokers in Finland in a large, pooled cohort. We pooled data from seven Finnish health cohorts from the period between 1972 and 2015 with 106 193 never smokers. The harmonized risk factors included education, alcohol consumption, physical activity, height, and BMI. We retrieved incident lung cancers from the nation-wide Finnish Cancer Registry. We estimated average annual percent change (AAPC) and the effects of risk factors on cause-specific hazard ratios (HRs) of lung cancer using Poisson regression. We detected 47 lung cancers in never smoking men (n = 31 859) and 155 in never smoking women (n = 74 334). The AAPC of lung cancer incidence was -3.30% (95% confidence interval [CI]: -5.68% - -0.88%, P = 0.009) in never smoking men and 0.00% (95% CI: -1.57%-1.60%, P = 0.996) in never smoking women. Of the five studied risk factors only greater height in women had a statistically significant increased risk of lung cancer (multivariate HR = 1.84, 95%CI: 1.08-3.12). It is plausible that tobacco control measures focused on working places have reduced passive smoking among men more than among women, which could explain the declining trend in lung cancer incidence in never smoker men but not in never smoker women. As tobacco control measures have not been targeted to domestic environments, it is likely that women's exposure to passive smoking has continued longer. This article is protected by copyright. All rights reserved.

Purpose Fifteen years ago, a European survey demonstrated widespread adoption of early clinical exposure (ECE) programmes but little emphasis in the curricula of medical schools. We now repeat the survey in light of the ample emerging data suggesting multiple positive outcomes of ECE. Methods Online cross-sectional survey in European medical schools conducted by the EURACT Basic Medical Education Committee in 2021. Descriptive quantitative analyses and a thematic analysis approach were used. Results Eighy-nine (48%) medical schools in 30 European countries responded. ECE was used in 65 (73%) of the medical schools, and 88% of ECE programmes took place in primary care. The median total time spent on the ECE programme was 5 days. Teaching methods covered unstructured learning opportunities such as observation or shadowing doctors, as well as work-based learning whilst seeing real patients or reflecting on own encounters. Learning goals included knowledge, skills, and attitudes. More than half of the respondents expressed barriers to implementing or expanding ECE. Conclusions Compared to the previous survey, there was no significant change in the adoption or curricular emphasis of ECE programmes. Institutional attitudes towards certain disciplines and a lack of willingness to experiment with new teaching methods may be partially responsible.

Background: Intravenous thrombolysis seems safe in acute ischemic stroke patients with saccular, unruptured intracranial aneurysms (UIAs), but little is known about the differences in cardiovascular risk factors and outcomes between intravenous thrombolysis-treated stroke patients with and without UIAs. We hypothesized that UIA patients would have a higher burden of cardiovascular risk factors and, therefore, a higher risk of an unfavorable outcome. Methods: In this prospective cohort study conducted in Helsinki University Hospital, we identified intravenous thrombolysis-treated patients with concurrent saccular UIAs admitted to a comprehensive stroke center between 2005 and 2019 using 2 overlapping methods. For each UIA patient, a control patient was identified and matched (1:1) for age, sex, admission year, and stroke severity. The primary outcome was an unfavorable outcome at 3 months, defined as a modified Rankin Scale (mRS) score 3 to 6. The secondary outcomes were an excellent outcome (mRS score 0–1) at 3 months and mRS difference in shift analysis. Results: In total, 118 UIA patients and 118 matched control patients were identified. The UIA patients were more often current smokers, and their admission systolic blood pressure was higher. The rate of hemorrhagic complications did not differ between the groups. UIAs were not associated with an unfavorable outcome in the conditional logistic regression analysis (odds ratio, 1.41 [95% CI, 0.79–2.54]; P =0.25). However, the UIA patients were less likely to have excellent outcomes (odds ratio for non-excellent outcome, 2.09 [95% CI, 1.13–3.85]; P =0.02). In shift analysis, UIAs were associated with higher mRS (odds ratio, 1.61 [95% CI, 1.03–2.49]; P =0.04). Conclusions: The intravenous thrombolysis-treated stroke patients with UIAs were more often current smokers and had higher systolic blood pressure than the matched patients without UIAs. They were as likely to have unfavorable outcomes at 3 months but seemed less likely to achieve excellent outcomes and were more likely to have higher mRS in shift analysis.

Publisher Copyright: © 2022. Published by The Company of Biologists Ltd. Isolated populations have been valuable for the discovery of rare monogenic diseases and their causative genetic variants. Finnish disease heritage (FDH) is an example of a group of hereditary monogenic disorders caused by single major, usually autosomal-recessive, variants enriched in the population due to several past genetic drift events. Interestingly, distinct subpopulations have remained in Finland and have maintained their unique genetic repertoire. Thus, FDH diseases have persisted, facilitating vigorous research on the underlying molecular mechanisms and development of treatment options. This Review summarizes the current status of FDH, including the most recently discovered FDH disorders, and introduces a set of other recently identified diseases that share common features with the traditional FDH diseases. The Review also discusses a new era for population-based studies, which combine various forms of big data to identify novel genotype-phenotype associations behind more complex conditions, as exemplified here by the FinnGen project. In addition to the pathogenic variants with an unequivocal causative role in the disease phenotype, several risk alleles that correlate with certain phenotypic features have been identified among the Finns, further emphasizing the broad value of studying genetically isolated populations.

In immune aplastic anemia (IAA), severe pancytopenia results from the immune-mediated destruction of hematopoietic stem cells. Several autoantibodies have been reported, but no clinically applicable autoantibody tests are available for IAA. We screened autoantibodies using a microarray containing >9000 proteins and validated the findings in a large international cohort of IAA patients (n = 405) and controls (n = 815). We identified a novel autoantibody that binds to the C-terminal end of cyclooxygenase 2 (COX-2, aCOX-2 Ab). In total, 37% of all adult IAA patients tested positive for aCOX-2 Ab, while only 1.7% of the controls were aCOX-2 Ab positive. Sporadic non-IAA aCOX-2 Ab positive cases were observed among patients with related bone marrow failure diseases, multiple sclerosis, and type I diabetes, whereas no aCOX-2 Ab seropositivity was detected in the healthy controls, in patients with non-autoinflammatory diseases or rheumatoid arthritis. In IAA, anti-COX-2 Ab positivity correlated with age and the HLA-DRB1*15:01 genotype. 83% of the >40 years old IAA patients with HLA-DRB1*15:01 were anti-COX-2 Ab positive, indicating an excellent sensitivity in this group. aCOX-2 Ab positive IAA patients also presented lower platelet counts. Our results suggest that aCOX-2 Ab defines a distinct subgroup of IAA and may serve as a valuable disease biomarker.

We aimed to identify serum metabolites related to abnormal glucose metabolism (AGM) among women with gestational diabetes mellitus (GDM). The study recruited 50 women diagnosed with GDM during mid-late pregnancy and 50 non-GDM matchees in a Singapore birth cohort. At the 5-year post-partum follow-up, we applied an untargeted approach to investigate the profiles of serum metabolites among all participants. We first employed OPLS-DA and logistic regression to discriminate women with and without follow-up AGM, and then applied area under the curve (AUC) to assess the incremental indicative value of metabolic signatures on AGM. We identified 23 candidate metabolites that were associated with postpartum AGM among all participants. We then narrowed down to five metabolites [p-cresol sulfate, linoleic acid, glycocholic acid, lysoPC(16:1) and lysoPC(20:3)] specifically associating with both GDM and postpartum AGM. The combined metabolites in addition to traditional risks showed a higher indicative value in AUC (0.92–0.94 vs. 0.74 of traditional risks and 0.77 of baseline diagnostic biomarkers) and R2 (0.67–0.70 vs. 0.25 of traditional risks and 0.32 of baseline diagnostic biomarkers) in terms of AGM indication, compared with the traditional risks model and traditional risks and diagnostic biomarkers combined model. These metabolic signatures significantly increased the AUC value of AGM indication in addition to traditional risks, and might shed light on the pathophysiology underlying the transition from GDM to AGM.

Context An inverse relationship between brown adipose tissue (BAT) and obesity has previously been reported in older children and adults but is unknown in young children. Objective We investigated the influence of BAT in thermoneutral condition on adiposity and metabolic profile in Asian preschool children. Design, Setting, and Participants A total of 198 children aged 4.5 years from a prospective birth cohort study, Growing Up in Singapore Towards Healthy Outcomes (GUSTO) were successfully studied with water-fat magnetic resonance imaging of the supraclavicular and axillary fat depot (FDSA). Regions within FDSA with fat-signal-fraction between 20% and 80% were considered BAT, and percentage BAT (%BAT; 100*BAT volume/ FDSA volume) was calculated. Main Outcome Measures Abdominal adipose tissue compartment volumes, ectopic fat in the soleus muscle and liver, fatty liver index, metabolic syndrome scores, and markers of insulin sensitivity. Results A 1% unit increase in %BAT was associated with lower body mass index, difference (95% CI), −0.08 (−0.10, −0.06) kg/m2 and smaller abdominal adipose tissue compartment volumes. Ethnicity and sex modified these associations. In addition, each unit increase in %BAT was associated with lower ectopic fat at 4.5 years in the liver, −0.008% (−0.013%, −0.003%); soleus muscle, −0.003% (−0.006%, −0.001%) of water content and lower fatty liver index at 6 years. Conclusions Higher %BAT is associated with a more favorable metabolic profile. BAT may thus play a role in the pathophysiology of obesity and related metabolic disorders. The observed ethnic and sex differences imply that the protective effect of BAT may vary among different groups.

Purpose: Ample evidence exists on the relationship between bicycle injuries and craniofacial fractures. However, as the mechanism behind these injuries is often multifactorial, the presence of associated injuries (AIs) in this study population requires further examination. We hypothesized that patients with craniofacial fracture injured in bicycle accidents are at high risk of sustaining severe AIs, especially those of the head and neck region. Patients and Methods: The investigators performed a retrospective study on all patients with bicyclerelated craniofacial fracture admitted to a tertiary trauma centre during 2013 to 2018. The predictor variable was defined as any type of craniofacial fracture. The outcome variable was defined as any kind of AI. Other study variables included demographic and injury-related parameters. Variables were analyzed using bivariate and Firth's logistic regression analyses. Results: A total of 407 patients were included in the analysis. Our results revealed that AIs were present in 150 (36.9%) patients; there were multiple AIs in 47 cases. Traumatic brain injuries followed by upper limb injuries were the most frequent AIs. Severe head and neck injuries were present in 20.1% of all patients with craniofacial fracture. AIs were observed in 57.4% of patients with combined midfacial fractures (P < .001). Helmet use had a protective effect against traumatic brain injuries (P < .001). Conclusions: Our results suggest that AIs are relatively common in this specific patient population. Close co-operation in multidisciplinary trauma centers allowing comprehensive evaluation and treatment can be recommended for patients with bicycle-related craniofacial fracture. (C) 2021 American Association of Oral and Maxillofacial Surgeons.

Abstract Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Purpose of Review The use and efficacy of various substances in the treatment of CH have been studied in several retrospective surveys. The aim of the study is to systematically review published survey studies to evaluate the reported efficacies of both established and unconventional substances in abortive and prophylactic treatment of both episodic and chronic CH, specifically assessing the consistency of the results. Recent Findings No systematic review have been conducted of these studies previously. A systematic literature search with a set of search terms was conducted on PubMed. Retrospective surveys that quantified the self-reported efficacy of two or more CH treatments, published in English during 2000-2020, were included. Several key characteristics and results of the studies were extracted. A total of 994 articles were identified of which 9 were found to be eligible based on the selection criteria. In total, 5419 respondents were included. Oxygen and subcutaneous triptan injections were most reported as effective abortive treatments, while psilocybin and lysergic acid diethylamide were most commonly reported as effective prophylactic treatments. The reported efficacy of most substances was consistent across different studies, and there were marked differences in the reported efficacies of different substances. The reported order of efficacy is generally in agreement with clinical studies. The findings suggest that retrospective surveys can be used to obtain supporting information on the effects of various substances used in the treatment of CH and to form hypotheses about novel treatment methods. The consistently reported efficacy of psilocybin and LSD in prophylactic treatment indicates need for clinical studies.

Publisher Copyright: Author Objective: In this work, we present a myoelectric interface that extracts natural motor synergies from multi-muscle signals and adapts in real-time with new user inputs. With this unsupervised adaptive myocontrol (UAM) system, optimal synergies for control are continuously co-adapted with changes in user motor control, or as a function of perturbed conditions via online non-negative matrix factorization guided by physiologically informed sparseness constraints in lieu of explicit data labelling. Methods: UAM was tested in a set of virtual target reaching tasks completed by able-bodied and amputee subjects. Tests were conducted under normative and electrode perturbed conditions to gauge control robustness with comparisons to non-adaptive and supervised adaptive myocontrol schemes. Furthermore, UAM was used to interface an amputee with a multi-functional powered hand prosthesis during standardized Clothespin Relocation Tests, also conducted in normative and perturbed conditions. Results: In virtual tests, UAM effectively mitigated performance degradation caused by electrode displacement, affording greater resilience over an existing supervised adaptive system for amputee subjects. Induced electrode shifts also had negligible effect on the real world control performance of UAM with consistent completion times (23.91±1.33 s) achieved across Clothespin Relocation Tests in the normative and electrode perturbed conditions. Conclusion: UAM affords comparable robustness improvements to existing supervised adaptive myocontrol interfaces whilst providing additional practical advantages for clinical deployment. Significance: The proposed system uniquely incorporates neuromuscular control principles with unsupervised online learning methods and presents a working example of a freely co-adaptive bionic interface.

Funding Information: NGS library preparation, sequencing and sequence analysis were performed by the Institute for Molecular Medicine Finland (FIMM) Technology Center, University of Helsinki. We thank laboratory technicians Jay Klievink in Hematology Research Unit Helsinki (HRUH) and Minna Suvela in FIMM for technical support with the DNA extractions and laboratory coordinator Minna Tuominen in FIMM for technical support with multiplex ligation-dependent probe amplification. We are grateful to the members of the HRUH for discussions and technical help. We thank research nurses Anne Gesterberg, Jenni Raali and Susanna Helkkula for help with clinical data. We thank Dr Veli Kairisto in Tykslab, Dr Taru Kuittinen in Kuopio University Hospital and clinical laboratory geneticists Anne Juvonen and Tarja Salonen in HUSLAB for help with clinical samples. The samples of this project were provided by Finnish University Hospital clinical laboratories and the Finnish Hematology Registry and Clinical Biobank (FHRB) with appropriate ethics approval (Dnro 202/06.01.00/2013). We thank all the patients for their generous participation. The FHRB Biobank is supported by the Finnish Association of Hematology, the Finnish Red Cross Blood Service, Institute for Molecular Medicine Finland, and the participating hospitals in Finland. This study was supported by the Doctoral Program in Clinical Research at the University of Helsinki and personal grants (to HH) from Emil Aaltonen Foundation, Ida Montin Foundation, Blood Disease Research Foundation, Finnish Hematology Association, Finnish Medical Foundation, Biomedicum Helsinki Foundation, Paulo Foundation, (to SM) Finnish Cancer Organizations, Sigrid Juselius Foundation, Signe and Ane Gyllenberg Foundation, Relander Foundation, and state funding for university-level health research in Finland. The laboratory analytics costs of this study were funded by Incyte. Funding Information: TS (not related to this study) is a member of the advisory board of Celgene and AbbVie; is a member of the advisory board of and received lecture fees from Pfizer and Janssen-Cilag; received lecture fees from Bristol Myers Squibb; received congress fees from and is a member of the advisory board of Novartis; received congress fees from Amgen. MP (not-related to this study) is a member of the advisory board of Pfizer and AbbVie; received lecture and congress fees from Novartis. OB received consultancy fees from Novartis and Sanofi. SM (not related to this study) received research funding from Novartis, BMS, Janpix, and Pfizer. All other authors have no conflicts of interest to disclose. Funding Information: NGS library preparation, sequencing and sequence analysis were performed by the Institute for Molecular Medicine Finland (FIMM) Technology Center, University of Helsinki. We thank laboratory technicians Jay Klievink in Hematology Research Unit Helsinki (HRUH) and Minna Suvela in FIMM for technical support with the DNA extractions and laboratory coordinator Minna Tuominen in FIMM for technical support with multiplex ligation-dependent probe amplification. We are grateful to the members of the HRUH for discussions and technical help. We thank research nurses Anne Gesterberg, Jenni Raali and Susanna Helkkula for help with clinical data. We thank Dr Veli Kairisto in Tykslab, Dr Taru Kuittinen in Kuopio University Hospital and clinical laboratory geneticists Anne Juvonen and Tarja Salonen in HUSLAB for help with clinical samples. The samples of this project were provided by Finnish University Hospital clinical laboratories and the Finnish Hematology Registry and Clinical Biobank (FHRB) with appropriate ethics approval (Dnro 202/06.01.00/2013). We thank all the patients for their generous participation. The FHRB Biobank is supported by the Finnish Association of Hematology, the Finnish Red Cross Blood Service, Institute for Molecular Medicine Finland, and the participating hospitals in Finland. Non

Background The choice of what patient outcomes are included in clinical quality registries is crucial for comparable and relevant data collection. Ideally, a uniform outcome framework could be used to classify the outcomes included in registries, steer the development of outcome measurement, and ultimately enable better patient care through benchmarking and registry research. The aim of this study was to compare clinical quality registry outcomes against the COMET taxonomy to assess its suitability in the registry context. Methods We conducted an organizational case study that included outcomes from 63 somatic clinical quality registries in use at HUS Helsinki University Hospital, Finland. Outcomes were extracted and classified according to the COMET taxonomy and the suitability of the taxonomy was assessed. Results HUS clinical quality registries showed great variation in outcome domains and in number of measures. Physiological outcomes were present in 98%, resource use in all, and functioning domains in 62% of the registries. Patient-reported outcome measures were found in 48% of the registries. Conclusions The COMET taxonomy was found to be mostly suitable for classifying the choice of outcomes in clinical quality registries, but improvements are suggested. HUS Helsinki University Hospital clinical quality registries exist at different maturity levels, showing room for improvement in life impact outcomes and in outcome prioritization. This article offers an example of classifying the choice of outcomes included in clinical quality registries and a comparison point for other registry evaluators.

Purpose The purpose of the study was to evaluate the long-term outcome after surgery for lumbar disc herniation in a young adult population. Methods A total of 526 consecutive patients between 18 and 40 years of age who underwent surgery for lumbar disc between 1990 and 2005 were included in the study. The primary outcomes were the need for new lumbar spine surgery during the follow-up and secondary outcomes were short-term subjective outcome, the Oswestry Disability Index (ODI) score, and the ability to carry out employment at the end of the long-term follow-up. Results A total of 96% of the patients had a reduction in their symptoms at the clinical follow-up (median of 50 days post-surgery). Twenty-one patients (4.0%) had a reoperation within 28 days. Excluding these early reoperations, 136 patients (26%) had additional lumbar spine surgery and 18 patients (3.4%) underwent lumbar fusion during the follow-up of median 18 years. The annual risk for new surgery was 1.4%. In total, 316 patients (60%) returned the ODI questionnaire, and their mean score was 8.1. Patients with a higher number of additional lumbar spine surgeries (p Conclusion Patients showed excellent short-term recovery from their symptoms. In the long term, the mean ODI score for the patients was comparable to the normative population. However, a notable proportion of the patients required additional lumbar surgery during the follow-up period, and a higher number of lumbar surgeries was associated with poor ODI scores.

Hypothesis To identify genetic factors predisposing to migraine-epilepsy phenotype utilizing a multi-generational family with known linkage to chr12q24.2-q24.3. Methods We used single nucleotide polymorphism (SNP) genotyping and next-generation sequencing technologies to perform linkage, haplotype, and variant analyses in an extended Finnish migraine-epilepsy family (n = 120). In addition, we used a large genome-wide association study (GWAS) dataset of migraine and two biobank studies, UK Biobank and FinnGen, to test whether variants within the susceptibility region associate with migraine or epilepsy related phenotypes in a population setting. Results The family showed the highest evidence of linkage (LOD 3.42) between rs7966411 and epilepsy. The haplotype shared among 12 out of 13 epilepsy patients in the family covers almost the entire NCOR2 and co-localizes with one of the risk loci of the recent GWAS on migraine. The haplotype harbors nine low-frequency variants with potential regulatory functions. Three of them, in addition to two common variants, show nominal associations with neurological disorders in either UK Biobank or FinnGen. Conclusion We provide several independent lines of evidence supporting association between migraine-epilepsy phenotype and NCOR2. Our study suggests that NCOR2 may have a role in both migraine and epilepsy and thus would provide evidence for shared pathophysiology underlying these two diseases.

The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network's core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network's data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community. The LifeCycle project received funding from the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 733206 LifeCycle). All study specific acknowledgements and funding are presented in the supplementary material. This manuscript reflects only the author’s view and the Commission is not responsible for any use that may be made of the information it contains.

Saija Inkeroinen,1 Jenni Koskinen,1,2 Mia Karlsson,3 Taina Kilpi,4 Helena Leino-Kilpi,1,5 Pauli Puukka,1 Ros-Marie Taponen,6 Riitta Tuominen,5 Heli Virtanen1 1Department of Nursing Science, University of Turku, Turku, Finland; 2Hematology and Stem Cell Transplantation Unit, Turku University Hospital, Turku, Finland; 3Kidney Center, Department of Medicine, Turku University Hospital, Turku, Finland; 4Turku City Welfare, City of Turku, Turku, Finland; 5Turku University Hospital, Turku, Finland; 6Abdominal Center Dialysis Unit, Hospital District of Helsinki and Uusimaa, Helsinki, FinlandCorrespondence: Saija InkeroinenDepartment of Nursing Science, University of Turku, Turku, 20014, FinlandTel +358400760698Email saanin@utu.fiPurpose: Patient education improves health and treatment adherence of patients with chronic kidney disease. However, evidence about the sufficiency of patients’ knowledge processed in patient education is limited. The purpose of this study was to evaluate subjective and objective sufficiency of knowledge processed in patient education in dialysis care and treatment.Patients and Methods: A cross-sectional study design was used. The sample (n=162) comprised patients in predialysis or home dialysis. All eligible patients during the data collection timeframe (2016– 2017) in two university hospital districts in Finland were invited to participate. Subjective sufficiency was evaluated with a structured questionnaire having 34 items divided into six dimensions of empowering knowledge (bio-physiological, functional, social, experiential, ethical, and financial) on a Likert scale (1=not sufficient at all, 4=very sufficient). Objective sufficiency was evaluated with a structured knowledge test with 10 items (score range 0– 10, correct=1, wrong/no knowledge=0) based on the multidimensional content of patient education emphasizing bio-physiological dimension.Results: In subjective sufficiency of knowledge, the mean was 3.27 (SD 0.54). The bio-physiological dimension of empowering knowledge was the most sufficient (mean 3.52, SD 0.49) and the experiential the least (mean 2.8, SD 0.88). In objective sufficiency, the means ranged 5.15– 5.97 (SD 2.37– 2.68) among patients in different modalities of dialysis care and treatment. The least sufficient objective scores were bio-physiological and functional knowledge. The subjective and objective sufficiency did not correlate with each other.Conclusion: Patients’ knowledge, either subjective or objective, does not seem to be sufficient. Hence, attention should be paid to supporting patients with more personalized knowledge. Furthermore, the relationship between subjective and objective sufficiency needs future consideration, as their non-correspondence was a new discovery.Keywords: chronic kidney disease, hemodialysis, home, patient education as topic, peritoneal dialysis, renal dialysis

We examined the associations of gestational diabetes mellitus (GDM) and women’s weight status from pre-pregnancy through post-delivery with the risk of developing dysglycaemia [impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes (T2D)] 4–6 years post-delivery. Using Poisson regression with confounder adjustments, we assessed associations of standard categorisations of prospectively ascertained pre-pregnancy overweight and obesity (OWOB), gestational weight gain (GWG) and substantial post-delivery weight retention (PDWR) with post-delivery dysglycaemia (n = 692). Women with GDM had a higher risk of later T2D [relative risk (95% CI) 12.07 (4.55, 32.02)] and dysglycaemia [3.02 (2.19, 4.16)] compared with non-GDM women. Independent of GDM, women with pre-pregnancy OWOB also had a higher risk of post-delivery dysglycaemia. Women with GDM who were OWOB pre-pregnancy and had subsequent PDWR (≥ 5 kg) had 2.38 times (1.29, 4.41) the risk of post-delivery dysglycaemia compared with pre-pregnancy lean GDM women without PDWR. No consistent associations were observed between GWG and later dysglycaemia risk. In conclusion, women with GDM have a higher risk of T2D 4–6 years after the index pregnancy. Pre-pregnancy OWOB and PDWR exacerbate the risk of post-delivery dysglycaemia. Weight management during preconception and post-delivery represent early windows of opportunity for improving long-term health, especially in those with GDM.

The association between HLA genotypes and type 1 diabetes is well known. We set out to examine incidence rates and ratios of type 1 diabetes depending on the risk afflicted by HLA genotype. Children with the high-risk ge-notype have a 45-fold disease risk compared to peers with neutral or protective genotypes.