Trajectories of Body Mass Index and Risk for Diabetes Complications and All-Cause Mortality in Finnish Type 2 Diabetes Patients

Zhiting Wang,1 Piia Lavikainen,2 Katja Wikström,1,3 Tiina Laatikainen1,3,4 1Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 2School of Pharmacy, University of Eastern Finland, Kuopio, Finland; 3Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; 4Joint Municipal Authority for North Karelia Social and Health Services, Joensuu, FinlandCorrespondence: Zhiting Wang, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, PO Box 1627, Kuopio, 70211, Finland, Tel +358 469589963, Email [email protected]: We aimed to assess how longitudinal body mass index (BMI) trajectories are associated with diabetes complications and all-cause mortality in Finnish patients with type 2 diabetes (T2D).Methods: In this cohort study, electronic health records from public primary and specialized healthcare services in all 13 municipalities of North Karelia, Finland, were utilized. This study included a total of 889 adults with newly diagnosed T2D in 2011 or 2012 (mean age at baseline 62.0 years). Individual BMI trajectories from the T2D diagnosis until 2014 were estimated and grouped by growth mixture modeling (GMM). Hazard ratios (HRs) with 95% confidence intervals (CIs) for microvascular complications, macrovascular complications, any diabetes complications, and all-cause mortality from 2015 to 2022 across BMI trajectory groups were estimated using Cox regression models.Results: Three distinct BMI trajectory groups were identified using GMM and labeled as follows: “stable” (n = 774, 87.1%), “decreasing” (n = 87, 9.8%), and “increasing” (n = 28, 3.1%). During a median follow-up of 8 years, there were 119 (13.3%) patients with microvascular complications, 187 (21.0%) with macrovascular complications, 258 (29.0%) with any diabetes complications, and 180 (20.2%) deaths. Compared with the “stable” BMI, the “increasing” BMI was associated with an increased risk of microvascular complications (HR = 2.88, 95% CI: 1.32 to 6.28), macrovascular complications (HR = 2.52, 95% CI: 1.17 to 5.43), and any diabetes complications (HR = 2.21, 95% CI: 1.16 to 4.20). The “decreasing” BMI was associated with an increased risk of all-cause mortality (HR = 1.90, 95% CI: 1.14 to 3.15), compared to the “stable” BMI.Conclusion: Our findings underscore the significance of continuous BMI monitoring and weight management in patients with T2D. Tailored treatments are crucial for efficiently preventing weight gain and reducing the risk of diabetes complications.Keywords: body mass index trajectory, type 2 diabetes, diabetes complications, all-cause mortalit

Specific status of Echinococcus canadensis (Cestoda Taeniidae) inferred from nuclear and mitochondrial gene sequences

The specific status of Echinococcus canadensis has long been controversial, mainly because it consists of the mitochondrial lineages G6, G7, G8 and G10 with different host affinity: G6 (camel strain) and G7 (pig strain) with domestic cycles and G8 (cervid strain) and G10 (Fennoscandian cervid strain) with sylvatic or semi-domestic cycles. There is an argument whether the mitochondria] lineages should be recognised as separate species which correspond to the biological or epidemiological aggregation. In the present study, the specific status of E. canadensis was investigated using mitochondrial DNA and single copy nuclear DNA markers. Nucleotide sequences of complete mitochondrial cytochrome c oxidase subunit 1 (cox1) and partial nuclear phosphoenolpyruvate carboxykinase (pepck) and DNA polymerase delta (pold) were determined for 48 isolates of E. canadensis collected from different hosts in a wide range of regions. The mitochondrial phylogeny of cox1 showed that all the isolates were clearly divided into three clades corresponding to G6/G7, G8 and G10. Five and three alleles were confirmed at pepck and pold loci, respectively. These alleles were generally divided into two groups corresponding to G6/G7 or G8 and G10. However, allele sharing was confirmed among individuals belonging to different lineages. The allele sharing occurred primarily in regions where different mitochondrial DNA lineages were found in sympatry. The resultant nuclear mitochondrial discordance suggests the genetic exchangeability among E. canadensis isolates belonging to different lineages. An apparently mosaic parasite fauna that reflects faunal mixing due to natural and anthropogenic disturbance, including introductions and invasion, precludes us from designating each of G6/G7, G8 and G10 into a different species. (C) 2017 Australian Society for Parasitology.Peer reviewe

Explainable Prediction of Long-Term Glycated Hemoglobin Response Change in Finnish Patients with Type 2 Diabetes Following Drug Initiation Using Evidence-Based Machine Learning Approaches

Gunjan Chandra,1,* Piia Lavikainen,2,* Pekka Siirtola,1 Satu Tamminen,1 Anusha Ihalapathirana,1 Tiina Laatikainen,3– 5 Janne Martikainen,2 Juha Röning1 1Biomimetics and Intelligent Systems Group, Faculty of Information Technology and Electrical Engineering, University of Oulu, Oulu, Finland; 2School of Pharmacy, University of Eastern Finland, Kuopio, Finland; 3North Karelia Wellbeing Services County (Siun Sote), Joensuu, Finland; 4Department of Public Health and Social Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; 5Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland*These authors contributed equally to this workCorrespondence: Gunjan Chandra, Biomimetics and Intelligent Systems Group, Faculty of ITEE, University of Oulu, Oulu, Finland, Email [email protected]: This study applied machine learning (ML) and explainable artificial intelligence (XAI) to predict changes in HbA1c levels, a critical biomarker for monitoring glycemic control, within 12 months of initiating a new antidiabetic drug in patients diagnosed with type 2 diabetes. It also aimed to identify the predictors associated with these changes.Patients and Methods: Electronic health records (EHR) from 10,139 type 2 diabetes patients in North Karelia, Finland, were used to train models integrating randomized controlled trial (RCT)-derived HbA1c change values as predictors, creating offset models that integrate RCT insights with real-world data. Various ML models—including linear regression (LR), multi-layer perceptron (MLP), ridge regression (RR), random forest (RF), and XGBoost (XGB)—were evaluated using R² and RMSE metrics. Baseline models used data at or before drug initiation, while follow-up models included the first post-drug HbA1c measurement, improving performance by incorporating dynamic patient data. Model performance was also compared to expected HbA1c changes from clinical trials.Results: Results showed that ML models outperform RCT model, while LR, MLP, and RR models had comparable performance, RF and XGB models exhibited overfitting. The follow-up MLP model outperformed the baseline MLP model, with higher R² scores (0.74, 0.65) and lower RMSE values (6.94, 7.62), compared to the baseline model (R²: 0.52, 0.54; RMSE: 9.27, 9.50). Key predictors of HbA1c change included baseline and post-drug initiation HbA1c values, fasting plasma glucose, and HDL cholesterol.Conclusion: Using EHR and ML models allows for the development of more realistic and individualized predictions of HbA1c changes, accounting for more diverse patient populations and their heterogeneous nature, offering more tailored and effective treatment strategies for managing T2D. The use of XAI provided insights into the influence of specific predictors, enhancing model interpretability and clinical relevance. Future research will explore treatment selection models.Keywords: type 2 diabetes, HbA1c, treatment effect estimation, machine learning, SHA

Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery : systematic review and network meta-analysis of randomised trials

OBJECTIVE To systematically compare the effect of direct oral anticoagulants and low molecular weight heparin for thromboprophylaxis on the benefits and harms to patients undergoing non-cardiac surgery. DESIGN Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), up to August 2021. REVIEW METHODS Randomised controlled trials in adults undergoing non-cardiac surgery were selected, comparing low molecular weight heparin (prophylactic (low) or higher dose) with direct oral anticoagulants or with no active treatment. Main outcomes were symptomatic venous thromboembolism, symptomatic pulmonary embolism, and major bleeding. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for network meta-analyses. Abstracts and full texts were screened independently in duplicate. Data were abstracted on study participants, interventions, and outcomes, and risk of bias was assessed independently in duplicate. Frequentist network meta-analysis with multivariate random effects models provided odds ratios with 95% confidence intervals, and GRADE (grading of recommendations, assessment, development, and evaluation) assessments indicated the certainty of the evidence. RESULTS 68 randomised controlled trials were included (51 orthopaedic, 10 general, four gynaecological, two thoracic, and one urological surgery), involving 45 445 patients. Low dose (odds ratio 0.33, 95% confidence interval 0.16 to 0.67) and high dose (0.19, 0.07 to 0.54) low molecular weight heparin, and direct oral anticoagulants (0.17, 0.07 to 0.41) reduced symptomatic venous thromboembolism compared with no active treatment, with absolute risk differences of 1-100 per 1000 patients, depending on baseline risks (certainty of evidence, moderate to high). None of the active agents reduced symptomatic pulmonary embolism (certainty of evidence, low to moderate). Direct oral anticoagulants and low molecular weight heparin were associated with a 2-3-fold increase in the odds of major bleeding compared with no active treatment (certainty of evidence, moderate to high), with absolute risk differences as high as 50 per 1000 in patients at high risk. Compared with low dose low molecular weight heparin, high dose low molecular weight heparin did not reduce symptomatic venous thromboembolism (0.57, 0.26 to 1.27) but increased major bleeding (1.87, 1.06 to 3.31); direct oral anticoagulants reduced symptomatic venous thromboembolism (0.53, 0.32 to 0.89) and did not increase major bleeding (1.23, 0.89 to 1.69). CONCLUSIONS Direct oral anticoagulants and low molecular weight heparin reduced venous thromboembolism compared with no active treatment but probably increased major bleeding to a similar extent. Direct oral anticoagulants probably prevent symptomatic venous thromboembolism to a greater extent than prophylactic low molecular weight heparin.Peer reviewe

Definitive Hosts of Versteria Tapeworms (Cestoda : Taeniidae) Causing Fatal Infection in North America

We previously reported fatal infection of a captive Bornean orangutan with metacestodes of a novel taeniid tapeworm, Versteria sp. New data implicate mustelids as definitive hosts of these tapeworms in North America. At least 2 parasite genetic lineages circulate in North America, representing separate introductions from Eurasia.Peer reviewe

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS) : introduction and methodology

Funding Information: The Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS) project was conducted by the Clinical Urology and Epidemiology (CLUE) Working Group and supported by the Academy of Finland (309387, 340957), Sigrid Jusélius Foundation and Competitive Research Funding of the Helsinki University Hospital (TYH2019321; TYH2020248). The sponsors had no role in the analysis and interpretation of the data or the manuscript preparation, review, or approval. Funding Information: KMA received a research grant from Astra Zeneca, and is consultant for Gedeon Richter, and received reimbursement for attending a scientific meeting from GSK (Tesaro Bio). RMT received reimbursement for attending a scientific meeting from Olympus. LIL, GHG, YL, RC, ALL, VJS, IEJK, PJK, RJC, RLA, KA, KMA, IB-L, MHB, JLC, SC, PJG, HAG-P, FZG, HAG, LH, MLI-K, KMJ, PKK, NK, TPK, AJK, TK, HL, AKM, BTN, TPN, CN, SMO, SP, NP, CBBR, ARR, TS, RMT, RWMV, YW, YX, LY, JH, and KAOT have no financial conflicts of interest. GHG and RC were panel members of the European Association of Urology (EAU) ad hoc Guideline on Thromboprophylaxis in Urological Surgery. KAOT was chair of the European Association of Urology (EAU) ad hoc Guideline on Thromboprophylaxis in Urological Surgery and panel member of the American Society of Hematology (ASH) Guideline Panel on Prevention of Venous Thromboembolism (VTE) in Surgical Hospitalized Patients. Publisher Copyright: © 2021, The Author(s).Background Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. Methods We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. Discussion This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. Systematic review registration PROSPERO CRD42021234119Peer reviewe

The clustering of health behaviours in Ireland and their relationship with mental health, self-rated health and quality of life

Health behaviours do not occur in isolation. Rather they cluster together. It is important to examine patterns of health behaviours to inform a more holistic approach to health in both health promotion and illness prevention strategies. Examination of patterns is also important because of the increased risk of mortality, morbidity and synergistic effects of health behaviours. This study examines the clustering of health behaviours in a nationally representative sample of Irish adults and explores the association of these clusters with mental health, self-rated health and quality of life

Risk of thrombosis and bleeding in gynecologic cancer surgery : systematic review and meta-analysis

Objective: This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery. Data Sources: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice. Study Eligibility Criteria: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin 2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures. Conclusion: Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.Peer reviewe