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Comparison of Stroke Recurrence, Cardiovascular Events, and Death Among Patients With Pregnancy-Associated vs Non-Pregnancy-Associated Stroke

JAMA Netw Open. 2023 Jun 1;6(6):e2315235. doi: 10.1001/jamanetworkopen.2023.15235.

ABSTRACT

IMPORTANCE: Women with pregnancy-associated stroke might have different risks of stroke recurrence, including during subsequent pregnancies, and other cardiovascular events due to pregnancy-specific stroke risk factors, such as gestational hypertension, preeclampsia, or gestational diabetes.

OBJECTIVE: To estimate the rate of stroke recurrence, cardiovascular hospitalization, and death in women with pregnancy-associated stroke compared with women with non-pregnancy-associated stroke.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all women aged 15 to 49 years in France who were affiliated with the general scheme of French health care insurance (94% of women) and had a first hospitalization for stroke between January 1, 2010, and December 31, 2018. Women were followed up until December 31, 2020, with the registration of stroke recurrence, hospitalization for cardiovascular conditions, and death. Data were from the French health care database Système National des Données de Santé. Statistical analyses were conducted between December 2021 and September 2022.

EXPOSURE: Pregnancy status at the time of stroke.

MAIN OUTCOMES AND MEASURES: Poisson regressions were used to estimate incidence rates of these events with 95% CIs. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) of each event during the follow-up for women with a pregnancy-associated stroke vs women with a non-pregnancy-associated stroke.

RESULTS: Among women aged between 15 and 49 years between 2010 and 2018 and living in France, 1204 had a pregnancy-associated stroke at a mean (SD) age of 31.5 (5.8) years, and 31 697 had a non-pregnancy-associated stroke at a mean age of 39.6 (8.2) years. Among the 1204 women with a pregnancy-associated stroke, the incidence rate was 11.4 (95% CI, 9.0-14.3) per 1000 person-years, with 2 recurrent events during a subsequent pregnancy. Compared with women with non-pregnancy-associated stroke, women with pregnancy-associated stroke had lower risks of ischemic stroke (adjusted HR, 0.53; 95% CI, 0.36-0.77), cardiovascular events (adjusted HR, 0.58; 95% CI, 0.49-0.69), and death (adjusted HR, 0.42; 95% CI, 0.22-0.79). In contrast, the risk of recurrent intracerebral hemorrhage and cerebral venous thrombosis did not differ significantly, whereas the risks of venous thromboembolism (HR, 2.02; 95% CI, 1.14-3.58) and acute coronary syndrome with ST-segment elevation (HR, 3.93; 95% CI, 1.10-14.0) were increased.

CONCLUSIONS AND RELEVANCE: In this cohort study, although the risks of ischemic stroke, overall cardiovascular events, and mortality were lower after a pregnancy-associated stroke than after a non-pregnancy-associated stroke, the risks of venous thromboembolism and acute coronary syndrome with ST-segment elevation were higher. Recurrent stroke during a subsequent pregnancy remained rare.

PMID:37285159 | DOI:10.1001/jamanetworkopen.2023.15235

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Comparative Effectiveness of Pharmacotherapies for the Risk of Attempted or Completed Suicide Among Persons With Borderline Personality Disorder

JAMA Netw Open. 2023 Jun 1;6(6):e2317130. doi: 10.1001/jamanetworkopen.2023.17130.

ABSTRACT

IMPORTANCE: Suicidal behavior is a significant clinical concern in individuals with borderline personality disorder (BPD), but the effectiveness of pharmacotherapy on reducing suicide risk has remained unknown.

OBJECTIVE: To study the comparative effectiveness of different pharmacotherapies in preventing attempted or completed suicides in patients with BPD in Sweden.

DESIGN, SETTING AND PARTICIPANTS: In this comparative effectiveness research study, nationwide Swedish register databases of inpatient care, specialized outpatient care, sickness absences, and disability pensions were used to identify patients aged 16 to 65 years with registered treatment contact due to BPD during 2006 to 2021. Data were analyzed from September to December 2022. A within-individual design was used, in which each patient was used as their own control to eliminate selection bias. To control protopathic bias, sensitivity analyses were conducted, in which the first 1 or 2 months of medication exposure were omitted from the analyses.

MAIN OUTCOMES AND MEASURES: Hazard ratio (HR) for attempted or completed suicide.

RESULTS: A total of 22 601 patients with BPD (3540 [15.7%] men; mean [SD] age, 29.2 [9.9] years) were included. During the 16-year follow-up (mean [SD] follow-up, 6.9 [5.1] years), 8513 hospitalizations due to attempted suicide and 316 completed suicides were observed. Attention-deficit/hyperactive disorder (ADHD) medication treatment, compared with its nonuse, was associated with a decrease in the risk of attempted or completed suicide (HR, 0.83; 95% CI, 0.73-0.95; false discovery rate [FDR]-corrected P = .001). Treatment with mood stabilizers did not have a statistically significant association with the main outcome (HR, 0.97; 95% CI, 0.87-1.08; FDR-corrected P = .99). Antidepressant (HR, 1.38; 95% CI, 1.25-1.53; FDR-corrected P < .001) and antipsychotic (HR, 1.18; 95% CI, 1.07-1.30; FDR-corrected P < .001) treatments were associated with an elevated risk of attempted or completed suicide. Of the investigated pharmacotherapies, treatment with benzodiazepines was associated with the highest risk of attempted or completed suicide (HR, 1.61; 95% CI, 1.45-1.78; FDR-corrected P < .001). These results remained similar when controlling for potential protopathic bias.

CONCLUSIONS AND RELEVANCE: In this comparative effectiveness research study of a Swedish nationwide cohort, ADHD medication was the only pharmacological treatment associated with reduced risk of suicidal behavior among patients with BPD. Conversely, the findings suggest that benzodiazepines should be used with care among patients with BPD due to their association with increased risk of suicide.

PMID:37285156 | DOI:10.1001/jamanetworkopen.2023.17130

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Cross-Sectional Analysis of Insurance Coverage for Lymphedema Treatments in the United States

JAMA Surg. 2023 Jun 7. doi: 10.1001/jamasurg.2023.2017. Online ahead of print.

ABSTRACT

IMPORTANCE: Lymphedema is a debilitating condition that affects approximately 1 in 1000 individuals in the United States. Complete decongestive therapy is currently the standard of care, and innovative surgical techniques have demonstrated potential to further improve outcomes. Despite the growing armamentarium of treatment options, a large proportion of patients with lymphedema continue to struggle because of limited access to care.

OBJECTIVE: To define the current state of insurance coverage for lymphedema treatments in the United States.

DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis of insurance reimbursement for lymphedema treatments in 2022 was designed. The top 3 insurance companies per state based on market share and enrollment data maintained by the Kaiser Family Foundation were included. Established medical policies were gathered from insurance company websites and phone interviews, and descriptive statistics were performed.

MAIN OUTCOMES AND MEASURES: Treatments of interest included nonprogrammable pneumatic compression, programmable pneumatic compression, surgical debulking, and physiologic procedures. Primary outcomes included level of coverage and criteria for coverage.

RESULTS: This study included 67 health insurance companies representing 88.7% of the US market share. Most insurance companies offered coverage for nonprogrammable (n = 55, 82.1%) and programmable (n = 53, 79.1%) pneumatic compression. However, few insurance companies offered coverage for debulking (n = 13, 19.4%) or physiologic (n = 5, 7.5%) procedures. Geographically, the lowest rates of coverage were seen in the West, Southwest, and Southeast.

CONCLUSIONS AND RELEVANCE: This study suggests that in the United States, less than 12% of individuals with health insurance, and even fewer patients without health insurance, have access to pneumatic compression and surgical treatments for lymphedema. The stark inadequacy of insurance coverage must be addressed through research and lobbying efforts to mitigate health disparities and promote health equity among patients with lymphedema.

PMID:37285151 | DOI:10.1001/jamasurg.2023.2017

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Preliminary Evidence for Genetic Nurture in Depression and Neuroticism Through Polygenic Scores

JAMA Psychiatry. 2023 Jun 7. doi: 10.1001/jamapsychiatry.2023.1544. Online ahead of print.

ABSTRACT

IMPORTANCE: Modeling genetic nurture (ie, the effects of parental genotypes through influences on the environment experienced by their children) is essential to accurately disentangle genetic and environmental influences on phenotypic variance. However, these influences are often ignored in both epidemiologic and genetic studies of depression.

OBJECTIVE: To estimate the association of genetic nurture with depression and neuroticism.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study jointly modeled parental and offspring polygenic scores (PGSs) across 9 traits to test for the association of genetic nurture with lifetime broad depression and neuroticism using data from nuclear families in the UK Biobank, with data collected between 2006 and 2019. A broad depression phenotype was measured in 38 702 offspring from 20 905 independent nuclear families, with most of these participants also reporting neuroticism scores. Parental genotypes were imputed from sibships or parent-offspring duos and used to calculate parental PGSs. Data were analyzed between March 2021 and January 2023.

MAIN OUTCOMES AND MEASURES: Estimates of genetic nurture and direct genetic regression coefficients on broad depression and neuroticism.

RESULTS: This study of 38 702 offspring with data on broad depression (mean [SD] age, 55.5 [8.2] years at study entry; 58% female) found limited preliminary evidence for a statistically significant association of genetic nurture with lifetime depression and neuroticism in adults. The estimated regression coefficient of the parental depression PGS on offspring neuroticism (β = 0.04, SE = 0.02, P = 6.63 × 10-3) was estimated to be approximately two-thirds (66%) that of the offspring’s depression PGS (β = 0.06, SE = 0.01, P = 6.13 × 10-11). Evidence for an association between parental cannabis use disorder PGS and offspring depression was also found (β = 0.08, SE = 0.03, P = .02), which was estimated to be 2 times greater than the association between the offspring’s cannabis use disorder PGS and their own depression status (β = 0.04, SE = 0.02, P = .07).

CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study highlight the potential for genetic nurture to bias results from epidemiologic and genetic studies on depression or neuroticism and, with further replication and larger samples, identify potential avenues for future prevention and intervention efforts.

PMID:37285136 | DOI:10.1001/jamapsychiatry.2023.1544

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A Precision Treatment Model for Internet-Delivered Cognitive Behavioral Therapy for Anxiety and Depression Among University Students: A Secondary Analysis of a Randomized Clinical Trial

JAMA Psychiatry. 2023 Jun 7. doi: 10.1001/jamapsychiatry.2023.1675. Online ahead of print.

ABSTRACT

IMPORTANCE: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT.

OBJECTIVE: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022.

INTERVENTIONS: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435).

MAIN OUTCOMES AND MEASURES: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline.

RESULTS: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P = .003) or treatment as usual (40.0% [2.7%]; P = .001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P = .007; self-guided i-CBT: 25.4% [8.8%]; P = .004; treatment as usual: 31.0% [9.4%]; P = .001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P = .14; treatment as usual: 53.0% [6.0%]; P = .25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P = .001; treatment as usual: 41.8% [3.2%]; P < .001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P = .07).

CONCLUSIONS AND RELEVANCE: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04780542.

PMID:37285133 | DOI:10.1001/jamapsychiatry.2023.1675

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Fertility Trends and Adverse Pregnancy Outcomes in Female Patients With Psoriasis in the UK

JAMA Dermatol. 2023 Jun 7. doi: 10.1001/jamadermatol.2023.1400. Online ahead of print.

ABSTRACT

IMPORTANCE: Evidence regarding fertility trends and obstetric outcomes among patients with psoriasis is limited by studies of small sample sizes, noninclusion of comparators, and the lack of accurate pregnancy records.

OBJECTIVE: To investigate fertility rates and obstetric outcomes of pregnancies in female patients with psoriasis compared with age- and general practice-matched comparators without psoriasis.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used data from 887 primary care practices that contributed to the UK Clinical Practice Research Datalink GOLD database between 1998 and 2019, linked to a pregnancy register and Hospital Episode Statistics. There were 6 223 298 patients of common childbearing ages (15-44 years), and 63 681 patients with psoriasis had at least 1 year of follow-up data prior to the diagnosis of psoriasis. For each patient with psoriasis, 5 patients were matched by age from the same general practice. The median follow-up duration was 4.1 years. Data analysis was performed in 2021.

EXPOSURES: Patients with psoriasis were identified using clinical diagnostic codes from consultations.

MAIN OUTCOMES AND MEASURES: Fertility rates were calculated as the number of pregnancies per 100 patient-years. The outcomes of each pregnancy recorded in the pregnancy register or Hospital Episode Statistics were screened to identify obstetric outcomes. A negative binomial model was used to examine the association between psoriasis and the fertility rate. Logistic regression was applied to compare the association between psoriasis and obstetric outcomes.

RESULTS: A total of 63 681 patients with psoriasis and 318 405 matched comparators were included in the analysis (median [IQR] age, 30 [22-37] years). Lower fertility rates (rate ratio, 0.75; 95% CI, 0.69-0.83) were found in patients with moderate to severe psoriasis. Compared with matched comparators without psoriasis, pregnancies in patients with psoriasis had a higher risk of loss (odds ratio, 1.06; 95% CI, 1.03-1.10); however, there was no increase in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes.

CONCLUSION AND RELEVANCE: In this cohort study, patients with moderate to severe psoriasis had a lower fertility rate, and the risk of pregnancy loss was higher than in matched comparators without psoriasis. Future research should identify the mechanism of increased risk of pregnancy loss among patients with psoriasis.

PMID:37285130 | DOI:10.1001/jamadermatol.2023.1400

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Salivary fluoride concentrations following toothbrushing with experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) filler

Clin Oral Investig. 2023 Jun 7. doi: 10.1007/s00784-023-05063-6. Online ahead of print.

ABSTRACT

BACKGROUND: Single-blind 9 case comparative studies were conducted to evaluate salivary fluoride concentrations following toothbrushing using experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) fillers. Preliminary tests were conducted in order to determine the volume of usage as well as the concentrations (wt %) of S-PRG filler. Based on the results given these experiments, we compared the salivary fluoride concentrations following toothbrushing with 0.5 g of 4 different types of toothpastes: 5 wt % S-PRG filler, 1400 ppm F AmF (amine fluoride), 1500 ppm F NaF (sodium fluoride), and MFP (monofluorophosphate) containing toothpaste.

METHODS: Of the 12 participants, 7 participated in the preliminary study and 8 in the main study. All participants brushed their teeth using the scrubbing method for 2 min. At first, 1.0 and 0.5 g of 20 wt % S-PRG filler toothpastes were used to compare, then followed by 0.5 g of 0 (control), 1, and 5 wt % S-PRG toothpastes, respectively. The participants spat out once and rinsed with 15 mL of distilled water for 5 s. Saliva was collected for 3 min each at different time intervals of 0 (baseline), 5, 10, 15, 30, 60, 120, and 180 min after the rinsing. Fluoride concentrations were determined using a fluoride electrode, and the area under the salivary clearance – time curve (AUC: ppm‧min) of each toothpaste was calculated as the salivary fluoride retention. The main study was then conducted to evaluate the salivary fluoride concentrations as well as the AUC value using 0.5 g of 5 wt % S-PRG filler toothpaste, followed by NaF, MFP, and AmF toothpastes.

RESULTS: Since there were no statistical differences between using 1.0 and 0.5 g of 20 wt % S-PRG toothpastes in salivary fluoride concentrations as well as the AUC value throughout the 180 min measurement, the volume was set as 0.5 g for the following studies. Concentrations of 5 and 20 wt % S-PRG toothpastes retained 0.09 ppm F or more in saliva even after 180 min. No statistical differences were seen in the salivary fluoride concentrations at any time intervals as well as the AUC value between 5 and 20 wt % S-PRG toothpastes. Based on these results, the concentration of 5 wt % S-PRG toothpaste was used for the main comparative study. MFP toothpaste resulted in by far the lowest salivary fluoride concentrations (0.06 ppm F at 180 min) and the AUC value (24.6 ppm‧min), whereas 5 wt % S-PRG toothpaste (0.15 ppm F at 180 min, 92.3 ppm‧min) displayed retention on par with AmF toothpaste which appeared to result in higher values (0.17 ppm F at 180 min, 103 ppm‧min), compared to NaF toothpaste (0.12 ppm F at 180 min, 49.3 ppm‧min).

CONCLUSIONS: The salivary fluoride concentrations following toothbrushing with 0.5 g of 5 wt % S-PRG filler containing toothpaste showed retention similar to the best performing 1400 ppm F AmF toothpaste even 180 min after toothbrushing.

PMID:37285102 | DOI:10.1007/s00784-023-05063-6

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The Efficacy and Safety of Patiromer for Heart Failure Patients: A Systematic Review and Meta-Analysis

Cardiovasc Drugs Ther. 2023 Jun 7. doi: 10.1007/s10557-023-07473-w. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of patiromer, a novel potassium binder, in reducing the risk of hyperkalemia in patients with heart failure and optimizing their RAASi therapy.

DESIGN: Systematic review and meta-analyses.

METHOD: The authors conducted a systematic search in Pubmed, Embase, Web of Science, and Cochrane Library for randomized controlled trials investigating the efficacy and safety of patiromer in heart failure patients from inception to 31 January 2023 and updated on 25 March 2023. The primary outcome was the association between the reduction of hyperkalemia and patiromer compared with placebo, and the secondary outcome was the association between optimization of RAASi therapy and patiromer.

RESULTS: A total of four randomized controlled trials (n = 1163) were included in the study. Patiromer was able to reduce the risk of hyperkalemia in heart failure patients by 44% (RR 0.56, 95% CI 0.36 to 0.87; I2 = 61.9%), improve tolerance to target doses of MRA in patients with heart failure (RR 1.15, 95% CI 1.02 to 1.30; I2 = 49.4%), and decrease the proportion of all-cause discontinuation of RAASi (RR 0.49, 95% CI 0.25 to 0.98; I2 = 48.4%). However, patiromer therapy was associated with an increased risk of hypokalemia (RR 1.51, 95% CI 1.07 to 2.12; I2 = 0%), while no other statistically significant adverse events were observed.

CONCLUSION: Patiromer appears to have a considerable effect on reducing the incidence of hyperkalemia in heart failure patients and on optimizing the therapy of RAASi in those patients.

PMID:37285082 | DOI:10.1007/s10557-023-07473-w

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Diagnostic accuracy of the Dutch version of the 4AT for delirium detection in a mixed patient population and setting

Aging Clin Exp Res. 2023 Jun 7. doi: 10.1007/s40520-023-02447-2. Online ahead of print.

ABSTRACT

BACKGROUND: Delirium is an acute disturbance in attention, awareness and cognition. Immediate detection in older adults is recommended because delirium is associated with adverse outcomes. The 4 ‘A’s Test (4AT) is a short screening instrument for delirium. The aim of this study is to evaluate diagnostic accuracy of the Dutch version of the screening tool 4AT for delirium detection in different settings.

METHODS: Prospective observational study conducted in two hospitals in patients aged ≥ 65 years in geriatric wards and the Emergency Department (ED). Each participant underwent two assessments; the index test 4AT, followed by the reference standard for delirium performed by a geriatric care specialist. The reference standard delirium is according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria.

RESULTS: A total of 71 geriatric inpatients and 49 older ED patients were included. The prevalence of delirium was 11.6% in the acute geriatric ward and 6.1% in the ED. The sensitivity and specificity of the 4AT in the acute geriatric ward were 0.88 and 0.69, respectively. In the ED, the sensitivity and specificity were 0.67 and 0.83, respectively. The area under the receiver operating characteristic curve was 0.80 for the acute geriatric ward setting and 0.74 for the ED setting.

CONCLUSION: The Dutch version of the 4AT is a reliable screening tool for delirium detection in both acute geriatric wards and ED. Due to its brevity and practicality (i.e., no special training is required to administer the tool), it is useful in clinical practice.

PMID:37285074 | DOI:10.1007/s40520-023-02447-2

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Building use-inspired species distribution models: using multiple data types to examine and improve model performance

Ecol Appl. 2023 Jun 7:e2893. doi: 10.1002/eap.2893. Online ahead of print.

ABSTRACT

Species distribution models (SDMs) are becoming an important tool for marine conservation and management. Yet while there is an increasing diversity and volume of marine biodiversity data for training SDMs, little practical guidance is available on how to leverage distinct data types to build robust models. We explored the effect of different data types on the fit, performance and predictive ability of SDMs by comparing models trained with four data types for a heavily exploited pelagic fish, the blue shark (Prionace glauca), in the Northwest Atlantic: two fishery-dependent (conventional mark-recapture tags, fisheries observer records) and two fishery-independent (satellite-linked electronic tags, pop-up archival tags). We found that all four data types can result in robust models, but differences among spatial predictions highlighted the need to consider ecological realism in model selection and interpretation regardless of data type. Differences among models were primarily attributed to biases in how each data type, and the associated representation of absences, sampled the environment and summarized the resulting species distributions. Outputs from model ensembles and a model trained on all pooled data both proved effective for combining inferences across data types and provided more ecologically realistic predictions than individual models. Our results provide valuable guidance for practitioners developing SDMs. With increasing access to diverse data sources, future work should further develop truly integrative modeling approaches that can explicitly leverage strengths of individual data types while statistically accounting for limitations, such as sampling biases.

PMID:37285072 | DOI:10.1002/eap.2893