Nevin Manimala

J Am Med Inform Assoc. 2023 Sep 2:ocad168. doi: 10.1093/jamia/ocad168. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe and appraise the use of artificial intelligence (AI) techniques that can cope with longitudinal data from electronic health records (EHRs) to predict health-related outcomes.

METHODS: This review included studies in any language that: EHR was at least one of the data sources, collected longitudinal data, used an AI technique capable of handling longitudinal data, and predicted any health-related outcomes. We searched MEDLINE, Scopus, Web of Science, and IEEE Xplorer from inception to January 3, 2022. Information on the dataset, prediction task, data preprocessing, feature selection, method, validation, performance, and implementation was extracted and summarized using descriptive statistics. Risk of bias and completeness of reporting were assessed using a short form of PROBAST and TRIPOD, respectively.

RESULTS: Eighty-one studies were included. Follow-up time and number of registers per patient varied greatly, and most predicted disease development or next event based on diagnoses and drug treatments. Architectures generally were based on Recurrent Neural Networks-like layers, though in recent years combining different layers or transformers has become more popular. About half of the included studies performed hyperparameter tuning and used attention mechanisms. Most performed a single train-test partition and could not correctly assess the variability of the model’s performance. Reporting quality was poor, and a third of the studies were at high risk of bias.

CONCLUSIONS: AI models are increasingly using longitudinal data. However, the heterogeneity in reporting methodology and results, and the lack of public EHR datasets and code sharing, complicate the possibility of replication.

REGISTRATION: PROSPERO database (CRD42022331388).

PMID:37659105 | DOI:10.1093/jamia/ocad168

Foot Ankle Int. 2023 Sep 2:10711007231175666. doi: 10.1177/10711007231175666. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to find the prevalence of peroneal tendon instability (PTI) accompanying different types of calcaneal fractures and to determine predictors of PTI based on preoperative CT scanning.

METHODS: In a retrospective cross-sectional study, preoperative CT scans of 400 consecutive calcaneal fractures undergoing surgery were reviewed for comminuted fragments in the lateral gutter of the ankle, fractures at the tip of the lateral malleolus, dislocated peroneal tendons, excessive displacement of the lateral calcaneal wall, calcaneal fracture-dislocation, superior peroneal retinaculum (SPR) avulsion fracture (fleck sign), and shape of the retromalleolar groove. The correlation of these variables with intraoperative SPR stress test, defined as the diagnostic criteria for PTI in calcaneal fractures, was evaluated.

RESULTS: In total, 369 patients (mean age, 39 ± 13; range, 11-72 years), with 321 (87.0%) of them male, were included. Among all calcaneal fractures, 67 cases (16.7%) had associated PTI as confirmed intraoperatively by an SPR stress test. A statistically significant association was found between PTI in calcaneal fractures and comminuted fragments in the lateral gutter of the ankle (P = .03), dislocated peroneal tendons (P < .001), calcaneal fracture-dislocation (P < .001), SPR avulsion fracture (P < .001), and Sanders type IV of calcaneal fracture (P = .02). There was no statistically significant relationship between PTI and the mechanism of injury (P = .98), side of fracture (P = .30), uni- or bilateral calcaneal fractures (P = .27), a fracture at the tip of lateral malleolus (P = .69), shape of the retromalleolar groove (P = .78), or excessive displacement of the lateral calcaneal wall (P = .06). The most specific CT finding to predict PTI accompanying calcaneal fractures was calcaneal fracture-dislocation (99.1%).

CONCLUSION: Following calcaneal fracture fixation, PTI was confirmed with intraoperative SPR stress test in one-sixth of cases. With the exception of calcaneal fracture-dislocation, preoperative findings on CT scanning and calcaneal fracture pathoanatomy are insufficient to diagnose PTI accompanying calcaneal fractures.

LEVEL OF EVIDENCE: Level III, retrospective case control study.

PMID:37658714 | DOI:10.1177/10711007231175666

Kaohsiung J Med Sci. 2023 Sep 2. doi: 10.1002/kjm2.12746. Online ahead of print.

ABSTRACT

Studies have revealed that both extracorporeal shock-wave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) can accelerate wound healing. This study aimed to compare the effectiveness of ESWT and HBOT in enhancing diabetic wound healing. A dorsal skin defect in a streptozotocin-induced diabetes rodent model was used. Postoperative wound healing was assessed once every 3 days. Histologic examination was performed with hematoxylin and eosin staining. Proliferation marker protein Ki-67 (Ki-67), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were evaluated with immunohistochemical (IHC) staining. The wound area was significantly reduced in the ESWT and HBOT groups compared to that in the diabetic controls. However, the wound healing time was significantly increased in the HBOT group compared to the ESWT group. Histological findings showed a statistical increase in neovascularization and suppression of the inflammatory response by both HBOT and ESWT compared to the controls. IHC staining revealed a significant increase in Ki-67, VEGF, and eNOS but suppressed 8-OHdG expression in the ESWT group compared to the HBOT group. ESWT facilitated diabetic wound healing more effectively than HBOT by suppressing the inflammatory response and enhancing cellular proliferation and neovascularization and tissue regeneration.

PMID:37658698 | DOI:10.1002/kjm2.12746

Eur Stroke J. 2023 Sep 2:23969873231197564. doi: 10.1177/23969873231197564. Online ahead of print.

ABSTRACT

INTRODUCTION: Patent foramen ovale (PFO)-closure is recommended for stroke prevention in selected patients with suspected PFO-associated stroke. However, studies on cerebrovascular event recurrence after PFO-closure are limited by relatively short follow-up periods and information on the underlying aetiology of recurrent events is scarce.

PATIENTS AND METHODS: All consecutive patients with a cerebral ischaemic event and PFO-closure at the University Hospital Graz were prospectively identified from 2004 to 2021. Indication for PFO-closure was based on a neurological-cardiological PFO board decision. Patients underwent standardized clinical and echocardiographic follow-up 6 months after PFO-closure. Recurrent cerebrovascular events were assessed via electronical health records.

RESULTS: PFO-closure was performed in 515 patients (median age: 49 years; Amplatzer PFO occluder: 42%). Over a median follow-up of 11 years (range: 2-18 years, 5141 total patient-years), recurrent ischaemic cerebrovascular events were observed in 34 patients (ischaemic stroke: n = 22, TIA: n = 12) and associated with age, hyperlipidaemia and smoking in multivariable analysis (p < 0.05 each). Large artery atherosclerosis and small vessel disease were the most frequent aetiologies of recurrent stroke/TIA (27% and 24% respectively), and only two events were related to atrial fibrillation (AF). Recurrent ischaemic cerebrovascular event rates and incident AF were comparable in patients treated with different PFO occluders (p > 0.1).

DISCUSSION AND CONCLUSION: In this long-term follow-up-study of patients with a cerebral ischaemic event who had received PFO-closure with different devices, rates of recurrent stroke/TIA were low and largely related to large artery atherosclerosis and small vessel disease. Thorough vascular risk factor control seems crucial for secondary stroke prevention in patients treated for PFO-related stroke.

PMID:37658692 | DOI:10.1177/23969873231197564

Sci Diabetes Self Manag Care. 2023 Sep 1:26350106231192362. doi: 10.1177/26350106231192362. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of the study was to examine the associations between perceived hypoglycemia and psycho-behavioral and clinical factors in persons with type 2 diabetes (T2D).

METHODS: Adults with T2D were recruited from outpatient clinics in a university hospital in Korea. Sociodemographics, psycho-behavioral and clinical factors, and body composition were assessed. The participants were divided into 2 groups reporting perceived hypoglycemia or not in the previous month based on an item of the Control Problem Scale. Group differences were compared at α = .05 using SPSS (version 26.0).

RESULTS: Of 177 participants, approximately one-third (n = 67) perceived hypoglycemia. The hypoglycemia group reported poor health-related quality of life, frequent blood monitoring and foot care, and sleep difficulties. However, no differences between groups were identified for diet, exercise, or glycosylated hemoglobin. The hypoglycemia group had a lower body mass index and a trend toward a lower skeletal muscle mass and fat free mass.

CONCLUSIONS: Perceived hypoglycemia was associated with psycho-behavioral factors and body composition. Importantly, some persons on oral antidiabetic medications that do not cause hypoglycemia still perceived hypoglycemia. Further investigation is warranted to examine the efficacy of strategies to minimize hypoglycemia and inappropriate fear of hypoglycemia. In addition, clinicians should be aware of the potential risk of hypoglycemia in persons with lower muscle mass.

PMID:37658651 | DOI:10.1177/26350106231192362

Child Care Health Dev. 2023 Sep 1. doi: 10.1111/cch.13169. Online ahead of print.

ABSTRACT

BACKGROUND: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada.

METHODS: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis.

RESULTS: Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites.

CONCLUSION: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.

PMID:37658639 | DOI:10.1111/cch.13169

J Diabetes. 2023 Sep 1. doi: 10.1111/1753-0407.13462. Online ahead of print.

ABSTRACT

BACKGROUND: We evaluated whether an abundance of first-trimester plasma mitochondrial DNA (mtDNA) fragments could predict the risk for the development of gestational diabetes mellitus (GDM) by the late second or early third trimester.

METHODS: It was a prospective study wherein we enrolled 150 women in their first trimester of gestation. Oral glucose tolerance test (OGTT) was administered both in the first and second trimesters to diagnose GDM.

RESULTS: Among our cohort, 23 women were diagnosed with GDM in the first trimester and excluded from the study. Of the remaining 127, 29 women were diagnosed with GDM in the second trimester, and 98 women who did not develop GDM served as controls. We amplified blood drawn from each participant during the first trimester for three distinct mtDNA gene sequences: COX, ND4, and D-loop. An abundance of each mtDNA sequence, estimated by the ΔCt method between mtDNA and 18S rRNA, correlated with GDM occurrence in the late second or early third trimester. There was a significant difference in ΔCt COX between controls and those with GDM occurrence in the second trimester (p = .006). These levels were not associated with age or fasting plasma glucose levels in the first trimester. ΔCt COX could predict GDM with a sensitivity of 90% and a specificity of 40%. Though ΔCt ND4 was higher in the GDM-positive group, the levels did not reach statistical significance. ΔCt D-loop was similar in GDM-positive cases and controls who did not develop GDM during pregnancy.

CONCLUSIONS: These results were in plasma samples collected 3 to 4 months before overt hyperglycemia diagnosis suggestive of GDM. The abundance of plasma mtDNA fragments represents a promising cost-effective, convenient early-stage biomarker for predicting GDM development. Importantly, it can be administered irrespective of the fasting status of the subject. Further assessment of the predictive capacity of these biomarkers within large, diverse populations is needed for effective clinical utility.

PMID:37658630 | DOI:10.1111/1753-0407.13462

Ann Clin Transl Neurol. 2023 Sep 1. doi: 10.1002/acn3.51894. Online ahead of print.

ABSTRACT

OBJECTIVE: Internal carotid artery stenosis is a main contributor to recurrent ischemic stroke. This study aimed to evaluate associations between recurrent stroke and changes in prestenting flow direction in the primary collaterals or both primary and secondary collaterals, and the potential interaction between extra- and intracranial arteries.

METHODS: This longitudinal study recruited stroke patients without intracranial stenosis who underwent right-side carotid stenting between 2011 and 2019. The main study outcome was recurrent stroke. Predictive factors were anterior circulation flow direction change (ACFDC), posterior circulation flow direction change, and reversal of ophthalmic artery/leptomeningeal anastomosis (ROALA) detected by transcranial color-coded duplex (TCCD) before carotid stenting. Patient follow-up was 9 years. Risk factors for recurrent stroke were identified by Kaplan-Meier plot and Cox regression analyses.

RESULTS: A total of 234 patients (mean age 70.88 ± 10.3 years, 86.32% male) were included, and 115 had recurrent stroke. Kaplan-Meier plot showed that patients with left ACFDC and ROALA had worse outcomes than those with ACFDC only, while patients with left ACFDC had worse outcome than those with right ACFDC (both p < 0.001). Cox regression analysis showed that recurrent stoke was associated with ACFDC at right (hazard ratio [95% CI]: 20.988 [2.549-172.790], p < 0.01), left (151.441 [20.100-1140.993], p < 0.001), and both sides (144.889 [19.089-1099.710], p < 0.001).

INTERPRETATION: Anterior circulation flow direction change is significantly associated with recurrent stroke in patients with unilateral carotid stenosis. Patients with ACFDC and ROALA together have worse outcomes compared to those with ACFDC only. Prestenting TCCD images help provide definitive information to predict outcomes after carotid stenting.

PMID:37658584 | DOI:10.1002/acn3.51894

Basic Clin Pharmacol Toxicol. 2023 Sep 1. doi: 10.1111/bcpt.13939. Online ahead of print.

ABSTRACT

Nucleus pulposus (NP) cell apoptosis is regarded as a critical risk factor for intervertebral disc degeneration (IVDD). Melatonin exerts a protective role on NP cells. The study concentrates on the role and mechanism of lncRNA MEG3 in melatonin-mediated effects on NP cells. An in-vitro IVDD model was constructed using IL-1β on human NP cells. qRT-PCR investigated MEG3, miR-15a-5p, and PGC-1α mRNA levels in tissues and NP cells. IL-1β treated NP cells subsequent to transfection, followed by melatonin treatment. NP cell proliferation, viability, apoptosis, and inflammatory reactions were assayed. Western blot checked the profiles of PGC-1α, SIRT1, and NF-κB p65. Student t-test or one-way analysis of variance (ANOVA) followed by Tukey’s test were used for statistical tests. As indicated by the data, melatonin weakened NP cell inflammation and apoptosis and enhanced MEG3 expression. MEG3 expression was attenuated in IVDD tissues. MEG3 knockdown impaired the function of melatonin, which was, however, strengthened by miR-15a-5p knockdown. MEG3 targeted miR-15a-5p, which targeted PGC-1α and repressed the PGC-1α/SIRT1 pathway. Collectively, this study has disclosed that the MEG3-miR-15a-5p-PGC-1α/SIRT1 pathway modulated by melatonin can hamper nucleus pulposus cell apoptosis and inflammation elicited by IL-1β.

PMID:37658573 | DOI:10.1111/bcpt.13939

Int J Immunogenet. 2023 Sep 1. doi: 10.1111/iji.12636. Online ahead of print.

ABSTRACT

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Chronic HCV infection is also an important cause of hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCV has the capacity to evade immune surveillance by altering the host immune response. Moreover, variations in immune-related genes can lead to differential susceptibility to HCV infection as well as interfere on the susceptibility to the development of hepatic fibrosis, cirrhosis and HCC. The human leucocyte antigen G (HLA-G) gene codes for an immunomodulatory protein known to be expressed in the maternal-foetal interface and in immune-privileged tissues. The HLA-G 3′ untranslated region (3’UTR) is important for mRNA stability, and variants in this region are known to impact gene expression. Studies, mainly focusing in a 14 bp insertion/deletion polymorphism, have correlated HLA-G 3’UTR with susceptibility to viral infections, but other polymorphic variants in the HLA-G 3’UTR might also affect HCV infection as they are inherited as haplotypes. The present study evaluated HLA-G 3’UTR polymorphisms and performed linkage disequilibrium test and haplotype assembly in 286 HCV infected patients who have developed fibrosis, cirrhosis or HCC, as well as in 129 healthy control subjects. Haplotypes UTR-1, UTR-2 and UTR-3 were the most observed in HCV+ patients, in the frequencies of 0.276, 0.255 and 0.121, respectively. No statistically significant difference was observed between HCV+ and control subjects, even when patients were grouped according to outcome (HCC, cirrhosis or fibrosis). Despite that, some trends in the results were observed, and therefore, we cannot rule out the possibility that variants associated to high HLA-G expression can be involved in HCV infection susceptibility.

PMID:37658479 | DOI:10.1111/iji.12636