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Cost-effectiveness analysis of patent foramen ovale closure versus medical therapy alone after cryptogenic stroke

PLoS One. 2022 Jun 3;17(6):e0268690. doi: 10.1371/journal.pone.0268690. eCollection 2022.

ABSTRACT

BACKGROUND: Closure of a patent foramen ovale reduces the risk of recurrent stroke compared with medical therapy alone in young patients with cryptogenic strokes revealed by randomized control trials. Some cost-effectiveness analyses outside Japan have shown that patent foramen ovale closure is cost-effective, but no studies have examined cost-effectiveness in Japan. The objective of this study is to assess cost-effectiveness, from the perspective of a Japanese healthcare payer, of patent foramen ovale closure versus medical therapy alone for patients with patent foramen ovale related to cryptogenic strokes.

METHODS: A cost-effectiveness study was conducted by developing a decision tree and a Markov model. Probabilities and a 5.9-year time horizon followed the RESPECT study. Utilities and costs were based upon published studies and assumptions. All assumptions were assessed by experts, including a cardiologist and a statistical expert. The target population comprised patients with cryptogenic stroke and patent foramen ovale, aged 60 years or younger. The model was discounted at 2.0% and its cycle was one month. A willingness-to-pay threshold is set at $50,000 / quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio was evaluated. Then one-way sensitivity analyses as deterministic sensitivity analysis, and probabilistic sensitivity analyses were performed to assess data robustness.

RESULTS: Incremental quality-adjusted life years, incremental costs, and incremental cost-effectiveness ratio were 0.464, $13,562, and $29,208 per QALY gained, respectively. One-way sensitivity analysis showed that the stable state utility score difference between patent foramen ovale closure and medical therapy had the largest impact on incremental cost-effectiveness ratio. Patent foramen ovale closure is cost-effective at a stable state utility score difference of >0.051, compared with medical therapy. Probabilistic sensitivity analyses demonstrated that patent foramen ovale closure was 50.3% cost-effective.

CONCLUSIONS: Patent foramen ovale closure was cost-effective compared with medical therapy for Japanese patients with cryptogenic stroke who were ≤60 years.

PMID:35657973 | DOI:10.1371/journal.pone.0268690

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Sub-national variations in general service readiness of primary health care facilities in Ghana: Health policy and equity implications towards the attainment of Universal Health Coverage

PLoS One. 2022 Jun 3;17(6):e0269546. doi: 10.1371/journal.pone.0269546. eCollection 2022.

ABSTRACT

BACKGROUND: Service availability and readiness are critical for the delivery of quality and essential health care services. In Ghana, there is paucity of literature that describes general service readiness (GSR) of primary health care (PHC) facilities within the national context. This study therefore assessed the GSR of PHC facilities in Ghana to provide evidence to inform heath policy and drive action towards reducing health inequities.

METHODS: We analysed data from 140 Service Delivery Points (SDPs) that were part of the Performance Monitoring and Accountability 2020 survey (PMA2020). GSR was computed using the Service Availability and Readiness Assessment (SARA) manual based on four out of five components. Descriptive statistics were computed for both continuous and categorical variables. A multivariable binary logistic regression model was fitted to assess predictors of scoring above the mean GSR. Analyses were performed using Stata version 16.0. Significance level was set at p<0.05.

RESULTS: The average GSR index of SDPs in this study was 83.4%. Specifically, the mean GSR of hospitals was 92.8%, whereas health centres/clinics and CHPS compounds scored 78.0% and 64.3% respectively. The least average scores were observed in the essential medicines and standard precautions for infection prevention categories. We found significant sub-national, urban-rural and facility-related disparities in GSR. Compared to the Greater Accra Region, SDPs in the Eastern, Western, Upper East and Upper West Regions had significantly reduced odds of scoring above the overall GSR. Majority of SDPs with GSR below the average were from rural areas.

CONCLUSION: Overall, GSR among SDPs is appreciable as compared to other settings. The study highlights the existence of regional, urban-rural and facility-related differences in GSR of SDPs. The reality of health inequities has crucial policy implications which need to be addressed urgently to fast-track progress towards the achievement of the SDGs and UHC targets by 2030.

PMID:35657970 | DOI:10.1371/journal.pone.0269546

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A semantics, energy-based approach to automate biomodel composition

PLoS One. 2022 Jun 3;17(6):e0269497. doi: 10.1371/journal.pone.0269497. eCollection 2022.

ABSTRACT

Hierarchical modelling is essential to achieving complex, large-scale models. However, not all modelling schemes support hierarchical composition, and correctly mapping points of connection between models requires comprehensive knowledge of each model’s components and assumptions. To address these challenges in integrating biosimulation models, we propose an approach to automatically and confidently compose biosimulation models. The approach uses bond graphs to combine aspects of physical and thermodynamics-based modelling with biological semantics. We improved on existing approaches by using semantic annotations to automate the recognition of common components. The approach is illustrated by coupling a model of the Ras-MAPK cascade to a model of the upstream activation of EGFR. Through this methodology, we aim to assist researchers and modellers in readily having access to more comprehensive biological systems models.

PMID:35657966 | DOI:10.1371/journal.pone.0269497

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Clinical Report: Correlation of Serum Vitamins and Chalazion

Optom Vis Sci. 2022 Jun 1;99(6):540-543. doi: 10.1097/OPX.0000000000001887. Epub 2022 Feb 25.

ABSTRACT

SIGNIFICANCE: We demonstrate the clinical correlation between the vitamin A level with chalazion in East Chinese children. Vitamin A deficiency is likely to be a potential cause of childhood chalazion.

PURPOSE: Chalazion is the most common lid inflammatory lesion of the eyelid, which can be caused by retention of tarsal gland secretions. Studies have revealed that vitamin deficiency is an essential risk factor for children with chalazion. In this study, we measured the serum levels of vitamin A and 25-hydroxyvitamin D (25(OH)D), in patients with chalazion.

METHODS: The study included 180 subjects (90 patients with chalazion and 90 control healthy subjects) with an average age of 4.13 ± 2.01 years, and 47.8% of whom were female. Serums came from blood samples collected and used to measure the levels of vitamin A and 25(OH)D.

RESULTS: Both groups had statistically similar baseline characteristics, including age and body mass index. The average serum vitamin A levels in patients with chalazion (0.54 ± 0.15 μmol/L) were significantly lower than in their control counterparts (0.60 ± 0.15 μmol/L; P = .01). There was no significant difference in the serum 25(OH)D levels between the patients (70.15 ± 19.73 nmol/L) and control subjects (71.64 ± 24.46 nmol/L). The percentage of vitamin A deficiency in chalazion group (52.2%) was much higher than the control counterparts (28.6%; P = .001). The percentage of 25(OH)D deficiency showed no significant difference between patients with chalazion and control subjects (58.9 vs. 56.7%).

CONCLUSIONS: Low serum vitamin A was significantly associated with chalazion in children. The serum 25(OH)D level exhibited no correlation with chalazion.

PMID:35657678 | DOI:10.1097/OPX.0000000000001887

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Mapping of Perfusion During Full-Thickness Blepharotomy Using Laser Speckle Contrast Imaging

Ophthalmic Plast Reconstr Surg. 2022 Jun 3. doi: 10.1097/IOP.0000000000002218. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to monitor how the blood perfusion in human upper eyelids is affected during full-thickness blepharotomy.

METHODS: Seven eyelids in 5 patients with upper eyelid retraction due to Graves’ disease underwent full-thickness blepharotomy. Perfusion was measured using laser speckle contrast imaging in the eyelid margin and in the conjunctival pedicle.

RESULTS: Immediately following the procedure, a nonsignificant reduction in perfusion was observed in the skin of the pretarsal eyelid margin, being 66% of the initial value (p = n.s.). However, a statistically significant decrease in perfusion, to 53% of the initial value (p < 0.01), was seen in the central pedicle of the conjunctiva. There were no surgical complications such as infection, signs of ischemia, or bleeding.

CONCLUSIONS: In this study, eyelid perfusion was mapped during full-thickness blepharotomy for the first time using laser speckle contrast imaging. The results showed that perfusion is sufficiently preserved during surgery, probably due to the rich vascular supply in the periocular region, which may explain the low risk of postoperative complications such as ischemia and infection.

PMID:35657677 | DOI:10.1097/IOP.0000000000002218

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Deep Phenotyping of Chinese Electronic Health Records by Recognizing Linguistic Patterns of Phenotypic Narratives With a Sequence Motif Discovery Tool: Algorithm Development and Validation

J Med Internet Res. 2022 Jun 3;24(6):e37213. doi: 10.2196/37213.

ABSTRACT

BACKGROUND: Phenotype information in electronic health records (EHRs) is mainly recorded in unstructured free text, which cannot be directly used for clinical research. EHR-based deep-phenotyping methods can structure phenotype information in EHRs with high fidelity, making it the focus of medical informatics. However, developing a deep-phenotyping method for non-English EHRs (ie, Chinese EHRs) is challenging. Although numerous EHR resources exist in China, fine-grained annotation data that are suitable for developing deep-phenotyping methods are limited. It is challenging to develop a deep-phenotyping method for Chinese EHRs in such a low-resource scenario.

OBJECTIVE: In this study, we aimed to develop a deep-phenotyping method with good generalization ability for Chinese EHRs based on limited fine-grained annotation data.

METHODS: The core of the methodology was to identify linguistic patterns of phenotype descriptions in Chinese EHRs with a sequence motif discovery tool and perform deep phenotyping of Chinese EHRs by recognizing linguistic patterns in free text. Specifically, 1000 Chinese EHRs were manually annotated based on a fine-grained information model, PhenoSSU (Semantic Structured Unit of Phenotypes). The annotation data set was randomly divided into a training set (n=700, 70%) and a testing set (n=300, 30%). The process for mining linguistic patterns was divided into three steps. First, free text in the training set was encoded as single-letter sequences (P: phenotype, A: attribute). Second, a biological sequence analysis tool-MEME (Multiple Expectation Maximums for Motif Elicitation)-was used to identify motifs in the single-letter sequences. Finally, the identified motifs were reduced to a series of regular expressions representing linguistic patterns of PhenoSSU instances in Chinese EHRs. Based on the discovered linguistic patterns, we developed a deep-phenotyping method for Chinese EHRs, including a deep learning-based method for named entity recognition and a pattern recognition-based method for attribute prediction.

RESULTS: In total, 51 sequence motifs with statistical significance were mined from 700 Chinese EHRs in the training set and were combined into six regular expressions. It was found that these six regular expressions could be learned from a mean of 134 (SD 9.7) annotated EHRs in the training set. The deep-phenotyping algorithm for Chinese EHRs could recognize PhenoSSU instances with an overall accuracy of 0.844 on the test set. For the subtask of entity recognition, the algorithm achieved an F1 score of 0.898 with the Bidirectional Encoder Representations from Transformers-bidirectional long short-term memory and conditional random field model; for the subtask of attribute prediction, the algorithm achieved a weighted accuracy of 0.940 with the linguistic pattern-based method.

CONCLUSIONS: We developed a simple but effective strategy to perform deep phenotyping of Chinese EHRs with limited fine-grained annotation data. Our work will promote the second use of Chinese EHRs and give inspiration to other non-English-speaking countries.

PMID:35657661 | DOI:10.2196/37213

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Randomised controlled trial of the short-term effects of osmotic-release oral system methylphenidate on symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder: CIAO-II study

Br J Psychiatry. 2022 Jun 3:1-11. doi: 10.1192/bjp.2022.77. Online ahead of print.

ABSTRACT

BACKGROUND: Research has shown that 20-30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders.

AIMS: To estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD.

METHOD: We conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16-25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression.

RESULTS: In the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI -2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm.

CONCLUSIONS: ADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.

PMID:35657651 | DOI:10.1192/bjp.2022.77

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Effect of Perioperative Dexmedetomidine on Delayed Graft Function Following a Donation-After-Cardiac-Death Kidney Transplant: A Randomized Clinical Trial

JAMA Netw Open. 2022 Jun 1;5(6):e2215217. doi: 10.1001/jamanetworkopen.2022.15217.

ABSTRACT

IMPORTANCE: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown.

OBJECTIVE: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant.

DESIGN, SETTING, AND PARTICIPANTS: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population.

INTERVENTIONS: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine.

MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30.

RESULTS: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

PMID:35657627 | DOI:10.1001/jamanetworkopen.2022.15217

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Analysis of Urine Drug Test Results From Substance Use Disorder Treatment Practices and Overdose Mortality Rates, 2013-2020

JAMA Netw Open. 2022 Jun 1;5(6):e2215425. doi: 10.1001/jamanetworkopen.2022.15425.

ABSTRACT

IMPORTANCE: Drug overdose deaths in the US are currently the highest ever recorded; data collected from public health surveillance sources can help to identify emerging drug use patterns associated with overdose mortality rates, but the time lag in results often limits utility. Urine drug testing (UDT) is one potentially underused source that could augment surveillance efforts through timely data collection.

OBJECTIVE: To evaluate the correlation between real-time UDT results from a proprietary national database and overdose mortality data from the National Vital Statistics System.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study included 500 000 urine specimens submitted for UDT by substance use disorder (SUD) treatment health care practices and collected between January 1, 2013, and December 31, 2020. Real-time UDT data were obtained from the Millennium Health proprietary national database, and overdose mortality data were obtained from the National Vital Statistics System of the Centers for Disease Control and Prevention (CDC WONDER). Specimens were analyzed for specific drugs in 5 categories (cocaine, heroin, methamphetamine, synthetic opioids, and other opioids) using liquid chromatography-tandem mass spectrometry. Participants were adults aged 18 years and older who provided urine specimens at SUD treatment practices.

EXPOSURES: Urine drug testing.

MAIN OUTCOMES AND MEASURES: The primary outcome was the correlation between UDT positivity rates and overdose mortality rates at national, state, and county levels. Univariate and multivariate regression models were also used to evaluate the association between state- and county-level overdose mortality and standardized UDT positivity rates.

RESULTS: Among 500 000 unique patient specimens collected from SUD treatment practices between 2013 and 2020, 288 534 specimens (57.7%) were from men, and the median age of the study population was 34 years (IQR, 17-51 years). On a national level, synthetic opioids and methamphetamine were highly correlated with overdose mortality (Spearman ρ = 0.96 for both). When synthetic opioids were coinvolved, methamphetamine (ρ = 0.98), heroin (ρ = 0.78), cocaine (ρ = 0.94), and other opioids (ρ = 0.83) were also highly correlated with overdose mortality. In the absence of synthetic opioids, all drug categories were highly correlated (ρ = 0.75 for other opioids, 0.81 for heroin, and 0.88 for methamphetamine), with the exception of cocaine (ρ = -0.37). Synthetic opioids (ρ = 0.77) and methamphetamine (ρ = 0.80) had the strongest state-level correlations over time, whereas other opioids had the lowest correlation for both total positivity (ρ = 0.31) and positivity in the absence of synthetic opioids (ρ = 0.23). In Ohio, county-level correlation was strongest for synthetic opioids (ρ = 0.71), followed by heroin (ρ = 0.69) and methamphetamine (ρ = 0.67). At the state level, the multivariate incidence rate ratio (IRR) for synthetic opioids was 1.16 (95% CI, 1.14-1.19; P < .001), and at the county level, the IRR was 1.13 (95% CI, 1.09-1.17; P < .001), suggesting that for every 1-SD increase in the UDT positivity rate, there were 16.2% and 12.8% increases, respectively, in monthly overdose deaths. Both methamphetamine (11.7% increase per 1-SD increase in UDT positivity rate; IRR, 1.12; 95% CI, 1.09-1.14; P < .001) and cocaine (5.1% increase per 1-SD increase in UDT positivity rate; IRR, 1.05; 95% CI, 1.03-1.07; P < .001) also had significant positive associations with mortality rates, but the effect sizes were smaller than that of synthetic opioids (IRR, 1.16).

CONCLUSIONS AND RELEVANCE: In this study, UDT results were highly correlated with mortality rates at national, state, and county levels. These findings suggest that real-time UDT surveillance can help to quickly identify changes in drug use patterns that might inform targeted harm reduction strategies designed to prevent overdose deaths.

PMID:35657623 | DOI:10.1001/jamanetworkopen.2022.15425

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Diagnostic accuracy of an artificial intelligence online engine in migraine: A multi-center study

Headache. 2022 Jun 3. doi: 10.1111/head.14324. Online ahead of print.

ABSTRACT

OBJECTIVE: This study assesses the concordance in migraine diagnosis between an online, self-administered, Computer-based, Diagnostic Engine (CDE) and semi-structured interview (SSI) by a headache specialist, both using International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria.

BACKGROUND: Delay in accurate diagnosis is a major barrier to headache care. Accurate computer-based algorithms may help reduce the need for SSI-based encounters to arrive at correct ICHD-3 diagnosis.

METHODS: Between March 2018 and August 2019, adult participants were recruited from three academic headache centers and the community via advertising to our cross-sectional study. Participants completed two evaluations: phone interview conducted by headache specialists using the SSI and a web-based expert questionnaire and analytics, CDE. Participants were randomly assigned to either the SSI followed by the web-based questionnaire or the web-based questionnaire followed by the SSI. Participants completed protocols a few minutes apart. The concordance in migraine/probable migraine (M/PM) diagnosis between SSI and CDE was measured using Cohen’s kappa statistics. The diagnostic accuracy of CDE was assessed using the SSI as reference standard.

RESULTS: Of the 276 participants consented, 212 completed both SSI and CDE (study completion rate = 77%; median age = 32 years [interquartile range: 28-40], female:male ratio = 3:1). Concordance in M/PM diagnosis between SSI and CDE was: κ = 0.83 (95% confidence interval [CI]: 0.75-0.91). CDE diagnostic accuracy: sensitivity = 90.1% (118/131), 95% CI: 83.6%-94.6%; specificity = 95.8% (68/71), 95% CI: 88.1%-99.1%. Positive and negative predictive values = 97.0% (95% CI: 91.3%-99.0%) and 86.6% (95% CI: 79.3%-91.5%), respectively, using identified migraine prevalence of 60%. Assuming a general migraine population prevalence of 10%, positive and negative predictive values were 70.3% (95% CI: 43.9%-87.8%) and 98.9% (95% CI: 98.1%-99.3%), respectively.

CONCLUSION: The SSI and CDE have excellent concordance in diagnosing M/PM. Positive CDE helps rule in M/PM, through high specificity and positive likelihood ratio. A negative CDE helps rule out M/PM through high sensitivity and low negative likelihood ratio. CDE that mimics SSI logic is a valid tool for migraine diagnosis.

PMID:35657603 | DOI:10.1111/head.14324