Economic evaluation of the "paramedics and palliative care: bringing vital services to Canadians" program compared to the status quo.

OBJECTIVE: Based on programs implemented in 2011-2013 in three Canadian provinces to improve the support paramedics provide to people receiving palliative care, the Canadian Partnership Against Cancer and Healthcare Excellence Canada provided support and funding from 2018 to 2022 to spread this approach in Canada. The study objectives were to conduct an economic evaluation of "the Program" compared to the status quo. METHODS: A probabilistic decision analytic model was used to compare the expected costs, the quality-adjusted life years (QALYs) and the return on investment associated with the Program compared to the status quo from a publicly funded healthcare payer perspective. Effectiveness data and Program costs, expressed in 2022 Canadian dollars, from each jurisdiction were supplemented with literature data. Probabilistic sensitivity analyses varying key model assumptions were conducted. RESULTS: Analyses of 5416 9-1-1 calls from five jurisdictions where paramedics provided support to people with palliative care needs between April 1, 2020 and March 31, 2022 indicated that 60% of the 9-1-1 calls under the Program enabled people to avoid transport to the emergency department and receive palliative care at home. Treating people at home saved paramedics an average of 31 min (range from 15 to 67). The Program was associated with cost savings of $2773 (95% confidence interval [CI] $1539-$4352) and an additional 0.00069 QALYs (95% CI 0.00024-0.00137) per 9-1-1 palliative care call. The Program return on investment was $4.6 for every $1 invested. Threshold analyses indicated that in order to be cost saving, 33% of 9-1-1 calls should be treated at home under the Program, the Program should generate a minimum of 97 calls per year with each call costing no more than $2773. CONCLUSION: The Program was cost-effective in the majority of the scenarios examined. These results support the implementation of paramedic-based palliative care at home programs in Canada.

RéSUMé: OBJECTIFS: En fonction des programmes mis en œuvre en 2011-2013 dans trois provinces canadiennes pour améliorer le soutien que les ambulanciers paramédicaux fournissent aux personnes recevant des soins palliatifs. le Partenariat canadien contre le cancer et Excellence des soins de santé Canada a fourni un soutien et du financement de 2018 à 2022 pour diffuser cette approche au Canada. Les objectifs de l'étude étaient d'effectuer une évaluation économique du « programme ¼ par rapport au statu quo. MéTHODES: Un modèle probabiliste d'analyse décisionnelle a été utilisé pour comparer les coûts prévus, les années de vie ajustées en fonction de la qualité (AVAQ) et le rendement du capital investi associés au Programme par rapport au statu quo du point de vue des payeurs de soins de santé financés par l'État. Les données sur l'efficacité et les coûts du Programme, exprimés en dollars canadiens de 2022, de chaque administration ont été complétées par des données documentaires. Des analyses probabilistes de sensibilité ont été effectuées en fonction de diverses hypothèses clés du modèle. RéSULTATS: Des analyses de 5416 appels 9-1-1 provenant de cinq administrations où des ambulanciers paramédicaux ont fourni du soutien aux personnes ayant des besoins en soins palliatifs entre le 1er avril 2020 et le 31 mars 2022 ont indiqué que 60 % des 9Les appels 1-1 dans le cadre du Programme ont permis aux gens d'éviter le transport vers les urgences et de recevoir des soins palliatifs à domicile. Le traitement à domicile a permis aux ambulanciers paramédicaux d'économiser en moyenne 31 minutes (de 15 à 67 minutes). Le programme a permis de réaliser des économies de 2 773 $ (intervalle de confiance [IC] de 95 %, de 1 539 $ à 4 352 $) et de 0,00069 AVAQ supplémentaires (IC à 95 %, de 0,00024 à 0,00137) par appel de soins palliatifs 9-1-1. Le rendement du capital investi du Programme était de 4,6 $ pour chaque dollar investi. Les analyses des seuils ont indiqué que pour réaliser des économies, 33 % des appels 9-1-1 devraient être traités à domicile dans le cadre du Programme, le Programme devrait générer un minimum de 97 appels par année, chaque appel ne dépassant pas 2773 $. CONCLUSION: Le Programme a été rentable dans la majorité des scénarios examinés. Ces résultats appuient la mise en œuvre de programmes de soins palliatifs paramédicaux à domicile au Canada.

[A voxel-based magnetic resonance study of cortical gray matter structures in intermittent exotropia].

Objective: To explore the changes in gray matter volume of the cerebral cortex in patients with intermittent exotropia (IXT) using the voxel-based analysis and to analyze the correlation between these changes and clinical manifestations. Methods: This was a cross-sectional study. A collection of 15 consecutive patients diagnosed with IXT at Tianjin Eye Hospital from March 2021 to May 2022 formed the exotropia group, which comprised 8 males and 7 females, with an average age of (23.5±5.2) years. Ten healthy individuals, 3 males and 7 females, with an average age of (27.0±7.5) years, were selected as the control group. All participants underwent assessments of exotropia severity and Titmus stereoacuity. Three-dimensional high-resolution brain images were obtained through MRI scans. Voxel-based morphometry was employed to preprocess the MRI data, and the SPM toolbox in MATLAB was utilized to analyze differences of images between the two groups. Regions of interest (ROI) with structural abnormalities in the gray matter volume analysis were selected, and the ratio of gray matter voxel values in the ROI to the mean gray matter voxel values of the whole brain for each participant was calculated using the MarsBaR software. The correlation between this ratio and exotropia severity as well as the common logarithm of Titmus stereoacuity was analyzed. Results: The differences in age, gender distribution, and refractive error between the two groups were not statistically significant (all P>0.05). However, there were statistically significant differences in the degree of strabismus and Titmus stereoacuity (both P<0.001). Compared to the control group, patients in the strabismus group exhibited decreased gray matter volume in several brain regions, including the wedges of the medial surface of the cerebral hemisphere (decreased by 89 voxels), the left lingual gyrus (decreased by 176 voxels), the left calcarine sulcus V3 area (decreased by 30 voxels), the central anterior gyrus of the right frontal lobe (decreased by 192 voxels), the gray matter of the left hippocampal gyrus (decreased by 20 voxels), and the bilateral lateral geniculate nuclei (decreased by 100 and 40 voxels on the left and right sides, respectively). These differences were all statistically significant (all P<0.001). Additionally, there was an increase in gray matter volume in several brain regions, including the bilateral caudate nuclei (increased by 60 and 76 voxels on the left and right sides, respectively) and the left precentral gyrus (increased by 36 voxels). These differences were also statistically significant (all P<0.001). A group-level analysis identified 10 brain regions with structural differences between the two groups, which were used as ROI. The gray matter volume ratio was negatively correlated with the degree of exotropia (all P<0.05) in the ROI of the left wedges (r=-0.670), left calcarine sulcus V3 area (r=-0.610), and left lingual gyrus (r=-0.684). The gray matter volume ratio was negatively correlated with lgTS (all P<0.05) in the ROI of the left wedges (r=-0.568) and the central anterior gyrus of the right frontal lobe (r=-0.563). Conclusions: Patients with IXT exhibit decreased gray matter volume in the horizontal connection areas between the primary visual cortices V1 and V2. The reduction in gray matter volume of the lingual gyrus and the dorsal visual pathway V3 area becomes more pronounced with increasing exotropia severity, while the gray matter volume of the precentral gyrus (BA6 area) decreases with worsening stereoacuity.

Associations and Potential Multiple Mechanisms between Subjective Hearing Loss and Cognitive Impairment.

BACKGROUND: Subjective hearing loss (SHL) refers to an individual's self-assessment of their hearing loss. The association and underlying mechanisms between SHL and cognitive impairment still necessitate elucidation. OBJECTIVES: To validate potential mechanisms between SHL and cognitive impairment. DESIGN: Cross-section. SETTING: Shanghai, China. PARTICIPANTS: A total of 2369 individuals from communities and the cognitive disorder clinic. MEASUREMENTS: All participants were subjected to a comprehensive neuropsychological assessment, encompassing the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S). The participants' brain ß-amyloid (Aß) deposition status, plasma biomarkers associated with Alzheimer's disease (AD), and cardiovascular risk factors were also collected. RESULTS: In individuals with a heightened SHL, elevated HHIE-S score was linked to diminished cognitive and daily functioning as well as heightened levels of depressed mood. This correlation was observed in auditory memory performance but not in visual memory. The influence of SHL on cognitive function was mediated by depressed mood. SHL was associated with diabetes and smoking, whereas cognitive function was associated with hyperlipidemia and alcohol consumption. In individuals with positive brain Aß deposition, SHL demonstrated associations with cognitive function independent of plasma Aß42/40 ratio, P-tau181, neurofilament light chain, and APOE allele status. CONCLUSION: SHL has an independent effect on cognitive impairment. The findings do no provide evidence for the common cause mechanism. Instead, the findings support the presence of a cognitive resource mechanism and an impoverished environment mechanism, along with the potential for a pathological interaction mechanism.

ASH2L, Core Subunit of H3K4 Methylation Complex, Regulates Amelogenesis.

Histone methylation assumes a crucial role in the intricate process of enamel development. Our study has illuminated the substantial prevalence of H3K4me3 distribution, spanning from the cap stage to the late bell stage of dental germs. In order to delve into the role of H3K4me3 modification in amelogenesis and unravel the underlying mechanisms, we performed a conditional knockout of Ash2l, a core subunit essential for the establishment of H3K4me3 within the dental epithelium of mice. The absence of Ash2l resulted in reduced H3K4me3 modification, subsequently leading to abnormal morphology of dental germ at the late bell stage. Notably, knockout of Ash2l resulted in a loss of polarity in ameloblasts and odontoblasts. The proliferation and apoptosis of the inner enamel epithelium cells underwent dysregulation. Moreover, there was a notable reduction in the expression of matrix-related genes, Amelx and Dspp, accompanied with impaired enamel and dentin formation. Cut&Tag-seq (cleavage under targets and tagmentation sequencing) analysis substantiated a reduction of H3K4me3 modification on Shh, Trp63, Sp6, and others in the dental epithelium of Ash2l knockout mice. Validation through real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence consistently affirmed the observed downregulation of Shh and Sp6 in the dental epithelium following Ash2l knockout. Intriguingly, the expression of Trp63 isomers, DNp63 and TAp63, was perturbed in Ash2l defect dental epithelium. Furthermore, the downstream target of TAp63, P21, exhibited aberrant expression within the cervical loop of mandibular first molars and incisors. Collectively, our findings suggest that ASH2L orchestrates the regulation of crucial amelogenesis-associated genes, such as Shh, Trp63, and others, by modulating H3K4me3 modification. Loss of ASH2L and H3K4me3 can lead to aberrant differentiation, proliferation, and apoptosis of the dental epithelium by affecting the expression of Shh, Trp63, and others genes, thereby contributing to the defects of amelogenesis.

[The application value of metagenomic next-generation sequencing technology in diagnosis and treatment of pulmonary infection in immunocompromised patients].

Objective: To evaluate the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of pulmonary infection in immunocompromised patients. Methods: A total of 78 patients with immunocompromised pulmonary infection [55 males and 23 females, aged (50.3±16.9) years] and 61 patients with non-immunocompromised pulmonary infection [42 males and 19 females, aged (63.6±15.9) years] in the Intensive Care Unit of the First Medical Center of College of the Pulmonary & Critical Care Medicine, Chinese PLA General Hospital from November 2018 to May 2022 were retrospectively selected. Patients in both groups received bronchoalveolar lavage fluid (BALF) mNGS and conventional microbiological tests (CMTs) while clinically diagnosed with pulmonary infection. The diagnostic positive rate, pathogen detection rate and clinical coincidence rate of the two methods were compared. At the same time, the difference of adjustment rate of anti-infective treatment strategy based on the results of mNGS detection was compared between the two groups. Results: The positive rates of mNGS in patients with pulmonary infection were 94.9% (74/78) and 82.0% (50/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of CMTs in patients with pulmonary infection were 64.1% (50/78) and 75.4% (46/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of mNGS and CMTs in patients with pulmonary infection in immunocompromised group showed a statistically significant difference (P<0.001). The detection rates of mNGS in the immunocompromised group for pneumocystis jirovecii and cytomegalovirus were 41.0% (32/78) and 37.2% (29/78), respectively, and the detection rates of Klebsiella pneumoniae, chlamydia psittaci and Legionella pneumophila were 16.4% (10/61), 9.8% (6/61) and 8.2% (5/61) in the non-immunocompromised patients, respectively, which were higher than those of CMTs [1.3% (1/78), 7.7% (6/78), 4.9% (3/61), 0 and 0] (all P<0.05). In the immunocompromised group, the clinical coincidence rates of mNGS and CMTs and were 89.7% (70/78) and 43.6% (34/78), respectively, with a statistically significant difference (P<0.001). In the non-immunocompromised group, the clinical coincidence rates of mNGS and CMTs were 83.6% (51/61) and 62.3% (38/61), with a statistically significant difference (P=0.008). In the immunocompromised group, according to the results of the etiology of mNGS, the adjustment rate of anti-infection treatment strategy was 87.2% (68/78), while in the non-immunocompromised group, the adjustment rate of anti-infective treatment strategy was 60.7% (37/61), with a statistically significant difference (P<0.001). Conclusion: In patients with immunocompromised pulmonary infection, mNGS has more advantages than CMTs in diagnostic positive rate, diagnosis rate of mixed infection, pathogen detection rate and guidance of anti-infection treatment strategy adjustment, which is worthy of clinical promotion and application.

[Efficacy and safety of transcatheter aortic valve replacement in the treatment of severe aortic stenosis].

Objective: To investigate the efficacy and safety of transcatheter aortic valve replacement (TAVR) in the treatment of severe aortic stenosis. Methods: The clinical data of patients with severe aortic stenosis who underwent TAVR at the People's Hospital of Xinjiang Uygur Autonomous Region between September 2016 and September 2022 were retrospectively analyzed. Changes in aortic transvalvular pressure gradients, valve orifice area, and activity tolerance of patients before and after the surgery were compared. Moreover, postoperative complications and follow-up results from 30 days to 6 years after the surgery were recorded. Results: A total of 76 patients were included in the study (50 males and 26 females), with an average age of (71.3±7.6) years, including 16 rheumatic valvular diseases, 60 senile degenerative diseases, 46 bicuspid valves and 30 tricuspid valves. The success rate of the operation was 96.1% (73/76). Compared with that before the operation, the mean aortic transvalvular pressure gradients decreased [(8.5±2.8) mmHg vs (68.5±19.2) mmHg (1 mmHg=0.133 kPa),P<0.001], but the valve orifice area increased [(1.91±0.31) cm2 vs (0.65±0.21) cm2, P<0.001]. Likewise, six-minute walking test (6MWT) showed that walking distance was longer after the surgery [(430±13) m vs (201±28) m, P<0.001]. There were 1 case of retroperitoneal hematoma, 1 case of stricture balloon dilatation after femoral artery suture concomitant with postoperative puncture site infection, 1 case of femoral artery surgical incision, 2 cases of valve-in-valve (ViV) and 5 cases of perivalvular leakage (4 cases were mild and 1 case was moderate) after the surgery, respectively. Moreover, acute left main artery occlusion during operation occurred in 1 case, ventricular rupture during operation occurred in 1 case and the patient was transferred to valve replacement surgery and finally dead, delayed coronary artery occlusion and death happened in 1 case, and all of the above-mentioned 3 cases were due to surgical failure. Postoperative pacemaker implantation due to third-degree atrioventricular block was performed in 5 cases. There were 1 case of pulmonary embolism, 1 case of transient right limb disorder, 1 case of gastrointestinal bleeding and 1 case of urethral bleeding after the surgery, respectively. The patients were followed up for (1.0±0.1) years (30 days to 6 years), and the results showed that 2 cases died, including 1 case died suddenly at home (the cause of death was unknown) and 1 case died of acute heart failure 8 months after the surgery. Chronic heart failure occurred repeatedly in 6 cases. The quality of life of other patients improved significantly. Conclusion: TAVR is effective and safe for patients with severe aortic stenosis.

Chinese Preclinical Alzheimer's Disease Study (C-PAS): Design and Challenge from PET Acceptance.

BACKGROUND: Large-scale preclinical Alzheimer's disease study based on ß-amyloid positron emission tomography (PET) has not been conducted in China. OBJECTIVES: Establish a cohort on Alzheimer's disease spectrum, especially the preclinical stages, and determine the factors influencing the acceptance of ß-amyloid PET scan screening in China. DESIGN: Longitudinal. SETTING: Shanghai, China. PARTICIPANTS: A total of 4386 participants were screened and 2451 participants who met enrollment criteria were eventually included in this report. MEASUREMENTS: The multidimensional data was collected, including comprehensive assessments, PET and magnetic resonance imaging scans, genetics, and plasma biomarkers. RESULTS: There were 571 participants in the normal cognition group, 625 participants in the subjective cognitive decline group, 155 participants in the objectively defined subtle cognitive decline group, 501 participants in the mild cognitive impairment group, 471 participants in Alzheimer's disease group, and 128 participants with cognitive impairment from other known causes. Significant differences in demographics, florbetapir PET, APOE, and neuropsychological tests were found among the groups. Eight hundred and seventeen participants (33.3%) completed the florbetapir PET scanning. Non-demented individuals with higher age, lower education years, male, with a family history of dementia, and higher self-report depression prefer to undergo PET scans. Acceptance of PET scans did not correlate with objectively assessed cognitive impairment. CONCLUSIONS: The Chinese Preclinical Alzheimer's Disease Study was designed to establish a large-scale cohort with comprehensive data collection. Our findings may help to understand the factors affecting the acceptance of ß-amyloid PET in urban areas of China and help us address the low acceptance challenge.

[Progress on health-related quality of life and its influencing factors in patients with tuberculosis sequelae].

With the emergence of new tuberculosis patients, the number of patients with tuberculosis sequelae is increasing, which not only increases the medical burden of tuberculosis sequelae year by year, but also affects the health-related quality of life (HRQOL) of patients. The HRQOL of patients with tuberculosis sequelae has gradually received attention, but there are few relevant studies. Studies have shown that HRQOL is related to various factors such as post-tuberculosis lung disease, adverse reaction to anti-tuberculosis drugs, decreased physical activity, psychological barriers, low economic status and marital status. This article reviewed the current situation of HRQOL in patients with sequelae of tuberculosis and its influencing factors, in order to provide a reference for improving the quality of life of patients with sequelae of tuberculosis.

Comparison of automated breast volume scanning with conventional ultrasonography, mammography, and MRI to assess residual breast cancer after neoadjuvant therapy by molecular type.

AIM: To compare the accuracy of hand-held ultrasonography (US), mammography (MG), magnetic resonance imaging (MRI), and automated breast volume scanning (ABVS) in defining residual breast cancer tumour size after neoadjuvant therapy (NAT). MATERIALS AND METHODS: Patients diagnosed breast cancer and who received NAT at the Breast Center, Peking University People's Hospital, were enrolled prospectively. Imaging was performed after the last cycle of NAT. The residual tumour size, intraclass correlation coefficients (ICCs), and receiver operating characteristic (ROC) to predict pathological complete response (pCR) were analysed. RESULTS: A total of 156 patients with 159 tumours were analysed. ABVS had a moderate correlation with histopathology residual tumour size (ICC = 0.666), and showed high agreement among triple-positive tumours (ICC = 0.797). With 5 mm as the threshold, the coincidence rate reached 64.7% between ABVS and pathological size, which was significantly higher than that between US, MG, MRI, and pathological size (50%, 45.1%, 41.4%; p=0.009, p=0.001, p<0.001, respectively). For ROC analysis, ABVS demonstrated a higher area under the ROC curve, but with no statistical difference, except for MG (0.855, 0.816, 0.819, and 0.788, respectively; p=0.183 for US, p=0.044 for MG, and p=0.397 for MRI, with ABVS as the reference). CONCLUSIONS: The longest tumour diameter on ABVS had a moderate correlation with pathological residual invasive tumour size. ABVS was shown to have good ability to predict pCR and would appear to be a potential useful tool for the assessment after NAT for breast cancer.

A meta-analysis of effects and safety of Tripterygium wilfordii polyglycoside in the treatment of IgA nephropathy.

OBJECTIVE: To evaluate the effects and safety of Tripterygium wilfordii polyglycoside (TWP) in the treatment of immunoglobulin A (IgA) nephropathy. SUBJECTS AND METHODS: A computer-assisted study search of Chinese Biomedical Database (CBM), Chinese Journal Full-text Database (CNKI), Wanfang Database, Chinese Scientific Journal Database (VIP), PubMed, Medline, EMBASE and Cochrane Library was performed, with the time range of retrieval set between the establishment of the database to December 31, 2019. Articles of randomized controlled trials on the treatment of IgA nephropathy by Tripterygium wilfordii polyglycoside were collected, and then screened according to the inclusion and exclusion criteria. Next, the quality of the papers was assessed, effective data were extracted, and a meta-analysis of the included studies was conducted using the Review Manager 5.3 software provided by the Cochrane Collaboration. RESULTS: Thirty randomized controlled trials (RCT) were included ultimately, and the meta-analysis showed that 1) Single (Sgl) TWP group was superior to angiotensin-converting enzyme inhibitor/angiotension receptor blocker (ACEI/ARB) group in terms of complete remission [odds ratio (OR) = 4.74, p-value < 0.00001], total remission (OR = 3.90, p-value < 0.0001), 24-hour proteinuria [mean difference (MD) = 1.18, p-value < 0.00001], and serum albumin (MD = - 8.23, p-value < 0.00001), and no significant difference in serum creatinine (MD = 2.09, p-value = 0.08) was found between Sgl TWP and control groups; TWP + ACEI/ARB group was superior in complete remission (OR = 2.57, p-value < 0.00001), total remission (OR = 4.36, p-value < 0.00001), serum albumin [standardized mean difference (SMD) = -0.68, p-value = 0.0005], 24-hour proteinuria (SMD = 1.24, p-value < 0.00001) and serum creatinine (SMD = 0.48, p-value = 0.006); 2) TWP group was superior to glucocorticoid group in complete remission (OR = 1.93, p-value < 0.0010), total remission (OR = 3.71, p-value < 0.00001), serum albumin (MD = -3.50, p-value = 0.002), 24-hour proteinuria (SMD = 0.93, p-value < 0.0001) and serum creatinine (SMD = 0.88, p-value = 0.006); 3) TWP group was better than mycophenolate mofetil (MMF) group in complete remission (OR = 2.05, p = 0.005), total remission (OR = 3.30, p-value = 0.002), 24-hour proteinuria (MD = 2.61, p-value < 0.0001), and serum albumin (MD = -6.43, p-value < 0.00001), but the differences in serum creatinine (MD = 1.28, p-value = 0.89) between TWP and control groups were not significant. Besides, TWP + ACEI/ARB group had a higher adverse reaction rate than the control group (OR = 2.21, p-value = 0.04), but there was no significant difference in the adverse reaction rate between other control and experimental groups (p-value > 0.05). CONCLUSIONS: The present evidence shows that Tripterygium wilfordii polyglycoside can effectively improve the remission rate, reduce proteinuria, and protect kidney function of IgA nephropathy patients, and also has good safety. However, limited by the quality of the included studies, the effects and safety of Tripterygium wilfordii polyglycoside in the treatment of IgA nephropathy need to be verified by more high-quality, large-scale, multi-center RCTs.

Normal pace walking is beneficial to young participants' executive abilities.

BACKGROUND: Exercise can improve cognitive function. The impact of acute exercise on cognition is related to exercise intensity. This study aimed to explore whether normal walking had a beneficial effect on cognition. METHODS: Compared with standing still, thirty healthy young men walked on a treadmill at a normal pace, and completed the Stroop test. Near-infrared spectroscopy was used to monitor the hemodynamic changes of the prefrontal cortex during the entire experiment. RESULTS: Studies showed that normal walking did not stimulate higher average cerebral oxygen in the PFC, but the peak cerebral oxygen in cognitive tests during walking was higher (Stroop Word: 2.56 ± 0.43 and 3.80 ± 0.50, P < 0.01, Stroop Color: 2.50 ± 0.37 and 3.66 ± 0.59, P < 0.05, Stroop Color-Word: 4.13 ± 0.55 and 5.25 ± 0.66, P < 0.01, respectively), and better results were achieved in the Stroop Color-Word test, which was reflected in faster reaction times (49.18 ± 1.68 s, 56.92 ± 2.29 s, respectively, P < 0.001) and higher accuracies (46.19 ± 0.69, 44.15 ± 0.91, respectively, P = 0.018). CONCLUSION: For healthy young people, even a normal walk is therefore good for cognition.

[The importance of intranasal trigeminal event-related potentials test for patients with olfactory dysfunction].

Objective: To analyze the characteristics of trigeminal event-related potentials (tERPs) in different kinds of olfactory disorders (OD), and to evaluate the importance of tERPs for the patients with olfactory dysfunction. Methods: Clinical data of 314 patients with olfactory dysfunction from the Smell and Taste Clinics in Beijing Anzhen Hospital from 2015 to 2021 were retrospectively reviewed, including 158 males and 156 females, aging from 6 to 78 years. The control group consisted of healthy people from medical examination center, who were gender and age matched. The clinical characteristics of OD were analyzed using Sniffin' Sticks test, olfactory event-related potentials (oERPs), tERPs and acoustic rhinometry test. SPSS 17.0 software was used to compare the difference of tERPs between the two groups, and to analyze the related factors affecting trigeminal function. Results: The ratio of tERPs presence was different in OD caused by different reasons: head traumatic OD (54.9%), post-virus infection OD (63.6%), sinonasal inflammatory OD (68.4%) and OD due to other causes (56.9%). Compared with controls, tERPs signals in OD patients showed a significant lower amplitude in the N1 wave (all P<0.001), and lower amplitude in the P2 wave in most OD patients (head trauma t=-4.11, P<0.001; sinonasal inflammation t=-2.04, P=0.046; others t=-2.40, P=0.020) except in OD by post-virus infection (t=-1.98, P=0.052). tERPs signals in OD patients by sinonasal inflammation showed longer latency in the N1 wave (t=2.15, P=0.036), but this difference was not observed in other OD patients (all P>0.05). tERPs signals were significantly correlated with the Sniffin' Sticks score, deficiency of oERPs and nasal minimum cross-sectional area (all P<0.05). Conclusions: OD patients show neurophysiologic deficits in trigeminal function. The absence of tERPs or lower amplitude in N1 waves are the important characteristics of patients with OD.

[Based on a Markov model, cost-effectiveness analysis of influenza vaccination among people aged 60 years and older in Shenzhen].

Objective: To assess the cost-effectiveness of influenza vaccination among people aged 60 years and older in Shenzhen. Methods: A Markov state transition model was constructed to evaluate the cost-effectiveness of annual influenza vaccination for preventing influenza infection compared with no vaccination among the elderly from the social perspective. Allowing seasonal variation of influenza activity, the model followed a five-year cohort using weekly cycles. We employed once the Chinese gross domestic product (GDP) per capita in 2019 (70 892 yuan) as the willingness-to-pay (WTP) threshold and calculated the net monetary benefit (NMB) with costs and quality-adjusted life-years (QALYs) discounted at 5% annually. The impact of parameter uncertainty on the results was examined using one-way and probabilistic sensitivity analyses (PSA). Results: The base case amounted to approximately 35 yuan of cost-saving and a net gain of 0.007 QALYs. Correspondingly, the NMB was 529 yuan per vaccinated person. One-way sensitivity analyses showed that the NMB was relatively sensitive to changes in the attack rate of influenza and vaccine effectiveness. Based on the results of PSA with 1 000 Monte Carlo simulations, influenza vaccination had a probability of being cost-effective in 100% of the repetitions. Conclusions: The present study provides evidence that influenza vaccination is a cost-saving disease prevention strategy for people aged 60 years and older in Shenzhen.

[Application of next-generation sequencing in detection of BRCA1/2 and homologous recombination repair pathway multi-genes germline mutation and correlation analysis].

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.

Association between Sleep Duration and Mild Cognitive Impairment at Different Levels of Metabolic Disease in Community-Dwelling Older Chinese Adults.

OBJECTIVES: The purpose of this study was to investigate the relationship between metabolic syndrome (MetS), sleep duration and mild cognitive impairment (MCI) in community-dwelling older Chinese adults. METHODS: The study comprised of 1367 community-dwelling Chinese participants (563 men; mean age: 71.0 years) recruited from Tianjin and Shanghai, China who were invited to participate in a comprehensive geriatric assessment. The International Diabetes Federation metabolic syndrome guidelines were used to define MetS. The Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale were used for the initial classification of patients with MCI. We divided sleep duration into five groups (≤6 h, 6-8 h which was used as the reference, 8-9 h, 9-10 h, and >10 h). Nutritional status was assessed by Mini Nutrition Assessment Short Form. RESULTS: The overall incidence of metabolic syndrome was 46.7%, the overall incidence of mild cognitive impairment was 17.4%. In logistic regression analysis model, after adjusting for multiple confounding factors such as nutritional status and physical activity level, there was a significant positive association between long sleep duration (> 10h) and mild cognitive impairment in general population and metabolic syndrome population (p<0.05), but the association was not significant in non-metabolic syndrome group. In addition, in the long sleep duration group, the components of metabolic syndrome, elevated blood glucose were significantly associated with mild cognitive impairment (p<0.05). CONCLUSIONS: Long sleep duration was significantly associated with increased risk of MCI in older adults with MetS, but not in those without MetS. The prevention of MCI may be more effective in the population of MetS with long sleep duration.

Validation of an algorithm to identify incident interstitial lung disease in patients with rheumatoid arthritis.

BACKGROUND/PURPOSE: Interstitial lung disease (ILD) is an important problem for patients with rheumatoid arthritis (RA). However, current approaches to ILD case finding in real-world data have been evaluated only in limited settings and identify only prevalent ILD and not new-onset disease. Our objective was to develop, refine, and validate a claims-based algorithm to identify both prevalent and incident ILD in RA patients compared to the gold standard of medical record review. METHODS: We used administrative claims data 2006-2015 from Medicare to derive a cohort of RA patients. We then identified suspected ILD using variations of ILD algorithms to classify both prevalent and incident ILD based on features of the data that included hospitalization vs. outpatient setting, physician specialty, pulmonary-related diagnosis codes, and exclusions for potentially mimicking pulmonary conditions. Positive predictive values (PPV) of several ILD algorithm variants for both prevalent and incident ILD were evaluated. RESULTS: We identified 234 linkable RA patients with sufficient data to evaluate for ILD. Overall, 108 (46.2%) of suspected cases were confirmed as ILD. Most cases (64%) were diagnosed in the outpatient setting. The best performing algorithm for prevalent ILD had a PPV of 77% (95% CI 67-84%) and for incident ILD was 96% (95% CI 85-100%). CONCLUSION: Case finding in administrative data for both prevalent and incident interstitial lung disease in RA patients is feasible and has reasonable accuracy to support population-based research and real-world evidence generation.

[Detection of drug resistance genes of mycobacterium tuberculosis by rolling circle amplification technique with multicolor fluorescent probes].

The aim of this study was to construct a simple, rapid and ultra-sensitive optical biosensing technique based on rolling circle amplification (RCA), and to apply it to multiple detection of drug-resistant genes of mycobacterium tuberculosis. The common mutation sites of isoniazid, rifampicin and streptomycin resistance genes are katG315 (AGC➝ACC), rpoB531 (CAC➝TAC) and rpsL43 (AAG➝AGG). For these three gene sites, from February 2020 to May 2021, in the Department of Laboratory Medicine of the First Affiliated Hospital of Army Military Medical University, the padlock probe (PLP), primers and capture probes were designed. And a solid-phase RCA constant temperature amplification reaction system based on magnetic beads was constructed and the experimental parameters were optimized. The RCA products were accurately captured by the multicolor fluorescent probes (Cy3/Cy5/ROX), and the single-tube multiple detection of three mutation genes was realized. The sensitivity, specificity and linear range of this method were further verified. The results showed that the response range of katG315 in the same reaction system ranged from 1.0 pmol/L to 0.1 nmol/L. The response range of rpoB531 and rpsL43 ranged from 1.0 pmol/L to 50.0 pmol/L and 1.0 pmol/L to 20.0 pmol/L, and the method had good specificity and sensitivity, and could accurately identify single base mutations in mixed targets, with the minimum detection limit as low as 1.0 pmol/L. The recoveries of simulated serum samples were 95.0%-105.2%. In conclusion, the constant temperature amplification multiple detection method constructed in this study can quickly realize the single-tube multiple detection of three drug resistance mutation sites. This technology is low-cost, simple and rapid, and does not rely on large equipment, providing a new analysis method for pathogen drug resistance gene detection.

Transcriptome analysis reveals the effect of high-grain pelleted and non-pelleted diets on ruminal epithelium of Hu-lamb.

High-grain non-pelleted (HG) and high-grain pelleted (HP) diets are becoming prevalent for ruminant feeding in intensive farms. However, rare information is about their effect on sheep and the comparison between these two kinds of diets. The current study investigated how HG and HP diets affected the transcriptome profiles of rumen epithelium in Hu-lamb. Fifteen male Hu-lambs were assigned randomly to three groups (n = 5 for each group). Lambs in the control (CON), HG, and HP groups were fed with low-grain non-pelleted diet (30% grain), HG diet (70% grain), and HP diet (70% grain), respectively, for 42 days. All these lambs were slaughtered to collect ruminal epithelium samples for transcriptome analysis. Results showed both HG and HP diets obviously changed the transcriptome profiles, and 192, 319, and three differentially expressed genes (DEGs) were identified for CON_HG, CON_HP, and HG_HP comparisons, respectively. Clusters of orthologous group functional classification of CON_HG and CON_HP DEG datasets both showed the enrichments of DEGs in pathways involved in protein biogenesis and modification as well as energy production and conversion. Kyoto encyclopedia of genes and genomes pathway analysis of CON_HG and CON_HP DEG datasets both displayed the enrichments of DEGs in ribosome and oxidative phosphorylation. Almost all these DEGs involved in translation and ribosomal structure and biogenesis as well as oxidative phosphorylation were downregulated in the HG and HP groups compared to the CON group. Furthermore, CON_HP comparison demonstrated more DEGs related to these two pathways than CON_HG comparison. In conclusion, both HG and HP diets inhibited energy production and conversion as well as protein synthesis and modification in ruminal epithelium. HP diet showed lower growth benefits, induced severer rumen acidosis, and more seriously inhibited energy production and protein synthesis as compared to HG diet.