Economic evaluations of electronic health interventions for people with age-related cognitive impairment and their caregivers: A systematic review.

OBJECTS: Dementia has physical, social and economic impacts, causing considerable distress for people with age-related cognitive impairment (PWACI) and their caregivers. Electronic health (e-health) interventions can provide convenient education to improve the coping competence of caregivers and have become an important approach to supporting them. Understanding the economic evidence of e-health interventions will facilitate the decision making and implementation of integrating e-health into routine health services. The present review aimed to appraise economic evidence related to e-health interventions for PWACI and their caregivers. METHODS: We systematically searched multiple cross-disciplinary databases from inception to February 28, 2023. Two reviewers independently selected the trials, assessed the quality, and checked the data. A descriptive-analytical narrative method was used to analyze the review findings. RESULTS: Thirteen studies were analyzed, including 12 randomized controlled trials and one quasi-experimental study. All included studies were conducted in developed countries. The included studies reported limited economic information. There were six cost-effectiveness analysis, five cost-consequence analysis and one partial economic evaluation. The included studies were heterogeneous, and varied in quality. The results demonstrated that e-health multicomponent interventions can reduce the cost of health service utilization in short term (10-104 weeks). CONCLUSIONS: Few studies calculated the incremental cost-effectiveness ratio to evaluate the cost-effectiveness of e-health interventions. Preliminary evidence indicates that e-health interventions can reduce the cost of health service utilization in the short term, but the cost-effectiveness of e-health interventions hasn't been identified. More robust evidence is needed to clarify the value of e-health interventions for PWACI and their caregivers.

High-level structural analysis of proanthocyanidins using full collision energy ramp-MS2 spectrum.

Proanthocyanidins (PACs) refer to a group of polyphenols consisting of flavan-3-ol units, and are ubiquitously distributed in fruits, vegetables, nuts and grains. PACs possess high-level structural diversity because of the fickle linkage manners amongst units, the polymerization degree and stereoisomeric forms, thus leading to a great challenge for structural analysis. Although LC-MS/MS currently serves as the workhorse to profile PACs in complicated matrices, it's still challenging to achieve confirmatively structural annotation even employing the cutting-edged high-resolution MS/MS techniques, and the key technical obstacle lies at isomeric discrimination. To pursue as many auxiliary structural clues as possible, full collision energy ramp-MS2 (FCER-MS2) spectrum was conceptually designed here to involve all mass fragmentation behaviors of a given compound, such as m/z, optimal collision energy (OCE) and the maximal relative ion intensity (RIImax) aiming to advance the structural annotation confidences of PACs through reliably differentiating isomers. Thirteen authentic compounds were collected to mine relationships between chemical structures and FCER-MS2 spectra that were correlated by three progressive steps: (1) recording MS/MS spectrum by LC-Q-TOF-MS; (2) proposing mass fragmentation pathways to assign those obvious fragment ion species; and (3) acquiring breakdown graph for each concerned fragment ion species by programming online energy-resolved mass spectrometry to compose FCER-MS2 spectrum. Afterwards, the rules were applied for PACs-focused chemical characterization of a medicinal herb namely Indigofera stachyodes (Chinese name: Xuerenshen), and as a result, 22 PACs were captured and more importantly, isomerically identified by deciphering FCER-MS2 spectra. Therefore, FCER-MS2 spectrum provides a promising way to achieve in-depth isomeric discrimination of, but not limited to, PACs.

Full Collision Energy Ramp-MS2 Spectrum in Structural Analysis Relying on MS/MS.

Albeit frequently being overlooked, MS2 spectrum variation against collision energy (CE) implies auxiliary structural clues for m/z values. Online energy-resolved MS (ER-MS) provides the opportunity to acquire the trajectory of ion intensity against CE for any fragment ion of interest, thus exactly offering the desired momentum to empower the conventional MS2 spectrum at a certain CE forward to a full-CE ramp MS2 spectrum (FCER-MS2). Efforts were made here to construct an FCER-MS2 spectrum and to evaluate its potential toward structural analysis. Flavonoids were employed as a proof of concept. MS2 spectra of 76 compounds were recorded by LC-Q-Exactive-MS, and online ER-MS was subsequently programmed using LC-Qtrap-MS to build a breakdown graph for each obvious fragment ion. After defining the greatest value amongst all regressive apices as 100%, the normalized breakdown graphs comprised an FCER-MS2 spectrum for each compound. The FCER-MS2 spectrum contained the MS2 spectrum at any CE as well as optimal CE (OCE) and maximal relative ion intensity (RIImax) of each fragment ion. Except the pronounced isomeric discrimination potential, either OCE or RIImax reflected certain structural properties, such as aglycone, glycosidic bond, and hydroxy, methoxy, and glycosyl substituents. These rules were subsequently applied for flavonoid-focused characterization of a famous herbal medicine, namely Scutellariae Radix, and high-level structural annotation was accomplished for 75 flavonoids. Above all, the FCER-MS2 spectrum includes m/z, OCEs, and RIImax features, thus facilitating confidence-advanced structural analysis.

[Isomeric discrimination of kaempferol versus luteolin by online energy-resolved mass spectrometry].

Isomers are widely distributed in Chinese herbal medicines,and can be discriminated by energy-resolved mass spectrometry( ER-MS). However,ER-MS was performed through direct injection of reference compounds with syringe pump,which encountered a significant technical barrier for high-throughput and automated measurements. Herein,online ER-MS was conducted using LC-MS platform,and a pair of isomers,kaempferol vs luteolin,were employed as a case study to illustrate and assess the utility of online ER-MS for isomeric discrimination. High-resolution tandem mass spectrometry data of both flavonoids were acquired on LC-QE-Orbitrap-MS,and the fragmentation pathways responsible for the primary fragment ions were proposed. The primary signal in MS1 occurred at m/z 285( [M-H]-),and the primary signals of either compound generated by retro-Diels-Alder fragmentation were observed at m/z 151 and 133. The spectral information was subsequently transferred onto LC-Qtrap-MS platform to carry out online ER-MS. Two precursor-to-product ion transition candidates were constructed as m/z 285>151 and 285>133,and either afterward derived a set of pseudo-ion transitions( PITs) and so forth,exactly corresponding to a series of progressive collision energies( eg-5,-8,-11 e V,and so on). All PITs were typed into the monitoring list of multiple reaction monitoring program to generate the peak area datasets. Either dataset was normalized using the highest values in the set and imported into Graph Pad Prism software to plot the Gaus-sian-shaped curve that was termed as the break-down graph. The apex of the regressive curve was termed as optimal collision energy( OCE). The OCE values corresponding to m/z 285>151 were calculated as-29. 06 e V and-35. 71 e V for kaempferol and luteolin,respectively. In the case of m/z 285>133,the OCEs were yielded as-44. 15 e V for kaempferol and-49. 01 e V for luteolin. With re-ference to their chemical structures,the location of hydroxyl group was regarded to be responsible for the differences of either m/z 285>151 or 285>133 between the isomers,attributing to their different bond properties. Above all,online ER-MS offers an eligible tool for isomeric discrimination,and provides meaningful information for the accurate chemical composition characterization based on LC-MS,which is not limited to Chinese herbal medicines.

[Analysis of chemical components of Chinese medicine Ligustici Radix by achiral-chiral liquid chromatography-predictive multiple reaction monitoring].

Ligustici Radix (Chinese name: maoqianhu) consists of the dried roots of Ligusticum brachylobum Franch., which is mainly distributed in the Yunnan and Sichuan provinces. This herbal medicine has been primarily used for the treatment of cough in traditional Chinese medicine. Ligustici Radix is rich in coumarin derivatives. Interestingly, enantiomers and diastereomers are widely used for these coumarins, thus posing a great challenge for in-depth chemical profile characterization. In the present study, a new analytical platform, achiral-chiral liquid chromatography-tandem mass spectrometry (achiral-chiral LC-MS/MS) was configured to profile the chemical composition of Ligustici Radix. Because achiral and chiral columns were serially coupled, especially enantiomers, both chemically and enantiomerically selective separations could be accomplished simultaneously. The newly configured achiral-chiral LC-MS/MS platform did not require any electronic valve; hence, it could overcome the drawbacks of heart-cutting achiral-chiral two-dimensional LC, i. e., sophisticated instrumentation and limited reproducibility due to the use of electronic valve(s) and the undesired retention time shift across different analytical runs. Some available candidates for chemically selective or enantiomerically selective separation were assayed; then, Capcell core RP-C18 column that was packed with core-shell type particles, and AD-RH column embedding amylose coated particles were employed the achiral and the chiral columns, respectively. The narrow-bore core-shell RP-C18 column served as the front tool to achieve efficient chemoselective separation of coumarin analogs, and enantioselective enantiomers were obtained by using a wide-bore AD-RH chiral column. The predictive multiple reaction monitoring (predictive MRM) mode allowed for the sensitive detection of potential components, and an enhanced product ion (EPI) scan, which was a unique function of Qtrap-MS, was programmed to record the MS2 spectra for all captured signals and thus aid structural annotation. Online energy-resolved mass spectrometry (online ER-MS) was introduced to pursue the suitable collision energy for each compound; in particular, inferior collision energy instead of the optimal one was utilized to suppress the response of the primary components such as praeruptorin A, B and pteryxin. The criteria to judge enantiomers or not included identical quantitative and qualitative precursor-to-product ion transitions, identical quantitative versus qualitative responses, and longer retention times from achiral-chiral LC over single-column achiral LC. As a result, a total of sixty components were observed and structurally identified. In particular, enantiomerically selective separations were achieved for eight enantiomers, cis-khellactone (CKL), qianhucoumarin G (QC-G), pteryxin (Pte), praeruptorin A (PA), cis-3'-isovaleryl-4'-acetylkhellactone (IAK), praeruptorin B (PB), praeruptorin E (PE), and cis-3',4'-diisovalerylkhellactone (DIK). Notably, none of the enantiomers were present as racemates; instead, the proportion of one enantiomer in each pair was greater than the other. Achiral-chiral LC-predictive MRM is a feasible choice for the quantitative and qualitative analyses of Ligustici Radix as well as other herbal medicines characterized by enantiomers and diastereomers.

A new ECG sign for sudden death: Transient prolonged QT interval following premature contraction. / 一种新的猝死预警心电图：期前收缩后短暂QT间期延长.

Early recognition and treatment for early warning electrocardiogram (ECG) of sudden death are very important to prevent and treat malignant arrhythmia and sudden death. Previous studies have found that R-on-T and T wave alternation, and QT interval prolongation are closely related to malignant arrhythmia or sudden death, which are included in the critical value of ECG.By analyzing the ECG characteristics of 4 patients with sudden death, we found that although the causes of the patients were different, there were transient prolongation of QT interval after premature contraction in 12 lead ECG, followed by malignant arrhythmia or sudden death. Thus, we thought that the transient prolongation of QT interval after premature contraction had a high value for warning malignant arrhythmia or sudden death. This phenomenon should be paid enough attention to reduce the risk of sudden death.

Liquid chromatography-three-dimensional mass spectrometry enables confirmative structural annotation of cistanoside F metabolites in rat.

Clarification the existence forms, including prototype and metabolite(s) is the prerequisite for understanding in-depth the therapeutic mechanisms of a given agent, particularly when oral administration. However, it is still a long distance for unambiguous structural identification of metabolites even employing the cutting-edge MS/MS technique, and the determinant obstacle is produced by its inherent isomer-blind disadvantage. To tackle with this drawback, online energy-resolved mass spectrometry (online ER-MS) was introduced to enable isomeric discrimination after that high-resolution MS/MS provided empirical molecular formula as well as substructures. In-depth metabolic characterization of cistanoside F (CF), an effective natural product, was conducted as a proof-of-concept for the new strategy namely three-dimensional MS that was configured by MS1, MS2 and online ER-MS as 1st, 2nd, and 3rd dimensions, respectively. Sensitive metabolite detection was assisted by predictive multiple-reaction monitoring function on Qtrap-MS, and the empirical formulas of all metabolites were calculated from the quasi-molecular ions yielded from IT-TOF-MS. Subsequently, substructures of each metabolite were constructed by combining the calculated element compositions and the well-defined mass fragmentation pathways. Finally, online ER-MS was responsible to generate optimal collision energies for bonds-of-interest, and enabled rational selection among candidate structures. A total of thirteen metabolites were detected and confirmatively identified in rat after oral treatment of CF using LC-3D MS. Acyl-migration, hydrolysis and sulfation played key roles for the metabolic fate of CF. More importantly, LC-3D MS is an eligible tool to achieve confidence-enhanced structural annotation of metabolites in biological matrices because of the unique isomeric differentiation ability from online ER-MS.

Confirmative Structural Annotation for Metabolites of (R)-7,3'-Dihydroxy-4'-methoxy-8-methylflavane, A Natural Sweet Taste Modulator, by Liquid Chromatography-Three-Dimensional Mass Spectrometry.

Flavonoids occupy the largest family of natural products and possess a broad spectrum of health benefits. Their metabolites are sometimes the truly effective molecules in vivo. It is still challenging, however, to unambiguously identify flavonoid metabolites using conventional LC-MS/MS. Herein, we aimed to pursue auxiliary structural clues to m/z values in both MS1 and MS2 spectra through LC coupled to three-dimensional MS (LC-3D MS). MS1, as the first dimension, was in charge of suggesting theoretical molecular formulas, MS2, the as second dimension, was responsible for offering substructures, and exactly, online energy-resolved MS (ER-MS), as the third dimension, provided optimal collision energies (OCEs) that reflected the linkage manners among the substructures. Metabolic characterization of a natural sweet taste modulator, namely, (R)-7,3'-dihydroxy-4'-methoxy-8-methylflavane (DHMMF), was conducted as a proof-of-concept. Extensive efforts, such as full MS1 and MS2 scans on IT-TOF-MS and predictive selected-reaction monitoring mode on Qtrap-MS, were made for in-depth metabolite mining. Seventeen metabolites (M1-M17) were captured from DHMMF-treated biological samples, including 17 (M1-M17), 10 (M4-M9, M11, M13, M14, and M16), and 2 (M5 and M10) metabolites from urine, plasma, and feces, respectively. Their structures were configured by integrating MS1, MS2, and OCE information. Except M10, all metabolites were new compounds. LC-MS/MS-guided chromatographic purification yielded three glucuronyl-conjugated metabolites (M5, M8, and M11), and NMR spectroscopic assays consolidated the structures transmitted from LC-3D MS. Demethylation, glucuronidation, and sulfation occurred as the primary metabolic pathways of DHMMF. Above all, LC-3D MS bridged LC-MS/MS from putatively structural annotation toward confidence-enhanced identification, beyond the metabolite characterization of flavonoids.

Analysis of situation of acute coronary syndrome based on the date of the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project: single-centre observational study.

BACKGROUND: We are currently faced with an increasing burden of cardiovascular disease in China and the inadequacy of the application of guidelines in clinical practice. In the past decade, China has been strengthening the healthcare system, but it still lacked a national performance measurement system and an appropriate quality improvement strategy. Therefore, in order to improve the implementation of guideline recommendations in clinical practice, China has learnt from the successful experience of Get With The Guidelines project in 2014. Under the guidance of the Medical and Health Hospital of the National Health and Family Planning Commission, the Chinese Society of Cardiology and the American Heart Association jointly launched the Improving Care for Cardiovascular Disease in China (CCC) project. The project team provided an analysis report on the completion of key medical quality evaluation indicators of each hospital every month, supplied guidance through education, training, experience exchange and on-site investigation for problems, and certified hospitals with outstanding performance and obvious progress. The circle pattern, including evaluation, training, improvement and re-evaluation, will boost the guidelines compliance on clinical practice in China and improve the quality of medical services. METHODS: This study was conducted in a centre of the Third Xiangya Hospital of Central South University. It included patients with ACS from December 2009 to December 2011 (n=225), patients with ACS in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project coming from the Third Xiangya Hospital of Central South University (n=665), 12 hospitals in Hunan Province (n=4333) and 150 hospitals in China (n=63 641) from November 2014 to April 2017. It assessed the situation of drug therapy, hospitalisation day, mortality during hospitalisation, median of door-to-needle (D-to-N) time and median of door-to-balloon (D-to-B) time of patients with ST-segment elevation myocardial infarction (STEMI), the proportion of D-to-N within 30 min and D-to-B within 90 min, and the proportion of reperfusion therapy. Patients with ACS from the centre from November 2014 to April 2017 were divided into five groups (every 6 months as a group according to time). The study observed change trends in all the above-mentioned indexes. RESULTS: Compared with before participating in the CCC project, there were increases after participating in the CCC project in the drug usage rates of aspirin, P2Y12 inhibitor (clopidogrel or ticagrelor), ß-blocker, statin and angiotensin converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB). Hospitalisation day and mortality during hospitalisation were shortened. D-to-N and D-to-B times of patients with STEMI were shorter. Compared with Hunan Province and China, the drug usage rates were higher; hospitalisation day and D-to-N time were shorter; D-to-B time was longer; and the proportion of reperfusion therapy was higher. The trend of drug usage rates was on the rise. There was no significant change in the hospitalisation day and D-to-N and D-to-B times. The mortality during hospitalisation showed a downward trend. The proportion of D-to-N within 90 min and reperfusion therapy showed upward trends. CONCLUSION: Quality of care for patients with ACS improved over time in the CCC project, including taking medicine following the guidelines, increased use of reperfusion therapy and faster time to treatment. Although overall mortality has improved, we also should attach importance to high-risk patients. The influence of the CCC project, which is based on guidelines on prognosis of ACS in the centre, presents an important clinical implication that it is necessary to enhance adherence to the guidelines in the treatment of ACS.

Sex differences in antihypertensive drug use and blood pressure control.

BACKGROUND: Hypertension is the most important modifiable cardiovascular risk factor. Epidemiological studies have shown the benefits of lowering blood pressure (BP), but BP control is a major challenge. Furthermore, there are significant sex differences in antihypertensive drug use and BP control. This study examined sex differences in antihypertensive drug use and BP control, with the aim of reducing the complications of hypertension and improving quality of life. METHODS: The study was performed in our outpatient hypertension clinic, and included 1529 patients without secondary hypertension or comorbidities. The study, investigated BP control rates and patterns of antihypertensive drug use in male and female. All data were collected using structured questionnaires and patient measurements. RESULTS: The study included 713 males and 816 females in this study. Fewer females had hypertension in the younger age group (16.2% vs 11.6%; p>0.05), but this difference disappeared in middle-aged (47.8% vs 49.9 %; p<0.05) and elderly age groups (36.0% vs 38.5%; p<0.05). BP control rates differed between males and females (35.6% in male, 31.9% in female, p<0.01). There was an overall difference in BP control rates between males and females (35.6% in males, 31.9% in females, p<0.01). In this aged 18-44 years, angiotensin converting enzyme inhibitors (ACEIs) showed the best control rate in males, while calcium channel blockers (CCBs) were least effective (61.5% with ACEIs, 28.6% with CCBs; p<0.05). In this aged 45-64 years, diuretics (DUs) showed the best control rate in females, while CCBs were least effective (47.5% with DUs, 28.3% with CCBs; p<0.05). CONCLUSIONS: Sex plays an important role in BP control. In those aged 18-44 years, males using ACEIs showed best control rates. In those aged 45-64 years, females using DUs showed best control rates. Our study provides a basis with the selection of antihypertensive drugs according to sex and age.

Effects of YC-1 on hypoxia-inducible factor 1 alpha in hypoxic human bladder transitional carcinoma cell line T24 cells.

OBJECTIVES: It was the aim of this study to explore the effects of 3-(5'-hydroxymethyl-2'-furyl)-l-benzyl indazole (YC-1) on transcription activity, cell proliferation and apoptosis of hypoxic human bladder transitional carcinoma cells (BTCC), mediated by hypoxia-inducible factor 1α (HIF-1α). METHODS: BTCC cell line T24 cells were incubated under normoxic or hypoxic conditions, adding different doses of YC-1. The protein expression of HIF-1α and HIF-1α-mediated genes was detected by Western blotting. RT-PCR was used to detect HIF-1α mRNA expression. Cell proliferation, apoptosis and migration activity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and transwell migration assay. The cells were pretreated by two ERK/p38 MAPK pathway-specific inhibitors, PD98059 or SB203580, and then incubated with YC-1 treatment under hypoxic condition. HIF-1α protein expression was detected by Western blotting. RESULTS: Hypoxic T24 cells expressed a higher level of HIF-1α, vascular endothelial growth factor, matrix metalloproteinases-2, B-cell lymphoma/leukemia-2 protein and HIF-1α mRNA compared with normoxic controls, in which the above-mentioned expression was downregulated by YC-1 in a dose-dependent manner. Cell proliferation and migration activity were inhibited while apoptosis was induced by YC-1 under hypoxic condition. Moreover, YC-1-downregulated HIF-1α expression was reversed by PD98059 and SB203580, respectively. CONCLUSIONS: YC-1 inhibits HIF-1α and HIF-1α-mediated gene expression, cell proliferation and migration activity and induces apoptosis in hypoxic BTCC. The ERK/p38 MAPK pathway may be involved in YC-1-mediated inhibition of HIF-1α.