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Based on a real-world collaboration with innovators in applying early health economic modeling, we aimed to offer practical steps that health technology assessment (HTA) researchers and innovators can follow and promote the usage of early HTA among research and development (R&D) communities.
Methods
The HTA researcher was approached by the innovator to carry out an early HTA ahead of the first clinical trial of the technology, a soft robotic sock for poststroke patients. Early health economic modeling was selected to understand the potential value of the technology and to help uncover the information gap. Threshold analysis was used to identify the target product profiles. Value-of-information analysis was conducted to understand the uncertainties and the need for further research.
Results
Based on the expected price and clinical effectiveness by the innovator, the new technology was found to be cost-saving compared to the current practice. Risk reduction in deep vein thrombosis and ankle contracture, the incidence rate of ankle contracture, the compliance rate of the new technology, and utility scores were found to have high impacts on the value-for-money of the new technology. The value of information was low if the new technology can achieve the expected clinical effectiveness. A list of parameters was recommended for data collection in the impending clinical trial.
Conclusions
This work, based on a real-world collaboration, has illustrated that early health economic modeling can inform medical innovation development. We provided practical steps in order to achieve more efficient R&D investment in medical innovation moving forward.
In adults with Clostridioides difficile infection (CDI), higher stool concentrations of toxins A and B are associated with severe baseline disease, CDI-attributable severe outcomes, and recurrence. We evaluated whether toxin concentration predicts these presentations in children with CDI.
Methods:
We conducted a prospective cohort study of inpatients aged 2–17 years with CDI who received treatment. Patients were followed for 40 days after diagnosis for severe outcomes (intensive care unit admission, colectomy, or death, categorized as CDI primarily attributable, CDI contributed, or CDI not contributing) and recurrence. Baseline stool toxin A and B concentrations were measured using ultrasensitive single-molecule array assay, and 12 plasma cytokines were measured when blood was available.
Results:
We enrolled 187 pediatric patients (median age, 9.6 years). Patients with severe baseline disease by IDSA-SHEA criteria (n = 34) had nonsignificantly higher median stool toxin A+B concentration than those without severe disease (n = 122; 3,217.2 vs 473.3 pg/mL; P = .08). Median toxin A+B concentration was nonsignificantly higher in children with a primarily attributed severe outcome (n = 4) versus no severe outcome (n = 148; 19,472.6 vs 429.1 pg/mL; P = .301). Recurrence occurred in 17 (9.4%) of 180 patients. Baseline toxin A+B concentration was significantly higher in patients with versus without recurrence: 4,398.8 versus 280.8 pg/mL (P = .024). Plasma granulocyte colony-stimulating factor concentration was significantly higher in CDI patients versus non-CDI diarrhea controls: 165.5 versus 28.5 pg/mL (P < .001).
Conclusions:
Higher baseline stool toxin concentrations are present in children with CDI recurrence. Toxin quantification should be included in CDI treatment trials to evaluate its use in severity assessment and outcome prediction.
Swirling waves frequently occur in a three-dimensional tank under a nearly resonant excitation with oblique excitation angle. The oblique excitation produces two excitation components and the secondary component triggers rotational waves. The detailed mechanism of the switch in circular direction is clearly described in this study. The evolution of the hydrodynamic forces (Fz) on the tank walls presents a beating phenomenon and the switch direction always occurs at the peak and trough of the envelope of the Fz history. The external excitation moment changes the circulation intensity, and finally the swirling wave becomes a single-direction wave, but only for a short time. The profile of the single-direction wave was determined by the dominant sloshing mode and the instantaneous tank motion was found to be a key factor to determine the consequent swirling flow circulating direction.
The carbonate-hosted Pb–Zn deposits in the Sichuan–Yunnan–Guizhou (SYG) triangle region are important Indosinian deposits in South China. The Tianbaoshan deposit is a typical large Pb–Zn deposit in the SYG area and occurs as pipe-like type, hosted by Sinian dolostone. It contains ∼26 Mt Zn–Pb ore (7.76–10.09 % Zn, 1.28–1.50 % Pb and 93.6 g t−1 Ag) and >0.1 Mt Cu ore (2.55 % Cu). In this study, the detailed mineral textures, mineral chemical and sulphur isotopic compositions of the various sulphides have been analysed to constrain the abnormal enrichment mechanism and mineralization relationship. Four mineralization stages have been recognized: Stage 1, minor early pyrite (Py1) with relics and infill of intergranular dolomite or quartz grains; Stage 2, Cu mineralization with coarse-grained, elliptical crystal chalcopyrite (Cp1); (3) Stage 3, Zn mineralization with dark fine-grained sphalerite (Sph1) and light coarse-grained sphalerite (Sph2); and (4) Stage 4, as represented by a quartz–calcite assemblage with galena, minor pyrite (Py2) and chalcopyrite (Cp2). The petrography of the sulphide minerals (Py1, Cp1, Sph1 and Sph2) demonstrates a mutual inclusion relationship. The nature of this relationship from core to rim and their similar sulphur isotope values (5.5–8.3 ‰) indicates a single sulphur source, suggesting that the different mineralization types are the result of different stages of a continuous hydrothermal system. Sphalerite geothermometer study suggests that sphalerite in the Tianbaoshan deposit formed in a low-temperature (<200 °C) hydrothermal system. The low concentrations of Mn and In, low In/Ge ratios and high Fe/Cd ratios in the sphalerite are consistent with those of Mississippi Valley-type (MVT) deposits, but different from those of magmatism-related deposits (e.g. epithermal, skarn and VMS deposits). The positive δ34S values for Py1 (5.1–7.9 ‰), Cp1 (5.1–7.2 ‰), Sph1 (4.7–7.4 ‰), Sph2 (3.9–8.7 ‰), Py2 (4.4–9.3 ‰) and Cp2 (5.0–6.8 ‰) indicate a sulphur source from thermochemical reduction of coeval seawater sulphate. Widely developed dissolved textures (caverns and breccias) with massive sulphide infillings and deformed host rock remnants suggest that replacement of host dolostones by ore fluids was volumetrically significant and the ore formed nearly simultaneously with the cavities. The Tianbaoshan deposit is a typical MVT deposit, which resulted from mixing of a H2S-rich fluid and a metal-rich fluid, with thermochemical sulphate reduction occurring before ore precipitation rather than during ore precipitation.
Although maternal mental illnesses have been found to influence child health and development, little is known about the impact of maternal positive well-being on child health and development. Therefore, this longitudinal study investigated the effects of prenatal subjective well-being on birth outcomes and child development by considering the potential modifier effect of parity.
Methods
Pregnant women in early stages of pregnancy were recruited at five selected hospitals in Taipei, Taiwan, during their prenatal appointments since 2011. Self-reported evaluations were conducted at seven time points up to 2 years postpartum. Linear regression and generalized estimating equation models were used for examination.
Results
Higher prenatal eudaimonic well-being was associated with longer gestational length (adjusted beta [aβ] = 0.36, 95% confidence interval [CI] = 0.03, 0.68) and higher birth weight (aβ = 124.71, 95% CI = 35.75, 213.66). Higher positive and negative affect were associated with longer gestational length (aβ = 0.38, 95% CI = 0.06, 0.70) and smaller birth weight (aβ = −93.51, 95% CI = −178.35, −8.67), respectively. For child’s outcomes, we found an association between higher prenatal eudaimonic well-being and decreased risks of suspected developmental delay, particularly for children of multiparous mothers (adjusted odds ratio = 0.18, 95% CI = 0.05, 0.70). Higher levels of prenatal depression and anxiety were significantly associated with increased risks of suspected developmental delay for children of primiparous mothers.
Conclusions
Positive prenatal maternal mental health may benefit birth outcomes and child development, particularly for children of multiparous mothers. Interventions for improving prenatal mental health may be beneficial for child development.
Caregiver-mediated intervention (CMI), based on parent skills training, is a family-mediated intervention model for children with neurodevelopmental disorders, in particular autism spectrum disorder. This study aimed to evaluate the effectiveness of CMI.
Methods:
Thirty-three children (aged 22–69 months from our department) and their caregivers participated in a two-week training course of ten 90-minute lessons. Caregivers were encouraged to try their best to apply intervention skills in both home routines and play routines to encourage the development of cognition, motion, social adaptability, and behavior of children. Demographic information, video-recorded data, and diagnostic scales were collected at two key time points: baseline and post-training (PT – within six months).
Results:
Three aspects were assessed – primary variables, secondary variables, and correlation analyses. Results showed an improvement in PT in (1) Adult/Child Interaction Fidelity Rating (P < 0.01) and (2) adaptability of Gesell Developmental Scale and stereotyped behaviors and limited interests of Autism Diagnostic Observation Schedule (P < 0.05, P < 0.01). Moreover, a negative correlation occurred between caregiver skill improvement and parent education (P < 0.05), but without correlations with other demographics.
Conclusions:
As an efficacious family intervention for both children and their caregivers, CMI is worth being generalized widely.
This study aimed to evaluate the efficacy and safety of high-frequency oscillation ventilation combined with intermittent mandatory ventilation in infants with acute respiratory distress syndrome after congenital heart surgery.
Methods:
We retrospectively analysed the clinical data of 32 infants who were ventilated due to acute respiratory distress syndrome after congenital heart surgery between January, 2020 and January, 2022. We adopted high-frequency oscillation ventilation combined with intermittent mandatory ventilation as the rescue ventilation mode for infants who were failing conventional mechanical ventilation.
Results:
After rescue high-frequency oscillation ventilation combined with intermittent mandatory ventilation, the dynamic compliance (Cdyn), PaO2 and PaO2/FiO2 ratio of the infants improved compared with conventional mechanical ventilation (p < 0.05). Moreover, high-frequency oscillation ventilation combined with intermittent mandatory ventilation resulted in a significant decrease in arterial-alveolar oxygen difference (AaDO2), FiO2, and oxygenation index (p < 0.05). No significant effect on haemodynamic parameters was observed. Moreover, no serious complications occurred in the two groups.
Conclusion:
Rescue high-frequency oscillation ventilation combined with intermittent mandatory ventilation significantly improved oxygenation in infants who failed conventional mechanical ventilation for acute respiratory distress syndrome after congenital heart surgery. Thus, this strategy is considered safe and feasible. However, further studies must be conducted to confirm the efficacy and safety of high-frequency oscillation ventilation combined with intermittent mandatory ventilation as a rescue perioperative respiratory support strategy for CHD.
The COVID-19 caused a world pandemic, posing a huge threat to global health. Widespread vaccination is the most effective way to control the pandemic. Vaccination with the third dose of the COVID-19 vaccine is currently underway. We aimed to determine the attitude of adolescents toward the third dose of COVID-19 vaccine.
Methods:
A structured questionnaire was administered between 16 August and 28 October 2021 among adolescents aged 12–17 years in three provinces of eastern region of China based on convenience sampling. The questionnaire was specifically developed to assess the adolescents’ attitude toward and willingness to accept a third dose of the COVID-19 vaccine.
Results:
In total, 94.3% (1742/1847) of the adolescents intended to accept the third dose of the COVID-19 vaccine. Age between 15–17 years, no worry about vaccine safety, confidence for vaccine effectiveness, and supporting opinion from parents were independently associated with acceptance of the third dose (p < 0.05).
Conclusions:
It is necessary for governments and school administrators to raise adolescents’ and parents’ awareness of the benefits and safety of the third dose of vaccination, which should be effective to increase the vaccination coverage among adolescents.
Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe and life-threatening complication, characterised by multi-organ failure and high short-term mortality. However, there is limited information on the impact of various comorbidities on HBV-ACLF in a large population. This study aimed to investigate the relationship between comorbidities, complications and mortality. In this retrospective observational study, we identified 2166 cases of HBV-ACLF hospitalised from January 2010 to March 2018. Demographic data from the patients, medical history, treatment, laboratory indices, comorbidities and complications were collected. The mortality rate in our study group was 47.37%. Type 2 diabetes mellitus was the most common comorbidity, followed by alcoholic liver disease. Spontaneous bacterial peritonitis, pneumonia and hepatic encephalopathy (HE) were common in these patients. Diabetes mellitus and hyperthyroidism are risk factors for death within 90 days, together with gastrointestinal bleeding and HE at admission, HE and hepatorenal syndrome during hospitalisation. Knowledge of risk factors can help identify HBV-ACLF patients with a poor prognosis for HBV-ACLF with comorbidities and complications.
Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.
Under global warming, many glaciers worldwide are receding. However, recent studies have suggested the extension of the Karakoram Anomaly, a region of anomalous glacier mass gain, into the western Kunlun and eastern Pamir mountains. However, the eastern limit of this anomaly in the Kunlun Mountains is unclear. This study, using changes in glacier area and surface elevation, estimates the eastern limit of the Kunlun-Pamir-Karakoram anomaly at ~85°E. Over the past 50 years, glaciers west of 85°E in the Kunlun Mountains decreased in area from 8401 to 7945 km2 at a rate of −0.12 ± 0.07% a−1, showed a reduction in the rate of retreat through time and have recently gained mass, with surface elevation changes of 0.15 ± 0.35 m a−1 over the period of 2000–2013. Glaciers east of 85°E have experienced greater rates of area change (−61 ± 12 km2 and −0.43 ± 0.13% a−1) over the past 50 years, accelerated area loss in recent years and elevation change rate of −0.51 ± 0.18 m a−1 between 2000 and 2013. These patterns of elevation and area change are consistent with regional increases in summer temperature in the eastern Kunlun Mountains and slight cooling in the western Kunlun Mountains.
This study evaluated the association between inflammatory diets as measured by the Dietary Inflammatory index (DII), inflammation biomarkers and the development of preeclampsia among the Chinese population. We followed the reporting guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology statement for observational studies. A total of 466 preeclampsia cases aged over 18 years were recruited between March 2016 and June 2019, and 466 healthy controls were 1:1 ratio matched by age (±3 years), week of gestation (±1 week) and gestational diabetes mellitus. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a seventy-nine item semiquantitative FFQ. Inflammatory biomarkers were analysed by ELISA kits. The mean E-DII scores were −0·65 ± 1·58 for cases and −1·19 ± 1·47 for controls (P value < 0·001). E-DII scores positively correlated with interferon-γ (rs = 0·194, P value = 0·001) and IL-4 (rs = 0·135, P value = 0·021). After multivariable adjustment, E-DII scores were positively related to preeclampsia risk (Ptrend < 0·001). The highest tertile of E-DII was 2·18 times the lowest tertiles (95 % CI = 1·52, 3·13). The odds of preeclampsia increased by 30 % (95 % CI = 18 %, 43 %, P value < 0·001) for each E-DII score increase. The preeclampsia risk was positively associated with IL-2 (OR = 1·07, 95 % CI = 1·03, 1·11), IL-4 (OR = 1·26, 95 % CI = 1·03, 1·54) and transforming growth factor beta (TGF-β) (OR = 1·17, 95 % CI = 1·06, 1·29). Therefore, proinflammatory diets, corresponding to higher IL-2, IL-4 and TGF-β levels, were associated with increased preeclampsia risk.
The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60–69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.
It is important to know how much of the increased atmospheric CO2 is derived from fossil fuel emissions. Here, we review the progress in atmospheric fossil fuel CO2 (CO2ff) tracing over recent years by measurement of Δ14C in Chinese cities. In this paper we make progress by expanding the analysis from some locations to more regional views, by combining observations with modeling, and by making a preliminary comparison of observation-derived CO2ff with inventory-derived CO2ff. We have obtained a general picture of Chinese urban CO2ff and characteristics of its spatio-temporal variations at different scale, and identified the corresponding influencing factors. Interestingly, we found that the weekend effect of CO2ff was less evident in Chinese cities. In addition, we observed simultaneous variations in CO2ff and PM2.5 in a winter haze event in Beijing and a simultaneous decrease in annual averages of CO2ff and PM2.5 in Xi’an based on multi-year (2011–2016) Δ14CO2 monitoring. We found that local coal combustion was the main source of CO2ff in Xi’an, which is located in the Guanzhong basin, by applying a WRF-Chem model and looking at δ13C signatures. Thus, reduction of coal consumption is a crucial target for carbon emissions reduction in China.
Recently, the nature of viscoelastic drag-reducing turbulence (DRT), especially the maximum drag reduction (MDR) state, has become a focus of controversy. It has long been regarded as polymer-modulated inertial turbulence (IT), but is challenged by the newly proposed concept of elasto-inertial turbulence (EIT). This study is to repicture DRT in parallel plane channels by introducing dynamics of EIT through statistical, structural and budget analysis for a series of flow regimes from the onset of drag reduction to EIT. Some underlying mechanistic links between DRT and EIT are revealed. Energy conversion between velocity fluctuations and polymers as well as pressure redistribution effects are of particular concern, based on which a new energy self-sustaining process (SSP) of DRT is repictured. The numerical results indicate that at low Reynolds number ($Re$), weak IT flow is replaced by a laminar regime before the barrier of EIT dynamics is established with the increase of elasticity, whereas, at moderate $Re$, EIT-related SSP can get involved and survive from being relaminarized. This further explains the reason why relaminarization phenomenon is observed for low $Re$ while the flow directly enters MDR and EIT at moderate $Re$. Moreover, with the proposed energy picture, the newly discovered phenomenon that streamwise velocity fluctuations lag behind those in the wall-normal direction can be well explained. The repictured SSP certainly justifies the conjecture that IT nature is gradually replaced by that of EIT in DRT with the increase of elasticity.
Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
Aims
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
Method
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
Results
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
Conclusions
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
This study explored the effects of condition notification based on virtual reality technology on the anxiety levels of parents of children with simple CHD.
Methods:
The subjects of the study were the parents of 60 children with simple CHD who were treated in our centre. The state anxiety scale was used to assess the anxiety status of the parents of the children before and after the condition notification in different ways (based on virtual reality explanations and written explanations).
Results:
In this study, a total of 55 parents of children with CHD successfully completed the survey. At the time of admission, there was no significant difference in the state anxiety scale scores of the parents between the two groups. The anxiety status of the virtual reality group was relieved after the condition notification assisted by virtual reality technology, and there was a significant difference compared with the control group.
Conclusion:
Condition notification based on virtual reality technology can effectively alleviate the anxiety of parents of children with simple CHD, which is worthy of clinical application.
In the presence of frictions, the existing literature shows that currency substitution is detrimental for domestic aggregate stability. This paper singles out the role of currency substitution and shows that diversified currency holdings operate as an automatic stabilizer that mitigates belief-driven cyclical fluctuations in Farmer’s (1997) indeterminate monetary economy. When the foreign inflation rate is lower than the domestic inflation rate, the model’s steady state always displays saddle-path stability. Hence, equilibrium indeterminacy originally present in the domestic country is entirely removed in the presence of diversified currency holdings. When the foreign inflation rate is higher than the domestic inflation rate, then depending on the degrees of currency substitution and relative risk aversion, indeterminacy is either impossible or the requisite level of the foreign inflation rate for indeterminacy is too high to square with data. The stabilizing effect of diversified currency holdings on domestic aggregate stability is robust to whether domestic and foreign currencies display as Edgeworth substitutes or complements, or are additively separable in the household’s preferences.