ObjectiveTo compare and contrast the perceived care needs of children with life-limiting conditions (CLLC) from the perspectives of the children, parents and healthcare providers.DesignA qualitative ...case study method using semistructured interviews was employed with a within-case and across-case analysis. Themes and subthemes emerging from the cases were compared and contrasted in the across-case analysis to explore the similarities and variations in participant perceptions.Setting/participantsThe setting was the paediatric departments of five regional hospitals in Hong Kong. Twenty-five sets of informants (CLLC–parent–healthcare provider) were recruited, with 65 individual interviews conducted.ResultsA total of 3784 units of analysis were identified, resulting in three themes with subthemes. ‘Living with the disease’ (55.8%) occupied the largest proportion, followed by ‘information and understanding about the disease’ (27.4%), and ‘care support and palliative care’ (16.8%). Healthcare provider support mainly focused on physical concerns. Family and social support were present, but carer stress created tension between couples. Doctors were the primary source of medical information, but the parents had to seek further information via the internet and support from patient groups. There was a perceived need for better coordination and collaboration of care. The palliative care approach coordinated by nurses was seen as helpful in addressing the care needs of the CLLC.ConclusionsThis original study identified the importance of palliative care with active engagement of parents which can address the service gap for CLLC.
As a prototype of genomics-guided precision medicine, individualized thiopurine dosing based on pharmacogenetics is a highly effective way to mitigate hematopoietic toxicity of this class of drugs. ...Recently, NUDT15 deficiency was identified as a genetic cause of thiopurine toxicity, and NUDT15-informed preemptive dose reduction was quickly adopted in clinical settings. To exhaustively identify pharmacogenetic variants in this gene, we developed massively parallel NUDT15 function assays to determine the variants’ effect on protein abundance and thiopurine cytotoxicity. Of the 3,097 possible missense variants, we characterized the abundance of 2,922 variants and found 54 hotspot residues atwhich variants resulted in complete loss of protein stability. Analyzing 2,935 variants in the thiopurine cytotoxicity-based assay, we identified 17 additional residues where variants altered NUDT15 activity without affecting protein stability. We identified structural elements key to NUDT15 stability and/or catalytical activity with single amino acid resolution. Functional effects for NUDT15 variants accurately predicted toxicity risk alleles in patients treated with thiopurines with far superior sensitivity and specificity compared to bioinformatic prediction algorithms. In conclusion, our massively parallel variant function assays identified 1,152 deleterious NUDT15 variants, providing a comprehensive reference of variant function and vastly improving the ability to implement pharmacogenetics-guided thiopurine treatment individualization.
•Inequality in urban greenspace exposure is assessed for 303 cities in China.•Dynamic inequality is characterized using multi-source geospatial data.•Severe inequality in greenspace exposure is ...pervasive in Chinese cities.•Dry cold climate and urban densification contribute to high inequality.
Given the important role of green environments playing in healthy cities, the inequality in urban greenspace exposure has aroused growing attentions. However, few comparative studies are available to quantify this phenomenon for cities with different population sizes across a country, especially for those in the developing world. Besides, commonly used inequality measures are always hindered by the conceptual simplification without accounting for human mobility in greenspace exposure assessments. To fill this knowledge gap, we leverage multi-source geospatial big data and a modified assessment framework to evaluate the inequality in urban greenspace exposure for 303 cities in China. Our findings reveal that the majority of Chinese cities are facing high inequality in greenspace exposure, with 207 cities having a Gini index larger than 0.6. Driven by the spatiotemporal variability of human distribution, the magnitude of inequality varies over different times of the day. We also find that exposure inequality is correlated with low greenspace provision with a statistical significance (p-value < 0.05). The inadequate provision may result from various factors, such as dry cold climate and urbanization patterns. Our study provides evidence and insights for central and local governments in China to implement more effective and sustainable greening programs adjusted to different local circumstances and incorporate the public participatory engagement to achieve a real balance between greenspace supply and demand for developing healthy cities.
Acute pancreatitis is a rare presentation in Burkitt lymphoma (BL) and may lead to delayed medical or unnecessary surgical treatment. Three cases of BL presenting as acute pancreatitis in the ...authors' institutions were described. Similar cases reported in the medical literature were collected and described along with the authors' cases. There were 12 cases described in the medical literature and hence a total of 15 cases of BL presenting as acute pancreatitis. Fourteen cases were the first diagnosis, and the other presented at lymphoma relapse. Twelve cases occurred in children under 15 years. Twelve patients had extrapancreatic disease. Three children were treated with surgery before diagnosis. Two patients died. Six of the remaining had adequate follow-up and were surviving in remission 8 months to 16 years after diagnosis. Lymphoma should be included in the differential diagnosis of acute pancreatitis in children. Acute pancreatitis in combination with malignant infiltration on imaging is highly suggestive of BL, especially in the jaundiced child.
To assess the health risk of PM2.5, it is necessary to accurately estimate the actual exposure level of the population to PM2.5. However, the spatial distribution of PM2.5 may be inconsistent with ...that of the population, making it necessary for a high-spatial-resolution and refined assessment of the population exposure to air pollution. This study takes the Yangtze River Delta (YRD) Region as an example since it has a high-density population and a high pollution level. The brightness reflectance of night-time light, and MODIS-based (Moderate Resolution Imaging Spectroradiometer) vegetation index, elevation, and slope information are used as independent variables to construct a random-forest (RF) model for the estimation of the population spatial distribution, before any combination with the PM2.5 data retrieved from MODIS. This enables assessment of the population exposure to PM2.5 (i.e., intensity of population exposure to PM2.5 and population-weighted PM2.5 concentration) at a 3-km resolution, using the year 2013 as an example. Results show that the variance explained for the RF-model-estimated population density reaches over 80%, while the estimated errors in half of counties are < 20%, indicating the high accuracy of the estimated population. The spatial distribution of population exposure to PM2.5 exhibits an obvious urban–suburban–rural difference consistent with the population distribution but inconsistent with the PM2.5 concentration. High and low PM2.5 concentrations are mainly distributed in the northern and southern YRD Region, respectively, with the mean proportions of the population exposed to PM2.5 concentrations > 35μg/m3 close to 100% in all four seasons. A high-level population exposure to PM2.5 is mainly found in Shanghai, most of the Jiangsu Province, the central Anhui Province, and some coastal cities of the Zhejiang Province. The highest risk of population exposure to PM2.5 occurs in winter, followed by spring and autumn, and the lowest in summer, consistent with the PM2.5 seasonal variation. Seasonal-averaged population-weighted PM2.5 concentrations are different from PM2.5 concentrations in the region, which are closely related to the urban-exposed population density and pollution levels. This work provides a novel assessment of the proposed population-density exposure to PM2.5 by using multi-satellite retrievals to determine the high-spatial-resolution risk of air pollution and detailed regional differences in the population exposure to PM2.5.
BACKGROUND—Magnetic resonance imaging (MRI) in the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial revealed that cardiosphere-derived cells (CDCs) ...decrease scar size and increase viable myocardium after myocardial infarction (MI), but MRI has not been validated as an index of regeneration after cell therapy. We tested the validity of contrast-enhanced MRI in quantifying scarred and viable myocardium after cell therapy in a porcine model of convalescent MI.
METHODS AND RESULTS—Yucatan minipigs underwent induction of MI and 2–3 weeks later were randomized to receive intracoronary infusion of 12.5×10 mismatched allogeneic CDCs or vehicle. Allogeneic CDCs induced mild local mononuclear infiltration but no systemic immunogenicity. MRI revealed that allogeneic CDCs attenuated remodeling, improved global and regional function, decreased scar size, and increased viable myocardium compared with placebo 2 months post-treatment. Extensive histological analysis validated quantitatively the MRI measurements of scar size, scar mass, and viable mass. CDCs neither altered gadolinium contrast myocardial kinetics nor induced changes in vascular density or architecture in viable and scarred myocardium. Histology demonstrated that CDCs lead to cardiomyocyte hyperplasia in the border zone, consistent with the observed stimulation of endogenous regenerative mechanisms (cardiomyocyte cycling, upregulation of endogenous progenitors, angiogenesis).
CONCLUSIONS—Contrast-enhanced MRI accurately measures scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. MRI represents a useful tool for assessing dynamic changes in the infarct and monitoring regenerative efficacy.
Gestational diabetes mellitus (GDM) is of public health concern. This trial examined whether a clinically proven lifestyle modification program (LMP) in early pregnancy was superior to routine ...antenatal care in improving GDM, maternal and infant outcomes. Chinese pregnant women at risk of GDM (n = 220) were recruited at or before 12-week gestation and randomized to either a LMP group or a routine care control group. Eighty subjects completed a dietitian-led LMP including dietary and exercise components from early pregnancy till 24-week gestation. Data were compared with those of 86 control subjects. Twenty three (26.7%) control subjects and 20 (25.0%) LMP subjects developed GDM (p = 0.798). The proportion of infants born large for gestational age and macrosomia was similar between groups. The LMP group showed a lower proportion of excessive gestational weight gain (GWG). Subgroup analysis suggested that those with higher LMP adherence showed more desirable dietary composition and energy intake, and lower proportion of excessive GWG compared with the low LMP adherence group and the control group. The potential effect of LMP on GDM and other maternal and infant outcomes, in particular GWG, as well as barriers for making lifestyle changes warrant further investigations (ClinicalTrials.gov NCT02368600).
Rapid development and urbanization can increase ambient exposure to NO_2 and its health risks in individuals. However, the association between NO_2 exposure and outpatient visits of patients with ...psoriasis has rarely been reported, though psoriasis is a major skin disease in rapidly urbanizing areas with high population densities. This study applied a time-stratified case-crossover design to investigate the effect of short-term exposure to ambient NO_2 on outpatient visits for psoriasis from 2014 to 2020 in Guangzhou, China (n = 62,305). A subgroup analysis was performed to evaluate NO_2 impacts on vulnerable subpopulations. Our results showed that the NO_2 concentration during the study period was lower than that of the level II threshold from China (PRC) but higher than that set by the WHO, indicating moderate air quality. However, a 10-μg m^(-3) increase in NO_2 concentration could still be associated with 3.1% higher outpatient visits for psoriasis (adjusted RR of lag 0 day:1.031 CI: 1.025, 1.037). NO_2 exposure can also pose long-term risks. Additionally, NO_2 impacts on psoriasis may be independent of other pollutants. Adjusting for PM_(2.5), SO_2, O_3, and meteorological factors, a 10-μg m^(-3) increase in NO_2 was associated with RRs of 1.043 CI: 1.033, 1.053, 1.022 CI: 1.014, 1.031, and 1.022 CI: 1.014, 1.031 at lag 0, lag 1, and lag 2 days, respectively. NO_2 risks were higher among older individuals (age ≥ 60 years) and those with medical insurance adjusted RRs: 1.045 (CI: 1.023, 1.066) and 1.047 (CI: 1.036, 1.058). Being a major pollutant in rapidly urbanizing areas with high population densities, NO_2 emission could be a crucial factor in psoriasis, although the daily pollution level was not above the air quality thresholds. Challenges associated with air quality control and health disparity create a necessity for the enhancement of health and environmental policies to reduce local and regional emissions (e.g., traffic-related pollution), and vulnerable subpopulations should be targeted.
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•January 2016 East Asia cold wave influenced the mortality for up to five weeks.•Unmarried and economically inactive were most vulnerable during the 2016 cold wave.•Respiratory ...diseases were the greatest medical problems.•Age/gender effects and cardiovascular diseases did not enhance fatal effect.•The excessive mortality was citywide, and not limited to particular locations.
Despite the fact that cold weather has been widely documented as a major factor that can elevate the mortality in a subtropical population due to a lack of adaptability, the disastrous impacts from a major cold event in East Asia caused by a super El Niño event in January 2016 have passed largely unreported. In order to minimize the catastrophic risk from such events given ongoing concerns about climate change, as also noted in the Sendai Framework for Disaster Risk Reduction 2015–2030 (SFDRR), it is important to evaluate the individual- and community-level shifts in mortality patterns during such cold waves, in order to develop health protocols for surveillance and disaster planning.
This study evaluated the impacts of the 2016 cold wave on mortality patterns in Hong Kong because this city has been highlighted as a city with severe negative impacts from the disaster by social media. Based on a sensitivity analysis, we found significantly higher daily mortality for up to ten weeks during this cold wave compared to the same calendar days between 2007 and 2015. We also found that the short-term impact of the cold wave was prolonged and fatal, with the potential to increase the mortality across the city for up to five weeks compared to the pre-disaster period. An examination of the individual- and community-level shifts in mortality patterns reveals that the unmarried and economically inactive were most vulnerable during the 2016 cold wave, and respiratory diseases were the greatest medical problems, while age and gender effects as well as cardiovascular diseases did not enhance the fatal effect. The excessive mortality was citywide, and not limited to particular locations or specific characteristics of a community within the city. Based on the results, disaster education as well as social and health services should be provided to all local people for an extended period in order to minimize the fatal and prolonged effects of future cold waves.
Background
Few studies have evaluated the impact of subclinical microstructural changes and psychosocial factors on cognitive function in patients with haemophilia.
Objectives
To determine the ...prevalence and characteristics of cognitive impairment in patients with haemophilia, and identify associated risk factors.
Methods
We recruited haemophilia A or B patients who were aged ≥10 years old from three public hospitals in Hong Kong. A neurocognitive battery was administered to evaluate their attention, memory, processing speed and cognitive flexibility performances. They also underwent magnetic resonance imaging to identify cerebral microbleeds. Validated self‐reported questionnaires were administered to assess their mental health status and adherence to prophylactic treatment. General linear modelling was used to investigate the association of neurocognitive outcomes with risks factors, adjusting for age and education attainment.
Results
Forty‐two patients were recruited (median age 32.0 years; 78.6% haemophilia A; 80.9% moderate‐to‐severe disease). Six patients (14.3%) had developed cerebral microbleeds. A subgroup of patients demonstrated impairments in cognitive flexibility (30.9%) and motor processing speed (26.2%). Hemarthrosis in the previous year was associated with worse attention (Estimate = 7.62, 95% CI: 1.92–15.33; p = .049) and cognitive flexibility (Estimate = 8.64, 95% CI: 2.52–13.29; p = .043). Depressive (Estimate = 0.22, 95% CI: 0.10–0.55; p = .023) and anxiety (Estimate = 0.26, 95% CI: 0.19–0.41; p = .0069) symptoms were associated with inattentiveness. Among patients receiving prophylactic treatment (71.4%), medication adherence was positively correlated with cognitive flexibility (p = .037).
Conclusion
A substantial proportion of patients with haemophilia demonstrated cognitive impairment, particularly higher‐order thinking skills. Screening for cognitive deficits should be incorporated into routine care. Future studies should evaluate the association of neurocognitive outcomes with occupational/vocational outcomes.
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