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Pemetrexed and immunotherapies (e.g., pembrolizumab) are approved for first-line maintenance (1LM) treatment of nonsquamous advanced/metastatic non-small-cell lung cancer (NSCLC), but real-world data on their use are limited. The objective of this study was to assess 1LM clinical outcomes, safety, and treatment patterns of immunotherapy versus immunotherapy+pemetrexed among patients with advanced/metastatic NSCLC from the EU4 (France, Germany, Italy, Spain)+UK.
Methods
Data from patients in the US, Canada, and EU4+UK with nonsquamous advanced/metastatic NSCLC without targetable mutations were collected via electronic case report form. Physician-identified patients (≥18 y) in the EU4+UK were eligible for this subgroup analysis if they achieved stable disease or complete or partial response with first-line platinum-based chemotherapy+immunotherapy (January 2019 to March 2021) and received 1LM immunotherapy or immunotherapy+pemetrexed. Patients were followed from index (1LM initiation) until last physician contact or death. Outcomes were overall survival (OS), progression-free survival (PFS), treatment patterns and duration, and adverse events.
Results
Among the selected 367 patients (male, 71.9%; mean±StDev age, 63.4±7.2 y; current/former smokers, 85.8%), 203 (55.3%) received immunotherapies, most commonly pembrolizumab (n=173; 85.2%), and 164 (44.7%) received immunotherapy+pemetrexed. Patients receiving immunotherapy had longer median adjusted OS and PFS compared to those receiving immunotherapy+pemetrexed (OS hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.36, 0.90; PFS HR: 0.58; 95% CI: 0.38, 0.79). Patients receiving immunotherapy versus patients receiving immunotherapy+pemetrexed had longer median treatment duration (14.0 vs 10.3 mo; p<0.001) and were less likely to experience anemia (19.7% vs 33.5%; p<0.01). Results were similar in the overall study population.
Conclusions
In this real-world study, among the selected patients with nonsquamous advanced/metastatic NSCLC who achieved stable disease or complete or partial response with first-line therapy, the addition of pemetrexed to immunotherapy in 1LM did not appear to confer a clinical benefit. Identifying treatments that can improve clinical outcomes for these patients remains an area of unmet need.
Item response theory (IRT) model applications extend well beyond cognitive ability testing, and various patient-reported outcomes (PRO) measures are among the more prominent examples. PRO (and like) constructs differ from cognitive ability constructs in many ways, and these differences have model fitting implications. With a few notable exceptions, however, most IRT applications to PRO constructs rely on traditional IRT models, such as the graded response model. We review some notable differences between cognitive and PRO constructs and how these differences can present challenges for traditional IRT model applications. We then apply two models (the traditional graded response model and an alternative log-logistic model) to depression measure data drawn from the Patient-Reported Outcomes Measurement Information System project. We do not claim that one model is “a better fit” or more “valid” than the other; rather, we show that the log-logistic model may be more consistent with the construct of depression as a unipolar phenomenon. Clearly, the graded response and log-logistic models can lead to different conclusions about the psychometrics of an instrument and the scaling of individual differences. We underscore, too, that, in general, explorations of which model may be more appropriate cannot be decided only by fit index comparisons; these decisions may require the integration of psychometrics with theory and research findings on the construct of interest.
Early life stress (ELS) and a Western diet (WD) promote mood and cardiovascular disorders, however, how these risks interact in disease pathogenesis is unclear. We assessed effects of ELS with or without a subsequent WD on behaviour, cardiometabolic risk factors, and cardiac function/ischaemic tolerance in male mice. Fifty-six new-born male C57BL/6J mice were randomly allocated to a control group (CON) undisturbed before weaning, or to maternal separation (3h/day) and early (postnatal day 17) weaning (MSEW). Mice consumed standard rodent chow (CON, n = 14; MSEW, n = 15) or WD chow (WD, n = 19; MSEW + WD, n = 19) from week 8 to 24. Fasted blood was sampled and open field test and elevated plus maze (EPM) tests undertaken at 7, 15, and 23 weeks of age, with hearts excised at 24 weeks for Langendorff perfusion (evaluating pre- and post-ischaemic function). MSEW alone transiently increased open field activity at 7 weeks; body weight and serum triglycerides at 4 and 7 weeks, respectively; and final blood glucose levels and insulin resistance at 23 weeks. WD increased insulin resistance and body weight gain, the latter potentiated by MSEW. MSEW + WD was anxiogenic, reducing EPM open arm activity vs. WD alone. Although MSEW had modest metabolic effects and did not influence cardiac function or ischaemic tolerance in lean mice, it exacerbated weight gain and anxiogenesis, and improved ischaemic tolerance in WD fed animals. MSEW-induced increases in body weight (obesity) in WD fed animals in the absence of changes in insulin resistance may have protected the hearts of these mice.
To accelerate high-intensity heavy-ion beams to high energy in the booster ring (BRing) at the High-Intensity Heavy-Ion Accelerator Facility (HIAF) project, we take the typical reference particle 238U35+, which can be accelerated from an injection energy of 17 MeV/u to the maximal extraction energy of 830 MeV/u, as an example to study the basic processes of longitudinal beam dynamics, including beam capture, acceleration, and bunch merging. The voltage amplitude, the synchronous phase, and the frequency program of the RF system during the operational cycle were given, and the beam properties such as bunch length, momentum spread, longitudinal beam emittance, and beam loss were derived, firstly. Then, the beam properties under different voltage amplitude and synchronous phase errors were also studied, and the results were compared with the cases without any errors. Next, the beam properties with the injection energy fluctuation were also studied. The tolerances of the RF errors and injection energy fluctuation were dictated based on the CISP simulations. Finally, the effect of space charge at the low injection energy with different beam intensities on longitudinal emittance and beam loss was evaluated.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
Cruznema velatum isolated from soil in a chestnut orchard located at Guangdong province, China, is redescribed with morphology, molecular barcoding sequences, and transcriptome data. The morphological comparison for C. velatum and six other valid species is provided. Phylogeny analysis suggests genus Cruznema is monophyletic. The species is amphimix, can be cultured with Escherichia coli in 7–9 days from egg to egg-laying adult, and has a lifespan of 11 to 14 days at 20°C. The transcription data generated 45,366 unigenes; 29.9%, 31.3%, 24.8%, and 18.6% of unigenes were annotated in KOG, SwissProt, GO, and KEGG, respectively. Further gene function analysis demonstrated that C. velatum share the same riboflavin, lipoic acid, and vitamin B6 metabolic pathways with Caenorhabditis elegans and Pristionchus pacificus.
Precision medicine envisages the integration of an individual’s clinical and biological features obtained from laboratory tests, imaging, high-throughput omics and health records, to drive a personalised approach to diagnosis and treatment with a higher chance of success. As only up to half of patients respond to medication prescribed following the current one-size-fits-all treatment strategy, the need for a more personalised approach is evident. One of the routes to transforming healthcare through precision medicine is pharmacogenomics (PGx). Around 95% of the population is estimated to carry one or more actionable pharmacogenetic variants and over 75% of adults over 50 years old are on a prescription with a known PGx association. Whilst there are compelling examples of pharmacogenomic implementation in clinical practice, the case for cardiovascular PGx is still evolving. In this review, we shall summarise the current status of PGx in cardiovascular diseases and look at the key enablers and barriers to PGx implementation in clinical practice.
This study aimed to evaluate the clinical significance of granulation tissue after endoscopic carbon dioxide laser surgery for glottic cancer.
Method
This was a retrospective review of 36 patients who underwent endoscopic carbon dioxide laser surgery for T1 and T2 glottic cancer. Post-operative, endoscopic examinations were rated by three blinded otolaryngologists for time to heal and presence of granulation. Patient and surgical factors were compared with time to heal and granulation.
Results
A total of 16 of 36 wounds (44 per cent) developed granulation tissue, and 24 wounds (67 per cent) healed without requiring surgical intervention. A total of 7 of 8 wounds biopsied more than 3.5 months after surgery had persistent cancer versus 1 of 4 wounds biopsied at equal to or less than 3.5 months (85.7 per cent vs 25 per cent; p = 0.03). Biopsy at more than 3.5 months was associated with 28-fold increased odds of cancer in biopsy compared with biopsy at equal to or less than 3.5 months (odds ratio, 28.0; 95 per cent confidence interval, 1.088–373.3).
Conclusion
After carbon dioxide laser surgery for glottic cancer, development of granulation tissue is common. Granulation that persists for more than 3.5 months necessitates biopsy because of increased risk of persistent cancer.
As the state has shifted its priorities towards social harmony and poverty alleviation, this study finds rhetorical resonance, combined with strong lineage solidarity, as an emerging strategy for villages to compete for government resources and investments. By articulating grassroots needs as being in line with local cadres’ performance goals, villages have successfully converted their needs into development proposals and mobilized lineage solidarity to persuade local cadres of the feasibility of such proposals. Drawing on three villages’ school-saving efforts in Fujian province, our fieldwork illustrates how one village retained its school by mobilizing lineage solidarity and converting education into a “model” village project to boost cultural tourism. Others failed to do so and lost their schools. Under the target-based cadre management system, the bottom-up competition for government support is largely shaped by the villages’ pre-existing development and resource structures, which may maximize management efficiency but may also reinforce socioeconomic inequalities between villages.
This manuscript details the strategy employed for categorising food items based on their processing levels into the four NOVA groups. Semi-quantitative food frequency questionnaires (FFQs) from the Nurses’ Health Studies (NHS) I and II, the Health Professionals Follow-up Study (HPFS) and the Growing Up Today Studies (GUTS) I and II cohorts were used. The four-stage approach included: (i) the creation of a complete food list from the FFQs; (ii) assignment of food items to a NOVA group by three researchers; (iii) checking for consensus in categorisation and shortlisting discordant food items; (iv) discussions with experts and use of additional resources (research dieticians, cohort-specific documents, online grocery store scans) to guide the final categorisation of the short-listed items. At stage 1, 205 and 315 food items were compiled from the NHS and HPFS, and the GUTS FFQs, respectively. Over 70 % of food items from all cohorts were assigned to a NOVA group after stage 2. The remainder were shortlisted for further discussion (stage 3). After two rounds of reviews at stage 4, 95⋅6 % of food items (NHS + HPFS) and 90⋅7 % items (GUTS) were categorised. The remaining products were assigned to a non-ultra-processed food group (primary categorisation) and flagged for sensitivity analyses at which point they would be categorised as ultra-processed. Of all items in the food lists, 36⋅1 % in the NHS and HPFS cohorts and 43⋅5 % in the GUTS cohorts were identified as ultra-processed. Future work is needed to validate this approach. Documentation and discussions of alternative approaches for categorisation are encouraged.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
We critically review potential involvement of trimethylamine N-oxide (TMAO) as a link between diet, the gut microbiota and CVD. Generated primarily from dietary choline and carnitine by gut bacteria and hepatic flavin-containing mono-oxygenase (FMO) activity, TMAO could promote cardiometabolic disease when chronically elevated. However, control of circulating TMAO is poorly understood, and diet, age, body mass, sex hormones, renal clearance, FMO3 expression and genetic background may explain as little as 25 % of TMAO variance. The basis of elevations with obesity, diabetes, atherosclerosis or CHD is similarly ill-defined, although gut microbiota profiles/remodelling appear critical. Elevated TMAO could promote CVD via inflammation, oxidative stress, scavenger receptor up-regulation, reverse cholesterol transport (RCT) inhibition, and cardiovascular dysfunction. However, concentrations influencing inflammation, scavenger receptors and RCT (≥100 µm) are only achieved in advanced heart failure or chronic kidney disease (CKD), and greatly exceed pathogenicity of <1–5 µm levels implied in some TMAO–CVD associations. There is also evidence that CVD risk is insensitive to TMAO variance beyond these levels in omnivores and vegetarians, and that major TMAO sources are cardioprotective. Assessing available evidence suggests that modest elevations in TMAO (≤10 µm) are a non-pathogenic consequence of diverse risk factors (ageing, obesity, dyslipidaemia, insulin resistance/diabetes, renal dysfunction), indirectly reflecting CVD risk without participating mechanistically. Nonetheless, TMAO may surpass a pathogenic threshold as a consequence of CVD/CKD, secondarily promoting disease progression. TMAO might thus reflect early CVD risk while providing a prognostic biomarker or secondary target in established disease, although mechanistic contributions to CVD await confirmation.
Schizophrenia is one of the most severe and chronic forms of mental illness. Quantum resonance spectrometer (QRS) test may be useful as a biological marker for the clinical diagnosis of psychiatric disorders of Schizophrenia.
Objectives
To evaluate reliability and psychiatric clinical value of QRS via thought disorder detection.
Methods
We studied 1014 schizophrenic patients, 155 patients with bipolar disorders patient, and 100 normal controls. Thought disorder symptoms of same subjects obtained from QRS test and psychiatrists' diagnoses were compared. Also Thought disorder symptoms of renumbered 65 schizophrenia patient and 100 normal controls were discriminated using QRS test.
Results
Kappa values of thought disorders detection and diagnosed were more than 65% in 6/9 symptoms of schizophrenia, and more than 74% in all 3 symptoms of bipolar disorder. Same consistency could also be seen in Pearson R value, and ROC AUC. In the discriminated analysis, sensitivity, specificity, positive predictive value and negative predictive of delusion, looseness of thought and paralogism thinking detected utilizing QRS are more than 70% same compared with psychiatrists diagnoses.
Conclusions
QRS in thought disorder detection seem to have a predictable value for outcome in schizophrenia and bipolar disorder, would become an objective identification and diagnosis instrument, and might promote psychiatric clinical diagnosis.
Many MRI studies have cited major depression, with or without anti-depressive treatment, associated with structural plasticity changing in several brain regions. Few of these studies researched the effect of the anti-depressive treatment, electroconvulsive therapy (ECT), on depression.
Objective
To assess the influence of ECT on the brain structure change during the treatment process by utilizing the voxel-based morphometry (VBM) analysis.
Aims
To determine whether ECT alter brain structure.
Methods
We performed HAMD ratings and MRI scans on 12 depressive patients during ECT, analyzing the data by VBM with SPM8 software's family-wise error correction (FWE).
Results
The researchers found volumes changes in white matter in 37 regions between pre-ECT and post-ECT1, but only one region changing between pre-ECT and post-ECT8. Seven regions changing in grey matter between pre-ECT and post-ECT 1⌧but none regions changing between pre-ECT and post-ECT8.
Conclusions
The density changes in several brain regions after a single ECT stimuli, but return to the original level after completing the eighth ECT. Our finding supports that ECT may play a temporary role in treating major depression but do not permanently alter the structures of brain.
Congenital and acquired heart diseases are highly prevalent in developing countries despite limited specialised care. Namibia established a paediatric cardiac service in 2009 with significant human resource and infrastructural constraints. Therefore, patients are referred for cardiac interventions to South Africa.
Objectives
To describe the diagnoses, clinical characteristics, interventions, post-operative morbidity and mortality, and follow-up of patients referred for care.
Methods
Demographics, diagnoses, interventions, intra- and post-operative morbidity and mortality, as well as longitudinal follow-up data of all patients referred to South Africa, were recorded and analysed.
Results
The total cohort constituted 193 patients of which 179 (93%) had CHD and 7% acquired heart disease. The majority of patients (78.8%) travelled more than 400 km to Windhoek before transfer. There were 28 percutaneous interventions. Palliative and definitive surgery was performed in 27 and 129 patients, respectively. Out of 156 patients, 80 (51.3%) had post-operative complications, of which 15 (9.6%) were a direct complication of surgery. Surgical mortality was 8/156 (5.1%, 95% confidence interval 2.2–9.8), with a 30-day mortality of 3.2%. Prolonged ICU stay was associated with a 5% increased risk of death with hazard ratio 1.05, 95% confidence interval 1.02–1.08, p=0.001. Follow-up was complete in 151 (78%) patients for more than 7 years.
Conclusions
Despite the challenges associated with a cardiac programme for referring patients seeking intervention in a neighbouring country and the adverse characteristics of multiple lesions and complexity associated with late presentation, we report good surgical and interventional outcomes. Our goal remains to develop a comprehensive sustainable cardiac service in Namibia.
Watching videotaped personal compulsions together with a therapist might enhance the effect of cognitive–behavioural therapy in obsessive–compulsive disorder (OCD) but little is known about how patients experience this.
Aims
To performed a qualitative study that describes how watching these videos influences motivation for treatment and whether patients report any adverse events.
Method
In this qualitative study, data were gathered in semi-structured interviews with 24 patients with OCD. The transcripts were coded by two researchers. They used a combination of open and thematic coding and discrepancies in coding were discussed.
Results
The experience of watching videos with personal compulsions helped patients to realise that these compulsions are aberrant and irrational. Patients report increased motivation to resist their OCD and to adhere to therapy. No adverse events were reported.
Conclusions
Videos with personal compulsions create more awareness in patients with OCD that compulsions are irrational, leading to enhanced motivation for treatment.
As part of a national initiative to reduce child obesity, a comprehensive school-based nutrition education intervention to change eating behaviours among grade 4 primary-school students was developed, implemented and evaluated.
Design
The intervention was developed by school staff, with technical assistance from outside health education specialists. The programme included school facility upgrades, school teacher/staff training, curriculum changes and activities for parents. Student scores on nine key eating behaviours were assessed prior to and after the programme. The quality of programme implementation in the schools was monitored by technical assistance teams.
Setting
Shandong Province (high household income) and Qinghai Province (low household income), China. Three programme schools and three control schools in each province.
Participants
Students in grade 4 (age 8–9 years).
Results
There were significant positive changes in self-reported eating behaviour scores from pre- to post-assessment in programme schools. At post-test students in programme schools had significantly higher scores than students in control schools after controlling for other variables. The programme was more effective in the high-income province. Observations by the technical assistance teams suggested the programme was implemented more completely in Shandong. The teams noted the challenges for implementing and evaluating programmes like these.
Conclusions
This intervention increased healthy eating behaviours among 4th graders in both provinces and had more effect in the more affluent province. Results suggest that a scaled-up initiative using existing school and public health resources could change eating practices in a large population over time. The intervention also provided lessons for implementing and evaluating similar nutrition programmes.
Superior and inferior rice grains have different weights and are located on the upper primary branch and lower secondary branches of the panicle, respectively. To study differences in germination vigour of these two types of grain, a number of factors were investigated from 0 to 48 h of germination. The present study demonstrated that in inferior grains the starch granule structure was looser at 0 h, with full water absorption at 48 h, while in superior grains the structure was tight and dense. Relative water content increased, and dry matter decreased, more rapidly in inferior grains than in superior ones. Abscisic acid and gibberellin levels, as well as α-amylase activity, also changed more rapidly in inferior grains, while soluble sugar content and amylase coding gene expression increased more rapidly in inferior than superior grains during early germination. The expression of OsGAMYB was higher in inferior grains at 24 h but higher in superior grains at 48 h. The phenotypic index of seedlings was higher in seedlings from superior grains at the two-leaf stage. However, the thousand-grain weight and yield per plant in superior and inferior plants showed no significant difference at harvest. The present study indicates that inferior grains germinate faster than superior ones in the early germination stage. Although inferior grains produced weaker seedlings, it is worthwhile using them in rice production due to their comparative yield potential over that of superior grains.
The probability of a Black African finding a matched unrelated donor for a hematopoietic stem cell transplant is minimal due to the high degree of genetic diversity amongst individuals of African origin. This problem could be resolved in part by the establishment of a public cord blood (CB) stem cell bank. The high prevalence of human immunodeficiency virus (HIV) amongst women attending antenatal clinics in sub-Saharan Africa together with the risk of mother-to-child transmission increases the risk of transplant transmissible infection. In addition to screening the mother in a period inclusive of 7 days prior to the following delivery, we propose that all CB units considered for storage undergo rigorous and reliable screening for HIV. The Ultrio-plus® assay is a highly specific and sensitive test for detecting HIV, hepatitis-B and hepatitis-C viruses in peripheral blood. We validated the Ultrio-plus® assay for analytical sensitivity in detecting HIV in CB at the level of detection of the assay. Until more comprehensive and sensitive methods are developed, the sensitivity and reliability of the Ultrio-plus® assay suggest that it could be used for the routine screening of CB units in conjunction with currently recommended maternal screening to reduce the risk of transplant transmissible infection.