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The growing use of real-world evidence (RWE) in pharmaceutical decision-making has prompted various guidelines, including REALISE (REAL World Data In ASia for HEalth Technology Assessment in Reimbursement). We compared RWE guidance from Asian, European, and North American health technology assessment (HTA) and regulatory bodies against the REALISE guidance.
Methods
Following a previous search for China/Japan guidelines in 2022, websites of the U.S. Food and Drug Administration (FDA), the National Institute for Health and Care Excellence (NICE), the European Medicines Agency (EMA), and the Canadian Agency for Drugs and Technologies in Health (CADTH) were searched for RWE guidance in May 2023. Sections from each guidance were mapped onto REALISE and categorized as “agree,” “mixed,” “disagree,” or “missing” based on coverage/consistency.
Results
Eleven guidelines were identified: four from Japan, three from China, and one each from FDA, NICE, EMA, and CADTH. No disagreements were found (all mapped sections were tagged “agree”/”mixed”); divergences were in coverage only. Most regulatory guidance had narrower scopes: EMA covered registry-based studies, the FDA’s framework mainly referenced other documents, while Japan had guidance for database and registry data. Conversely, HTA guidelines (CADTH, NICE) were more comprehensive and provided specific recommendations on preferred methods (e.g., transparent reporting) that were “missing” (45 to 46%) from REALISE’s more conceptual discussions. Chinese regulatory guidance was the exception, with similar coverage as REALISE (77% “agree”/“mixed”).
Conclusions
Guidelines varied in scope, but there was overall concordance where recommendations could be mapped across documents. While regulatory bodies could focus on specific types of RWE, reflecting the specific role of RWE in regulatory evaluations (for example demonstrating safety), guidance for HTA was broader to account for different possible use cases in demonstrating comparative effectiveness and value.
A recent study published in Oryx proposed that the extinct Javan tiger Panthera tigris sondaica may still survive on the Island of Java, Indonesia, based on mitochondrial DNA analysis of a single hair sample collected from a location where a tiger was reportedly encountered. However, upon reanalysing the genetic data presented in that study, we conclude that there is little support for this claim. The sequences of the putative tiger hair and Javan tiger museum specimens generated are not from tiger cytoplasmic mitochondrial DNA but more likely the nuclear pseudogene copies of mitochondrial DNA. In addition, the number of mismatches between the two Javan tiger sequences is unusually high for homologous sequences that are both from tigers, suggesting potential issues with data reliability. The paper provides insufficient details on quality control measures, making it impossible to rule out the possibility that errors were introduced during the analysis. Consequently, it is inappropriate to use the sequences presented in that study to infer the existence of the Javan tiger.
Scholarly and practitioner interest in authentic leadership has grown at an accelerating rate over the last decade, resulting in a proliferation of publications across diverse social science disciplines. Accompanying this interest has been criticism of authentic leadership theory and the methods used to explore it. We conducted a systematic review of 303 scholarly articles published from 2010 to 2023 to critically assess the conceptual and empirical strengths and limitations of this literature and map the nomological network of the authentic leadership construct. Results indicate that much of the extant research does not follow best practices in terms of research design and analysis. Based on the findings obtained, an agenda for advancing authentic leadership theory and research that embraces a signaling theory perspective is proposed.
Malnutrition significantly hampers wound healing processes. This study aimed to compare the effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) and Subjective Global Assessment (SGA) in diagnosing malnutrition and predicting wound healing in patients with diabetic foot ulcers (DFU). GLIM criteria were evaluated for sensitivity (SE), specificity (SP), positive predictive value, negative predictive value and kappa (κ) against SGA as the reference. Modified Poisson regression model and the DeLong test investigated the association between malnutrition and non-healing ulcers over 6 months. This retrospective cohort study included 398 patients with DFU, with a mean age of 66·3 ± 11·9 years. According to SGA and GLIM criteria, malnutrition rates were 50·8 % and 42·7 %, respectively. GLIM criteria showed a SE of 67·3 % (95 % CI 60·4 %, 73·7 %) and SP of 82·7 % (95 % CI 76·6 %, 87·7 %) in identifying malnutrition, with a positive predictive value of 80·0 % and a negative predictive value of 71·1 % (κ = 0·50) compared with SGA. Multivariate analysis demonstrated that malnutrition, as assessed by SGA, was an independent risk factor for non-healing (relative risk (RR) 1·84, 95 % CI 1·45, 2·34), whereas GLIM criteria were associated with poorer ulcer healing in patients with estimated glomerular filtration rate ≥ 60 ml/min/1·73m2 (RR: 1·46, 95 % CI 1·10, 1·94). SGA demonstrated a superior area under the receiver’s operating characteristic curve for predicting non-healing compared with GLIM criteria (0·70 (0·65–0·75) v. 0·63 (0·58–0·65), P < 0·01). These findings suggest that both nutritional assessment tools effectively identify patients with DFU at increased risk, with SGA showing superior performance in predicting non-healing ulcers.
The REAL World Data (RWD) In Asia for Health Technology Assessment (HTA) guidance was developed by a regional working group to facilitate the increasing acceptance of real-world evidence (RWE) in Asia. We compared the consistency of REALISE against guidance from Japan and China.
Methods
Country-specific guidance for RWE/RWD use in pharmaceutical development were identified in May 2022 through governmental websites, with validation searches via Google. Sections from local guidance were mapped onto REALISE and categorized as “agree”, “mixed”, “disagree” or “missing” based on coverage and consistency.
Results
Five Japanese and three Chinese documents were mapped. Most sections in Chinese guidance (77%) and 36 percent of sections in Japanese guidance were tagged “agree” or “mixed”, with general alignment on definitions and good practice considerations (study design, accountability); however, 63 percent of Japanese sections were tagged “missing” from REALISE. As local documents took the regulatory perspective, they lacked REALISE’s discussion of translating RWD to RWE for HTA/economic evaluations specifically. Local guidance focused on practicalities of RWD collection in local contexts, including descriptions of specific actions (e.g., evaluating RWD sources, ensuring data security) rather than overarching principles described in REALISE; specifically, Japanese guidance described how to access and analyze databases/registries, reflecting Japan’s landscape of robust sources of national healthcare data, but lacked discussion of other RWE study types, data sources and specialized analytical methods. While Chinese guidance had a broader view of RWD types (more similar to REALISE), they also contained discussions on pharmacovigilance and omics data, communication with regulatory bodies, and incorporation of RWE into the approval pathway for traditional Chinese medicines.
Conclusions
Despite differing purposes (with no RWE guidance from local HTA bodies), local and regional guidance align on general principles/good practice in generating/using RWE, providing common ground for increasing usage of RWE in HTA in Asia.
The mumps resurgence has frequently been reported around the world in recent years, especially in many counties mumps vaccines have been widely used. This study aimed to describe the spatial epidemiological characteristics of mumps in Jiangsu, and provide a scientific basis for the implementation and adjustment of strategies to prevent and control mumps. The epidemiological characteristics were described with ratio or proportion. Spatial autocorrelation, Tango's flexible spatial scan statistics, and Kulldorff's elliptic spatiotemporal scan statistics were applied to identify the spatial autocorrelation, detect hot and cold spots of mumps incidence, and aggregation areas. A total of 172 775 cases were reported from 2004 to 2020 in Jiangsu. The general trend of mumps incidence is declining with a bimodal seasonal distribution identified mainly in summer and winter, respectively. Children aged 5–10 years old are the main risk group. A migration trend of hot spots from southeast to northwest over time was found. Similar high-risk aggregations were detected in the northwestern parts through spatial-temporal analysis with the most likely cluster time frame around 2019. Local medical and health administrations should formulate and implement targeted health care policies and allocate health resources more appropriately corresponding to the epidemiological characteristics of mumps.
Mounting evidence showed that insula contributed to the neurobiological mechanism of suicidal behaviors in bipolar disorder (BD). However, no studies have analyzed the dynamic functional connectivity (dFC) of insular Mubregions and its association with personality traits in BD with suicidal behaviors. Therefore, we investigated the alterations of dFC variability in insular subregions and personality characteristics in BD patients with a recent suicide attempt (SA).
Methods
Thirty unmedicated BD patients with SA, 38 patients without SA (NSA) and 35 demographically matched healthy controls (HCs) were included. The sliding-window analysis was used to evaluate whole-brain dFC for each insular subregion seed. We assessed between-group differences of psychological characteristics on the Minnesota Multiphasic Personality Inventory-2. Finally, a multivariate regression model was adopted to predict the severity of suicidality.
Results
Compared to NSA and HCs, the SA group exhibited decreased dFC variability values between the left dorsal anterior insula and the left anterior cerebellum. These dFC variability values could also be utilized to predict the severity of suicidality (r = 0.456, p = 0.031), while static functional connectivity values were not appropriate for this prediction. Besides, the SA group scored significantly higher on the schizophrenia clinical scales (p < 0.001) compared with the NSA group.
Conclusions
Our findings indicated that the dysfunction of insula–cerebellum connectivity may underlie the neural basis of SA in BD patients, and highlighted the dFC variability values could be considered a neuromarker for predictive models of the severity of suicidality. Moreover, the psychiatric features may increase the vulnerability of suicidal behavior.
Schizophrenia is a severe and complex psychiatric disorder that needs treatment based on extensive experience. Antipsychotic drugs have already become the cornerstone of the treatment for schizophrenia; however, the therapeutic effect is of significant variability among patients, and only around a third of patients with schizophrenia show good efficacy. Meanwhile, drug-induced metabolic syndrome and other side-effects significantly affect treatment adherence and prognosis. Therefore, strategies for drug selection are desperately needed. In this study, we will perform pharmacogenomics research and set up an individualised preferred treatment prediction model.
Aims
We aim to create a standard clinical cohort, with multidimensional index assessment of antipsychotic treatment for patients with schizophrenia.
Method
This trial is designed as a randomised clinical trial comparing treatment with different kinds of antipsychotics. A total sample of 2000 patients with schizophrenia will be recruited from in-patient units from five clinical research centres. Using a computer-generated program, the participants will be randomly assigned to four treatment groups: aripiprazole, olanzapine, quetiapine and risperidone. The primary outcomes will be measured as changes in the Positive and Negative Syndrome Scale of schizophrenia, which reflects the efficacy. Secondary outcomes include the measure of side-effects, such as metabolic syndromes. The efficacy evaluation and side-effects assessment will be performed at baseline, 2 weeks, 6 weeks and 3 months.
Results
This trial will assess the efficacy and side effects of antipsychotics and create a standard clinical cohort with a multi-dimensional index assessment of antipsychotic treatment for schizophrenia patients.
Conclusion
This study aims to set up an individualized preferred treatment prediction model through the genetic analysis of patients using different kinds of antipsychotics.
The aim of this study was to assess the current status of disease-related knowledge and to analyze the relationship among the general condition, illness perception, and psychological status of patients with coronavirus disease 2019 (COVID-19).
Methods:
A hospital-based cross-sectional study was conducted on 118 patients using convenience sampling. The general questionnaire, disease-related knowledge questionnaire of COVID-19, Illness Perception Questionnaire (IPQ), and Profile of Mood States (POMS) were used to measure the current status of participants.
Results:
The overall average score of the disease-related knowledge of patients with COVID-19 was (79.19 ± 14.25), the self-care situation was positively correlated with knowledge of prevention and control (r = 0.265; P = 0.004) and total score of disease-related knowledge (r = 0.206; P = 0.025); the degree of anxiety was negatively correlated with the knowledge of diagnosis and treatment (r = −0.182; P = 0.049). The score of disease-related knowledge was negatively correlated with negative cognition (volatility, consequences, emotional statements) and negative emotions (tension, fatigue, depression) (P < 0.05); positively correlated with positive cognition (disease coherence) and positive emotion (self-esteem) (P < 0.05).
Conclusions:
It was recommended that we should pay more attention to the elderly and low-income groups, and increase the knowledge about diagnosis and treatment of COVID-19 and self-care in the future health education for patients.
The coronavirus disease 2019 (COVID-19) pandemic is a major threat to the public. However, the comprehensive profile of suicidal ideation among the general population has not been systematically investigated in a large sample in the age of COVID-19.
Methods
A national online cross-sectional survey was conducted between February 28, 2020 and March 11, 2020 in a representative sample of Chinese adults aged 18 years and older. Suicidal ideation was assessed using item 9 of the Patient Health Questionnaire-9. The prevalence of suicidal ideation and its risk factors was evaluated.
Results
A total of 56,679 participants (27,149 males and 29,530 females) were included. The overall prevalence of suicidal ideation was 16.4%, including 10.9% seldom, 4.1% often, and 1.4% always suicidal ideation. The prevalence of suicidal ideation was higher in males (19.1%) and individuals aged 18–24 years (24.7%) than in females (14.0%) and those aged 45 years and older (11.9%). Suicidal ideation was more prevalent in individuals with suspected or confirmed infection (63.0%), frontline workers (19.2%), and people with pre-existing mental disorders (41.6%). Experience of quarantine, unemployed, and increased psychological stress during the pandemic were associated with an increased risk of suicidal ideation and its severity. However, paying more attention to and gaining a better understanding of COVID-19-related knowledge, especially information about psychological interventions, could reduce the risk.
Conclusions
The estimated prevalence of suicidal ideation among the general population in China during COVID-19 was significant. The findings will be important for improving suicide prevention strategies during COVID-19.
The upsurge in the number of people affected by the COVID-19 is likely to lead to increased rates of emotional trauma and mental illnesses. This article systematically reviewed the available data on the benefits of interventions to reduce adverse mental health sequelae of infectious disease outbreaks, and to offer guidance for mental health service responses to infectious disease pandemic. PubMed, Web of Science, Embase, PsycINFO, WHO Global Research Database on infectious disease, and the preprint server medRxiv were searched. Of 4278 reports identified, 32 were included in this review. Most articles of psychological interventions were implemented to address the impact of COVID-19 pandemic, followed by Ebola, SARS, and MERS for multiple vulnerable populations. Increasing mental health literacy of the public is vital to prevent the mental health crisis under the COVID-19 pandemic. Group-based cognitive behavioral therapy, psychological first aid, community-based psychosocial arts program, and other culturally adapted interventions were reported as being effective against the mental health impacts of COVID-19, Ebola, and SARS. Culturally-adapted, cost-effective, and accessible strategies integrated into the public health emergency response and established medical systems at the local and national levels are likely to be an effective option to enhance mental health response capacity for the current and for future infectious disease outbreaks. Tele-mental healthcare services were key central components of stepped care for both infectious disease outbreak management and routine support; however, the usefulness and limitations of remote health delivery should also be recognized.
Cardiac fibroma is a rare benign primary tumour of the heart. In the paediatric population, it has been reported as the second most common benign cardiac tumour following rhabdomyoma. However, the prevalence of cardiac fibroma is rarely reported in the adult population. Signs and symptoms are nonspecific, including palpitations, cardiac murmur, arrhythmias, dyspnoea, cyanosis, chest pain, and sudden mortality, whereas, a number of patients with cardiac fibroma are asymptomatic. Surgical resection should be considered as the best option in symptomatic patients. This study reported four surgical cases of adults with cardiac fibroma arising from the left ventricle and a literature review regarding the clinical and pathological features, diagnostic modalities, therapeutic aspects, and prognosis of this rare entity.
The razor clam, Sinonovacula constricta, contains high levels of long-chain PUFA (LC-PUFA), which are critical for human health. In addition, S. constricta is the first marine mollusc demonstrated to possess Δ6 fatty acyl desaturase (Fad) and complete LC-PUFA biosynthetic ability, providing a good representative to investigate the molecular mechanism of sterol regulatory element binding proteins (SREBP) in regulating Δ6 Fad for LC-PUFA biosynthesis in marine molluscs. Herein, S. constricta SREBP and Δ6 Fad promoter were cloned and characterised. Subsequently, dual luciferase and electrophoretic mobility shift assays were conducted to explore the SREBP binding elements in the core regulatory region of S. constricta Δ6 Fad promoter. Results showed that S. constricta SREBP had a very conservative basic helix-loop-helix-leucine zipper motif, while S. constricta Δ6 Fad promoter exhibited very poor identity with teleost Fads2 promoters, indicating their differentiation during evolution. A 454 bp region harbouring a core sequence in S. constricta Δ6 Fad promoter was predicted to be essential for the transcriptional activation by SREBP. This was the first report on the regulatory mechanism of LC-PUFA biosynthesis in marine molluscs, which would facilitate optimising the LC-PUFA biosynthetic pathway of bivalves in further studies.
Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs).
Methods
PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months.
Results
Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an ‘enriched’ randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization.
Conclusions
The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.
The aim of this study was to investigate the in vivo degradation mechanism and the mechanical properties of poly(lactide-co-glycolide)/beta-tricalcium phosphate (PLGA/β-TCP) composite anchors. Anchors composed of PLGA and β-TCP were implanted in the dorsal subcutaneous tissue of beagle dogs for 6, 12, 16, and 26 weeks. The degradation of the materials was evaluated by measuring the changes in thermal behavior, crystallinity, and mechanical properties. Scanning electron microscope (SEM) was used to observe the surface and longitudinal section of the material. The evaluation of mechanical strength retention and degradation properties suggest that the addition of β-TCP particles efficiently enhances their mechanical properties and thermal characteristics and delays their degradation rate. By analyzing the results of SEM, X-ray diffraction, and differential scanning calorimetry, we can infer that after 12 weeks, the connection between β-TCP and PLGA becomes less compact, which accelerates the decline of mechanical strength.
Dipetalonema gracile is a common parasite in squirrel monkeys (Saimiri sciureus), which can cause malnutrition and progressive wasting of the host, and lead to death in the case of massive infection. This study aimed to identify a suspected D. gracile worm from a dead squirrel monkey by means of molecular biology, and to amplify its complete mitochondrial genome by polymerase chain reaction (PCR) and sequence analysis. The results identified the worm as D. gracile, and the full length of its complete mitochondrial genome was 13,584 bp, which contained 22 tRNA genes, 12 protein-coding genes, two rRNA genes, one AT-rich region and one small non-coding region. The nucleotide composition included A (16.89%), G (20.19%), T (56.22%) and C (6.70%), among which A + T = 73.11%. The 12 protein-coding genes used TTG and ATT as start codons, and TAG and TAA as stop codons. Among the 22 tRNA genes, only trnS1AGN and trnS2UCN exhibited the TΨC-loop structure, while the other 20 tRNAs showed the TV-loop structure. The rrnL (986 bp) and rrnS (685 bp) genes were single-stranded and conserved in secondary structure. This study has enriched the mitochondrial gene database of Dipetalonema and laid a scientific basis for further study on classification, and genetic and evolutionary relationships of Dipetalonema nematodes.
A gradient structure was synthesized on the surface of Zr55Al10Ni5Cu30 alloy with high glass-forming ability by laser surface melting (LSM). Along the laser incident direction, the surface remelted alloy exhibits gradient microstructure distributed in the sequence of amorphous structure, nanocrystal- reinforced amorphous matrix composite (transitional layer A), dendrites–amorphous phase composite (transitional layer B), and crystalline phases from the top surface to the substrate. The formation mechanism of this gradient structure is discussed based on the experimental results of the microstructure together with the finite volume simulation of the process of LSM treatment. The friction coefficient of the transitional layer A is ∼2.5 times lower than those of the other layers under the same sliding friction condition, and possible reasons for this phenomenon are discussed in connection with the rolling motion and material transfer mechanism. The transitional layer B exhibits the best wear resistance among all the structures studied here, which is related to the optimized ratio of microhardness to reduced Young’s modulus (H/Er).
Ni- and Cu-free Zr–Al–Co–Ag bulk metallic glasses (BMGs) with diameters up to 20 mm were synthesized by copper mold casting. The effects of Ag alloying on the superior glass-forming ability (GFA) of Zr–Al–Co–Ag alloys were studied based on the localized atomic structure and crystallization behavior. High-energy synchrotron radiation x-ray diffraction result reveals that Ag addition in Zr–Al–Co system results in a more homogeneous local atomic structure, which could be an origin for the improved GFA of the Zr–Al–Co–Ag alloy. Crystallization products of the Zr–Al–Co–Ag glassy alloy are more complex than those of the Zr–Al–Co glassy alloy. The Zr–Al–Co–Ag BMGs free from highly toxic elements Ni and Cu exhibited a combination of superior GFA, high compressive fracture strength over 2000 MPa, low Young’s modulus of 93 to 94 GPa, and good corrosion resistance in phosphate-buffered solution (PBS), inspiring their potential biomedical applications.
The compositional dependence of glass formation and thermal and elastic properties was clarified for the ternary La–Al–Co bulk glass-forming system. The existing linear correlation between La concentration and characteristic temperatures, i.e., the glass transition temperature Tg and the onset temperature of crystallization Tx, as well as the elastic moduli in this system can give a useful guideline for the chemical design of desirable bulk metallic glasses (BMGs) with tunable physical properties in advance. The relationship between Tg and elastic constants for the La–Al–Co BMGs can be quantitatively described using a microscopic model proposed by T. Egami.