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1.
Lancet Reg Health West Pac ; 45: 101053, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38585173

RESUMO

Background: Prompt professional care for postpartum depression (PPD) is difficult to obtain in China. Though online consultations improve accessibility and reduce stigma, the quality of services compared to in-person consultations is unclear. Methods: Five trained, undisclosed "standardized patients" (SPs) made "asynchronous webchats" visits and in-person visits with psychiatrists. Visits were made to 85 psychiatrists who were based in 69 hospitals in ten provincial capital cities. The care between online and in-person consultations with the same psychiatrist was compared, including diagnosis, guideline adherence, and patient-centeredness. False discovery rate (FDR) was used to adjust p values. Third visits using asynchronous webchats were made to psychiatrists who offered discrepant diagnoses. Thematic content analysis was used for the discrepancies. Findings: The proportion of diagnostic accuracy was lower for online than in-person visits (76.5% [65/85] vs 91.8% [78/85]; pFDR = 0.0066), as were the proportions of completing questions involving clinical history (16.6% vs 42.7%; pFDR < 0.0001), and management decisions (16.2% vs 27.5%; pFDR < 0.0001) consistent with recommended guidelines. Patient-centeredness was lower online than in-person (pFDR < 0.0001). Fifteen of 16 psychiatrists completed third visits, most of them considered lack of nonverbal information online as a key barrier. Interpretation: Online consultations using asynchronous webchats were inferior to in-person consultations, with respect to diagnostic accuracy, adherence to recommended clinical guidelines, and patient-centeredness. To fully realise the potential benefits of online consultations and to prevent safety issues, there is an urgent need for major improvement in the quality and oversight of these consultations. Funding: China Medical Board, National Natural Science Foundation of China, and Swiss Agency for Development and Cooperation Global Cooperation Department.

2.
BMJ Qual Saf ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688711

RESUMO

Direct-to-onsumer telemedicine (DTCT) has become popular as an alternative to traditional care. However, uncertainties about the potential risks associated with the lack of comprehensive quality evaluation could influence its long-term development. This study aimed to assess the quality of care provided by DTCT platforms in China using unannounced standardised patients (USP) between July 2021 and January 2022. The study assessed consultation services on both hospital and enterprise-sponsored platforms using the Institute of Medicine quality framework. It employed 10 USP cases, covering conditions such as diabetes, asthma, common cold, gastritis, angina, low back pain, child diarrhoea, child dermatitis, stress urinary incontinence and postpartum depression. Descriptive and regression analyses were employed to examine platform characteristics and compare quality across platform types. The results showed that of 170 USP visits across 107 different telemedicine platforms, enterprise-sponsored platforms achieved a 100% success in access, while hospital-sponsored platforms had a success rate of only 47.5% (56/118). Analysis highlighted a low overall correct diagnosis rate of 45% and inadequate adherence to clinical guidelines across all platforms. Notably, enterprise-sponsored platforms outperformed in accessibility, response time and case management compared with hospital-sponsored platforms. This study highlights the suboptimal quality of DTCT platforms in China, particularly for hospital-sponsored platforms. To further enhance DTCT services, future studies should compare DTCT and in-person care, aiming to identify gaps and potential risks associated with using DTCT as alternatives or supplements to traditional care. The potential of future development in enhancing DTCT services may involve exploring the integration of hospital resources with the technology and market capabilities of enterprise-sponsored platforms.

3.
Hum Vaccin Immunother ; 20(1): 2315663, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38439589

RESUMO

The United Nations reported that the mortality risk of Corona Virus Disease 2019 (COVID-19) is five times higher in the elderly than the global average. Although the COVID-19 vaccine effectively prevents infections and reduce mortality among the elderly, vaccine hesitancy among the Chinese elderly poses a significant threat. This study, utilizing the "Confidence, Convenience and Complacency (3 Cs)" vaccine hesitancy model, aimed to explore factors contributing to vaccine hesitancy among the Chinese elderly and assess national countermeasures and potential improvement approaches. Thirteen elderly with vaccine hesitancy and eleven vaccine-related staff participated in semi-structured interviews. Thematic analysis revealed three key determinants of vaccine hesitancy among the elderly: perceived low threat of COVID-19, lack of confidence in COVID-19 vaccine, and poor accessibility to vaccination. China has implemented strategies, including advocacy through diverse channels, joint multi-sectoral promotion vaccination, and enhancing ongoing vaccination services. Recommendations from the vaccine-related staff emphasize improving vaccine awareness among the elderly, and prioritizing the vaccination environment and process. The study underscores the importance of targeted vaccination promotion programs addressing hesitation reasons to improve vaccination rates. Furthermore, existing countermeasures can serve as a foundation for enhancing vaccination strategies, including improved publicity, administration, and management approaches.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Idoso , Humanos , COVID-19/prevenção & controle , Vacinação , Povo Asiático , China/epidemiologia
4.
BMC Pregnancy Childbirth ; 24(1): 176, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448846

RESUMO

BACKGROUND: The objective of the current study was to investigate the correlation between trajectories of maternal perinatal depression (PND) spanning from early pregnancy to one year postpartum and developmental delays observed in one-year-old children. METHODS: The dataset under examination encompassed 880 women who took part in a mother-child birth study conducted in China. Latent class growth analysis (LCGA) was employed to identify patterns in Edinburgh Postnatal Depression Scale (EPDS) scores of women, spanning from early pregnancy to one year postpartum. To assess the neurodevelopment of one-year-old children, a Chinese version of the Bayley Scale of Infant Development (BSID-CR) was employed. Logistic regression was employed to explore the association between PND trajectories and developmental delays in children, with appropriate covariate adjustments. RESULTS: The trajectories of maternal PND identified in this study included a minimal-stable symptom group (n = 155), low-stable symptom group (n = 411), mild-stable symptom group (n = 251), and moderate-stable symptom group (n = 63). Logistic regression analysis revealed that mothers falling into the moderate-stable symptom group exhibited a notably heightened risk of having a child with psychomotor developmental delays at the age of one year. CONCLUSIONS: The findings drawn from a representative sample in China provide compelling empirical evidence that bolsters the association between maternal PND and the probability of psychomotor developmental delays in children. It is imperative to develop tailored intervention strategies and meticulously design mother-infant interactive intervention programs for women with PND.


Assuntos
Desenvolvimento Infantil , Depressão , Feminino , Humanos , Lactente , Gravidez , Povo Asiático , China/epidemiologia , Depressão/epidemiologia , Relações Mãe-Filho
6.
Proc Natl Acad Sci U S A ; 121(7): e2313789121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38335257

RESUMO

Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus, suggesting its classification as the prototype of a new genus within the family Filoviridae. The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region.


Assuntos
Quirópteros , Filoviridae , Animais , Filogenia , China , Mamíferos
7.
J Affect Disord ; 345: 18-23, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-37863368

RESUMO

BACKGROUND: To investigate the relationship between depression in early pregnancy and sleep quality in mid-pregnancy, and explore whether sleep disorders independently predicts depression across the perinatal period within women with or without depression in early pregnancy. METHODS: Data were collected at 7 time points from 12 weeks of pregnancy to 6 weeks postpartum. Multiple logistic regression and survival analysis were used to explore the relationship between sleep quality in mid-pregnancy and perinatal depression within women with or without depression in early pregnancy. RESULTS: 390 women were included. Women with depression in early pregnancy were more likely to have sleep disorders and perinatal depression. Women with sleep disorders had a higher risk of perinatal depression compared to women without sleep disorders in mid-pregnancy. Stratified analysis based on whether depressed at 12 weeks of pregnancy found that among women without depression, those with sleep disorders in mid-pregnancy were more likely to have subsequent perinatal depression and appeared earlier; whereas, among women with depression, mid-pregnancy sleep disorders was not a predictor of subsequent perinatal depression. LIMITATION: High rates of missed visits may lead to sample bias, with depression and sleep quality being assessed by self-report. CONCLUSIONS: Women with depression in early pregnancy are more likely to have sleep disorders in mid-pregnancy. There is a strong correlation between sleep quality in mid-pregnancy and perinatal depression among women without depression in early pregnancy. Routine screening and intervention for sleep disorders should be a priority in perinatal care to reduce the incidence of perinatal depression.


Assuntos
Depressão Pós-Parto , Complicações na Gravidez , Transtornos do Sono-Vigília , Gravidez , Feminino , Humanos , Depressão/epidemiologia , Estudos Prospectivos , Sono , Parto , Transtornos do Sono-Vigília/epidemiologia , Complicações na Gravidez/epidemiologia
8.
J Affect Disord ; 348: 191-199, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38154584

RESUMO

BACKGROUND: Postpartum depression (PPD) is an important public health problem worldwide. China is planning to launch PPD screening in community settings, but there are questions on the community prevalence of PPD and validated screening tools. METHODS: We sought to recruit all eligible new mothers during postnatal home visits in two districts of Changsha, China, and after informed consent, screened them for PPD using three self-administered questionnaires-the Edinburgh Postpartum Depression Scale (EPDS), the Patient Health Questionnaire (PHQ-9), and Whooley Questions for Depression Screening. Video structured diagnostic interviews were performed online according to Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) by qualified specialists who were blinded to screening results. Optimal screening was determined based on the acceptability of scales and diagnostic accuracy metrics including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Out of 3004 eligible women, 2730 (90.9 %) completed the screening questionnaires. Among those screened, the video structured diagnostic interview was administered to 1862 (68.2 %) and 62 (3.3 %) were diagnosed with a current depressive condition. The optimal screening approach involved combining Whooley Questions (at least one "yes") with EPDS (cutoff >10) in series, with sensitivity of 0.76 (95 % CI 0.63 to 0.85), specificity of 0.93 (0.92 to 0.94), PPV of 0.28 (0.21 to 0.36) and NPV of 0.99 (0.98 to 1.00). LIMITATIONS: Due to the regional sample and exclusion of mothers with telephone contact rather than home visits, our findings may not be fully generalizable to the entire population. CONCLUSIONS: The prevalence of PPD among women in this sample was substantially lower than those reported in previous studies in China, the majority of which used screen positivity in measuring prevalence. Combining Whooley Questions with EPDS in series is the most optimal screening approach in this population, though this would still result in a high number of false positives at current prevalence.


Assuntos
Depressão Pós-Parto , Feminino , Humanos , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/prevenção & controle , Sensibilidade e Especificidade , Programas de Rastreamento/métodos , Prevalência , Escalas de Graduação Psiquiátrica
9.
Vet Microbiol ; 288: 109947, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101077

RESUMO

Rotavirus B (RVB) is a causative agent leading to acute viral gastroenteritis diarrhea in both children and young animals, and has been commonly detected in piglets. In order to determine the causative agent of diarrheal outbreak occurring in December 2022 in piglets from a pig herd in Luoyang, Henan province of China, four common viral pathogens causing piglet diarrhea-three coronaviruses and rotavirus A (RVA) were first tested and found negative, therefore metagenomic sequencing was performed to explore other potential pathogens in the diarrheal samples. Unexpectedly, the most abundant viral reads mapped to RVB, and were de novo assembled to complete 11 viral gene segments. Sequence comparisons revealed that 5 gene segments encoding VP1, VP2, VP3, NSP3 and NSP4 of RVB strain designated as HNLY-2022 are most closely related to RVB strains derived from herbivores with low nucleotide similarities of 65.7-75.3%, and the remaining segments were relatively close to porcine RVB strains with the VP4 gene segment showing very low nucleotide identity (65.0%) with reference strains, indicating HNLY-2022 is a new reassortant RVB strain. Based on the previously proposed genotype classification criterion, the genotype constellation of RVB strain HNLY-2022 is G6-P[6]-I4-R6-C6-M6-A7-N5-T7-E5-H4 with more than half of the genotypes (P[6], R6, C6, M6, T7 and E5) newly reported. Therefore, the new reassortant RVB strain is the likely causative agent for the diarrheal outbreak of piglets occurred in China and more epidemiological studies should be conducted to monitor the spread of this newly identified porcine RVB strain.


Assuntos
Infecções por Rotavirus , Rotavirus , Doenças dos Suínos , Animais , Suínos , Rotavirus/genética , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/veterinária , Genoma Viral , Filogenia , Diarreia/epidemiologia , Diarreia/veterinária , Nucleotídeos , Genótipo
10.
Virol Sin ; 38(5): 663-670, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37660950

RESUMO

Four species of porcine circoviruses (PCV1-4) have been reported to circulate in Chinese domestic pigs, while the epizootiology of these viruses in free-ranging wild boars in China remains unknown. In this study, tissue and serum samples collected from diseased or apparently healthy wild boars between 2018 and 2020 in 19 regions of China were tested for the prevalence of PCV1-4 infections. Positive rates of PCV1, PCV2, and PCV3 DNA in the tissue samples of Chinese wild boars were 1.6% (4/247), 58.3% (144/247), and 10.9% (27/247) respectively, with none positive for PCV4. Sequence analysis of viral genome showed that the four PCV1 strains distributed in Hunan and Inner Mongolia shared 97.5%-99.6% sequence identity with global distributed reference strains. Comparison of the ORF2 gene sequences showed that 80 PCV2 strains widely distributed in 18 regions shared 79.5%-100% sequence identity with reference strains from domestic pigs and wild boars, and were grouped into PCV2a (7), PCV2b (31) and PCV2d (42). For PCV3, 17 sequenced strains shared 97.2%-100% nucleotide identity at the genomic level and could be divided into PCV3a (3), PCV3b (2) and PCV3c (12) based on the phylogeny of ORF2 gene sequences. Serological data revealed antibody positive rates against PCV1 and PCV2 of 11.4% (19/167) and 53.9% (90/167) respectively. The data obtained in this study improved our understanding about the epidemiological situations of PCVs infection in free-ranging wild boars in China and will be valuable for the prevention and control of diseases caused by PCVs infection.


Assuntos
Infecções por Circoviridae , Circovirus , Doenças dos Suínos , Suínos , Animais , Sus scrofa/genética , Circovirus/genética , Genoma Viral , China/epidemiologia , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/veterinária , Filogenia
11.
Infect Genet Evol ; 113: 105472, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37353186

RESUMO

South-East Asia (SEA) and South Asia (SA) are two important geographic regions with the most severe enzootic rabies in the world. In these regions, phylogenetic analysis of rabies virus (RABV) has been conducted only at a country level; the results obtained from different countries are scattered and unequal, with a non-uniform system to name RABV genotypes. Therefore, it is difficult to undertake origin-tracking and compare inter-country RABV evolution and transmission. To avoid the confusion in understanding and to generate a panoramic picture of RABV genetic diversity, distribution, and transmission in SEA and SA, the present study conducted a systematic phylogenetic analysis by combining all sequences representing 2368 RABV strains submitted to GenBank by 14 rabies endemic SEA and SA countries. The results showed that RABVs circulating in two regions were classified into four major clades and many subclades: the Asia clade is circulating only in SEA, the Indian subcontinent, and Arctic-like clades only in SA, while the Cosmopolitan clade has been detected in both regions. The results also showed a wide range of hosts were infected by divergent RABV subclades, with dogs being the major transmission source. However, wildlife rabies was also found to be an important issue with 6 wild carnivore species identified as potential sources of spillover risk for sylvatic rabies to humans, domestic animals, and other wild animals. Current findings indicate that the two regions have separate virus clades circulating thus indicating the absence of cross-transmission between the regions. The study emphasizes the importance of phylogenetic analysis in the regions using uniform genotyping and naming systems for rabies surveillance, to coordinate actions of member countries to eliminate dog-mediated human rabies by 2030.


Assuntos
Vírus da Raiva , Raiva , Animais , Humanos , Cães , Vírus da Raiva/genética , Raiva/epidemiologia , Raiva/veterinária , Filogenia , Ásia Meridional , Animais Selvagens , Variação Genética
12.
BMJ Open ; 13(5): e071783, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37164474

RESUMO

INTRODUCTION: As direct-to-consumer teleconsultation (hereafter referred to as 'teleconsultation') has gained popularity, an increasing number of patients have been leaving online reviews of their teleconsultation experiences. These reviews can help guide patients in identifying doctors for teleconsultation. However, few studies have examined the validity of online reviews in assessing the quality of teleconsultation against a gold standard. Therefore, we aim to use unannounced standardised patients (USPs) to validate online reviews in assessing both the technical and patient-centred quality of teleconsultations. We hypothesise that online review results will be more consistent with the patient-centred quality, rather than the technical quality, as assessed by the USPs. METHODS AND ANALYSIS: In this cross-sectional study, USPs representing 11 common primary care conditions will randomly visit 253 physicians via the three largest teleconsultation platforms in China. Each physician will receive a text-based and a voice/video-based USP visit, resulting in a total of 506 USP visits. The USP will complete a quality checklist to assess the proportion of clinical practice guideline-recommended items during teleconsultation. After each visit, the USP will also complete the Patient Perception of Patient-Centeredness Rating. The USP-assessed results will be compared with online review results using the intraclass correlation coefficient (ICC). If ICC >0.4 (p<0.05), we will assume reasonable concordance between the USP-assessed quality and online reviews. Furthermore, we will use correlation analysis, Lin's Coordinated Correlation Coefficient and Kappa as supplementary analyses. ETHICS AND DISSEMINATION: This study has received approval from the Institutional Review Board of Southern Medical University (#Southern Medical Audit (2022) No. 013). Results will be actively disseminated through print and social media, and USP tools will be made available for other researchers. TRIAL REGISTRATION: The study has been registered at the China Clinical Trials Registry (ChiCTR2200062975).


Assuntos
Médicos , Consulta Remota , Humanos , Estudos Transversais , Consulta Remota/métodos , Pacientes , China
13.
Front Immunol ; 14: 1181620, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37143650

RESUMO

The treatment of B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement poses a significant clinical challenge because most chemotherapeutic agents exhibit weak permeability to the blood-brain barrier (BBB). In addition, current anti-CNS leukemia treatments often bring short or long-term complications. Immunotherapy including chimeric antigen T-cell therapy and bispecific antibody have shown profound treatment responses in relapsed/refractory B-ALL. However, there is a lack of data on the efficacy of bispecific antibody in treating B-ALL with CNS involvement. Here, we report two ALL patients with CNS leukemia who received blinatumomab. Case 1 was diagnosed with chronic myeloid leukemia in lymphoid blast phase. The patient developed CNS leukemia and bone marrow relapse during the treatment with dasatinib. Case 2 was diagnosed with B-ALL and suffered early hematologic relapse and cerebral parenchyma involvement. After treatment with one cycle of blinatumomab, both patients achieved complete remission in the bone marrow and CNS. Furthermore, this is the first report on the efficacy of blinatumomab in treating CNS leukemia with both of the cerebral spinal fluid and the cerebral parenchymal involvement. Our results suggest that blinatumomab might be a potential option for the treatment of CNS leukemia.


Assuntos
Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Recidiva , Sistema Nervoso Central
15.
BMC Pregnancy Childbirth ; 23(1): 230, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37020285

RESUMO

BACKGROUND: Timely screening and referral can improve the outcomes of perinatal depression (PND). However, uptake rates of referral after PND screening are low in China and the reasons are unclear. The aim of this article is to explore the barriers and facilitators for referring women with positive results of PND screening in the Chinese primary maternal health care system. METHODS: Qualitative data were collected from four primary health centers located in four different provinces of China. Each of the four investigators conducted 30 days of participant observations in the primary health centers from May to August 2020. Data were collected via participant observations and semi-structured in-depth interviews with new mothers who had positive results of PND screening, their family members, and primary health providers. Two investigators analyzed qualitative data independently. A thematic analysis was conducted, and data were framed using the social ecological model. RESULTS: A total of 870 hours of observation and 46 interviews were carried out. Five themes were identified: individual (new mothers' knowledge of PND, perceived need to seek help), interpersonal (new mothers' attitudes towards providers, family support), institutional (providers' perception of PND, lack of training, time constraints), community (accessibility to mental health services, practical factors), and public policy (policy requirements, stigma). CONCLUSIONS: The likelihood of new mothers accepting PND referral is related to factors in five areas. Intervention strategies can be developed around these themes and may include educating new mothers and their families about PND, training primary health providers to improve their awareness of condition and indication for referral, building mental health support in routine postpartum home visits, and providing support through mobile technology.


Assuntos
Depressão , Serviços de Saúde Materna , Mães , Feminino , Humanos , Gravidez , Saúde Mental , Mães/psicologia , Pesquisa Qualitativa , China , Acessibilidade aos Serviços de Saúde , Encaminhamento e Consulta
16.
Nat Commun ; 14(1): 2488, 2023 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-37120646

RESUMO

Wildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk.


Assuntos
COVID-19 , Quirópteros , Vírus , Animais , Animais Domésticos/virologia , Animais Selvagens/virologia , Animais de Zoológico/virologia , Quirópteros/virologia , Mamíferos/virologia , Pangolins/virologia , Filogenia , Zoonoses/virologia
17.
J Med Internet Res ; 25: e42777, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-37067855

RESUMO

BACKGROUND: Internet-based intervention platforms may improve access to mental health care for women with perinatal depression (PND). Though the majority of platforms in the market lack an evidence base, a small number of them are supported by research evidence. OBJECTIVE: This study aims to assess the current status of internet-based PND intervention platforms supported by published evidence, understand the reasons behind the disappearance of any of these previously accessible platforms, examine adjustments made by those active platforms between research trials and market implementation, and evaluate their current quality. METHODS: A cohort of internet-based PND intervention platforms was first identified by systematic searches in multiple academic databases from database inception until March 26, 2021. We searched on the World Wide Web and the iOS and Android app stores to assess which of these were available in the marketplace between April and May 2021. The basic characteristics of all platforms were collected. For inaccessible platforms, inquiries were made via email to the authors of publications to determine the reasons for their unavailability. We compared the intervention-related information of accessible platforms in the marketplace with that reported in original publications and conducted quality assessments using the App Evaluation Model of the American Psychiatric Association. Fisher exact tests were used to compare the functional characteristics in publications of available and unavailable platforms and to investigate potential associations between functional adjustments or quality indices and platform survival time. RESULTS: Out of 35 platforms supported by research evidence, only 19 (54%) were still accessible in the marketplace. The main reason for platforms disappearing was the termination of research projects. No statistically significant differences were found in functional characteristics between available and unavailable platforms. A total of 18 (95%) platforms adapted their core functions from what was reported in related publications. The adjustments included changes to intervention methods (11/19, 58%), target population (10/19, 53%), human resources for intervention support (9/19, 47%), mood assessment and monitoring (8/19, 42%), communication modality (4/19, 21%), and platform type (2/19, 11%). Quality issues across platforms included low frequency of update, lack of crisis management mechanism, poor user interactivity, and weak evidence base or absence of citation of supporting evidence. Platforms that survived longer than 10 years had a higher tendency to use external resources from third parties compared to those that survived less than 10 years (P=.04). No significant differences were found for functional adjustments or other quality indices. CONCLUSIONS: Internet-based platforms supported by evidence were not effectively translated into real-world practice. It is unclear if adjustments to accessible platforms made during actual operation may undermine the proven validity of the original research. Future research to explore the reasons behind the success of the implementation of evidence-based platforms in the marketplace is warranted.


Assuntos
Transtorno Depressivo , Intervenção Baseada em Internet , Gravidez , Humanos , Feminino , Estados Unidos , Depressão/terapia , Estudos de Coortes
18.
Blood Adv ; 7(17): 4913-4925, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36897251

RESUMO

We conducted a single-arm, open-label, single-center phase 1 study to assess the safety and efficacy of multicycle-sequential anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in combination with autologous CD19+ feeding T cells (FTCs) and tyrosine kinase inhibitor (TKI) as consolidation therapy in patients under the age of 65 years with de novo Ph-positive CD19+ B-cell acute lymphoblastic leukemia. Participants were given induction chemotherapy as well as systemic chemotherapy with TKI. Afterward, they received a single cycle of CD19 CAR T-cell infusion and another 3 cycles of CD19 CAR T-cell and CD19+ FTC infusions, followed by TKI as consolidation therapy. CD19+ FTCs were given at 3 different doses. The phase 1 results of the first 15 patients, including 2 withdrawals, are presented. The most common adverse events were cytopenia (13/13) and hypogammaglobinemia (12/13). There was no incidence of cytokine release syndrome above grade 2 or immune effector cell-associated neurotoxicity syndrome or grade 4 nonhematological toxicities. All 13 patients achieved complete remission, including 12 patients with a complete molecular response (CMR) at the data cutoff. The relapse-free survival was 84%, and the overall survival was 83% with a median follow-up of 27 months. The total number of CD19-expressing cells decreased with an increasing CMR rate. CD19 CAR T cells survived for up to 40 months, whereas CD19+ FTCs vanished in 8 patients 3 months after the last infusion. These findings could form the basis for the development of an allo-HSCT-free consolidation paradigm. This trial was registered at www.clinicaltrials.gov as #NCT03984968.


Assuntos
Antígenos CD19 , Imunoterapia Adotiva , Linfoma de Células B , Síndromes Neurotóxicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Idoso , Humanos , Antígenos CD19/imunologia , Antígenos CD19/uso terapêutico , Quimioterapia de Consolidação , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T , Imunoterapia Adotiva/métodos
19.
Br J Pharmacol ; 180(1): 44-61, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36070072

RESUMO

BACKGROUND AND PURPOSE: Liver fibrosis is a serious cause of morbidity and mortality worldwide characterized by accumulation of extracellular matrix produced by hepatic stellate cells (HSCs). The protein kinase CK2 is a pro-survival kinase overexpressed in human tumours. However, the biological role of CK2 in liver fibrosis is largely unknown. We aimed to investigate the mechanism by which CK2 promotes liver fibrosis. EXPERIMENTAL APPROACH: In vitro, LX-2 cells were stimulated with transforming growth factor-ß (TGF-ß). HSCs were also isolated for research. In vivo, the adeno-associated virus AAV-sh-csnk2a1 was used to knockdown CK2α specifically in HSCs, and CX-4945 was used to pharmacologically inhibit the enzymatic activity of CK2 in murine models of fibrosis induced by carbon tetrachloride (CCl4 ) and a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of CK2 in regulation of fibrogenic and fibrolytic factors as well as activation properties of HSCs. KEY RESULTS: HSC-specific genetic invalidation of CK2α or pharmacological inhibition of CK2 protected mice treated with CCl4 or fed a DDC diet against liver fibrosis and HSC accumulation. Mechanistically, CK2α, which bound to Smoothened (SMO), was a positive regulator of the Hedgehog signal transduction pathway. CK2 prevented ubiquitination and proteasomal degradation of SMO, which was abolished by knockdown of CK2α or pharmacological inhibition of CK2. CONCLUSIONS AND IMPLICATIONS: CK2 activation is critical to sustain the activated and fibrogenic phenotype of HSCs via SMO stabilization. Therefore, inactivation of CK2 by CX-4945 may be of therapeutic interest for liver fibrotic diseases.


Assuntos
Proteínas Hedgehog , Células Estreladas do Fígado , Camundongos , Humanos , Animais , Células Estreladas do Fígado/metabolismo , Proteínas Hedgehog/metabolismo , Caseína Quinase II/efeitos adversos , Caseína Quinase II/metabolismo , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Tetracloreto de Carbono , Fibrose
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