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BACKGROUND: Cognitive impairment and dementia are frequently under-recognized. Health system strategies anchored in primary care are essential to address gaps in timely, comprehensive diagnosis. The goal of this paper is to describe the adaptation of a tablet-based brain health assessment (TabCAT-BHA) intervention and the study protocol to test its effectiveness in improving the detection of cognitive impairment, including dementia. METHODS: This mixed-methods, pragmatic, cluster randomized, hybrid effectiveness-implementation trial is being conducted in two 18-month waves with 26 Kaiser Permanente Southern California primary care clinics, with 13 serving as intervention clinics and 13 as usual care clinics. Patients 65 years and older with memory concerns (n ~ 180,000) receiving care at the 26 clinics will be included in the analyses. Primary care clinics are provided the following practice supports as part of the TabCAT-BHA intervention: brief education and training on neurocognitive disorders and study workflows; digital tools to assess cognitive function and support clinician decision making and documentation; and registered nurse support during the work-up and post-diagnosis periods for primary care providers, patients, and families. The intervention was adapted based on engagement with multiple levels of clinical and operational leaders in the healthcare system. Effectiveness outcomes include rates of cognitive impairment diagnosis in primary care and rates of completed standardized cognitive assessments and specialist referrals with incident diagnoses. Implementation outcomes include acceptability-appropriateness-feasibility, adoption, and fidelity. RESULTS: We identified seven themes organized by system-, provider-, and patient-level domains that were used to adapt the TabCAT-BHA intervention. Accordingly, changes were made to the provider education, diagnostic work-up, and post-diagnostic support. Results will be reported in fall of 2027. CONCLUSIONS: Our engagement with multiple primary and specialty care clinical and operational leaders to adapt the TabCAT-BHA intervention to these primary care clinics has informed the protocol to evaluate the intervention's effectiveness for improving the detection of cognitive impairment, including dementia, in an integrated healthcare system. TRIAL REGISTATION: Clinicaltrials.gov: NCT06090578 (registered 10/24/23).
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Disfunción Cognitiva , Atención Primaria de Salud , Humanos , Disfunción Cognitiva/diagnóstico , Anciano , Demencia/diagnóstico , Participación de los Interesados , Computadoras de Mano , Ensayos Clínicos Pragmáticos como Asunto , California , FemeninoRESUMEN
Knee osteoarthritis (OA) poses a significant health care burden globally, necessitating innovative therapeutic approaches. CCoat, a novel poly(2-[methacryloyloxy]ethyl phosphorylcholine) (pMPC)ylated liposome device, protects the cartilage surface of the joint from mechanical wear through an entropy-favored process. Two preclinical studies were performed to explore the safety of CCoat following repeated intra-articular (IA) injections into the knee joint (i.e., femorotibial joint) in Sprague-Dawley rats. The studies involved 2 or 3 IA injections, at an interval of 2 or 3 weeks, and an observation period of 1 or 13 weeks after the last injection. Assessments included clinical, histopathological, and immunofluorescent evaluations. In study 1, no mortality or abnormal clinical signs occurred. At 1 week post last injection, histopathology revealed minimal vacuolated macrophages beneath the synovial membrane, predominantly M2-like, indicating a nonadverse response. Immunofluorescent staining supported M2-like macrophage predominance. Study 2 confirmed these findings with no systemic effects over 13 weeks. Statistical analyses indicated no significant differences in body weight, clinical pathology, or organ weights compared with controls. Results affirming the safety of pMPCylated liposomes following repeated IA injections in rat. This novel lubricant coating approach shows promise in OA therapy, with this safety assessment supporting its potential clinical application.
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Polylactic acid (PLA) is widely known for its biocompatibility, biodegradability, and high transparency. However, it still has varied limitations such as flammability, UV sensitivity, and poor oxygen barrier properties. To address these issues, a bio-based compound, hexasubstituted cyclotriphosphazene (HVP), was synthesized by using vanillin and hexachlorocyclotriphosphazene to enhance the overall performance of PLA. The resulting PLA/HVP composites demonstrated improved mechanical strength and UV resistance. Specifically, PLA/3HVP, with a 3 wt% HVP loading, achieved a UL-94 V-0 rating and a high limiting oxygen index of 26.5 %. Cone calorimeter tests revealed that PLA/3HVP possessed a significantly longer ignition time and a lower peak heat release rate compared to pure PLA. These burning testing results indicated the enhanced fire resistance. Additionally, the oxygen transmission rate of PLA/3HVP was reduced by 81.1 % compared to pure PLA. When used as food packaging, the weight loss of mangoes covered with PLA/3HVP film was 2.2 % after 7 days, compared to 2.5 % with pure PLA film, highlighting its potential for food preservation applications.
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BACKGROUND AND AIMS: Endoscopic submucosal dissection is increasingly promoted for the treatment of all large nonpedunculated colorectal polyps (LNPCPs) to cure potential low-risk cancers (superficial submucosal invasion without additional high-risk histopathologic features). The effect of a universal en bloc strategy on oncologic outcomes for the treatment of LNPCPs in the right colon is unknown. We evaluated this in a large Western population. METHODS: A prospective cohort of patients referred for endoscopic resection (ER) of LNPCPs was analyzed. Patients found to have cancer after ER and those referred directly to surgery were included. The primary outcome was to determine the proportion of right colon LNPCPs with low-risk cancer. RESULTS: Over 180 months until June 2023, 3294 sporadic right colon LNPCPs in 2956 patients were referred for ER at 7 sites (median size 30 [interquartile range 15] mm). A total of 63 (2.1%) patients were referred directly to surgery, and cancer was proven in 56 (88.9%). A total of 2851 (96.4%) of 2956 LNPCPs underwent ER (median size 35 [interquartile range 20] mm), of which 75 (2.6%) were cancers. The overall prevalence of cancer in the right colon was 4.4% (n = 131 of 2956). Detailed histopathologic analysis was possible in 115 (88%) of 131 cancers (71 after ER, 44 direct to surgery). After excluding missing histopathologic data, 23 (0.78%) of 2940 sporadic right colon LNPCPs were low-risk cancers. CONCLUSIONS: The proportion of right colon LNPCPs referred for ER containing low-risk cancer amenable to endoscopic cure was <1%, in a large, multicenter Western cohort. A universal endoscopic submucosal dissection strategy for the management of right colon LNPCPs is unlikely to yield improved patient outcomes given the minimal impact on oncologic outcomes. CLINICALTRIALS: gov, Numbers: NCT01368289, NCT02000141.
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INTRODUCTION: While piecemeal endoscopic mucosal resection (EMR) for T1a oesophageal adenocarcinoma is acceptable, enbloc-R0 excision is advocated for T1b disease as it may offer a potential cure and mitigate recurrence. Thus, distinguishing between T1a and T1b disease is imperative under current treatment paradigms. We sought to ascertain whether expert Barrett's endoscopists were able to make this distinction based on optical evaluation. METHODS: Sixty sets of endoscopic images of histologically confirmed high grade dysplasia (HGD), T1a and T1b disease (n=20 for each) were compiled from consecutive patients at a single institution. Each set contained four images, and were standardized to include an overview, a close-up in high-definition white light, a near-focus magnification image, and a narrow-band image. Experts were invited to predict histology for each set. RESULTS: 19 experts from 8 countries (Australia, USA, Italy, Netherlands, Germany, Canada, Belgium, and Portugal) participated. The majority had been practicing for >20 years, with a median annual case volume for Barrett's EMR of 50 (IQR 18-75), and Barrett's ESD of 25 (IQR 10-45). Oesophageal adenocarcinoma (T1a/b) could be distinguished from HGD, with a pooled sensitivity of 89.1% (95% CI:84.7-93.4. When predicting T-stage for T1b adenocarcinoma cases, pooled sensitivity was 43.8% (95% CI:29.9-57.7). Fleiss' kappa was 0.421 (95% CI:0.399-0.442, P<0.001), indicating fair-to-moderate agreement. CONCLUSIONS: Expert Barrett's endoscopists can reliably differentiate T1a/T1b oesophageal adenocarcinoma from HGD. Although there is fair-to-moderate agreement for T-staging, T1b disease cannot be reliably distinguished from T1a disease. This may have implications on clinical decision making and selection of endoscopic treatment methods.
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BACKGROUND: The encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy resistance cell states. Here, we deploy time series measurements of triple negative breast cancer (TNBC) single-cell transcriptomes, along with co-measured single-cell CN fitness, identifying genomic and transcriptomic mechanisms in drug-associated transcriptional cell states. RESULTS: We present scRNA-seq data (53,641 filtered cells) from serial passaging TNBC patient-derived xenograft (PDX) experiments spanning 2.5 years, matched with genomic single-cell CN data from the same samples. Our findings reveal distinct clonal responses within TNBC tumors exposed to platinum. Clones with high drug fitness undergo clonal sweeps and show subtle transcriptional reversion, while those with weak fitness exhibit dynamic transcription upon drug withdrawal. Pathway analysis highlights convergence on epithelial-mesenchymal transition and cytokine signaling, associated with resistance. Furthermore, pseudotime analysis demonstrates hysteresis in transcriptional reversion, indicating generation of new intermediate transcriptional states upon platinum exposure. CONCLUSIONS: Within a polyclonal tumor, clones with strong genotype-associated fitness under platinum remained fixed, minimizing transcriptional reversion upon drug withdrawal. Conversely, clones with weaker fitness display non-genomic transcriptional plasticity. This suggests CN-associated and CN-independent transcriptional states could both contribute to platinum resistance. The dominance of genomic or non-genomic mechanisms within polyclonal tumors has implications for drug sensitivity, restoration, and re-treatment strategies.
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Resistencia a Antineoplásicos , Análisis de la Célula Individual , Transcriptoma , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Humanos , Animales , Resistencia a Antineoplásicos/genética , Femenino , Ratones , Variaciones en el Número de Copia de ADN , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Transición Epitelial-Mesenquimal/genéticaRESUMEN
INTRODUCTION: Complete excision of upper gastrointestinal sub-epithelial lesions (U-SELs) eliminates diagnostic uncertainty, obviates the need for surveillance and may be necessary for definitive diagnosis and management. Current guidelines lack precision and cohesion, and surgery is associated with significant morbidity. Herein, we describe and report on the outcomes of our SEL algorithm for endoscopic (SAFE) resection. METHODS: U-SELs were enrolled prospectively over 115 months until March 2023. All underwent axial (CT) imaging and endoscopic-ultrasonography (EUS) to exclude a large exophytic component or invasion into local structures, and assess for muscularis propria involvement. RESULTS: 106 U-SELs were resected (mean age 60.6±13.4, 51.9% male; 41 oesophageal, 65 gastric). Oesophageal U-SELs underwent ESD (n=22) or STER if MP involvement was suspected (n=19). Gastric U-SELs underwent STER (n=6 at cardia), ESD (n=47) or exposing-EFTR (n=12). Technical success was 97.6% and 92.3% respectively. Five (7.7%) were completed laparoscopically due to deep and broad full-thickness involvement. Five (7.7%) required laparoscopic gastrotomy and surgical retrieval after successful resection and closure due to a large lesion size (mean 47 mm). There was no delayed bleeding, perforation or recurrence at 13 months. CONCLUSION: U-SELs may be effectively and safely treated by endoscopic resection. The SAFE approach provides a framework that facilitates structured decision-making. Oesophageal U-SELs suspected to involve the MP should undergo STER. Gastric SELs can be best managed by ESD with a view to proceed to exposing-EFTR. A laparoscopic UGI surgeon should be available in case surgical retrieval of the specimen or laparoscopic completion is required.
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Soft tissue injuries often involve muscle and peripheral nerves and are qualitatively distinct from single-tissue injuries. Prior research suggests that damaged innervation compromises wound healing. To test this in a traumatic injury context, we developed a novel mouse model of nerve and lower limb polytrauma, which features greater pain hypersensitivity and more sustained macrophage infiltration than either injury in isolation. We also show that macrophages are crucial mediators of pain hypersensitivity in this model by delivering macrophage-targeted nanoemulsions laden with the cyclooxygenase-2 (COX-2) inhibitor celecoxib. This treatment was more effective in males than females, and more effective when delivered 3 days post-injury than 7 days post-injury. The COX-2 inhibiting nanoemulsion drove widespread anti-inflammatory changes in cytokine expression in polytrauma-affected peripheral nerves. Our data shed new light on the modulation of inflammation by injured nerve input and demonstrate macrophage-targeted nanoimmunomodulation can produce rapid and sustained pain relief following complex injuries.
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Celecoxib , Inhibidores de la Ciclooxigenasa 2 , Ciclooxigenasa 2 , Macrófagos , Animales , Macrófagos/efectos de los fármacos , Masculino , Femenino , Celecoxib/farmacología , Celecoxib/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Ratones , Ciclooxigenasa 2/metabolismo , Traumatismo Múltiple/complicaciones , Emulsiones/química , Emulsiones/farmacología , Ratones Endogámicos C57BL , Dolor/tratamiento farmacológico , Modelos Animales de Enfermedad , Citocinas/metabolismo , Inmunomodulación/efectos de los fármacosRESUMEN
BACKGROUND: Periodontal disease constitutes a widely prevalent category of non-communicable diseases and ranks among the top 10 causes of disability worldwide. Little however is known about diagnostic errors in dentistry. In this work, by retrospectively deploying an electronic health record (EHR)-based trigger tool, followed by gold standard manual review, we provide epidemiological estimates on the rate of diagnostic misclassification in dentistry through a periodontal use case. METHODS: An EHR-based trigger tool (a retrospective record review instrument that uses a list of triggers (or clues), i.e., data elements within the health record, to alert reviewers to the potential presence of a wrong diagnosis) was developed, tested and run against the EHR at the two participating sites to flag all cases having a potential misdiagnosis. All cases flagged as potentially misdiagnosed underwent extensive manual reviews by two calibrated domain experts. A subset of the non-flagged cases was also manually reviewed. RESULTS: A total of 2,262 patient charts met the study's inclusion criteria. Of these, the algorithm flagged 1,124 cases as potentially misclassified and 1,138 cases as potentially correctly diagnosed. When the algorithm identified a case as potentially misclassified, compared to the diagnosis assigned by the gold standard, the kappa statistic was 0.01. However, for cases the algorithm marked as potentially correctly diagnosed, the review against the gold standard showed a kappa statistic of 0.9, indicating near perfect agreement. The observed proportion of diagnostic misclassification was 32 %. There was no significant difference by clinic or provider characteristics. CONCLUSION: Our work revealed that about a third of periodontal cases are misclassified. Diagnostic errors have been reported to happen more frequently than other types of errors, and to be more preventable. Benchmarking diagnostic quality is a first step. Subsequent research endeavor will delve into comprehending the factors that contribute to diagnostic errors in dentistry and instituting measures to prevent them. CLINICAL SIGNIFICANCE: This study sheds light on the significance of diagnostic excellence in the delivery of dental care, and highlights the potential role of technology in aiding diagnostic decision-making at the point of care.
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Algoritmos , Errores Diagnósticos , Registros Electrónicos de Salud , Enfermedades Periodontales , Humanos , Errores Diagnósticos/estadística & datos numéricos , Estudios Retrospectivos , Enfermedades Periodontales/diagnóstico , Enfermedades Periodontales/clasificación , Enfermedades Periodontales/epidemiología , Femenino , Masculino , Persona de Mediana Edad , AdultoRESUMEN
BACKGROUND AND AIMS: Conventional hot snare endoscopic mucosal resection (H-EMR) is effective for the management of large (≥20 mm) non-pedunculated colon polyps (LNPCPs) however, electrocautery-related complications may incur significant morbidity. With a superior safety profile, cold snare EMR (C-EMR) of LNPCPs is an attractive alternative however evidence is lacking. We conducted a randomised trial to compare the efficacy and safety of C-EMR to H-EMR. METHODS: Flat, 15-50 mm adenomatous LNPCPs were prospectively enrolled and randomly assigned to C-EMR or H-EMR with margin thermal ablation at a single tertiary centre. The primary outcome was endoscopically visible and/or histologically confirmed recurrence at 6 months surveillance colonoscopy. Secondary outcomes were clinically significant post-EMR bleeding (CSPEB), delayed perforation and technical success. RESULTS: 177 LNPCPs in 177 patients were randomised to C-EMR arm (n=87) or H-EMR (n=90). Treatment groups were equivalent for technical success 86/87 (98.9%) C-EMR versus H-EMR 90/90 (100%); p=0.31. Recurrence was significantly greater in C-EMR (16/87, 18.4% vs 1/90, 1.1%; relative risk (RR) 16.6, 95% CI 2.24 to 122; p<0.001).Delayed perforation (1/90 (1.1%) vs 0; p=0.32) only occurred in the H-EMR group. CSPEB was significantly greater in the H-EMR arm (7/90 (7.8%) vs 1/87 (1.1%); RR 6.77, 95% CI 0.85 to 53.9; p=0.034). CONCLUSION: Compared with H-EMR, C-EMR for flat, adenomatous LNPCPs, demonstrates superior safety with equivalent technical success. However, endoscopic recurrence is significantly greater for cold snare resection and is currently a limitation of the technique. TRIAL REGISTRATION NUMBER: NCT04138030.
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Conventional G-banded karyotype is an essential tool for detecting chromosomal variants in patients undergoing fertility evaluation. In Australia, 15 cells are traditionally analysed or counted, to enhance detection of mosaic chromosomal variants. However, this protocol is not backed by clinical evidence. This study aims to assess the test performance of an abbreviated 5-cell karyotype analysis protocol in adult patients undergoing fertility evaluation. A retrospective review of 53,293 blood karyotype tests, performed between 2019 and 2023, was conducted on a patient cohort primarily referred by reproductive endocrinology specialists. There were 513 variants reported in this cohort. Low level mosaic variants, where the variant was observed in less than 40% of cells, were reported in 13 cases, or one in 4,100 patients. Due to reduced sensitivity for low level mosaic variants, a 5-cell protocol is estimated to have a test sensitivity of 97.3% and a negative predictive value of 99.97%. A decision-making flowchart is proposed and we show that additional chromosome analysis and/or counts would be triggered in fewer than one in 10 cases using a 5-cell protocol, whilst remaining appropriate for detecting clinically significant mosaicism. A 5-cell karyotype analysis protocol therefore maintains analytical and clinical validity in adult patients undergoing fertility-related blood karyotyping. Future research is recommended to validate these findings across laboratories and to explore their application to other clinical contexts.
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Blending conjugated polymers with insulating matrices is often utilized for engineering extrinsic properties in organic electronics. Semiconductor/insulator blends are typically processed to form a uniformly distributed network of conductive domains within the insulating matrix, marrying electronic and physical properties from individual components. Understanding of polymer-polymer interactions in such systems is thus crucial for property co-optimization. One of the commonly overlooked parameters is the structural configuration of the insulator on the resulting properties, especially the electronic properties. This study investigated how the tacticity of the matrix polymer, among other relevant parameters in play, impacts solid state crystallization in semiconductor/matrix blends and hence the resulting charge transport properties. We found an intricate dependence of the film morphology, aggregation behavior, electronic charge transport, and mixed ionic-electronic coupling properties on the insulator's tacticity. Our experimentally iterative approach shows that for a given application, when selecting semiconductor/insulator combinations, the tacticity of the matrix can be leveraged to optimize performance and vary solid-state structure.
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Emerging research suggests that psychological inflexibility may be a factor contributing to the development and maintenance of insomnia. However, less is known about the potential cognitive pathways that may explain this relationship. In this study, we investigated the serial mediating effects of psychological inflexibility and daytime insomnia-related rumination on the association between dysfunctional beliefs and attitudes about sleep (DBAS) and insomnia symptoms. The sample included 490 college students who underwent assessments at two time points over a 1-month period. The results of our mediational tests yielded significant indirect effects, supporting the prediction that psychological inflexibility and daytime insomnia rumination serially mediate the relationship between DBAS and insomnia. The study provides insights into potential mechanisms for insomnia, emphasizing the role of psychological inflexibility in perpetuating maladaptive cognitive processes associated with insomnia. Future researchers should explore other maladaptive responses to insomnia-related concerns and distress, such as worry and safety behaviors, and replicate findings in clinically elevated insomnia samples.
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INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise and international representation to establish evidence-based guidance on the mitigation of neuromodulation complications. This Neurostimulation Appropriateness Consensus Committee (NACC)® project intends to update evidence-based guidance and offer expert opinion that will improve efficacy and safety. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to October 2023. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant. RESULTS: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The NACC recommends best practices regarding the mitigation of complications associated with neurostimulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.
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Consenso , Terapia por Estimulación Eléctrica , Humanos , Terapia por Estimulación Eléctrica/métodos , Terapia por Estimulación Eléctrica/efectos adversos , Terapia por Estimulación Eléctrica/normas , Terapia por Estimulación Eléctrica/instrumentación , Medicina Basada en la Evidencia/normasRESUMEN
INTRODUCTION: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines. RESEARCH DESIGN AND METHODS: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications. RESULTS: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m2, HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m2 (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes. CONCLUSIONS: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events. TRIAL REGISTRATION NUMBER: NCT04049149.
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Diabetes Mellitus Tipo 2 , Secreción de Insulina , Medicina de Precisión , Humanos , Femenino , Masculino , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Adulto , Medicina de Precisión/métodos , Persona de Mediana Edad , China/epidemiología , Edad de Inicio , Adulto Joven , Insulina/uso terapéutico , Hipoglucemiantes/uso terapéutico , Estudios de Seguimiento , Glucemia/análisis , Hemoglobina Glucada/análisis , Pueblo Asiatico , Biomarcadores/análisis , Pronóstico , Pueblos del Este de AsiaRESUMEN
The Dimensional Obsessive-Compulsive Scale (DOCS) is widely used to measure obsessive-compulsive disorder (OCD) severity across four broad symptom dimensions (i.e., contamination, responsibility for harm, unacceptable thoughts, symmetry). Despite its proven utility, there is reason to suspect that the unacceptable thoughts subscale conflates different types of unacceptable thoughts that are meaningfully distinct from one another. In the current study, we first evaluated the psychometric properties of a newly developed DOCS violent and/or aggressive thoughts subscale. We then examined the factor structure, psychometric properties, and diagnostic sensitivity of a seven-factor version of the DOCS that includes the four original DOCS subscales and three more-specific versions of the unacceptable thoughts scale (i.e., sexually intrusive thoughts, violent and/or aggressive thoughts, and scrupulous or religious thoughts). The sample included 329 residential and intensive outpatients, the majority of which had a diagnosis of OCD (75.2%). The new unacceptable thoughts subscales demonstrated convergent and discriminant validity with unique associations between the subscales and depression, suicide, and perceived threat from emotions that were not present in the broader unacceptable thoughts subscale. The seven-factor version of the DOCS demonstrated slightly lower levels of diagnostic sensitivity than the original DOCS. Thus, the four-factor version of the DOCS is recommended for screening purposes. A score of 40 or higher on the seven-factor version of the DOCS best predicted a diagnosis of OCD. Overall, the three additional unacceptable thoughts subscales appear to be distinct factors that have potential value in research and clinical settings.
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Trastorno Obsesivo Compulsivo , Escalas de Valoración Psiquiátrica , Psicometría , Pensamiento , Humanos , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/psicología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Escalas de Valoración Psiquiátrica/normas , Reproducibilidad de los Resultados , Adulto Joven , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Emerging evidence supports mindfulness as a potential psychotherapy for post-traumatic stress disorder (PTSD). Individuals with subthreshold PTSD experience significant impairment in their daily life and functioning due to PTSD symptoms, despite not meeting the full diagnostic criteria for PTSD in DSM-5. Mindfulness skills, including non-judgmental acceptance, attentional control and openness to experiences may help alleviate PTSD symptoms by targeting characteristics such as intensified memory processing, dysregulated hyperarousal, avoidance, and thought suppression. This trial aims to test the effects of mindfulness-based cognitive therapy (MBCT) when compared to an active control. METHOD AND ANALYSIS: This 1:1 randomised controlled trial will enroll 160 participants with PTSD symptoms in 2 arms (MBCT vs. Seeking Safety), with both interventions consisting of 8 weekly sessions lasting 2 h each week and led by certified instructors. Assessments will be conducted at baseline (T0), post-intervention (T1), and 3 months post-intervention (T2), with the primary outcome being PTSD symptoms measured by the PTSD checklist for DSM-5 (PCL-5) at T1. Secondary outcomes include depression, anxiety, attention, experimental avoidance, rumination, mindfulness, and coping skills. Both intention-to-treat and per-protocol analyses will be performed. Mediation analysis will investigate whether attention, experimental avoidance, and rumination mediate the effect of mindfulness on PTSD symptoms. DISCUSSION: The proposed study will assess the effectiveness of MBCT in improving PTSD symptoms. The findings are anticipated to have implications for various areas of healthcare and contribute to the enhancement of existing intervention guidelines for PTSD. TRIAL REGISTRATION NUMBER: ChiCTR2200061863.
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Atención Plena , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/terapia , Trastornos por Estrés Postraumático/psicología , Atención Plena/métodos , Adulto , Terapia Cognitivo-Conductual/métodos , Femenino , Masculino , China , Persona de Mediana Edad , Resultado del Tratamiento , Pueblos del Este de AsiaRESUMEN
Background: The orthopaedic in-training examination (OITE) is a 275-question test for orthopaedic residents administered annually. As the field of orthopaedics changes, the OITE evolves its content. The incidence of hip preservation-related procedures has increased substantially over the past decade; nonetheless, an analysis of the trends of hip preservation questions on the OITE has not yet been performed. Purpose/Hypothesis: The purpose of the study was to evaluate the number and type of questions on the OITE related to hip preservation to determine whether trends over time paralleled the increases in hip-related care in clinical practice. It was hypothesized that the frequency of hip preservation questions on the OITE would increase with time. Study Design: Cross-sectional study. Methods: Each OITE between 2002 and 2021 was reviewed for questions related to hip preservation. The types of questions included under "hip preservation" were those related to femoroacetabular impingement (FAI), athletic soft tissue injuries of the hip, acetabular labral tears, hip arthroscopy, and surgical management of adult hip dysplasia-excluding arthroplasty. Questions were quantified and categorized by topic, taxonomy level, associated imaging, and cited sources. Results: There were 30 hip preservation-related questions between 2002 and 2021. Of these, 77% occurred within the past 10 years. Also, 14 questions (47%) had associated images in the question stem-the most common being radiographs (n = 8 questions). The most commonly tested subcategories were FAI (n = 11 questions [37%]), athletic injuries (n = 7 questions [23%]), and anatomy (n = 7 questions [23%]). Over the last 10 years, 97.9% of citations were from journal articles-the most common being the Journal of the American Academy of Orthopaedic Surgeons, Clinical Orthopedics and Related Research, and the American Journal of Sports Medicine. Conclusion: The frequency of hip preservation-related questions on the OITE has increased with time, reflecting trends in clinical practice.
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BACKGROUND: Lymphopenia is known for its significance on poor survivals in breast cancer patients. Considering full dosimetric data, this study aimed to develop and validate predictive models for lymphopenia after radiotherapy (RT) in breast cancer. MATERIAL AND METHODS: Patients with breast cancer treated with adjuvant RT were eligible in this multicenter study. The study endpoint was lympopenia, defined as the reduction in absolute lymphocytes and graded lymphopenia after RT. The dose-volume histogram (DVH) data of related critical structures and clinical factors were taken into account for the development of dense neural network (DNN) predictive models. The developed DNN models were validated using external patient cohorts. RESULTS: A total of 918 consecutive patients with invasive breast cancer enrolled. The training, testing, and external validating datasets consisted of 589, 203, and 126 patients, respectively. Treatment volumes at nearly all dose levels of the DVH were significant predictors for lymphopenia following RT, including volumes at very low-dose 1 Gy (V1) of organs at risk (OARs) including lung, heart and body, especially ipsilateral-lung V1. A final DNN model, combining full DVH dosimetric parameters of OARs and three key clinical factors, achieved a predictive accuracy of 75 % or higher. CONCLUSION: This study demonstrated and externally validated the significance of full dosimetric data, particularly the volume of low dose at as low as 1 Gy of critical structures on lymphopenia after radiation in patients with breast cancer. The significance of V1 deserves special attention, as modern VMAT RT technology often has a relatively high value of this parameter. Further study is warranted for RT plan optimization.