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The Korean Journal of Gastroenterology... Jun 2024Crohn's disease and ulcerative colitis are lifelong chronic inflammatory conditions, with many patients requiring ongoing immunomodulatory drug therapy for maintenance... (Review)
Review
Crohn's disease and ulcerative colitis are lifelong chronic inflammatory conditions, with many patients requiring ongoing immunomodulatory drug therapy for maintenance treatment. Recent therapeutic goals in inflammatory bowel disease (IBD) are not only aimed at symptomatic remission but also at achieving mucosal healing to improve the natural course of the disease. In this context, therapeutic approaches are being applied in clinical settings that involve early and appropriate use of drugs, such as immunomodulators or biologics, that have the potential to induce healing of the inflamed intestine before irreversible intestinal damage occurs. All drugs that continuously control intestinal inflammation in IBD can heal the mucosa and potentially reduce the incidence of colitis-associated bowel cancer; however, the continuous use of immunosuppressants can potentially increase the risk of malignancies. The safety issues of the drugs used in clinical practice are partly confirmed during their development processes or shortly after initial marketing, but in other cases, they are estimated through post-marketing case reports or epidemiological studies, sometimes decades after drug approval. This review explores the risks associated with malignancies related to the treatment of IBD, focusing on drugs currently approved in Republic of Korea.
Topics: Humans; Inflammatory Bowel Diseases; Immunosuppressive Agents; Antibodies, Monoclonal; Neoplasms; Risk Factors; Colitis, Ulcerative
PubMed: 38918036
DOI: 10.4166/kjg.2024.053 -
EBioMedicine Jun 2024External radiation therapy (RT) is often a primary treatment for inoperable meningiomas in the absence of established chemotherapy. Histone deacetylase 6 (HDAC6)...
BACKGROUND
External radiation therapy (RT) is often a primary treatment for inoperable meningiomas in the absence of established chemotherapy. Histone deacetylase 6 (HDAC6) overexpression, commonly found in cancer, is acknowledged as a driver of cellular growth, and inhibiting HDACs holds promise in improving radiotherapeutic efficacy. Downregulation of HDAC6 facilitates the degradation of β-catenin. This protein is a key element in the Wnt/β-catenin signalling pathway, contributing to the progression of meningiomas.
METHODS
In order to elucidate the associations and therapeutic potential of HDAC6 inhibitors (HDAC6i) in conjunction with RT, we administered Cay10603, HDAC6i, to both immortalised and patient-derived meningioma cells prior to RT in this study.
FINDINGS
Our findings reveal an increase in HDAC6 expression following exposure to RT, which is effectively mitigated with pre-treated Cay10603. The combination of Cay10603 with RT resulted in a synergistic augmentation of cytotoxic effects, as demonstrated through a range of functional assays conducted in both 2D as well as 3D settings; the latter containing syngeneic tumour microenvironment (TME). Radiation-induced DNA damage was augmented by pre-treatment with Cay10603, concomitant with the inhibition of β-catenin and minichromosome maintenance complex component 2 (MCM2) accumulation within the nucleus. This subsequently inhibited c-myc oncogene expression.
INTERPRETATION
Our findings demonstrate the therapeutic potential of Cay10603 to improve the radiosensitisation and provide rationale for combining HDAC6i with RT for the treatment of meningioma.
FUNDING
This work was funded by Brain Tumour Research Centre of Excellence award to C Oliver Hanemann.
PubMed: 38917510
DOI: 10.1016/j.ebiom.2024.105211 -
Journal of Medical Internet Research Jun 2024Cancer has emerged as a considerable global health concern, contributing substantially to both morbidity and mortality. Recognizing the urgent need to enhance the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cancer has emerged as a considerable global health concern, contributing substantially to both morbidity and mortality. Recognizing the urgent need to enhance the overall well-being and quality of life (QOL) of cancer patients, a growing number of researchers have started using online mindfulness-based interventions (MBIs) in oncology. However, the effectiveness and optimal implementation methods of these interventions remain unknown.
OBJECTIVE
This study evaluates the effectiveness of online MBIs, encompassing both app- and website-based MBIs, for patients with cancer and provides insights into the potential implementation and sustainability of these interventions in real-world settings.
METHODS
Searches were conducted across 8 electronic databases, including the Cochrane Library, Web of Science, PubMed, Embase, SinoMed, CINAHL Complete, Scopus, and PsycINFO, until December 30, 2022. Randomized controlled trials involving cancer patients aged ≥18 years and using app- and website-based MBIs compared to standard care were included. Nonrandomized studies, interventions targeting health professionals or caregivers, and studies lacking sufficient data were excluded. Two independent authors screened articles, extracted data using standardized forms, and assessed the risk of bias in the studies using the Cochrane Bias Risk Assessment Tool. Meta-analyses were performed using Review Manager (version 5.4; The Cochrane Collaboration) and the meta package in R (R Foundation for Statistical Computing). Standardized mean differences (SMDs) were used to determine the effects of interventions. The Reach, Effectiveness, Adoption, Implementation, and Maintenance framework was used to assess the potential implementation and sustainability of these interventions in real-world settings.
RESULTS
Among 4349 articles screened, 15 (0.34%) were included. The total population comprised 1613 participants, of which 870 (53.9%) were in the experimental conditions and 743 (46.1%) were in the control conditions. The results of the meta-analysis showed that compared with the control group, the QOL (SMD 0.37, 95% CI 0.18-0.57; P<.001), sleep (SMD -0.36, 95% CI -0.71 to -0.01; P=.04), anxiety (SMD -0.48, 95% CI -0.75 to -0.20; P<.001), depression (SMD -0.36, 95% CI -0.61 to -0.11; P=.005), distress (SMD -0.50, 95% CI -0.75 to -0.26; P<.001), and perceived stress (SMD -0.89, 95% CI -1.33 to -0.45; P=.003) of the app- and website-based MBIs group in patients with cancer was significantly alleviated after the intervention. However, no significant differences were found in the fear of cancer recurrence (SMD -0.30, 95% CI -1.04 to 0.44; P=.39) and posttraumatic growth (SMD 0.08, 95% CI -0.26 to 0.42; P=.66). Most interventions were multicomponent, website-based health self-management programs, widely used by international and multilingual patients with cancer.
CONCLUSIONS
App- and website-based MBIs show promise for improving mental health and QOL outcomes in patients with cancer, and further research is needed to optimize and customize these interventions for individual physical and mental symptoms.
TRIAL REGISTRATION
PROSPERO CRD42022382219; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=382219.
Topics: Adult; Female; Humans; Male; Internet; Internet-Based Intervention; Mindfulness; Neoplasms; Quality of Life
PubMed: 38917445
DOI: 10.2196/47704 -
International Journal of... Apr 2024Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease...
BACKGROUND
Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions.
METHODS
We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022.
RESULTS
We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases.
CONCLUSION
The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.
Topics: Humans; Antitubercular Agents; Male; Retrospective Studies; Female; Middle Aged; Acute Kidney Injury; Aged; Adult; Renal Insufficiency, Chronic; Rifampin; Isoniazid; Nephritis, Interstitial; Tuberculosis; Pyrazinamide; Glomerulonephritis; Immune Reconstitution Inflammatory Syndrome
PubMed: 38916390
DOI: 10.4103/ijmy.ijmy_33_24 -
PeerJ 2024In Japan, the number of older adults requiring long-term care insurance (LTCI) is increasing and the cost is becoming a social problem. In these fields, the role of...
BACKGROUND
In Japan, the number of older adults requiring long-term care insurance (LTCI) is increasing and the cost is becoming a social problem. In these fields, the role of geriatric rehabilitation includes maintaining the physical function and LTCI certification levels. The prevalence of sarcopenia is high among older adults requiring LTCI certification, and there are many opportunities to assess the handgrip strength, walking speed, and muscle mass. This study aimed to identify sarcopenia-related assessments sensitive to transitions in LTCI certification levels and determine cut-off values to predict them.
METHODS
This prospective cohort study analyzed 98 daycare users (mean age ± standard error: 78.5 ± 0.8 years) between March 2019 and 2023. The participants received LTCI certification before the study, and their levels were renewed between baseline and follow-up (six months later). The measurements included handgrip strength, usual walking speed, body composition, and SARC-F score. Participants were classified into maintenance, deterioration, and improvement groups according to the changes in their LTCI certification levels. We identified factors contributing to the deterioration of LTCI certification levels using baseline and before and after comparisons, multivariate analyses, and receiver operating characteristic analyses.
RESULTS
No significant differences were observed in the baseline data among the groups. Only the deterioration group showed significant changes in the usual walking speed (baseline: 0.64 ± 0.25 m/s, follow-up: 0.53 ± 0.21 m/s, = 0.008) and body fat percentage (baseline: 29.2 ± 9.9%, follow-up: 27.7 ± 10.3%, = 0.047). Binomial logistic regression showed that changes in usual walking speed ( = 0.042) and body fat percentage ( = 0.011) were significantly associated with the deterioration of LTCI certification levels, even after adjustment. The cutoff values of change to discriminate the deterioration of LTCI certification levels were -0.14 m/s at the usual walking speed ( = 0.047) and -1.0% for body fat percentage ( = 0.029).
CONCLUSIONS
Decreases in usual walking speed and body fat percentage may predict worse certification levels in older adults requiring LTCI.
Topics: Humans; Walking Speed; Male; Female; Aged; Insurance, Long-Term Care; Prospective Studies; Hand Strength; Japan; Sarcopenia; Body Composition; Certification; Adipose Tissue; Geriatric Assessment
PubMed: 38915385
DOI: 10.7717/peerj.17529 -
Systematic Reviews Jun 2024Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a...
BACKGROUND
Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS
We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
DISCUSSION
Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-ID CRD42023410645.
Topics: Humans; Systematic Reviews as Topic; Network Meta-Analysis; Schizophrenia, Treatment-Resistant; Transcranial Direct Current Stimulation; Antipsychotic Agents; Transcranial Magnetic Stimulation; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 38915121
DOI: 10.1186/s13643-024-02585-2 -
BMC Psychiatry Jun 2024Recent years have seen a growing interest in the use of digital tools for delivering person-centred mental health care. Experience Sampling Methodology (ESM), a... (Randomized Controlled Trial)
Randomized Controlled Trial
Strategies, processes, outcomes, and costs of implementing experience sampling-based monitoring in routine mental health care in four European countries: study protocol for the IMMERSE effectiveness-implementation study.
BACKGROUND
Recent years have seen a growing interest in the use of digital tools for delivering person-centred mental health care. Experience Sampling Methodology (ESM), a structured diary technique for capturing moment-to-moment variation in experience and behaviour in service users' daily life, reflects a particularly promising avenue for implementing a person-centred approach. While there is evidence on the effectiveness of ESM-based monitoring, uptake in routine mental health care remains limited. The overarching aim of this hybrid effectiveness-implementation study is to investigate, in detail, reach, effectiveness, adoption, implementation, and maintenance as well as contextual factors, processes, and costs of implementing ESM-based monitoring, reporting, and feedback into routine mental health care in four European countries (i.e., Belgium, Germany, Scotland, Slovakia).
METHODS
In this hybrid effectiveness-implementation study, a parallel-group, assessor-blind, multi-centre cluster randomized controlled trial (cRCT) will be conducted, combined with a process and economic evaluation. In the cRCT, 24 clinical units (as the cluster and unit of randomization) at eight sites in four European countries will be randomly allocated using an unbalanced 2:1 ratio to one of two conditions: (a) the experimental condition, in which participants receive a Digital Mobile Mental Health intervention (DMMH) and other implementation strategies in addition to treatment as usual (TAU) or (b) the control condition, in which service users are provided with TAU. Outcome data in service users and clinicians will be collected at four time points: at baseline (t), 2-month post-baseline (t), 6-month post-baseline (t), and 12-month post-baseline (t). The primary outcome will be patient-reported service engagement assessed with the service attachment questionnaire at 2-month post-baseline. The process and economic evaluation will provide in-depth insights into in-vivo context-mechanism-outcome configurations and economic costs of the DMMH and other implementation strategies in routine care, respectively.
DISCUSSION
If this trial provides evidence on reach, effectiveness, adoption, implementation and maintenance of implementing ESM-based monitoring, reporting, and feedback, it will form the basis for establishing its public health impact and has significant potential to bridge the research-to-practice gap and contribute to swifter ecological translation of digital innovations to real-world delivery in routine mental health care.
TRIAL REGISTRATION
ISRCTN15109760 (ISRCTN registry, date: 03/08/2022).
Topics: Humans; Mental Health Services; Germany; Belgium; Slovakia; Mental Disorders; Ecological Momentary Assessment; Europe; Cost-Benefit Analysis
PubMed: 38915006
DOI: 10.1186/s12888-024-05839-4 -
JMIR MHealth and UHealth Jun 2024Digital mental health services are increasingly being provided by employers as health benefit programs that can improve access to and remove barriers to mental health... (Observational Study)
Observational Study
BACKGROUND
Digital mental health services are increasingly being provided by employers as health benefit programs that can improve access to and remove barriers to mental health care. Stratified care models, in particular, offer personalized care recommendations that can offer clinically effective interventions while conserving resources. Nonetheless, clinical evaluation is needed to understand their benefits for mental health and their use in a real-world setting.
OBJECTIVE
This study aimed to examine the changes in clinical outcomes (ie, depressive and anxiety symptoms and well-being) and to evaluate the use of stratified blended care among members of an employer-sponsored digital mental health benefit.
METHODS
In a large prospective observational study, we examined the changes in depressive symptoms (9-item Patient Health Questionnaire), anxiety symptoms (7-item Generalized Anxiety Disorder scale), and well-being (5-item World Health Organization Well-Being Index) for 3 months in 509 participants (mean age 33.9, SD 8.7 years; women: n=312, 61.3%; men: n=175, 34.4%; nonbinary: n=22, 4.3%) who were newly enrolled and engaged in care with an employer-sponsored digital mental health platform (Modern Health Inc). We also investigated the extent to which participants followed the recommendations provided to them through a stratified blended care model.
RESULTS
Participants with elevated baseline symptoms of depression and anxiety exhibited significant symptom improvements, with a 37% score improvement in depression and a 29% score improvement in anxiety (P values <.001). Participants with baseline scores indicative of poorer well-being also improved over the study period (90% score improvement; P=.002). Furthermore, over half exhibited clinical improvement or recovery for depressive symptoms (n=122, 65.2%), anxiety symptoms (n=127, 59.1%), and low well-being (n=82, 64.6%). Among participants with mild or no baseline symptoms, we found high rates of maintenance for low depressive (n=297, 92.2%) and anxiety (n=255, 86.7%) symptoms and high well-being (n=344, 90.1%). In total, two-thirds of the participants (n=343, 67.4%) used their recommended care, 16.9% (n=86) intensified their care beyond their initial recommendation, and 15.7% (n=80) of participants underused care by not engaging with the highest level of care recommended to them.
CONCLUSIONS
Participants with elevated baseline depressive or anxiety symptoms improved their mental health significantly from baseline to follow-up, and most participants without symptoms or with mild symptoms at baseline maintained their mental health over time. In addition, engagement patterns indicate that the stratified blended care model was efficient in matching individuals with the most effective and least costly care while also allowing them to self-determine their care and use combinations of services that best fit their needs. Overall, the results of this study support the clinical effectiveness of the platform for improving and preserving mental health and support the utility and effectiveness of stratified blended care models to improve access to and use of digitally delivered mental health services.
Topics: Humans; Female; Male; Adult; Prospective Studies; Longitudinal Studies; Mental Health Services; Middle Aged; Surveys and Questionnaires; Depression; Telemedicine
PubMed: 38913405
DOI: 10.2196/48298 -
Advances in Drug and Alcohol Research 2024The Methadone Maintenance Treatment (MMT) program has been proven to be beneficial in reducing illicit opioid use, increasing access to and retention of HIV treatment...
The Methadone Maintenance Treatment (MMT) program has been proven to be beneficial in reducing illicit opioid use, increasing access to and retention of HIV treatment and other therapies, and reducing HIV transmission, and other drug-related morbidities and mortalities. However, determinants of treatment retention and outcomes for opioid-dependent persons accessing MMT in Kenya are limited. We sought to identify factors contributing to poor treatment outcomes among opioid-dependent persons enrolled in the Mombasa MMT program, between 2017 and 2019. We conducted a retrospective records review for opioid-dependent persons receiving Methadone treatment in the Kisauni MAT clinic enrolled during 2017-2019. We defined poor clinical or health-related treatment outcome as any client Lost-To-Follow-Up (LTFU), turned HIV or Viral hepatitis positive, and/or missed two or more antiretroviral therapy (ART) appointments intake during MMT. Variables abstracted from clinical and pharmacological MMT service delivery tools included socio-demographic characteristics, clinical history, risk factors, and MMT outcomes. Data were analyzed using . We calculated Prevalence Odds Ratios (POR) and 95% Confidence Intervals (CI) to identify factors associated with adverse health outcomes. Of the total 443 eligible records, the mean age was 37 years (SD ± 7.2) and males comprised 90.7%. The majority of females clients, 79.1% (34/43), were aged ≤35 years, 7.0% (3/43) had no education, 32.6% (14/43) were employed, 39.5% (17/43) were HIV positive and 18.6% (8/43) were HCV-positive. Overall, adverse treatment outcomes were at 27.5% (122/443), namely: LTFU at 22.8% (101/443), new HIV cases at 1.0% (4/391), HCV at 1.2% (5/405), and Hepatitis B Virus (HBV) at 1.2% (5/411), and 1.1% (5/443) died. Of HIV-infected clients linked to Comprehensive Care Clinic (CCC), 3.6% (2/56) defaulted from ART, and 25% (2/8) had detectable Viral Load of those retested. Lack of formal education (POR: 2.7, 95% CI: 1.3-5.7), unemployment (POR: 2.4, 95% CI: 1.4-4.0), and being a Non-Injector (POR: 1.7, 95% CI: 1.0-2.9) were negatively associated with treatment retention. Females were younger, and more educated with higher HIV and HCV prevalence. Being a Non-injector, unemployment, and lack of formal education may increase the likelihood of poor treatment outcomes among MMT clients. Closer monitoring of MMT clients with these characteristics is recommended with the integration of CCC into MMT services.
PubMed: 38912085
DOI: 10.3389/adar.2024.11791 -
International Journal of Chronic... 2024Current guidelines recommend triple therapy maintenance inhalers for patients with recurrent exacerbations of chronic obstructive pulmonary disease (COPD); however,...
PURPOSE
Current guidelines recommend triple therapy maintenance inhalers for patients with recurrent exacerbations of chronic obstructive pulmonary disease (COPD); however, these maintenance therapies are underutilized. This study aimed to understand how physicians make COPD treatment decisions, and how combination maintenance therapies are utilized in a real-world setting.
PATIENTS AND METHODS
This exploratory, hypothesis-generating, non-interventional study used a cross-sectional online survey that was administered to a sample of practicing physicians in the United States. The survey included five fictitious vignettes detailing common symptoms experienced by patients with COPD. Survey questions included factors physicians consider in their decisions, and perceived barriers to prescribing treatments. Repeated measures multivariable analyses were conducted to evaluate how likely physicians were to switch to triple therapy versus no change to patient's current maintenance therapy or change to another maintenance therapy.
RESULTS
In total, 200 physicians completed the survey. Cost of treatment and patient access to treatment were reported as the most common barriers physicians consider in their prescribing decisions. Physicians were more likely to switch a patient's maintenance inhaler to triple therapy versus no change to maintenance inhaler if they considered the patient's history of new symptoms, insurance status, and clinical guidelines in their decision. Physicians with more experience treating patients with COPD, and those who treat more patients with COPD per week, were more likely to switch to triple therapy versus no change to maintenance inhaler.
CONCLUSION
This study demonstrates the complexity of factors that can influence physicians' decisions when prescribing treatments for patients with COPD, including considerations of treatment cost, patient access and adherence, patient comorbidities, efficacy of current treatment, clinical guidelines, and provider's level of experience treating COPD. Further research may help elucidate the relative importance of the factors influencing physicians' decisions and inform what types of decision-support tools would be most beneficial.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Cross-Sectional Studies; Practice Patterns, Physicians'; Male; Clinical Decision-Making; Female; Middle Aged; United States; Health Care Surveys; Bronchodilator Agents; Administration, Inhalation; Nebulizers and Vaporizers; Drug Therapy, Combination; Attitude of Health Personnel; Treatment Outcome; Health Knowledge, Attitudes, Practice; Drug Costs; Lung; Aged; Practice Guidelines as Topic; Adult; Health Services Accessibility
PubMed: 38912054
DOI: 10.2147/COPD.S454877