Early Stages Of Treatment Research Articles

Cocaine abstinence during the “critical period” of a contingency management trial predicts future abstinence in people with cocaine use disorder

BackgroundContingency Management (CM) is being piloted as a treatment for stimulant use disorder in several US states, highlighting the need for treatment optimization. One important goal of optimization is decreasing drug use during the early stages of treatment, which has predicted success in other interventions. However, this “critical period” has not been reported in CM trials. The purpose of this analysis was to determine if, after accounting for baseline abstinence and incentive condition, abstinence in a CM trial for people with Cocaine Use Disorder (CUD) could be predicted by cocaine use during a first-week critical period. MethodsEighty-seven participants with CUD were randomized to receive contingent high or low value incentives for cocaine abstinence or were in a non-contingent control group. Generalized estimating equations (GEE) were used to analyze urine test results over 36 timepoints during the 12-week intervention. To assess for a critical period, the first three visits were included in the GEE as a covariate for remaining urine test results. ResultsParticipants who provided more negative samples during the critical period were significantly more likely to produce a negative urine sample during the remainder of the trial, though some effects of group remained after controlling for the critical period. ConclusionsThese results indicate that a critical period exists for CM trials, and it can explain a substantial amount of future performance. Early contact with an abstinence-contingent high magnitude alternative reinforcer may explain additional performance beyond the critical period, further justifying the use of high magnitude alternative reinforcers.

Consecutive treatments of methamphetamine promote the development of cardiac pathological symptoms in zebrafish.

Chronic methamphetamine use, a widespread drug epidemic, has been associated with cardiac morphological and electrical remodeling, leading to the development of numerous cardiovascular diseases. While methamphetamine has been documented to induce arrhythmia, most results originate from clinical trials from users who experienced different durations of methamphetamine abuse, providing no documentation on the use of methamphetamine in standardized settings. Additionally, the underlying molecular mechanism on how methamphetamine affects the cardiovascular system remains elusive. A relationship was sought between cardiotoxicity and arrhythmia with associated methamphetamine abuse in zebrafish to identify and to understand the adverse cardiac symptoms associated with methamphetamine. Zebrafish were first treated with methamphetamine 3 times a week over a 2-week duration. Immediately after treatment, zebrafish underwent electrocardiogram (ECG) measurement using an in-house developed acquisition system for electrophysiological analysis. Subsequent analyses of cAMP expression and Ca2+ regulation in zebrafish cardiomyocytes were conducted. cAMP is vital to development of myocardial fibrosis and arrhythmia, prominent symptoms in the development of cardiovascular diseases. Ca2+ dysregulation is also a factor in inducing arrhythmias. During the first week of treatment, zebrafish that were administered with methamphetamine displayed a decrease in heart rate, which persisted throughout the second week and remained significantly lower than the heart rate of untreated fish. Results also indicate an increased heart rate variability during the early stage of treatment followed by a decrease in the late stage for methamphetamine-treated fish over the duration of the experiment, suggesting a biphasic response to methamphetamine exposure. Methamphetamine-treated fish also exhibited reduced QTc intervals throughout the experiment. Results from the cAMP and Ca2+ assays demonstrate that cAMP was upregulated and Ca2+ was dysregulated in response to methamphetamine treatment. Collagenic assays indicated significant fibrotic response to methamphetamine treatment. These results provide potential insight into the role of methamphetamine in the development of fibrosis and arrhythmia due to downstream effectors of cAMP.

Transplantation of autologous bone marrow–derived mononuclear cells into cerebrospinal fluid in a canine model of spinal cord injury

IntroductionSpinal cord injury (SCI) is associated with severe dysfunction of nervous tissue, and repair via the transplantation of bone marrow–derived mononuclear cells (BM-MNCs) into cerebrospinal fluid yields promising results. It is essential to understand the underlying mechanisms; therefore, this study aimed to evaluate the regenerative potential of autologous BM-MNC transplantation in a canine model of acute SCI. MethodsSix dogs were included in this study, and SCI was induced using an epidural balloon catheter between L2 and L3, particularly in the area of the anterior longitudinal ligament. BM-MNC transplantation was performed, and T2-weighted magnetic resonance imaging (MRI) was conducted at specific time points (i.e., immediately after inducing SCI and at 1, 2, and 4 weeks after inducing SCI); moreover, the expression of growth-associated protein 43 (GAP-43) was evaluated. ResultsMRI revealed that the signal intensity reduced over time in both BM-MNC–treated and control groups. However, the BM-MNC–treated group exhibited a significantly faster reduction than the control group during the early stages of SCI induction (BM-MNC–treated group: 4.82 ± 0.135 cm [day 0], 1.71 ± 0.134 cm [1 week], 1.37 ± 0.036 cm [2 weeks], 1.21 cm [4 weeks]; control group: 4.96 ± 0.211 cm [day 0], 2.49 ± 0.570 cm [1 week], 1.56 ± 0.045 cm [2 weeks], 1.32 cm [4 weeks]). During the early stages of treatment, GAP-43 was significantly expressed at the proximal end of the injured spinal cord in the BM-MSC–treated group, whereas it was scarcely expressed in the control group. ConclusionsIn SCI, transplanted BM-MNCs can activate the expression of GAP-43, which is involved in axonal elongation (an important process in spinal cord regeneration). Thus, cell therapy with BM-MNCs can provide favorable outcomes in terms of better regenerative capabilities compared with other therapies.

A review on reconstruction algorithms and hardware implementation in electrical impedance tomography

The current medical imaging techniques can only be used in a few diagnostic scenarios after the development of qualitative lesions, and they frequently include the use of radiation, among other things. Electrical impedance tomography, in contrast, uses no radiation and is non-invasive. Electric impedance tomography (EIT), which has these benefits, is frequently utilized for the early stages of disease detection and treatment. This study discusses the research advancements, image reconstruction methods, hardware system design, and clinical applications of EIT in the treatment of lung disorders for the application of EIT in the treatment of lung lesions. The intricacy of EIT systems and their solutions is explained by looking at and introducing a few key components of EIT technology. This provides research ideas for future studies and confirms the technology’s extensive development prospects. The outcome demonstrates that EIT is still in a relatively early stage of development and that image reconstruction algorithms are now being utilized to improve imaging resolution. The accuracy of data collection and processing is increasing, and hardware technology is also advancing quickly. EIT is also employed in clinical settings for pathology in the bladder, brain, and lungs. Future uses of EIT in medicine have a lot of potential for real-time, long-term monitoring and early diagnosis.

A systematic review of clozapine-associated inflammation and related monitoring.

Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6,915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: i) the impact of clozapine on inflammatory markers, ii) monitoring cardiac and other organ function during clozapine-associated inflammatory processes, and iii) monitoring non-specific signs and symptoms of inflammation. Elevated levels of C-reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4 to 8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically-relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine-associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence-based guidelines for the monitoring of clozapine-associated inflammation.

A targeted strategic peer support intervention to increase adherence to video teletherapy exposure and response prevention treatment for obsessive-compulsive disorder: a retrospective observational analysis.

Exposure and response prevention (ERP) therapy, a form of cognitive-behavioral therapy, is a first-line, evidence-based treatment for obsessive-compulsive disorder (OCD) for adults and children. It is effective for the majority of those who engage in it, but treatment adherence can be challenging for some due to the stress involved in the treatment as well as different life circumstances that arise. To help improve treatment adherence, NOCD, a provider of video teletherapy ERP, identifies those at risk of non-adherence using a prediction algorithm trained on a data set of N = 13,809 and provides targeted peer support interventions by individuals ("Member Advocates") who successfully completed ERP treatment for OCD. Member Advocates, using lived OCD experience as well as experience with ERP, engage at-risk patients through digital messaging to engage, educate, and encourage patients in the early stages of treatment. From June 2022 to August 2022, N = 815 patients deemed at risk were reached out to and n = 251 responded and engaged with the Member Advocates. In the at-risk patients who engaged, the intervention resulted in a significant mean 30.4% more therapy hours completed compared to those who did not engage. Additionally, engaged patients had greater reductions in OCD severity. These results have implications for how data science, digital interventions, and strategic peer-to-peer communication and support can be combined to enhance the effectiveness of treatment.

Evaluation of the knowledge and practice of family physicians in the management of diabetes mellitus type 2 in Iran

BackgroundThe increasing prevalence and occurrence of type 2 diabetes has made it a widespread epidemic. Being the first line of care, family doctors can play an essential role in this field. The knowledge of these doctors about how to deal with the prevention, diagnosis, and correct treatment of patients is fundamental in reducing the burden of this disease in the community. In this study, we decided to evaluate the knowledge and practice of family doctors in Shiraz-Iran and its related factors in managing Diabetes.MethodThis analytical cross-sectional study was conducted among family doctors of two primary healthcare centers, Shahadai Wal-Fajr Health Center and the Enghlab Health Center in Shiraz, Iran, from March 2021 to August 2021. A researcher-designed diabetes questionnaire consisting of 21 items and a data collection form including demographic information and other related factors was used in this study. An interviewer asked the questions from participants at their workplace and completed the questionnaires. The data were analyzed by SPSS-20 software. A linear regression test was used to investigate the factors affecting the questionnaire score. A one-way ANOVA test was used to compare questionnaire scores among multiple groups.ResultsOn average, the participants obtained 62.5% of the total score. The average scores for each question in the screening, the diagnosis, and the treatment sections were 0.5 ± 0.28, 0.65 ± 0.2, and 0.66 ± 0.17, respectively. Physicians’ knowledge about the blood sugar threshold for diagnosing Diabetes was suboptimal, and 81.9, 47, 43 correctly mentioned the FBS, 2hrpp BS, and HbA1c threshold, respectively. Although 95% knew the first line medication but 33.6% prescribed 2nd or 3rd medication for DM treatment. Only 43% knew the goal of therapy. Sixty-three doctors (42%) have not registered any referrals for newly diagnosed uncomplicated diabetic patients, and 37.6% referred these new DM cases to an internist or endocrinologist at the first visit. Microvascular complication screening, such as testing for microalbuminuria and ophthalmologist consultation reported by 32. 89% and 8% of physicians, respectively. Years since graduation was the determining factor of the knowledge level of doctors in this study. Regarding the preferred education method, most participants selected the workshop method as the preferred training method. Virtual education was ranked as the second preferred educational method.ConclusionThe knowledge and practice of general family doctors were lower than the optimal level in diabetes screening, diagnosis, and treatment. In the treatment of patients, the knowledge of most of the physicians was appropriate in the early stages of treatment, such as determining the time to start the medication and the first line of treatment, but in the follow-up and more advanced treatment, the knowledge and performance of the doctors were less than expected. They prefer to refer patients to higher levels in the healthcare system. Recently graduated physicians had better knowledge and approach to DM management. Therefore, effective periodic training should be conducted as soon as possible to address this pitfall and improve the quality of care. Workshops and virtual education were the most preferred education methods from the participants’ points of view. So, it is suggested that these methods be used as the first training methods. Implementing the specialty training program for family medicine (which has been started in our country for a few years) is the best final solution. In addition, A clinical guideline should be designed for family physicians highlighting these physicians’ roles in the management of Diabetes.

Recent Advances in the Development of Non‐Invasive Imaging Probes for Cancer Immunotherapy

AbstractThe last two decades have witnessed a major revolution in the field of tumor immunology including clinical progress using various immunotherapy strategies. These advances have highlighted the potential for approaches that harness the power of the immune system to fight against cancer. While cancer immunotherapies have shown significant clinical successes, patient responses vary widely due to the complex and heterogeneous nature of tumors and immune responses, calling for reliable biomarkers and therapeutic strategies to maximize the benefits of immunotherapy. Especially, stratifying responding individuals from non‐responders during the early stages of treatment could help avoid long‐term damage and tailor personalized treatments. In efforts to develop non‐invasive means for accurately evaluating and predicting tumor response to immunotherapy, multiple affinity‐based agents targeting immune cell markers and checkpoint molecules have been developed and advanced to clinical trials. In addition, researchers have recently turned their attention to substrate and activity‐based imaging probes that can provide real‐time, functional assessment of immune response to treatment. Here, we highlight some of those recently designed probes that image functional proteases as biomarkers of cancer immunotherapy with a focus on their chemical design and detection modalities and discuss challenges and opportunities for the development of imaging tools utilized in cancer immunotherapy.

Recent Advances in the Development of Non-Invasive Imaging Probes for Cancer Immunotherapy.

The last two decades have witnessed a major revolution in the field of tumor immunology including clinical progress using various immunotherapy strategies. These advances have highlighted the potential for approaches that harness the power of the immune system to fight against cancer. While cancer immunotherapies have shown significant clinical successes, patient responses vary widely due to the complex and heterogeneous nature of tumors and immune responses, calling for reliable biomarkers and therapeutic strategies to maximize the benefits of immunotherapy. Especially, stratifying responding individuals from non-responders during the early stages of treatment could help avoid long-term damage and tailor personalized treatments. In efforts to develop non-invasive means for accurately evaluating and predicting tumor response to immunotherapy, multiple affinity-based agents targeting immune cell markers and checkpoint molecules have been developed and advanced to clinical trials. In addition, researchers have recently turned their attention to substrate and activity-based imaging probes that can provide real-time, functional assessment of immune response to treatment. Here, we highlight some of those recently designed probes that image functional proteases as biomarkers of cancer immunotherapy with a focus on their chemical design and detection modalities and discuss challenges and opportunities for the development of imaging tools utilized in cancer immunotherapy.

Suburban Blues: Urbanicity, healthcare service mix and spatial patterns of admissions for depression

Abstract Objectives Medical practice variation is a key target for policy makers aiming to improve the efficiency of healthcare delivery. Studies point to strong regional variation in healthcare utilization in Austria which seems to be a by-product of institutional rules and healthcare service mix rather than variance in epidemiology. Methods We use a set of routine healthcare data on hospital admissions for depressive episodes (ICD-10 F320-F329) of adult Austrian patients from 2009 to 2014 on the municipality level to explore spatial patterns of supply-induced demand by nearby hospitals (“Roemer's law”) in hospital admission rates. The dataset covers 99,844 hospital episodes of 69,555 patients in 2,114 municipalities. We estimate a random effects spatial autoregressive model to regress log hospital admission rates on hospital supply and urbanicity as proxies for the municipalities’ healthcare service mix alongside a set of relevant socio-economic/-demographic characteristics. Preliminary results Hospital admission rates per 1,000 inhabitants in the population for depressive episodes vary strongly between municipalities (min=0, max=37.7, mean=1.9, SD = 1.8). We find higher admission rates in the population of suburban municipalities (0.10, 95%-CI: 0.58 - 0.13) and municipalities with hospitals (0.07, 95%-CI: 0.01 - 0.1), regardless of hospital type and size. The spatial structure suggests positive spill-over effects on the hospital admission rates between neighbouring municipalities. Conclusions Our results suggest that high admission rates are a seemingly suburban phenomenon and that healthcare service mix is a driving factor for admission rates. Though it is not clear whether the regional variation in medical practice reflects under- or oversupply of hospital care, promoting timely access to primary care and early-stage treatments may reduce the burden of avoidable hospitalizations for patients and public budgets, and close a gap of unmet need for care of vulnerable populations. Key messages • Hospital admission rates for depression of adults per 1,000 inhabitants in the population for depressive episodes vary strongly between municipalities. • Hospital supply and urbanicity are major driving factors of the spatial patterns in regional varation of hospital admissions.

Real-world safety of icosapent ethyl: analysis based on spontaneous reports in FAERS database

ABSTRACT Background The triglyceride-lowering drug, icosapent ethyl (IPE), was granted a new indication for the reduction of atherosclerotic cardiovascular disease risk in 2019. This study aimed to investigate the safety profile of IPE by mining the FDA Adverse Event Reporting System (FAERS) database. Methods The reporting odds ratio was used to analyze IPE’s adverse events (AEs) based on the FAERS data from July 2012 to December 2022. We described the characteristics of AE reports and evaluated the clinical prioritization of AEs. Then we defined and analyzed nine interested adverse drug reactions (ADRs) in both overall and subgroups, and investigated the times to onset. Results The findings of our study strengthen the evidence for an increased risk of atrial fibrillation using IPE. IPE alone may not increase the risk of bleeding unless combined with antithrombotic drugs. Similar to statins, IPE alone can increase the risk of musculoskeletal pain, drug-related hepatic disorders, and hyperglycemia, but the risk could not double when IPE was combined with statins. Most ADRs occur in the early stage of treatment. Conclusions This study provides a comprehensive real-world safety profile of IPE, which indicates that IPE is well-tolerated.

The role of co-occurring disorders in criminal recidivism and psychiatric recovery among adults with opioid use disorder and criminal-legal involvement: A statewide retrospective cohort study

IntroductionIndividuals with opioid use disorder (OUD) in the criminal-legal system commonly present co-occurring mental health disorders. However, evidence-based treatment for high-risk populations such as those with co-occurring disorders is often unavailable within jails and prisons. Coordination of timely and affordable access to behavioral health treatment following incarceration is critical to address the multidimensional needs of people with co-occurring needs. However, the role of co-occurring disorders among adults with OUD and criminal-legal involvement who are accessing community-based treatment is understudied. MethodsThis retrospective cohort study investigated community and recovery outcomes among 2039 adults with OUD and criminal-legal involvement enrolled in a statewide forensic treatment initiative between October 2015 to March 2018. Using court records and clinical data, we assessed the impact of co-occurring OUD and mental health disorders on criminal recidivism and psychiatric recovery and the moderating role of co-occurring disorders on the relationship between community-based treatment and these outcomes. ResultsWe found that 47 % of those with OUD also had an underlying mental health disorder. Co-occurring OUD and mental health disorders predicted higher rates of recidivism during the early stages of treatment. Furthermore, group and individual therapy services were associated with lower odds of recidivism. A co-occurring disorder was an important predictor of more severe behavioral health needs when exiting community-based services and did moderate the relationship between service utilization—specifically group therapy and substance use outpatient services—and psychiatric recovery (i.e., behavioral health needs at exit). ConclusionsCo-occurring mental health disorders are highly prevalent among adults with OUD who have criminal-legal involvement, but it appears that they can benefit from social support services in the community. Given the multidimensional needs of this high-risk population, criminal-legal stakeholders and community-based clinicians must work in tandem to develop tailored treatment plans that give individuals with co-occurring OUD and mental health disorders the best chance for success post-incarceration rather than a siloed approach to overlapping disorders.

Modified interactive Q-learning for attenuating the impact of model misspecification with treatment effect heterogeneity.

A sequential multiple assignment randomized trial, which incorporates multiple stages of randomization, is a popular approach for collecting data to inform personalized and adaptive treatments. There is an extensive literature on statistical methods to analyze data collected in sequential multiple assignment randomized trials and estimate the optimal dynamic treatment regime. Q-learning with linear regression is widely used for this purpose due to its ease of implementation. However, model misspecification is a common problem with this approach, and little attention has been given to the impact of model misspecification when treatment effects are heterogeneous across subjects. This article describes the integrative impact of two possible types of model misspecification related to treatment effect heterogeneity: omitted early-stage treatment effects in late-stage main effect model, and violated linearity assumption between pseudo-outcomes and predictors despite non-linearity arising from the optimization operation. The proposed method, aiming to deal with both types of misspecification concomitantly, builds interactive models into modified parametric Q-learning with Murphy's regret function. Simulations show that the proposed method is robust to both sources of model misspecification. The proposed method is applied to a two-stage sequential multiple assignment randomized trial with embedded tailoring aimed at reducing binge drinking in first-year college students.

Elucidating Interfacial Dynamics of Ti-Al Systems Using Molecular Dynamics Simulation and Markov State Modeling.

Due to their remarkable mechanical and chemical properties, Ti-Al-based materials are attracting considerable interest in numerous fields of engineering, such as automotive, aerospace, and defense. With their low density, high strength, and resistance to corrosion and oxidation, these intermetallic alloys and metal-compound composites have found diverse applications. However, additive manufacturing and heat treatment of Ti-Al alloys frequently lead to brittleness and severe formation of defects. The present study delves into the interfacial dynamics of these Ti-Al systems, particularly focusing on the behavior of Ti and Al atoms in the presence of TiAl3 grain boundaries under experimental heat treatment conditions. Using a combination of molecular dynamics and Markov state modeling, we scrutinize the kinetic processes involved in the formation of TiAl3. The molecular dynamics simulation indicates that at the early stage of heat treatment, the predominating process is the diffusion of Al atoms toward the Ti surface through the TiAl3 grain boundaries. Markov state modeling identifies three distinct dynamic states of Al atoms within the Ti/Al mixture that forms during the process, each exhibiting a unique spatial distribution. Using transition time scales as a qualitative measure of the rapidness of the dynamics, it is observed that the Al dynamics is significantly less rapid near the Ti surface compared to the Al surface. Put together, the results offer a comprehensive understanding of the interfacial dynamics and reveal a three-stage diffusion mechanism. The process initiates with the premelting of Al, proceeds with the prevalent diffusion of Al atoms toward the Ti surface, and eventually ceases as the Ti concentration within the mixture progressively increases. The insights gained from this study could contribute significantly to the control and optimization of manufacturing processes for these high-performing Ti-Al-based materials.

Changes in the Endophytic Bacterial Community of Brassica rapa after Application of Systemic Insecticides.

Insecticides not only control target pests but also adversely affect non-target communities including humans, animals, and microbial communities in host plants and soils. The effect of insecticides on non-target communities, especially endophytic bacterial communities, remains poorly understood. Two phases of treatments were conducted to compare the trends in endophytic bacterial response after insecticide application. Endophytic bacteria were isolated at 2 and 4 weeks after germination. Most insecticide treatments showed a declining trend in bacterial diversity and abundance, whereas an increasing trend was observed in the control. Therefore, insecticide use negatively affected non-target endophytic bacterial communities. Bacillus spp. was mostly dominant in the early stage in both insecticide treatment and control groups. Nevertheless, in the matured stage, mostly bacteria including Pseudomonas spp., Priestia spp. were dominant in groups treated with high insecticide concentrations. Therefore, plants can regulate and moderate their microbiome during their lifecycle depending on surrounding environmental conditions.

HMGB1 Mediates Inflammation-Induced DMT1 Increase and Dopaminergic Neurodegeneration in the Early Stage of Parkinsonism.

Both neuroinflammation and iron accumulation play roles in the pathogenesis of Parkinson's disease (PD). However, whether inflammation induces iron dyshomeostasis in dopaminergic neurons at an early stage of PD, at which no quantifiable dopaminergic neuron loss can be observed, is still unknown. As for the inflammation mediators, although several cytokines have been reported to increase in PD, the functions of these cytokines in the SN are double-edged and controversial. In this study, whether inflammation could induce iron dyshomeostasis in dopaminergic neurons through high mobility group protein B1 (HMGB1) in the early stage of PD is explored. Lipopolysaccharide (LPS), a toxin that primarily activates glia cells, and 6-hydroxydopamine (6-OHDA), the neurotoxin that firstly impacts dopaminergic neurons, were utilized to mimic PD in rats. We found a common and exceedingly early over-production of HMGB1, followed by an increase of divalent metal transporter 1 with iron responsive element (DMT1+) in the dopaminergic neurons before quantifiable neuronal loss. HMGB1 neutralizing antibody suppressed inflammation in the SN, DMT1+ elevation in dopaminergic neurons, and dopaminergic neuronal loss in both LPS and 6-OHDA administration-induced PD models. On the contrary, interleukin-1β inhibitor diacerein failed to suppress these outcomes induced by 6-OHDA. Our findings not only demonstrate that inflammation could be one of the causes of DMT1+ increase in dopaminergic neurons, but also highlight HMGB1 as a pivotal early mediator of inflammation-induced iron increase and subsequent neurodegeneration, thereby HMGB1could serve as a potential target for early-stage PD treatment.

Individual-Level Risk Prediction of Return to Use During Opioid Use Disorder Treatment

No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder. To develop an individual-level prediction tool for risk of return to use in opioid use disorder. This decision analytical model used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks' duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016. The clinical trials covered a variety of treatment settings, including federally licensed treatment sites, physician practices, and inpatient treatment facilities. All 3 trials enrolled adult participants older than 18 years, with broad pragmatic inclusion and few exclusion criteria except for major medical and unstable psychiatric comorbidities. All participants received 1 of 3 medications for opioid use disorder: methadone, buprenorphine, or extended-release naltrexone. Predictive models were developed for return to use, which was defined as 4 consecutive weeks of urine drug screen (UDS) results either missing or positive for nonprescribed opioids by week 12 of treatment. The overall sample included 2199 trial participants (mean [SD] age, 35.3 [10.7] years; 728 women [33.1%] and 1471 men [66.9%]). The final model based on 4 predictors at treatment entry (heroin use days, morphine- and cocaine-positive UDS results, and heroin injection in the past 30 days) yielded an area under the receiver operating characteristic curve (AUROC) of 0.67 (95% CI, 0.62-0.71). Adding UDS in the first 3 treatment weeks improved model performance (AUROC, 0.82; 95% CI, 0.78-0.85). A simplified score (CTN-0094 OUD Return-to-Use Risk Score) provided good clinical risk stratification wherein patients with weekly opioid-negative UDS results in the 3 weeks after treatment initiation had a 13% risk of return to use compared with 85% for those with 3 weeks of opioid-positive or missing UDS results (AUROC, 0.80; 95% CI, 0.76-0.84). The prediction model described in this study may be a universal risk measure for return to opioid use by treatment week 3. Interventions to prevent return to regular use should focus on this critical early treatment period.

Characteristics of persistent depression in the long-term: Randomized controlled trial and two-year observational study

Major depressive disorder is a chronic condition that can recur and relapse. It would be clinically useful to know the patient background to predict the chronicity of depressive symptoms, and the change in diagnosis of bipolar disorder. This study included 197 patients enrolled in a six-week randomized controlled trial with a two-year follow-up. We conducted multiple logistic regression analyses to identify the clinical and sociodemographic characteristics associated with persistent depressive disorder (PDD), relapse, and changes in bipolar disorder diagnosis. The significantly correlated factors were residual symptoms, including insight, work and activity, and general somatic symptoms at week six. We could not identify any factors that contributed to relapse or change in the diagnosis of bipolar disorder. We found that the specific residual symptoms of acute treatment affected long-term treatment outcomes for depression. Attention should be paid to the residual symptoms of depression in the early stages of treatment, and measures should be considered to improve them. There are several limitations to this study, including the fact that PDD may exist among patients who discontinued treatment, treatment was not standardized during the study period, and adherence was confirmed verbally.

Improving colorectal cancer screening disparities among Somali-speaking patients in an Internal Medicine Residency Clinic

Colorectal cancer (CRC) is the third-most lethal cancer in the USA, and early detection through screening is crucial for improving outcomes. However, significant disparities in access and utilisation of CRC...

The future opportunities and remaining challenges in the application of nanoparticle-mediated hyperthermia combined with chemo-radiotherapy in cancer.

A pivotal cause of death in the modern world, cancer is an insidious pathology that should be diagnosed at an early stage for successful treatment. Development of therapeutic interventions with minimal invasiveness and high efficacy that can discriminate between tumor and normal cells is of particular interest to the clinical science, as they can enhance patient survival. Nanoparticles are an invaluable asset that can be adopted for development of such diagnostic and therapeutic modalities, since they come in very small sizes with modifiable surface, are highly safe and stable, and can be synthesized in a controlled fashion. To date, different nanoparticles have been incorporated into numerous modalities such as tumor-targeted therapy, thermal therapy, chemotherapy, and radiotherapy. This review article seeks to deliver a brief account of recent advances in research and application of nanoparticles in hyperthermia-based cancer therapies. The most recent investigations are summarized to highlight the latest advances in the development of combined thermo-chemo-radiotherapy, along with the challenges associated with the application of nanoparticles in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.