Nevin Manimala

Cancer Med. 2024 Feb;13(4):e7005. doi: 10.1002/cam4.7005.

ABSTRACT

BACKGROUND: MCD (MYD88^L265P /CD79B^mut ) diffuse large B-cell lymphoma has a poor prognosis. There is no published clinical research conclusion regarding zanubrutinib or orelabrutinib for the initial treatment of MCD DLBCL.

AIMS: This study aimed to analyse the efficacy and safety of Bruton’s tyrosine kinase inhibitor (BTKi) (zanubrutinib or orelabrutinib) therapy for newly diagnosed DLBCL patients with MYD88^mut and/or CD79B^mut .

MATERIALS AND METHODS: Twenty-three newly diagnosed DLBCL patients with MYD88^mut and/or CD79B^mut from June 2020 to June 2022 received BTKi combined with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab + lenalidomide (R² ). A control group of 17 patients with MYD88^mut and/or CD79B^mut DLBCL who received the standard R-CHOP therapy was also assessed. We retrospectively analysed clinical characteristics, safety, overall response rate (ORR), complete response (CR) rate and progression-free survival (PFS) of the two groups.

RESULTS: The main clinical features were a high International Prognostic Index (IPI) score (≥3, 22/40, 55%) and a high rate of extranodal involvement (27/40,67.5%). Among the 23 DLBCL patients, 18 received BTKi + R-CHOP, and five elderly DLBCL patients were treated with BTKi + R² . Compared with those in the control group (ORR 70.6%, CRR 52.9%, 1-year PFS rate 41.2%), improved ORR, CRR and PFS results were observed in the BTKi + R-CHOP group (100%, 94.4% and 88.9%, p = 0.019, 0.007, and 0.0001). In subgroup analyses based on genetic subtypes, cell origin, dual expression or IPI score, patients in the BTKi + R-CHOP group had better PFS than patients in the control group. In the BTKi + R-CHOP group, no significant difference was found in ORR, CRR and PFS based on subtype analysis, while BTKi-type subgroups exhibited statistically significant differences in 1-year PFS (p = 0.028). There were no significant differences in grade 3-4 haematological toxicity (p = 1) and grade 3-4 non-haematological toxicity (p = 0.49) between the BTKi + R-CHOP and R-CHOP treatment groups. In the BTKi + R² group, the ORR was 100%, the CRR was 80%, and the 1-year PFS rate was 80%. The incidences of grade 3-4 haematologic toxicity and non-haematological toxicity were both 40%. No bleeding or cardiovascular events of grade 3 or higher occurred in any patients.

DISCUSSION: The efficacy of BTKi combined with R-CHOP was similar to previous reports, which was significantly better than R-CHOP alone. It is necessary to fully consider that 14 patients in the BTKi + R-CHOP group received a BTKi as maintenance therapy when evaluating efficacy. Meanwhile, the addition of a BTKi may improve the prognosis of non-GCB, DEL or high-IPI-score DLBCL patients with MYD88^mut and/or CD79B^mut . In our study, five elderly DLBCL patients with MYD88^mut and/or CD79B^mut were achieved better ORR, CRR, PFS than the historical data of R-miniCHOP treatment and Ibrutinib + R² treatment. However, the efficacy and benefit of BTKis for this type of DLBCL need to be further analysed using a larger sample size.

CONCLUSION: This study suggests that newly diagnosed DLBCL patients with MYD88^mut and/or CD79B^mut may benefit from BTKis according to real-world clinical data.

PMID:38457222 | DOI:10.1002/cam4.7005

JMIR Res Protoc. 2024 Mar 8;13:e52882. doi: 10.2196/52882.

ABSTRACT

BACKGROUND: Despite strong and growing interest in ending the ongoing opioid health crisis, there has been limited success in reducing the prevalence of opioid addiction and the number of deaths associated with opioid overdoses. Further, 1 explanation for this is that existing interventions target those who are opiate-dependent but do not prevent opioid-naïve patients from becoming addicted.

OBJECTIVE: Leveraging behavioral economics at the patient level could help patients successfully use, discontinue, and dispose of their opioid medications in an acute pain setting. The primary goal of this project is to evaluate the effect of the 3 versions of the Opioid Management for You (OPY) tool on measures of opioid use relative to the standard of care by leveraging a pragmatic randomized controlled trial (RCT).

METHODS: A team of researchers from the Center for Learning Health System Sciences (CLHSS) at the University of Minnesota partnered with M Health Fairview to design, build, and test the 3 versions of the OPY tool: social influence, precommitment, and testimonial version. The tool is being built using the Epic Care Companion (Epic Inc) platform and interacts with the patient through their existing MyChart (Epic Systems Corporation) personal health record account, and Epic patient portal, accessed through a phone app or the MyChart website. We have demonstrated feasibility with pilot data of the social influence version of the OPY app by targeting our pilot to a specific cohort of patients undergoing upper-extremity procedures. This study will use a group sequential RCT design to test the impact of this important health system initiative. Patients who meet OPY inclusion criteria will be stratified into low, intermediate, and high risk of opiate use based on their type of surgery.

RESULTS: This study is being funded and supported by the CLHSS Rapid Prospective Evaluation and Digital Technology Innovation Programs, and M Health Fairview. Support and coordination provided by CLHSS include the structure of engagement, survey development, data collection, statistical analysis, and dissemination. The project was initially started in August 2022. The pilot was launched in February 2023 and is still running, with the data last counted in August 2023. The actual RCT is planned to start by early 2024.

CONCLUSIONS: Through this RCT, we will test our hypothesis that patient opioid use and diverted prescription opioid availability can both be improved by information delivery applied through a behavioral economics lens via sending nudges directly to the opioid users through their personal health record.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06124079; https://clinicaltrials.gov/study/NCT06124079.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52882.

PMID:38457203 | DOI:10.2196/52882

J Med Internet Res. 2024 Mar 8;26:e40406. doi: 10.2196/40406.

ABSTRACT

BACKGROUND: College athletes are a group often affected by anxiety. Few interventional studies have been conducted to address the anxiety issues in this population.

OBJECTIVE: We conducted a mobile-delivered mindfulness intervention among college athletes to study its feasibility and efficacy in lowering their anxiety level and improving their mindfulness (measured by the Five Facet Mindfulness Questionnaire [FFMQ]).

METHODS: In April 2019, we recruited 290 college athletes from a public university in Shanghai, China, and 288 of them were randomized into an intervention group and a control group (closed trial), with the former (n=150) receiving a therapist-guided, smartphone-delivered mindfulness-based intervention and the latter receiving mental health promotion messages (n=138). We offered in-person instructions during the orientation session for the intervention group in a classroom, with the therapist interacting with the participants on the smartphone platform later during the intervention. We used generalized linear modeling and the intent-to-treat approach to compare the 2 groups’ outcomes in dispositional anxiety, precompetition anxiety, and anxiety during competition, plus the 5 dimensions of mindfulness (measured by the FFMQ).

RESULTS: Our intent-to-treat analysis and generalized linear modeling found no significant difference in dispositional anxiety, precompetition anxiety, or anxiety during competition. Only the “observation” facet of mindfulness measures had a notable difference between the changes experienced by the 2 groups, whereby the intervention group had a net gain of .214 yet fell short of reaching statistical significance (P=.09). Participants who specialized in group sports had a higher level of anxiety (β=.19; SE=.08), a lower level of “nonjudgemental inner experience” in FFMQ (β=-.07; SE=.03), and a lower level of “nonreactivity” (β=-.138; SE=.052) than those specializing in individual sports.

CONCLUSIONS: No significant reduction in anxiety was detected in this study. Based on the participant feedback, the time availability for mindfulness practice and session attendance for these student athletes in an elite college could have compromised the intervention’s effectiveness. Future interventions among this population could explore a more student-friendly time schedule (eg, avoid final exam time) or attempt to improve cognitive and scholastic outcomes.

TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024449; https://www.chictr.org.cn/showproj.html?proj=40865.

PMID:38457201 | DOI:10.2196/40406

JAMA Netw Open. 2024 Mar 4;7(3):e241556. doi: 10.1001/jamanetworkopen.2024.1556.

ABSTRACT

IMPORTANCE: The optimal timing for fixation of extremity fractures after traumatic brain injury (TBI) remains controversial.

OBJECTIVE: To investigate whether patients who underwent extremity fixation within 24 hours of TBI experienced worse outcomes than those who had the procedure 24 hours or more after TBI.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Patients 16 years or older with TBI who underwent internal extremity fixation met inclusion criteria. To compare outcomes, patients who underwent the procedure within 24 hours were propensity score matched with those who underwent it 24 hours or later. Patients were treated from December 9, 2014, to December 17, 2017. Data analysis was conducted between August 1, 2022, and December 25, 2023.

MAIN OUTCOMES AND MEASURES: The primary outcome was an unfavorable functional status at 6 months (Glasgow Outcome Scale-Extended [GOSE] score ≤4).

RESULTS: A total of 253 patients were included in this study. The median age was 41 (IQR, 27-57) years, and 184 patients (72.7%) were male. The median Injury Severity Score (ISS) was 41 (IQR, 27-49). Approximately half of the patients (122 [48.2%]) had a mild TBI while 120 (47.4%) had moderate to severe TBI. Seventy-four patients (29.2%) underwent an internal extremity fixation within 24 hours, while 179 (70.8%) had the procedure 24 hours or later. At 6 months, 86 patients (34.0%) had an unfavorable functional outcome. After propensity score matching, there were no statistically significant differences in unfavorable functional outcomes at 6 months (odds ratio [OR], 1.12 [95% CI, 0.51-1.99]; P = .77) in patients with TBI of any severity. Similar results were observed in patients with mild TBI (OR, 0.71 [95% CI, 0.22-2.29]; P = .56) and moderate to severe TBI (OR, 1.08 [95% CI, 0.32-3.70]; P = .90).

CONCLUSIONS AND RELEVANCE: The outcomes of extremity fracture fixation performed within 24 hours after TBI appear not to be worse than those of procedures performed 24 hours or later. This finding suggests that early fixation after TBI could be considered in patients with mild head injuries.

PMID:38457181 | DOI:10.1001/jamanetworkopen.2024.1556

JAMA Netw Open. 2024 Mar 4;7(3):e241632. doi: 10.1001/jamanetworkopen.2024.1632.

ABSTRACT

IMPORTANCE: Previous studies have suggested that radiation therapy may contribute to an increased risk of subsequent nonkeratinocyte (ie, not squamous and basal cell) skin cancers.

OBJECTIVE: To test the hypothesis that radiation therapy for breast cancer increases the risk of subsequent nonkeratinocyte skin cancers, particularly when these cancers are localized to the skin of the breast or trunk.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used longitudinal data from the Surveillance, Epidemiology, and End Results (SEER) Program for January 1, 2000, to December 31, 2019. The SEER database includes population-based cohort data from 17 registries. Patients with newly diagnosed breast cancer were identified and were evaluated for subsequent nonkeratinocyte skin cancer development. Data analysis was performed from January to August 2023.

EXPOSURES: Radiation therapy, chemotherapy, or surgery for breast cancer.

MAIN OUTCOMES AND MEASURES: The primary outcomes were standardized incidence ratios (SIRs) for subsequent nonkeratinocyte skin cancer development from 2000 to 2019 based on treatment type (radiation therapy, chemotherapy, or surgery), skin cancer site on the body, and skin cancer subtype.

RESULTS: Among the 875 880 patients with newly diagnosed breast cancer included in this study, 99.3% were women, 51.6% were aged older than 60 years, and 50.3% received radiation therapy. A total of 11.2% patients identified as Hispanic, 10.1% identified as non-Hispanic Black, and 69.5% identified as non-Hispanic White. From 2000 to 2019, there were 3839 patients with nonkeratinocyte skin cancer, including melanoma (3419 [89.1%]), Merkel cell carcinoma (121 [3.2%]), hemangiosarcoma (104 [2.7%]), and 32 other nonkeratinocyte skin cancers (195 [5.1%]), documented to occur after breast cancer treatment. The risk of nonkeratinocyte skin cancer diagnosis after breast cancer treatment with radiation was 57% higher (SIR, 1.57 [95% CI, 1.45-1.7]) than that of the general population when considering the most relevant site: the skin of the breast or trunk. When risk at this site was stratified by skin cancer subtype, the SIRs for melanoma and hemangiosarcoma were both statistically significant at 1.37 (95% CI, 1.25-1.49) and 27.11 (95% CI, 21.6-33.61), respectively. Receipt of radiation therapy was associated with a greater risk of nonkeratinocyte skin cancer compared with chemotherapy and surgical interventions.

CONCLUSIONS AND RELEVANCE: In this study of patients with breast cancer, an increased risk of melanoma and hemangiosarcoma after breast cancer treatment with radiation therapy was observed. Although occurrences of nonkeratinocyte skin cancers are rare, physicians should be aware of this elevated risk to help inform follow-up care.

PMID:38457179 | DOI:10.1001/jamanetworkopen.2024.1632

Work. 2024 Mar 7. doi: 10.3233/WOR-230537. Online ahead of print.

ABSTRACT

BACKGROUND: Transition programs for newly graduated nurses in hospital settings are reported to provide learning opportunities, strengthening confidence, workplace integration and skills, retention and job satisfaction. Still, our knowledge of long-term effects is scarce and few studies have used control groups.

OBJECTIVE: To explore the long-term impact of having attended a transition program on the nurses’ experiences of the first years of practice. More specifically, ideology-infused psychological contract, ethical stress, perceived organizational support, job satisfaction, opportunities for learning, and intention to stay in the nursing profession, were explored as outcome variables.

METHODS: A questionnaire survey was carried out among registered nurses from November 2019 to January 2020, with a 54% response rate. The analysis was based on 149 nurses who had attended a transition program, and 72 who had not attended. The nurses had seniority between one and three years. Independent samples t-test were used to investigate differences between the groups.

RESULTS: The two groups showed small and non-significant differences in the outcome variables. However, regarding the frequency of ethical value conflicts induced by insufficient resources, as well as experiences of ethical value conflict distress, the group of nurses who had attended a transition program showed statistically significantly higher mean values, although the effect sizes were small.

CONCLUSION: Newly graduated nurses need more than transition programs and skills training to progress in their nursing role and develop competence, increase job satisfaction, and reduce stress. Achieving these goals requires a long-term supportive learning environment that is integrated into everyday work.

PMID:38457173 | DOI:10.3233/WOR-230537

Work. 2024 Mar 7. doi: 10.3233/WOR-230309. Online ahead of print.

ABSTRACT

BACKGROUND: Dairy industry workers face numerous ergonomic risk factors in their workplace, including improper posture, manual material handling, and musculoskeletal disorders (MSDs). Fewstudies have been conducted on the correlation of postural stress, MSDs, and chronic fatigue among workers in the dairy industry.

OBJECTIVE: This study aimed to investigate the relationship between the level of postural stress, MSDs, and chronic fatigue in a dairy company.

METHODS: In this cross-sectional study, 260 male workers were included in the research based on specific inclusion criteria. The Cornell Musculoskeletal Discomfort Questionnaire, Chalder Fatigue Scale, and a researcher-made demographic questionnaire were used to collect data. The posture of workers was evaluated using RULA and REBA software, and the evaluation of the manual lifting of loads was assessed using the WISHA lifting calculator. Finally, the collected data were entered into the SPSS software version 26.0 and analyzed.

RESULTS: The findings revealed a significant statistical relationship between the level of postural stress and chronic fatigue and a significant positive correlation between MSDs and chronic fatigue. Furthermore, a statistically significant relationship was observed between MSDs, chronic fatigue, and ergonomics training experience.

CONCLUSIONS: The results obtained in this study support the notion that high levels of postural stress and MSDs can produce an increase in chronic fatigue among workers, and lack of ergonomics training for workers can increase both MSDs and chronic fatigue. Therefore, it is necessary to carry out intervention measures in the field of ergonomics management in similar industries through the implementation of ergonomic intervention programs with a focus on proactive and preventive measures and the use of participatory ergonomic programs and educational demands assessment.

PMID:38457168 | DOI:10.3233/WOR-230309

NeuroRehabilitation. 2024 Mar 5. doi: 10.3233/NRE-230367. Online ahead of print.

ABSTRACT

BACKGROUND: Many authors have emphasized the need for individualized treatments in rehabilitation, but no tailored robotic rehabilitation protocol for stroke patients has been established yet.

OBJECTIVE: To evaluate the effectiveness of a robot-mediated upper limb rehabilitation protocol based on clinical assessment for customized treatment of stroke patients.

METHODS: Clinical data from 81 patients with subacute stroke, undergoing an upper limb robot-mediated rehabilitation, were analyzed retrospectively. 49 patients were treated using a customized robotic protocol (experimental group, EG) based on a clinically guided flowchart, while 32 were treated without it (control group, CG). Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Motricity Index (MI), modified Barthel Index (mBI) and Numerical Rating Scale (NRS) measured before (T0) and after (T1) rehabilitation intervention were used as clinical outcomes.

RESULTS: There was statistically significant improvement in both groups in terms of FMA-UE, MI, and mBI, while no change in NRS. Intergroup analysis showed significantly greater improvement of the FMA-UE (P = 0.002) and MI (P < 0.001) in the EG, compared with the CG.

CONCLUSION: The implementation of our robotic protocol for customized treatment of stroke patients yielded greater recovery in upper limb motor function and strength over robotic treatment without a defined protocol.

PMID:38457161 | DOI:10.3233/NRE-230367

NeuroRehabilitation. 2024 Mar 2. doi: 10.3233/NRE-230282. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with prolonged disorders of consciousness (pDOC) pose significant challenges to healthcare workers due to their severe motor impairments and limited interaction with the environment. Non-invasive brain stimulation such as high-definition transcranial direct current stimulation (HD-tDCS) and music stimulation show promise in awakening this population.

OBJECTIVE: In this study, we present a protocol aiming at investigating the efficacy of combined HD-tDCS and music stimulation in awakening patients with pDOC through a single-blind, randomized controlled trial.

METHODS: Ninety patients with pDOC will be randomly divided into three groups: active HD-tDCS with music stimulation, active HD-tDCS, and sham HD-tDCS. All participants will receive 20 treatment sessions over a period of 10 days and the Coma Recovery Scale-Revised, Glasgow Outcome Scale and electroencephalogram will be used as assessment measures to evaluate their level of consciousness throughout the study. Adverse events and complications will be recorded during treatment. Within-group pre-post comparisons and between-group efficacy comparisons will be conducted to identify the most effective intervention approach. Statistical analysis will be performed using SPSS software with a significance level set at P < 0.05.

CONCLUSION: The pursuit of awakening therapy for patients with pDOC remains a clinical research challenge. This study protocol is designed with the aim of introducing an innovative non-pharmacological approach which combined HD-tDCS and music stimulation to facilitate the reinstatement of consciousness in patients with pDOC.

PMID:38457160 | DOI:10.3233/NRE-230282

J Neonatal Perinatal Med. 2024;17(1):49-55. doi: 10.3233/NPM-230029.

ABSTRACT

INTRODUCTION: Retinopathy of prematurity (ROP) is one of the main reasons of preventable childhood blindness. In the development of ROP, MicroRNAs may be effective in the balance of factors that inhibit and activate angiogenic factors. We aimed to determine the changes in the blood levels of miR-146a, miR-143, miR-210, miR-21, miR-126, miR-211, miR-221, miR-106 and let 7f and to investigate their association with ROP. We hypothesed that the level of these miRNAs changed significantly in ROP cases.

MATERIALS AND METHODS: This observational study was conducted prospectively in preterm infants with ROP. Serum levels of 8 miRNAs were measured. The relationship between disease stage and progression with miRNA gene expression was analysed. Preterm infants without ROP were taken as the control group.

RESULTS: 47 patients with ROP and 14 controls, were included in the study. In the ROP group, miR-210, miR-146a, miR-21 were statistically significantly lower. In the ROP group the expression level of miR-143 was insignificantly lower, miRNA-221 was insignificantly higher, and miR-106, miR-126 and let 7f were variable.

CONCLUSION: It was observed that miR-210, miR-146a, miR-21 and miR-143 were significantly lower in patients with ROP compared to the control group. However, no association could be established between the type of miRNA and stage of ROP. These miRNAs may be used as adjunctive biomarkers for diagnosis of ROP.

PMID:38457157 | DOI:10.3233/NPM-230029