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BACKGROUND: Unilateral vocal fold paralysis (UVFP), characterized by immobility of one vocal fold, results from injuries of recurrent laryngeal nerves. Voice therapy is a conservative intervention aiming to address these symptoms, but standard protocols are lacking. In this study, we provided an updated review of voice therapy for UVFP over the past 3 years and analyzed the effect of voice therapy from the perspective of voice assessment recommended by the guidelines of the European Laryngological Society and the Union of the European Phoniatricians in 2023. METHODS: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 statement, we searched the databases, including PubMed, Embase, Web of Science, the Cochrane Library, and SCOPUS, from their earliest records to December 1, 2023. Quality assessment utilized Cochrane Risk of Bias and Risk Of Bias In Non-randomized Studies of Interventions tools. Data extraction encompassed study design, participant characteristics, therapy protocols, and outcome measures, including subjective and objective assessments. We performed heterogeneity analysis by calculating the I2 statistic and meta-analysis by calculating the standardized difference of means and weighted mean differences. RESULTS: Our systematic review and meta-analysis included 12 studies encompassing 459 patients. The review revealed a predominance of female participants across studies. Therapy protocols primarily included breathing control, laryngeal manipulation, and resonance training, often supplemented by home exercises. Outcome measures demonstrated significant improvements in subjective parameter: Voice Handicap Index ((standard mean difference) SMD = -1.51, P < 0.001), acoustic parameters: fundamental frequency (SMD = -0.38, P = 0.003), jitter (SMD = -0.97, P < 0.001), shimmer (SMD = -0.94, P < 0.001), and noise-to-harmonic ratio (SMD = -0.89, P < 0.001), and aerodynamic parameters: maximum phonation time (SMD = 1.29, P < 0.001), with early intervention yielding enhanced rate of complete glottal closure. DISCUSSION: Two randomized controlled trials (RCTs) involved patients aware of their allocation to the treatment group, and the remaining 10 studies were retrospective, leading to bias from deviations in the intended intervention. Subjective and aerodynamic parameter inconsistency was observed, but after excluding studies with the onset of UVFP greater than 12 months, the heterogeneity of VHI scores decreased. The funnel plot was grossly symmetrical in the publication bias test. Significant improvements were noted in subjective, acoustic, and aerodynamic outcomes after intervention. Besides, there were commonalities in protocols, such as breathing control, laryngeal manipulation, and resonance training, often supplemented by home exercises. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on March 28, 2024, registration number: CRD42024529750.
ABSTRACT
BRAFV600E mutation is a driver mutation in the serrated pathway to colorectal cancers. BRAFV600E drives tumorigenesis through constitutive downstream extracellular signal-regulated kinase (ERK) activation, but high-intensity ERK activation can also trigger tumor suppression. Whether and how oncogenic ERK signaling can be intrinsically adjusted to a 'just-right' level optimal for tumorigenesis remains undetermined. In this study, we found that FAK (Focal adhesion kinase) expression was reduced in BRAFV600E-mutant adenomas/polyps in mice and patients. In Vil1-Cre;BRAFLSL-V600E/+;Ptk2fl/fl mice, Fak deletion maximized BRAFV600E's oncogenic activity and increased cecal tumor incidence to 100%. Mechanistically, our results showed that Fak loss, without jeopardizing BRAFV600E-induced ERK pathway transcriptional output, reduced EGFR (epidermal growth factor receptor)-dependent ERK phosphorylation. Reduction in ERK phosphorylation increased the level of Lgr4, promoting intestinal stemness and cecal tumor formation. Our findings show that a 'just-right' ERK signaling optimal for BRAFV600E-induced cecal tumor formation can be achieved via Fak loss-mediated downregulation of ERK phosphorylation.
Subject(s)
Cecal Neoplasms , Focal Adhesion Kinase 1 , Proto-Oncogene Proteins B-raf , Animals , Proto-Oncogene Proteins B-raf/metabolism , Proto-Oncogene Proteins B-raf/genetics , Phosphorylation , Mice , Humans , Cecal Neoplasms/metabolism , Cecal Neoplasms/genetics , Cecal Neoplasms/pathology , Focal Adhesion Kinase 1/metabolism , Focal Adhesion Kinase 1/genetics , Extracellular Signal-Regulated MAP Kinases/metabolism , Extracellular Signal-Regulated MAP Kinases/genetics , MAP Kinase Signaling System , ErbB Receptors/metabolism , ErbB Receptors/genetics , Carcinogenesis/genetics , Carcinogenesis/metabolism , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , MaleABSTRACT
Introduction: Therapeutic alliance (TA), or the extent to which patients feel a sense of caring and trust with their physician, may have an impact on health care utilization. We sought to determine if TA is associated with: (1) emergency department (ED) visits within 30 days of death and (2) hospice enrollment. Methods and Materials: This is a secondary analysis of data from a randomized clinical trial. We used restricted cubic splines to assess the relationship between TA scores and health care utilization. Results: Six hundred seventy-two patients were enrolled in the study, with 331 (49.3%) dying within 12 months. Patients with higher TA were less likely to have an ED visit in the last 30 days of life, but there was no evidence of a relationship between TA and enrollment in hospice. Conclusions: Higher TA was associated with decreased ED visits within 30 days of death. There was no association between TA and rates of hospice enrollment. Clinical Registration Number: NCT02712229.
Subject(s)
Hospice Care , Hospices , Neoplasms , Therapeutic Alliance , Humans , Emergency Service, Hospital , Neoplasms/therapy , Patient Acceptance of Health Care , Randomized Controlled Trials as TopicABSTRACT
Introduction: Immunotherapy has resulted in pathologic responses in hepatocellular carcinoma (HCC), but the benefits and molecular mechanisms of neoadjuvant immune checkpoint blockade are largely unknown. Methods: In this study, we evaluated the efficacy and safety of preoperative nivolumab (anti-PD-1) in patients with intermediate and locally advanced HCC and determined the molecular markers for predicting treatment response. Results: Between July 2020 and November 2021, 20 treatment-naive HCC patients with intermediate and locally advanced tumors received preoperative nivolumab at 3 mg/kg for 3 cycles prior to surgical resection. Nineteen patients underwent surgical resection on trial. Seven (36.8%) of the 19 patients had major pathologic tumor necrosis (≥60%) in the post-nivolumab resection specimens, with 3 having almost complete (>90%) tumor necrosis. The tumor necrosis was hemorrhagic and often accompanied by increased or dense immune cell infiltrate at the border of the tumors. None of the patients developed major adverse reactions contradicting hepatectomy. RNA-sequencing analysis on both pre-nivolumab tumor biopsies and post-nivolumab resected specimens showed that, in cases with major pathologic necrosis, the proportion of CD8 T cells in the HCC tissues predominantly increased after treatment. Moreover, to investigate noninvasive biomarker for nivolumab response, we evaluated the copy number variation (CNV) using target-panel sequencing on plasma cell-free DNA of the patients and derived a CNV-based anti-PD-1 score. The score correlated with the extent of tumor necrosis and was validated in a Korean patient cohort with anti-PD-1 treatment. Conclusion: Neoadjuvant nivolumab demonstrated promising clinical activity in intermediate and locally advanced HCC patients. We also identified useful noninvasive biomarker predicting responsiveness.
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BRAF mutation is a driver mutation in colorectal cancer (CRC), and BRAFV600E mutation is found in 10-15 % of all CRCs. BRAF mutant CRCs in patients are primarily localized in the right colon, including the cecum. However, in the Vill-Cre;BRAFV600E/+ mice, adenomas mainly developed in the small intestines of the mice, and no tumor formed in the cecum. The mice model of BRAFV600E-mutant CRC with tumors in the cecum is lacking. Dextran Sulfate Sodium (DSS) treatment induces colitis in mice. Acute DSS treatment does not lead to tumor formation. We show that DSS treatment and BRAFV600E mutation synergistically induced cecal tumorigenesis, and cecal tumors formed within three months after five-day DSS treatment. The location of the adenomas supports the patient relevance of the model. Our BRAFV600E/DSS model provides a valuable in vivo model for future identification and validation of novel therapeutic approaches for treating BRAF-mutant CRC. Our results are consistent with the notion that BRAFV600E mutation is an oncogenic event that can shift controlled regeneration to unrestrained oncogenesis.
ABSTRACT
BRAF V600E mutation is a driver mutation in the serrated pathway to colorectal cancers. BRAFV600E drives tumorigenesis through constitutive downstream extracellular signal-regulated kinase (ERK) activation, but high-intensity ERK activation can also trigger tumor suppression. Whether and how oncogenic ERK signaling can be intrinsically adjusted to a "just-right" level optimal for tumorigenesis remains undetermined. In this study, we found that FAK (Focal adhesion kinase) expression was reduced in BRAFV600E-mutant adenomas/polyps in mice and patients. In Vill-Cre;BRAFV600E/+;Fakfl/fl mice, Fak deletion maximized BRAFV600E's oncogenic activity and increased cecal tumor incidence to 100%. Mechanistically, our results showed that Fak loss, without jeopardizing BRAFV600E-induced ERK pathway transcriptional output, reduced EGFR (epidermal growth factor receptor)-dependent ERK phosphorylation. Reduction in ERK phosphorylation increased the level of Lgr4, promoting intestinal stemness and cecal tumor formation. Our findings show that a "just-right" ERK signaling optimal for BRAFV600E-induced cecal tumor formation can be achieved via Fak loss-mediated downregulation of ERK phosphorylation.
ABSTRACT
Aurora kinase A (Aurora-A), a serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer, including lung cancer, colorectal cancer, and breast cancer. Alteration of Aurora-A impacts multiple cancer hallmarks, especially, immortalization, energy metabolism, immune escape and cell death resistance which are involved in cancer progression and resistance. This review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance, including chemoresistance (taxanes, cisplatin, cyclophosphamide), targeted therapy resistance (osimertinib, imatinib, sorafenib, etc.), endocrine therapy resistance (tamoxifen, fulvestrant) and radioresistance. Specifically, the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair, feedback activation bypass pathways, resistance to apoptosis, necroptosis and autophagy, metastasis, and stemness. Noticeably, our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1, ARID1A and MYC gene mutation tumors, and potential synergistic strategy for mTOR, PAK1, MDM2, MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A kinase. In addition, we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.
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Prolonged sitting with poor posture can lead to various health problems, including upper back pain, lower back pain, and cervical pain. Maintaining proper sitting posture is crucial for individuals while working or studying. Existing pressure sensor-based systems have been proposed to recognize sitting postures, but their accuracy ranges from 80% to 90%, leaving room for improvement. In this study, we developed a sitting posture recognition system called SPRS. We identified key areas on the chair surface that capture essential characteristics of sitting postures and employed diverse machine learning technologies to recognize ten common sitting postures. To evaluate the accuracy and usability of SPRS, we conducted a ten-minute sitting session with arbitrary postures involving 20 volunteers. The experimental results demonstrated that SPRS achieved an impressive accuracy rate of up to 99.1% in recognizing sitting postures. Additionally, we performed a usability survey using two standard questionnaires, the System Usability Scale (SUS) and the Questionnaire for User Interface Satisfaction (QUIS). The analysis of survey results indicated that SPRS is user-friendly, easy to use, and responsive.
Subject(s)
Low Back Pain , Sitting Position , Humans , Posture , Neck Pain , Machine LearningABSTRACT
Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and normal human colon epithelial cells. In vivo animal models were used to document the antitumor activity of HQ and baicalin. The mechanism of growth inhibitory activity of HQ is due to inhibition of proliferative signaling pathways including the CDK-RB pathway. In addition, HQ enhanced the antitumor effects of 5-FU and capecitabine in vivo. Furthermore, we identified baicalin as an active component of HQ. The combination of baicalin and 5-FU demonstrated synergistic activity against 5-FU-resistant RKO-R10 cells. The combination significantly inhibited in vivo tumor growth greater than each treatment alone. RPPA results showed that the signaling pathway alterations in CRC cells were similar following HQ and baicalin treatment. Together, these results indicate that HQ and its component baicalin enhance the effect of 5-fluorouracil-based chemotherapy via inhibition of CDK-RB pathway. These findings may provide the rational basis for developing agents that can overcome the development of cellular drug resistance. Video Abstract.
Subject(s)
Colorectal Neoplasms , Fluorouracil , Humans , Animals , Mice , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Scutellaria baicalensis , Signal Transduction , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Cell Proliferation , Cell Line, TumorABSTRACT
Porters play an important role in supporting hospital operations. Their responsibilities include transporting patients and medical equipment between wards and departments. They also need to deliver specimens, drugs, and patients' notes to the correct place at the right time. Therefore, maintaining a trustworthy and reliable porter team is crucial for hospitals to ensure the quality of patient care and smooth the flow of daily operations. However, most existing porter systems lack detailed information about the porter movement process. For example, the location of porters is not transparent to the dispatch center. Thus, the dispatcher does not know if porters are spending all their time providing services. The invisibility makes it difficult for hospitals to assess and improve the efficiency of porter operations. In this work, we first developed an indoor location-based porter management system (LOPS) on top of the infrastructure of indoor positioning services in the hospital National Taiwan University Hospital YunLin Branch. The LOPS provides real-time location information of porters for the dispatcher to prioritize tasks and manage assignments. We then conducted a 5-month field trial to collect porters' traces. Finally, a series of quantitative analyses were performed to assess the efficiency of porter operations, such as the movement distribution of porters in different time periods and areas, workload distribution among porters, and possible bottlenecks of delivering services. Based on the analysis results, recommendations were given to improve the efficiency of the porter team.
Subject(s)
Hospitals , Workload , HumansABSTRACT
BACKGROUND: Palliative care specialists are experts in conducting advance care planning (ACP) but are a limited resource. Oncology nurses often have special relationships with their patients and thus may be poised to provide primary palliative care. We sought to determine the impact of a nurse-led primary palliative care intervention on ACP uptake among patients with advanced cancer. METHODS: We performed a secondary analysis of a cluster randomized controlled trial examining the impact of nurse-based primary palliative care. In the parent trial, patients with advanced cancer received either monthly primary palliative care visits with trained nurses within their cancer center or standard care. Nurses in the intervention arm received special training in ACP. ACP uptake was assessed at enrollment and 3 months later evaluating (1) whether an end-of-life conversation (EOLC) occurred with one's oncologist, and (2) completion of an advance directive (AD). Multivariable logistic regression tested differences in ACP uptake by treatment arm adjusted for age, religious importance, education, time with current oncologist, and performance status. RESULTS: Of 672 patients enrolled, 182/336 (54%) patients in the intervention arm and 196/336 (58%) in the standard care arm lacked an EOLC at baseline and completed the 3-month assessment. Of those, 82/182 (45.1%) patients in the intervention arm and 29/196 (14.8%) in the standard care arm reported having an EOLC at 3 months (adjusted odds ratio, 5.28; 95% CI, 3.10-8.97; P<.001). Similarly, 111/336 (33%) patients in the intervention arm and 105/336 (31%) in the standard care arm lacked an AD at baseline and completed the 3-month assessment. Of those, 48/111 (43.2%) patients in the intervention arm and 19/105 (18.1%) in the standard care arm completed an AD over the study period (adjusted odds ratio, 3.68; 95% CI, 1.89-7.16; P<.001). CONCLUSIONS: Nurse-led primary palliative care increased ACP uptake among patients with advanced cancer. Training oncology nurses embedded within community cancer centers to provide primary palliative care may help improve ACP access.
Subject(s)
Advance Care Planning , Neoplasms , Humans , Palliative Care , Neoplasms/therapy , Medical OncologyABSTRACT
Cellular protein synthesis is accelerated in human colorectal cancer (CRC), and high expression of protein synthesis regulators in CRC patients is associated with poor prognosis. Thus, inhibition of protein synthesis may be an effective therapeutic strategy for CRC. We previously demonstrated that the quassinoid bruceantinol (BOL) had antitumor activity against CRC. Herein, potent tumor growth suppression (>80%) and STAT3 inhibition was observed in two different mouse models following BOL administration. Loss of body and spleen weight was observed but was eliminated upon nanoparticle encapsulation while maintaining strong antitumor activity. STAT3 siRNA knockdown exhibited modest suppression of cell proliferation. Surprisingly, STAT3 inhibition using a PROTAC degrader (SD-36) had little effect on cancer cell proliferation suggesting the possibility of additional mechanism(s) of action for quassinoids. BOL-resistant (BR) cell lines, HCT116BR and HCA7BR, were equally sensitive to standard CRC therapeutic agents and known STAT3 inhibitors but resistant to homoharringtonine (HHT), a known protein synthesis inhibitor. The ability of quassinoids to inhibit protein synthesis was dependent on the structure of the C15 sidechain. Of note, BOL did not inhibit protein synthesis in normal human colon epithelial cells whereas HHT and napabucasin remained effective in these normal cells. Novel quassinoids were designed, synthesized, and evaluated in pre-clinical CRC models. Treatment with the most potent analog, 5c, resulted in significant inhibition of cell proliferation and protein synthesis at nanomolar concentrations. These quassinoid analogs may represent a novel class of protein synthesis inhibitors for the treatment of human CRC.
Subject(s)
Colorectal Neoplasms , Quassins , Animals , Mice , Humans , Colorectal Neoplasms/metabolism , Quassins/pharmacology , Cell Proliferation , Cell Line, Tumor , Xenograft Model Antitumor Assays , STAT3 Transcription Factor/metabolismABSTRACT
Background: Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering 'booster' doses of COVID-19 vaccines beyond the standard two-dose series, for this group of patients. Therefore, studying the efficacy of these additional vaccine doses against SARS-CoV-2 and variants of concern is of utmost importance in this immunocompromised patient population. Methods: We conducted a prospective single arm clinical trial enrolling patients with cancer that had received two doses of mRNA or one dose of AD26.CoV2.S vaccine and administered a third dose of mRNA vaccine. We further enrolled patients that had no or low responses to three mRNA COVID vaccines and assessed the efficacy of a fourth dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity, and neutralization activity, which were again assessed at baseline and 4 weeks. Results: We demonstrate that a third dose of COVID-19 vaccine leads to seroconversion in 57% of patients that were seronegative after primary vaccination series. The immune response is durable as assessed by anti-SARS-CoV-2 (anti-S) antibody titers, T-cell activity, and neutralization activity against wild-type (WT) SARS-CoV2 and BA1.1.529 at 6 months of follow-up. A subset of severely immunocompromised hematologic malignancy patients that were unable to mount an adequate immune response (titer <1000 AU/mL) after the third dose and were treated with a fourth dose in a prospective clinical trial which led to adequate immune boost in 67% of patients. Low baseline IgM levels and CD19 counts were associated with inadequate seroconversion. Booster doses induced limited neutralization activity against the Omicron variant. Conclusions: These results indicate that third dose of COVID vaccine induces durable immunity in cancer patients and an additional dose can further stimulate immunity in a subset of patients with inadequate response. Funding: Leukemia Lymphoma Society, National Cancer Institute. Clinical trial number: NCT05016622.
People with cancer have a higher risk of death or severe complications from COVID-19. As a result, vaccinating cancer patients against COVID-19 is critical. But patients with cancer, particularly blood or lymphatic system cancers, are less likely to develop protective immunity after COVID-19 vaccination. Immune suppression caused by cancer or cancer therapies may explain the poor vaccine response. Booster doses of the vaccine may improve the vaccine response in patients with cancer. But limited information is available about how well booster doses protect patients with cancer against COVID-19. Thakkar et al. show that a third dose of a COVID-19 vaccine can induce a protective immune response in half of the patients with cancer with no immunity after the first two doses. In the experiments, Thakkar et al. tracked the immune reaction to COVID-19 booster shots in 106 cancer patients. A third booster dose protected patients for up to four to six months and reduced breakthrough infection rates to low levels. Eighteen patients with blood cancers and severe immune suppression had an inadequate immune response after three doses of the vaccine; a fourth dose boosted the immune response for two-thirds of them, which for some included neutralization of variants such as Omicron. The experiments show that booster doses can increase COVID-19 vaccine protection for patients with cancer, even those who do not respond to the initial vaccine series. Thakkar et al. also show that pre-vaccine levels of two molecules linked to the immune system, (immunoglobin M and the CD19 antigen) predicted the patients' vaccine response, which might help physicians identify which individuals would benefit from booster doses.
Subject(s)
COVID-19 , Neoplasms , Humans , COVID-19 Vaccines , Ad26COVS1 , Prospective Studies , RNA, Viral , COVID-19/prevention & control , SARS-CoV-2 , Neoplasms/therapy , Immunity , Antibodies, ViralABSTRACT
BACKGROUND: Veliparib is a poly-ADP-ribose polymerase (PARP) inhibitor, and it has clinical activity with every 3 weeks carboplatin and paclitaxel. In breast cancer, weekly paclitaxel is associated with improved overall survival. We aimed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib with weekly carboplatin and paclitaxel as well as safety, pharmacokinetics, and preliminary clinical activity in triple negative breast cancer (TNBC). METHODS: Patients with locally advanced/metastatic solid tumors and adequate organ function were eligible. A standard 3 + 3 dose-escalation design was followed by a TNBC expansion cohort. Veliparib doses ranging from 50 to 200 mg orally bid were tested with carboplatin (AUC 2) and paclitaxel (80 mg/m2) given weekly in a 21-day cycle. Adverse events (AE) were evaluated by CTCAE v4.0, and objective response rate (ORR) was determined by RECIST 1.1. RESULTS: Thirty patients were enrolled, of whom 22 had TNBC. Two dose-limiting toxicities were observed. The RP2D was determined to be 150 mg PO bid veliparib with weekly carboplatin and paclitaxel 2 weeks on, 1 week off, based on hematologic toxicity requiring dose reduction in the first 5 cycles of treatment. The most common grade 3/4 AEs included neutropenia, anemia, and thrombocytopenia. PK parameters of veliparib were comparable to single-agent veliparib. In 23 patients with evaluable disease, the ORR was 65%. In 19 patients with TNBC with evaluable disease, the ORR was 63%. CONCLUSION: Veliparib can be safely combined with weekly paclitaxel and carboplatin, and this triplet combination has promising clinical activity.
Subject(s)
Anemia , Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Carboplatin , Paclitaxel , Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/etiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Anemia/chemically inducedABSTRACT
BACKGROUND: The knee adduction moment, a biomechanical risk factor of knee osteoarthritis, is typically measured in a gait laboratory with expensive equipment and inverse dynamics modeling software. We aimed to develop a framework for a portable knee adduction moment estimation for healthy female individuals using deep learning neural networks and custom instrumented insole and evaluated its accuracy compared to the standard inverse dynamics approach. METHODS: Feed-forward, convolutional, and recurrent neural networks were applied to the data extracted from five piezo-resistive force sensors attached to the insole of a shoe. RESULTS: All models predicted knee adduction moment variables during walking with high correlation coefficients, r > 0.72, and low root mean squared errors (RMSE), ranging from 0.5% to 1.2%. The convolutional neural network is the most accurate predictor of average knee adduction moment (r = 0.96; RMSE = 0.5%) followed by the recurrent and feed-forward neural networks. CONCLUSION: These findings and the methods presented in the current study are expected to facilitate a cost-effective clinical analysis of knee adduction moment for healthy female individuals and to facilitate future research on prediction of other biomechanical risk factors using similar methods.
Subject(s)
Deep Learning , Osteoarthritis, Knee , Humans , Female , Shoes , Biomechanical Phenomena , Knee Joint , Gait , Walking , Neural Networks, ComputerABSTRACT
Purpose: Primary palliative care (PPC) interventions are needed to address unmet symptom needs within standard oncology care. We designed an oncology nurse-led PPC intervention using shared care planning to facilitate patient engagement. This analysis examines the prevalence and severity of symptoms reported by patients and how symptoms were addressed on shared care plans (SCPs). Methods: Secondary analysis of a cluster randomized PPC intervention trial. Adult patients with metastatic solid tumors whose oncologist "would not be surprised if the patient died within a year" were included. Twenty-three oncology nurses received PPC training and conducted up to three monthly visits with patients. Symptom prevalence and severity were assessed before each visit using the Edmonton Symptom Assessment Scale (ESAS). Nurses collaboratively developed treatment strategies with patients, targeting the most bothersome symptoms for improvement. Results: Among 571 nurse-led PPC visits with 235 patients, the most prevalent and severe symptoms were tiredness (reported at 86% of visits; ESAS ≥4 in 55% of visits), low sense of wellbeing (78%; ESAS ≥4 in 38%), and poor appetite (69%; ESAS ≥4 in 42%). Moderately severe symptoms were addressed on SCPs ranging from 4% (drowsiness) to 35% (tiredness) of the time. Symptom management plans developed by PPC-trained oncology nurses primarily focused on nonpharmaceutical interventions (70%) compared with pharmaceutical interventions (30%). Conclusion: The symptoms that patients report most frequently and as most severe on SCPs were addressed less frequently than expected. Further research is needed to understand how PPC interventions can be designed to more effectively target and improve bothersome symptoms for patients with advanced cancer. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02712229.
Subject(s)
Hospice and Palliative Care Nursing , Neoplasms , Adult , Humans , Palliative Care , Nurse's Role , Neoplasms/pathology , Medical OncologyABSTRACT
CONTEXT: Palliative care offers patient and family centered approaches that may mitigate risk of caregiver burden and poor mood. OBJECTIVES: To determine whether a palliative care intervention (CONNECT) improved burden, mood, and self-efficacy among caregivers of patients with advanced cancer. METHODS: In this cluster randomized trial, patients and their caregivers were recruited from 17 Oncology clinics in Pennsylvania. Participants attended nurse-led monthly visits, addressing patient symptoms, goals of care, and advance care planning. At baseline and three months, we measured caregiver burden using Zarit Burden Interview (ZBI-12; range 0-48), caregiver anxiety and depression using Hospital Anxiety and Depression Scales (HADS-A, range 0-21; HADS-D, range 0-21). We measured caregiver self-efficacy at three months using Caregiver Inventory (CGI; range 0-189). RESULTS: We enrolled 441 caregivers and 381 completed three-month assessments. We found no significant differences in caregiver burden (adjusted mean difference -0.39; 95% CI -1.07-0.29, P = 0.90), depression (adjusted mean difference -0.22, 95% CI -0.97-0.55, P = 0.26), or anxiety (adjusted mean difference 0.09; 95% CI -1.25-1.43, P = 0.58), between the intervention and standard care at three months. Caregiver self-efficacy was higher at three months in the intervention compared to standard care (adjusted mean difference 9.36; 95% CI 0.95-17.77, P = 0.030). CONCLUSION: Caregivers in CONNECT did not experience improved burden or mood, however, they reported higher self-efficacy compared to caregivers receiving standard care. This study highlights the need for strategies to optimize caregiver outcomes in palliative care interventions.
Subject(s)
Caregivers , Neoplasms , Humans , Quality of Life , Neoplasms/therapy , Palliative Care , PatientsABSTRACT
This Viewpoint discusses therapeutic drug monitoring as a necessary treatment paradigm and the need for regulatory agencies to provide the conditions to make it happen.
Subject(s)
Accidents, Traffic , Drug Monitoring , Humans , Models, StatisticalABSTRACT
BACKGROUND: Palliative care clinicians display less burnout than oncology clinicians. Little is known about the impact of providing both oncology care and primary palliative care in the same setting. OBJECTIVES: The aim was to determine whether nurses providing primary palliative care in addition to oncology care would experience less burnout over time than nurses providing oncology care only. METHODS: The authors performed secondary analysis of the CONNECT study. Three groups of nurses were evaluated: primary palliative care, non-primary palliative care, and standard care. On study enrollment and after one year, nurses completed the Maslach Burnout Inventory. Multivariable regression analyses were performed to test differences in follow-up burnout scores between groups. FINDINGS: Overall burnout rates were low at enrollment for all groups. There were no differences in burnout scores at one year between nurses who provided palliative care and nurses in the other two groups. .