Completion Of Treatment Research Articles

The Intersecting Time, Administrative and Financial Burdens of a Cancer Diagnosis.

Cancer and its care create substantial financial, time, and administrative burdens both for patients and their loved ones. While cancer-related financial burdens have been well documented in the past decade, time and administrative burdens of cancer care have received substantially less attention. We define time burdens as the burden patients and caregivers experience due to the time needed to complete cancer-related treatment and tasks that take away from other life responsibilities. Relatedly, we conceptualize administrative burdens as those burdens patients and caregivers experience due to cancer-related, resource-consuming bureaucratic and logistical tasks. Finally, financial hardship can be conceptualized as problems patients experience related to the cost of medical care. These burdens do not exist in isolation; time, administrative, and financial burdens intersect with and compound each other. Currently, we have limited evidence-based measures on the objective (e.g., scheduling time, transportation, wait time) and subjective (e.g., mental, emotional and physical stress) measures of time and administrative burden. We have even more limited evidence of the risk factors for and outcomes from increased time and administrative burdens, and how they differentially impact populations across social and demographic groups. In this commentary, we present a research agenda to map, measure, evaluate, and mitigate the time, administrative, and financial burdens of cancer and its care.

A NOVEL TREATMENT FOR PTOSIS COMPLICATION AFTER PRESEPTAL CELLULITIS IN DIABETIC PATIENT (CASE REPORT

Background: Preseptal cellulitis (PC) is an inflammation of the eyelid and surrounding soft tissues covering the anterior portion of the orbital septum (palpebral fascia) characterized by eyelids unilateral swelling, can develop to orbital cellulitis and be fatal for diabetics after complication. Two main mechanisms of the PC development are distinguished. One of them is based on a spread of local infection on the eyelid. The second group of PC causes include eye surgery, trauma or insect bites. In most cases, serious complications are rare, but sometimes sight-threatening infections behind the orbital septum may develop. It is important to be able to distinguish periorbital cellulitis from orbital cellulitis, and treat according to the diagnosis. In this paper, we discuss a case of PC and successful recovery after medical intervention even though due to late presentation to the Clinic, patient developed ptosis. A clinical case of PC developed to complete ptosis, treatment and successful elimination of all residual symptoms in diabetic patient with is described. We used a novel approach to PC treatment and ptosis after PC. Results: We achieved complete recovery from ptosis after PS in a diabetic patient thanks to novel approach to treatment Findings: 1. The use of nepafenac instead of diclofenac helps to enhance the effectiveness of treatment and prevent the spread of infection to nearby tissues during PС. 2. For the treatment PC complication, ptosis, we suggest the simultaneous, not separated in time use of proserin in combination with glycine.

The Effects of Having a Child with Cancer on Parental Psychology: A Cross-Sectional Study

Objective: In childhood cancers, parents are affected psychologically as well as children. We aimed to evaluate the effect of childhood cancer type and stage, as well as elapsed time from diagnosis, on the anxiety and stress indicators among parents. Materials and Methods: Patients aged between 0–18 years and diagnosed with cancer who were receiving chemotherapy (0–1 month, 1–6 month, 6–12 month) and completed treatment were included. Parents of those children (mother or father) who agreed to participate this study were also included. The personal information form and three psychological assessment scales (Beck Hopelessness Scale (PSS), Psychological Resilience Scale (PRS), Uncertainty Intolerance Scale (IUS)) were used for assessment of mental health of the parents. Scores of the scales and clinical features of the children with cancer were compared statistically. Results: The study included 84 parents (57 mothers, 27 fathers) and 84 children. The rate of children with solid tumors was 60% (n:50) and 40% of them were metastatic, which means advanced stage. The rate of the children with leukemia was 40% (n:34) and 23% of them were in high-risk group. According to the type (leukemia vs. solid tumors) and stage (high risk/advanced stage vs. others) of the cancer, there was no statistical difference among parents in the psychological scales (p > 0.05). Additionally, results of the psychological scales showed no significant difference between mothers and fathers (p > 0.05). The hopelessness scores are significantly higher among parents whose child’s treatment is terminated compared with those whose active therapy is ongoing, and resilience scores are higher among parents who have less than 1 month since diagnosis of childhood cancer than later periods. Conclusions: The regular assessment of mental health among parents of children with cancer across all the survivorship trajectory: at the time of diagnosis, during active therapy, and after treatment.

Anlotinib treatment for rapidly progressing pediatric embryonal rhabdomyosarcoma in the maxillary gingiva: a case report

BackgroundEmbryonal rhabdomyosarcoma (ERMS) is a highly aggressive form of soft-tissue sarcoma that predominantly affects children. Due to limited benefits and resistance to therapy, there is an unmet need to explore alternative therapeutic strategies.Case presentationIn this report, we present a rare case of pediatric ERMS located on the right side of the maxillary gingiva. A composite reference guide integrating clinical, radiographic, and histopathologic findings was used for a definitive diagnosis. Targeted next-generation sequencing of tumor biopsy was performed to identify genetic alterations. A 12-year-old female was admitted to the Pediatric Intensive Care Unit (PICU) and underwent a tracheotomy to relieve asphyxiation caused by a 5.5 cm diameter mass compressing the tongue root and pharyngeal cavity. Hematoxylin and eosin staining revealed a hybrid morphology characterized by clusters of round and spindle cells. Further immunohistochemistry assays indicated positive immunoreactivity for desmin, myogenin, and MyoD1. Various genetic alterations were identified, including mutations in GNAS, HRAS, LRP1B, amplification of MDM2 and IGF1R, and two novel IGF1R fusions. Negative PAX-FOXO1 fusion status supported the clinical diagnosis of ERMS. Initial treatment involved standard chemotherapy; however, the tumor persisted in its growth, reaching a maximum volume of 12 cm × 6 cm × 4 cm by the completion of treatment. Subsequent oral administration of anlotinib yielded a significant antitumor response, characterized by substantial tumor necrosis and size reduction. Following the ligation of the tumor pedicle and its removal, the patient developed a stabilized condition and was successfully discharged from PICU.ConclusionsOur study highlights the importance of accurate diagnosis established on multifaceted assessment for the effective treatment of ERMS. We present compelling evidence supporting the clinical use of anlotinib as a promising treatment strategy for pediatric ERMS patients, especially for those resistant to conventional chemotherapy.

The Effect of Night-time versus Full-time Bracing on the Sagittal Profile in Adolescent Idiopathic Scoliosis: A Propensity Score-matched Study.

Retrospective multicenter cohort study. To investigate the impact of night-time bracing (NTB) and full-time bracing (FTB) on the sagittal profile in adolescent idiopathic scoliosis (AIS) patients. Recent studies have shown that FTB in AIS patients may induce hypokyphosis. Whether this effect differs between NTB and FTB is unknown. We included skeletally immature AIS patients with main curves ranging from 20-45° treated with either NTB or FTB. The two cohorts were propensity-score matched on Risser stage, age, major curve size, and kyphosis at brace initiation. Coronal and sagittal radiographic parameters were gathered at the initiation and completion of brace treatment. Two-hundred fifty-seven patients were eligible for inclusion. The matched cohorts included 62 patients in each group. During bracing, the thoracic kyphosis increased from 31±11° to 35±13° in the NTB group compared to a decrease from 30±12° to 28±13° in the FTB group (P=0.011). Eight percent were hypokyphotic (<20°) after bracing in the NTB group compared to 24% in the FTB group (P=0.015). Pelvic incidence, sacral slope, and pelvic tilt were not significantly different between the groups. In the coronal plane, curve progression >50° was seen in 50% in the NTB group and 31% in FTB (P=0.028). We saw a small increase in thoracic kyphosis in the NTB group vs. a small decrease in the FTB group. Eight percent in the NTB group vs 24% in the FTB group showed substantial hypokyphosis after bracing. The impact of minor changes in thoracic kyphosis remains uncertain; however, a threefold difference in the occurrence of hypokyphosis is notable and merits further attention.

Targeting chronic pain care to rural women veterans: A feasibility pilot.

For rural women veterans, significant barriers exist in accessing high-quality, multicomponent behavioral pain self-management interventions. As such, a telehealth behavioral pain self-management intervention designed specifically for rural-dwelling women veterans with chronic pain was piloted for this study. This mixed methods, single-arm preliminary study examined the feasibility and acceptability of this intervention and completed a responder analysis. Participants completed surveys before and 1-month following the intervention, and they completed a qualitative interview following the intervention. About one quarter (24%) of potentially eligible participants who were sent a letter about the study consented to participate (N = 44). All participants identified as female and were rural dwelling, with mean age of 56 years (range = 34-80), and the majority of the sample (81%) self-identified as White and non-Hispanic or Latino. Average baseline scores on the Pain, Enjoyment of Life, and General Activity three-item scale (PEG-3) measure indicated severe pain and functional interference (MPEG-3 total = 6.88, SD = 1.62). Of the 44 participants who consented, 70% completed the intervention. About half of treatment completers (47%, 14/30) were deemed responders, reporting ≥ 30% reduction on their PEG-3 total scores. On the Global Impression of Change scale, 87% reported improvement. Study completers indicated that the telehealth platform facilitated their engagement and that they perceived the intervention to be beneficial and credible. Qualitative data emphasized themes of connection with other women veterans who experienced chronic pain while perceiving a retained sense of individual identity. These preliminary data support feasibly of this intervention for rural-dwelling women veterans with chronic pain. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Bedaquiline versus injectable containing regimens for rifampicin-resistant and multidrug-resistant tuberculosis in a reference center in Brazil – a real-world evidence study using a retrospective design

BackgroundDrug resistance (DR) is one of the several challenges to global tuberculosis (TB) control. The implementation of bedaquiline (BED) for DR-TB after more than 40 years was expected to improve treatment outcomes as well as microbiologic conversion and adverse events (AE) occurrence.MethodsRetrospective cohort study based on secondary data of patients with rifampicin-resistant (RR) or multidrug-resistant (MDR) TB reported to the Outpatient Clinic of Mycobacterial Diseases of the Thorax Diseases Institute – Federal University of Rio de Janeiro - Brazil, between 2016 and 2023. We aimed to evaluate microbiologic conversion, AE and TB treatment outcomes and compare them according to the treatment regimen used for RR/MDR-TB patients under routine conditions [Injectable Containing Regimens (ICR) versus BED Containing Regimens (BCR)]. Logistic regression and survival analysis using Cox regression and Kaplan Meier curve were used for statistical analysis.ResultsOf the 463 DR-TB patients notified during the study period, 297 (64.1%) were included for analysis (ICR = 197 and BCR = 100). Overall AEs were more frequent (83.7 vs. 16.3%, p < 0.001) and occurred earlier in the ICR group (15 days vs. 65 days, p = 0.003). There were no cases of cardiotoxicity requiring interruption of BED treatment. None of the regimens of treatment tested were associated with smear or culture conversion on Cox regression analysis (p = 0.60 and 0.88, respectively). BED-containing regimens were also associated with favorable outcomes in multivariable logistic regression [adjusted odds ratio (aOR) = 2.63, 95% confidence interval (CI)1.36–5.07, p = 0.004], as higher years of schooling, primary drug resistance, and no previous TB treatment. In the survival analysis, BCR was inversely associated with the occurrence of AE during treatment follow-up (aHR 0.24, 95% CI 0.14–0.41, p < 0.001). In addition, TB treatment regimens with BED were also associated with favorable outcomes (aHR 2.41, 95% CI 1.62–3.57, p < 0.001), along with no illicit drug use and primary drug resistance.ConclusionsThe implementation of a fully oral treatment for RR/MDR-TB in a reference center in Brazil was safe and associated with favorable outcomes under routine conditions, despite social, demographic, and behavioral factors that may influence TB treatment completion.

Secondary Preventive Management of Kitibha Kushta (Plaque Psoriasis) - A case study

Levels of prevention has been a wide idea concept which includes all the aspects related to health and disease like preventive, curative, promotive and rehabilitative measures. Applicability of this concept in Ayurveda has elaborative understanding in a more simplified manner. Despite leading to both physical and psychological issues, the importance given to skin diseases is always the least. Changing food habits and lifestyle is being the major reason in the current era for increased prevalence of skin diseases especially in young adults. In a way to cope up with fast living culture, people are compromising with their health and well being which needs immediate attention and action. Early diagnosis and complete treatment is the basis of Kushta Chikitsa (treatment of skin diseases) and the same has been highlighted as a secondary preventive measure. One such case is being discussed here which is diagnosed initially and treated as per Ayurveda chikitasa siddhtanta (Ayurvedic treatment principle), considering Dosha (bio-forces of body), Agni(metabolism), Bala (Strength), Ritu (season) etc giving complete relief and self confidence of the patient. This not only prevents the further occurrence of complications due to chronicity but also brings back the faith in Ayurveda treatment modalities. It is high time to make the young minds realize the importance of healthy living, which otherwise can impair the health status of the nation, dragging back its growth and development.

Prediction of pathological complete response to chemotherapy for breast cancer using deep neural network with uncertainty quantification.

The I-SPY 2 trial is a national-wide, multi-institutional clinical trial designed to evaluate multiple new therapeutic drugs for high-risk breast cancer. Previous studies suggest that pathological complete response (pCR) is a viable indicator of long-term outcomes of neoadjuvant chemotherapy for high-risk breast cancer. While pCR can be assessed during surgery after the chemotherapy, early prediction of pCR before the completion of the chemotherapy may facilitate personalized treatment management to achieve an improved outcome. Notably, the acquisition of dynamic contrast-enhanced magnetic resonance (DCEMR) images at multiple time points during the I-SPY 2 trial opens up the possibility of achieving early pCR prediction. In this study, we investigated the feasibility of the early prediction of pCR to neoadjuvant chemotherapy using multi-time point DCEMR images and clinical data acquired in the I-SPY2 trial. The prediction uncertainty was also quantified to allow physicians to make patient-specific decisions on treatment plans based on the level of associated uncertainty. The dataset used in our study included 624 patients with DCEMR images acquired at 3 time points before the completion of the chemotherapy: pretreatment (T0), after 3 cycles of treatment (T1), and after 12 cycles of treatment (T2). A convolutional long short-term memory (LSTM) network-based deep learning model, which integrated multi-time point deep image representations with clinical data, including tumor subtypes, was developed to predict pCR. The performance of the model was evaluated via the method of nested 5-fold cross validation. Moreover, we also quantified prediction uncertainty for each patient through test-time augmentation. To investigate the relationship between predictive performance and uncertainty, the area under the receiver operating characteristic curve (AUROC) was assessed on subgroups of patients stratified by the uncertainty score. By integrating clinical data and DCEMR images obtained at three-time points before treatment completion, the AUROC reached 0.833 with a sensitivity of 0.723 and specificity of 0.800. This performance was significantly superior (p<0.01) to models using only images (AUROC=0.706) or only clinical data (AUROC=0.746). After stratifying the patients into eight subgroups based on the uncertainty score, we found that group #1, with the lowest uncertainty, had a superior AUROC of 0.873. The AUROC decreased to 0.637 for group #8, which had the highest uncertainty. The results indicate that our convolutional LSTM network-based deep learning model can be used to predict pCR earlier before the completion of chemotherapy. By combining clinical data and multi-time point deep image representations, our model outperforms models built solely on clinical or image data. Estimating prediction uncertainty may enable physicians to prioritize or disregard predictions based on their associated uncertainties. This approach could potentially enhance the personalization of breast cancer therapy.

Self-Reported Late Effects in Childhood Cancer Survivors in Kenya

Background: The number of children surviving cancer in low and middle-income countries is expected to grow in the coming years. Knowledge about late effects and follow-up preferences in Kenya is lacking.Objectives: This study assessed self-reported late effects in Kenyan childhood cancer survivors and explored their preferences for survivorship care.Methods: Childhood cancer survivors, having successfully completed treatment for at least one year, were interviewed using semi-structured questionnaires during clinic or home visits between 2021-2022. Medical records were reviewed for patient and treatment characteristics.Results: Twenty-six survivors of hematological malignancies (n=19, 73%), solid tumors (n=6, 23%), unknown tumor type (n=1, 4%), were interviewed. Most survivors (n=19, 73%) solely received chemotherapy and one survivor (4%) was irradiated. Median time since treatment completion was seven years. Fifteen survivors (58%) were previously lost to follow-up. Many survivors (n=19; 73%) self-reported late effects, predominantly pain and fatigue. Survivors (n=11, 42%) were limited in daily life activities: physical work (n=10, 38%), personal care (n=6, 23%), social activities (n=6, 23%). Eight survivors (31%) recalled being informed about late effects. Some survivors experienced a negative attitude toward cancer in regional hospitals. Follow-up duration was longer among informed patients (p=0.043). Survivors recommended education and survivor meetings and preferred their follow-up to be done at the referral center.Conclusions: Kenyan childhood cancer survivors self-report late effects, comparable in frequency, nature and severity to other survivors worldwide. Survivors and healthcare providers require education about the lifelong impact of childhood cancer and should have access to survivorship expertise to continue follow-up. Keywords: Pediatrics; survivorship; neoplasms; aftercare.

7373 CAM2029, Octreotide Subcutaneous Depot, Provides Sustained Biochemical Control of Acromegaly: Interim Results From a Phase 3 Study (ACROINNOVA 2)

Abstract Disclosure: D. Ferone: Consulting Fee; Self; Camurus AB, Recordati, Novartis-AAA, Ipsen. Grant Recipient; Self; Camurus AB, Recordati, Novartis-AAA, Ipsen. Research Investigator; Self; Camurus AB. J. Silverstein: Consulting Fee; Self; Xeris Pharmaceuticals. Research Investigator; Self; Camurus AB. P. Freda: Research Investigator; Self; Camurus AB. L. Katznelson: Advisory Board Member; Self; Camurus AB, Recordati. F. Gatto: Advisory Board Member; Self; Camurus AB. Research Investigator; Self; Camurus AB. P. Kadioglu: None. P. Maffei: Research Investigator; Self; Camurus AB. J. Seufert: Research Investigator; Self; Camurus AB. J.L. Spencer-Segal: Advisory Board Member; Self; Camurus AB. Research Investigator; Self; Camurus AB. E. Isaeva: None. A. Dreval: None. M. Harrie: Employee; Self; Camurus AB. Stock Owner; Self; Camurus AB. A. Svedberg: Employee; Self; Camurus AB. Stock Owner; Self; Camurus AB. A.M. Pedroncelli: Employee; Self; Camurus AB. Stock Owner; Self; Camurus AB. F. Tiberg: Employee; Self; Camurus AB. Stock Owner; Self; Camurus AB. Background: Acromegaly is characterized by excess growth hormone (GH) and insulin-like growth factor 1 (IGF-1) production. A key treatment goal is long-term biochemical control to minimize adverse effects of prolonged excess GH. CAM2029 is a novel, subcutaneous, octreotide depot, designed for convenient monthly self-administration using a pre-filled injection/pen. In a 24-week Phase 3 trial (ACROINNOVA 1, NCT04076462), CAM2029 achieved superior IGF-1 control vs placebo (IGF-1 ≤ upper limit of normal [ULN]: 72.2 vs 37.5%; P=0.0018) in acromegaly patients previously controlled with standard-of-care (SoC; octreotide long-acting repeatable/lanreotide Autogel). On trial completion, patients could roll over to a Phase 3, 52-week, open-label, long-term safety trial (ACROINNOVA 2, NCT04125836). Here, we report data from an interim analysis of roll-over patients in ACROINNOVA 2. Methods: Roll-over patients received monthly CAM2029 20 mg for 28 weeks in ACROINNOVA 2. Primary endpoint: occurrence of adverse events (AEs). Key secondary endpoints: proportion of patients with available assessments who had (i) IGF-1 ≤1x ULN (mean of weeks 50/52 measurements) and (ii) both IGF-1 ≤1x ULN (weeks 50/52 mean) and mean GH &amp;lt;2.5 µg/L (week 52). Data are reported according to prior treatment in ACROINNOVA 1. Safety data from the whole trial period are reported. Results: Fifty-four of the 64 patients completing ACROINNOVA 1 (prior CAM2029 n=36; prior placebo n=18) entered ACROINNOVA 2. At data cut-off (May 23, 2023) 28 and 15 patients in the prior CAM2029 and prior placebo groups, respectively, had completed treatment week 52; 7 and 3 were ongoing; 1 and 0 had discontinued. The medication was well tolerated with a safety profile comparable to SoC treatment; no new safety signals were observed. One treatment-related serious AE (cholelithiasis, moderate severity, resolved) occurred in the prior placebo group. Injection site treatment-emergent AEs (Grade ≤2) occurred in 50% of patients in the prior CAM2029 (18/36) and prior placebo (9/18) groups. Of evaluable patients in the prior CAM2029 and prior placebo groups, 89.3% (25/28) and 100% (15/15) had IGF ≤1x ULN at weeks 50/52; 88.5% (23/26) and 100% (14/14) had both IGF ≤1x ULN (week 50/52) and GH &amp;lt;2.5 µg/L (week 52). Mean IGF-1 levels remained &amp;lt;ULN throughout the 52-week study period for the prior CAM2029 group; in the prior placebo group, mean IGF-1 increased above 1x ULN during placebo treatment, returning to &amp;lt;ULN after switching to CAM2029 for 28 weeks. All patients previously treated with placebo regained IGF-I control upon switching to CAM2029. Conclusions: The safety profile of CAM2029 was consistent with SoC, with no new or unexpected safety signals during extended treatment. CAM2029 provided persistent control of IGF-1 and GH during 52 weeks of treatment. All patients in the prior placebo group regained biochemical control of acromegaly after switching to CAM2029. Presentation: 6/1/2024

8043 IgG4-related disease with isolated involvement of the pituitary gland: case report

Abstract Disclosure: J.M. Ramos: None. Female patient, 36 years old, presented to our service complaining of a headache lasting five weeks, mainly in the frontal and left periorbital region, radiating to the occipital region. The pain was intense and intermittent, lasting about 40 minutes. No nausea or vomiting was reported, but the patient experienced dizziness and double vision. During the symptomatic interview, the patient mentioned increased thirst and urinary volume. In her medical history, she denied comorbidities, with only frequent episodes of tension-type headaches. She had no continuous medication use and no known drug allergies. The patient had undergone two cesarean sections, with the last one in December 2021. On physical examination, she had horizontal binocular double vision in all three gazes to the left, accompanied by pain during eye movement. Increased facial sensitivity on the left in branches V1 and V2 was observed. The rest of the physical examination showed no abnormalities. Initial general laboratory tests were normal. Evaluation of pituitary function was mostly normal, except for slightly elevated prolactin. A cranial MRI revealed an expansive lesion with sellar and suprasellar components measuring 1.2x1.1x1.2cm. Additional imaging of the sella turcica showed an intra- and suprasellar expansive lesion, predominantly isointense on T1, hyperintense on T2, with discreetly heterogeneous enhancement with gadolinium. In consultation with the neuroradiology team, a hypointensity on T2 at the left margin of the pituitary was noted, suggesting an inflammatory etiology. Based on this, laboratory tests were conducted, and treatment with methylprednisolone 1g per day for 7 days was initiated. After treatment completion, the IgG4 level was found to be 146.7 mg/dL (upper limit of reference: 86 mg/dL). A follow-up MRI, five days after the steroid pulse therapy, showed a reduction in lesion size to 0.8 cm in the cranio-caudal dimension, with a preserved appearance of the optic chiasm. The patient experienced considerable symptom improvement and was discharged with oral corticosteroids and a scheduled initiation of rituximab. The patient meets criteria confirming the diagnosis of IgG4-related hypophysitis, a rare condition representing 30% of hypophysitis cases. Isolated pituitary involvement is even rarer, and its association with diabetes insipidus has been described. Treatment involves corticosteroids, and rituximab can be considered, especially in recurrent cases. Presentation: 6/3/2024

12255 Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue And Cognitive Impairment In Mice

Abstract Disclosure: R. Dantzer: None. Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue and Cognitive Impairment in Mice Brandon Chelette, PhD, Anand Singh, PhD, Robert Dantzer, DVM, PhDDept. of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA Fatigue and cognitive impairments are commonly reported by cancer patients undergoing chemotherapy. The mechanisms of these neurotoxicities are still obscure. We hypothesize that they are mediated by mitokines that are released by cells undergoing mitochondrial stress in response to chemotherapy. For the present study, we have focused on growth differentiation factor 15 (GDF15) which acts in the brain by activating its receptor, GDNF family receptor alpha-like (GFRAL). Chemotherapy-induced fatigue was assessed by reduced voluntary wheel running. Cognitive impairment was assessed by altered performance in the Puzzle Box Test that measures executive function. We first checked whether commonly used chemotherapeutic drugs can induce GDF15. Mice were injected with cisplatin, paclitaxel, or bortezomib, and their effects on plasma levels of GDF15 were measured 24 h after (ELISA). Cisplatin was used in the following experiments in the form of one or two cycles of daily injections for five days with a rest of five days between cycles. To determine whether GFRAL mediates the effects of cisplatin on wheel running and performance in the puzzle box, mice were injected with a neutralizing antibody targeted to GFRAL (GFRALna) during or after cisplatin treatment. All studies were carried out in male and female C57BL/6 J mice using a 2 (+ chemotherapy) x 2 (+ GFRALna) factorial design with a minimum of 6 mice/group. Mitochondrial dysfunction was measured via Seahorse XF Analyzer Mito Stress Test. To determine whether activation of the GDF15/GFRAL axis recruits a central GDF15 compartment, Gdf15 mRNA was measured by qRT-PCR in the brain parenchyma, meninges, and choroid plexus. All the chemotherapeutic agents we tested induced statistically significant increases in circulating GDF15. GFRALna administered during cisplatin treatment (prevention) or after completion of cisplatin treatment (cure) abrogated cisplatin-induced decrease in wheel running and the deficit displayed by cisplatin-treated mice in the first hard trial run in the puzzle box. GFRALna also blocked the decrease in maximal oxygen consumption rate of mitochondrial in synaptosomes from cisplatin-treated mice. Cisplatin did not induce Gdf15 mRNA in the brain parenchyma but increased its expression in the meninges and choroid plexus. Although the role of this GDF15 brain compartment in the neurotoxicity of cisplatin remains to be determined, the present findings can be interpreted to suggest that GDF15-GFRAL signaling represents a new target for the treatment of chemotherapy-induced fatigue and cognitive impairment. Count: 2,246 characters Presentation: 6/1/2024

Socioeconomic Deprivation Correlates With Incomplete Radiotherapy Treatment in Head and Neck Cancer

There is a high burden of socioeconomic deprivation across Merseyside and, along with this, poorer cancer outcomes. The incidence of head and neck squamous cell carcinoma (HNSCC) within this region is higher than the national average and there are often additional complexities to individual treatment pathways such as poor health literacy, lack of social support and transport options which can impact on adherence to prescribed treatments. AimsThis work aims to understand the impact of deprivation on patients diagnosed with HNSCC undergoing chemoradiotherapy (CRT) or radiotherapy (RT) treatment by identifying barriers to adherence. Materials and methodsPatients with HNSCC treated between June 2022 and June 2023 were included and data was collected through retrospective case note review. Approval was obtained from relevant NHS institution audit departments. Key examined variables were indices of multiple deprivation (IMD), unplanned admission rate, hospital transport use, social support network and provision of additional ad hoc appointments during treatment courses. All were correlated with missed radiotherapy appointments. ResultsOut of 359 evaluable patients there were high levels of unplanned appointments with health professionals during CRT/RT (71% of those receiving CRT and 55% of those having RT). 11% (n = 39) missed at least one radiotherapy appointment with the commonest reason being unplanned admission to hospital. Despite missed appointments, 25/39 patients completed treatment within prescribed window due to effective RT compensation strategies. On multivariate analysis, unplanned admission, hospital-provided transport and crime deprivation quintiles (p=<0.001, p = 0.007 and p = 0.027, respectively) were found to significantly increase the chance of missed radiotherapy treatment appointments. ConclusionHigh levels of unplanned encounters with health care professionals are encouraging adherence to non-surgical HNSCC treatments. Formalising these ad hoc appointments will provide an equitable, robust service. Undertaking hospital transport increases the potential for missed treatment appointments. Gaining insight into patient experiences and investing in improved transport services are essential for maximising adherence.

Hepatitis C infection screening and connection to care among postpartum patients and exposed infants in two community hospitals, 3-year follow-up - Oregon, 2019-2024.

Determine prevalence of hepatitis C virus (HCV) positivity among postpartum patients to inform prenatal screening recommendations, postpartum connection to care, and infant HCV screening practices. Convenience sample of postpartum patients at one urban and one suburban hospital to undergo rapid fingerstick testing for hepatitis C antibodies. Of 2060 postpartum participants successfully screened, 20 (0.97%) had evidence of past or current HCV infection. One co-infection with syphilis occurred. After a median follow-up of 3.75 years, 6 of 12 participants (50.0%) with chronic HCV infection completed treatment with cure, and 9 of 20 infants (45.0%) completed screening. One neonatal transmission event occurred (5.8%). HCV infection was more common in our postpartum population than other viral infections routinely screened for during pregnancy. Efforts to decrease perinatal HCV transmission should focus on early postpartum connection to treatment team, early screening in infants aged 2-6 months, and pediatric test completion.

Decision regret analysis in early URSL vs medical expulsive therapy 1 for ureteric calculi ≤ 1cm

BackgroundThe study assesses the decisional regret following Shared Decision-making (SDM) in patients selecting either early ureteroscopic lithotripsy (URSL) or medical expulsive therapy (MET) for ureteric stones ≤ 1 cm, with the aim to evaluate their decisional Conflict, satisfaction, and regret regarding their opted treatment choices.MethodsAdults aged more than 18 years with one stone up to 1 cm in either ureter were included. After SDM, the patients were allocated into their opted group viz. URSL or MET. Patients in each group were reassessed at “treatment completion”. Cambridge Ureteric Stone PROM (CUSP) questionnaire for HRQoL, Decision Regret Scale and the OPTION scale (SDM) were filled at treatment completion.Findings111 patients opted for MET, while 396 patients opted for early URSL. Mean stone size was larger in URSL group (7.16 ± 1.63 mm vs. 5.50 ± 1.89; p < 0.001). Decisional conflict was higher in patients opting for URSL (77.3% vs. 57.7%; p < 0.001). Stone-free rate at four weeks was higher in URSL group (87.1%vs68.5%, p < 0.001). Decisional regret was higher in patients opting for MET (33.24 ± 30.89 vs. 17.26 ± 12.92; p = 0.002). Anxiety, was higher in patients opting for MET (6.94 ± 1.89 vs. 5.85 ± 1.54; p < 0.001). Urinary symptoms and interference in patients’ travel plans and work-related activities were more in URSL group (6.21 ± 1.57 vs. 5.59 ± 1.46; p < 0.001 and 6.56 ± 1.59 vs. 6.05 ± 1.72; p < 0.001 respectively).InterpretationAfter SDM, decisional regret is higher in patients opting for MET mainly due protracted treatment duration with increased pain and anxiety during the treatment course and the need for additional procedure for attaining stone clearance and the. Despite higher decisional conflict, a larger proportion of patients opt for early URSL with the aim of avoiding anxiety and achieving early stone clearance.

Not all types of depressed patients who persist with their antidepressant treatment improve in side effect complaints: A comparison of treatment completers and dropouts in the STAR*D trial.

There is a "traditional belief" that antidepressant side effect complaints improve with medication persistence; however, support for this theory has remained inconclusive. We aimed to examine if side effect complaints improved over time by modeling the relationship between side effect complaints and time at dropout for patients receiving citalopram during the first level of acute treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. We categorized the 2833 patients into five patterns by week of dropout. We used pattern-mixture modeling to model change in side effect complaints (frequency, intensity, and burden) over the 12-week course of treatment, while accounting for attrition and depressive severity. Using post-hoc linear contrasts, we compared the attrition patterns with the completers' pattern for severity of side effect complaints at each respective last visit prior to dropout as well as averaged side effect complaints across the duration of treatment. We also reported frequencies and tolerability of side effects for nine organ/function systems over the course of treatment. Patients who dropped out early exhibited worsening side effect burden and patients who dropped out later showed improvements in side effect frequency and intensity. Treatment completers improved in all side effect complaints over the course of treatment. Early attrition patterns had more severe side effect complaints for both tests of post-hoc linear contrasts than later attrition patterns and completers. Side effect complaints from antidepressant treatment improve over time, but only for some types of patients. As a precaution for early dropout, clinicians should monitor patients who exhibit worsening and more severe side effect complaints-especially in the first 6 weeks of antidepressant treatment. In addition, clinicians may want to consider changing the type of treatment early on for these patients, rather than encouraging them to persist with their current medication.

A comparative effectiveness study of usual care, simple Chuna manual therapy, and complex Chuna manual therapy for the treatment of pelvic biomechanical lesions in patients with non-acute low back pain: a protocol for multicenter, randomized controlled trial

BackgroundChuna manual therapy (CMT), a Korean manual therapy technique predominantly used for treating low back pain (LBP) and related disorders, lacks well-conceived research focusing on its comparative effectiveness, safety, and economic evaluation, particularly with respect to complex CMT with established CMT diagnostic algorithms. This study aims to illustrate a protocol for a randomized clinical study for comparative effectiveness and cost-effectiveness of complex CMT with simple CMT and usual care.MethodsThis is a protocol for a three-armed, multicenter, assessor-blinded, pragmatic, randomized controlled trial study. A total of 81 patients suffering from non-acute LBP with pelvic biomechanical lesions (PBL), characterized by a pain duration of at least two weeks and a Numeric Rating Scale (NRS) score of 5 or higher, will be recruited from two Korean medicine hospitals. These participants will be randomly assigned to one of three groups: complex CMT plus usual care (UC; n = 27), simple CMT plus UC (n = 27), or UC groups (n = 27). They will undergo treatment for 4 weeks, and follow-up assessments will be performed 8 weeks after treatment completion. The primary outcome will be the NRS score of LBP, and secondary outcomes will include the Oswestry Disability Index, Patient Global Impression of Change, credibility and expectancy questionnaire, three-dimensional posture analysis indicators, quality of life assessment, economic evaluation, and safety assessments.DiscussionThis will be the first study to assess the comparative effectiveness, safety, and cost-effectiveness of complex CMT compared to UC and simple/complex CMT in patients with LBP and PBL. We will also analyze useful diagnostic methods to help in clinical practice for CMT diagnosis.Trial registrationClinical Research Information Service (CRIS), KCT0009210. Registered on February 28, 2024.

Mechanisms of functional asymmetry of the face formation in patients with dysfunctional condition of temporomandibular joint

Objective. To give a detailed description of clinical manifestations, diagnosis and treatment of functional asymmetry of the face in patients with dysfunctional condition of temporomandibular joint (TMJ). Materials and methods. A complete examination of 34 (25 %) patients with symptomatic facial asymmetry of the 3rd type according to H.S. Hwang classification was carried out. The group consisted of 5 males (14,71 %) and 29 females (85,29 %). Screening protocol included standard dental care, cone beam computer tomography of both jaws and TMJ, MRI of TMJ with functional load. Results. 24 patients (70.59 %) completed complex dental treatment; 10 (29.41 %) people stopped treatment for various reasons and were excluded from further study. Complete restoration of facial symmetry was achieved in 21 people (87.5 %), partial restoration in 3 (12.5 %) patients. The height of the lower facial part and the synchrony of occlusal contacts were restored in all patients. Noise in the joint area persisted in 3 (8.8 %) cases, which is associated with arthrosis in the articular heads. In patients with unreducible dislocations, the intensity of the clicks decreased, and there was no pain at the end of treatment. It should be noted that all patients of this group refused subsequent surgical treatment. Conclusion. Functional asymmetry of the face results from multifactorial impact on the human organism and is multimorbid by nature. This condition is accompanied by complicated dental pathology, such as increased hard tooth tissues attrition, functional overload with traumatic nodes formation, disturbance of muscles and TMJ functions. It requires following diagnostic and treatment algorithm under the supervision of internal medicine specialists to correct sleep, postural stability, impaired psychoneurological status.

Barriers to the Completion of Radiation Therapy in Cervical Cancer Treatment in Nigeria: A Review of Socioeconomic, Geographical, and Psychosocial Factors.

Cervical cancer is a major health concern in Nigeria, where it is one of the primary causes of cancer-related deaths among women. Despite the crucial role of radiation therapy in treating cervical cancer, many patients in Nigeria do not complete their prescribed treatment courses. This review examines the barriers contributing to this issue. Factors such as low awareness and utilization of Pap smears, inadequate HPV vaccination, financial constraints, insufficient radiotherapy infrastructure, and the psychological burden of cancer treatment are explored. Limited screening and vaccination efforts exacerbate the high incidence of cervical cancer in Nigeria. Financial barriers are a primary obstacle, with many patients unable to afford the high cost of radiotherapy. Nigeria's radiotherapy infrastructure is severely lacking leading to significant treatment delays and cancellations. Geographical barriers further complicate access, as many patients must travel long distances to reach treatment centers. Psychosocial issues, including anxiety and depression, significantly impact treatment adherence and completion. These psychological factors, coupled with the physical side effects of radiotherapy, contribute to high rates of treatment interruption. To address these challenges, the review suggests enhancing cervical cancer prevention through increased human papillomavirus (HPV) vaccination and screening, expanding radiotherapy capacity by increasing the number of treatment centers, and providing comprehensive support systems to address financial and psychosocial barriers. By implementing these strategies, it is possible to improve treatment adherence and outcomes for cervical cancer patients in Nigeria.