Termination Of Treatment Research Articles

Treatment Terminations during Radiation Therapy: A Ten-Year Experience

Disruptionsin cancer care adversely affect clinical outcomes, particularly when a patient does not complete the prescribed course of treatment. The impact of treatment termination (TT) during radiation therapy has not been well studied. This study addresses TT in a large multi-center department of radiation oncology over a 10-year time period. TTs of patients undergoing radiation treatment between January 2013 and December 2022 were prospectively tracked as part of departmentalquality and safety monitoring. A TT was defined as the discontinuation of therapy at any point following consent and simulation. Causes of TTs were categorized as: hospice/death, physician choice related to toxicity, physician choice unrelated to toxicity, patient choice related to toxicity, patient choice unrelated to toxicity, progression of disease, non-cancer illness, or other. The rate of TT was calculated as a percentage of all new patients who start radiation treatments. As part of our ongoing department quality and safety program, incremental changes were made to pre-treatment evaluation and scheduling processes, collectively referred to as the "No-Fly" policy. TT rates during three iterations of this policy were compared. Outof 28,707 planned treatment courses, a total of 1,467 TTs were identified (5.1%). 688 (46.9%) involved patients treated with curative intent, 770 (52.5%) with palliative intent, and 9 (0.6%) for benign disease. The rate of TT decreased from 9.3% in 2013 to 3.3% in 2022. Relative to evolutions of our No-Fly policy, the overall TT rate decreased from 8.8% under No-Fly 1 (2013-2014), to 5.2% during No-Fly 2 (2015-2018), and 4.0% with No-Fly 3 (2019-2022) (ANOVA, p<0.001). The most common sites for TT were H&N (19.3%), CNS (17.9%), and Bone Metastases (17.9%). The most common cause of TT was hospice and/or death (36.5%), 69.1% of which were in patients receiving palliative treatments. Other common causes included patient choice unrelated to toxicity (35%), physician choice unrelated to toxicity (8.8%), and progression of disease (7.6%). There were 473 TTs without radiation dose given (1.6% of planned treatments, 32.3% of TTs). Radiation TTs reflect major deviations from the original care plan. This large cohort study highlights the value of open departmental discourse about TTs, which prompted quality improvement changes that reduced TTs over time. Future studies addressing clinical outcomes can direct treatment decision-making and improve care for our patients.

Retrospective Review of the Factors Limiting Optune Initiation in GBM patients

Tumor Treating Fields (TTFields) are a proven treatment that prolongs survival in Glioblastoma Multiforme (GBM) patients. The duration of usage of TTFields correlates with its effectiveness. This study aims to identify socioeconomic and clinical factors that prevent GBM patients at a single institution from starting and remaining on TTFields treatment. This is a retrospective review from a single institution. Data were analyzed for each patient with a diagnosis of GBM that was seen in new patient consultation with a radiation oncologist. Data from 2015 to present were available. 178 patients were included in the study. Insurance status (private vs Medicare/Medicaid vs uninsured), zip code, expected income status, race, ethnicity, preferred primary language, work status, performance status (KPS) at time of diagnosis, and family support at home (Spouse vs Other) were analyzed. For those that initiated TTFields, we examined the duration of treatment, usage rates, patient reported tolerability, and reasons for discontinuation. Early termination of treatment was defined as treatment with TTFields for less than 3 months. Of the 178 diagnosed GBM patients, 96 (54%) were offered TTFields and 48 (27%) agreed to treatment, with 46 actually starting. Of 89 Non-Hispanic patients, 53 were offered TTFields (60%) whereas of 73 Hispanic patients, 35 were offered TTFields (48%) (no statistically significant difference). The number one reason for refusing TTFields treatment was rapid deterioration (14/48 patients). The next most common reason was the patient feeling overwhelmed by managing or wearing the device (10/48) as well as the patient's decision to participate in any other clinical trial (10/48). The 3-month dropout rate for patients who received TTFields was 35% (17/48). 5 of the 17 stopped early due to skin rash or annoyance with the device. Patient's median income and insurance status did not predict whether they would start TTFields. 33 out of 109 (31%) patients with spousal support at home started treatment with TTFields compared to 13 of 69 (19%) of those without spousal support (p = .0895, Chi-Square test). TTFields were offered to more patients each successive year, but many patients had no documented discussion offering TTFields, which may indicate room for improvement at our institution. Median income and insurance status did not play a role in patient access to TTFields, most likely due to Novocure sponsorship of un- or under-insured patients. Among those who declined treatment, 21% did so because of perceived difficulty managing the device. The strongest single trend predictive of successful initiation of TTFields is spousal support at home. Further interventions may focus on improving patient support at home, such as home health nursing visits or community support.

OA11 Osteoporosis, denosumab, and hypocalcaemia in multimorbid renal impairment

Abstract Introduction Osteoporosis affects approximately 30% of patients with chronic kidney disease (CKD) at stages 3-5, with 10% of women and 5% of men experiencing a fragility fracture within a given three-year follow up period. First-line management of osteoporosis with bisphosphonates is often precluded in CKD, with alendronate and zoledronate being contraindicated in creatinine clearances of &amp;lt; 35mL/min, and risedronate if &amp;lt; 30mL/min. Denosumab, a RANK-ligand inhibiting monoclonal antibody, can be used in cases of poorer renal function, however causes hypocalcaemia more commonly than bisphosphonates. Concomitant CKD compounds this risk if creatinine clearance falls below 30mL/min, presenting additional challenges for management. Case description A 75-year old woman with known osteoporosis and chronic kidney disease secondary to hypertension and a pauci-immune necrotising glomerulonephritis was found to have a serum calcium of 2.08mmol/L approximately three months after commencing six-monthly denosumab. Her lumbar spine T-score on dual x-ray absorptiometry showed severe osteoporosis at −2.9, with a fragility fracture of the humerus sustained four years prior. Her baseline eGFR was 23mL/min/1.73m2, and creatinine clearance was 22mL/min. Her past medical history was extensive and included secondary hyperparathyroidism due to CKD and resulting vitamin D deficiency, with a PTH of 23.0pmol/L, serum calcium of 2.26mmol/L, and a serum 25-OH vitamin D3 level of 33.5nmol/L four months prior to denosumab therapy. The history also included Sjögren’s syndrome on long-term daily prednisolone 7.5mg, alternate-day hydroxychloroquine 200mg, and daily leflunomide 10mg for accompanying synovitis of the hands, hypothyroidism controlled with daily levothyroxine 50mcg, hypertension controlled with daily 2.5mg bisoprolol, peripheral neuropathy secondary to vitamin B12 deficiency on three-monthly hydroxocobalamin, myocardial infarction with percutaneous coronary intervention to three arteries, diverticular disease with abscess perforation requiring laparotomy and intensive care admission, and a previous deep vein thrombosis on long-term anticoagulation with apixaban. The patient had received risedronate in the past while her creatinine clearance still permitted this. Her vitamin D deficiency had been managed orally with Adcal-D3 and colecalciferol 800IU once daily, which was uptitrated to 1600IU once daily prior to commencing denosumab. However, despite the patient’s serum vitamin D levels rising from 33.5 to 37.2nmol/L in the months preceding her first denosumab infusion, serum calcium had fallen below normal range on post-infusion blood tests. Serum phosphate returned at 0.91mmol/L, and vitamin D had fallen to 23.1nmol/L in the three months following denosumab treatment. Consequently, the patient was commenced on longer term intensive vitamin D supplementation. Discussion This case raises the issue of multifactorial hypocalcaemia against a backdrop of osteoporosis, persistent vitamin D deficiency, and medical comorbidity limiting management options. The significance of CKD in this case highlights the importance of monitoring and replacing vitamin D. While the hypocalcaemia detected at three months post-infusion may have occurred in part due to the direct effect of denosumab, the patient’s vitamin D deficiency no doubt also played a role in this, and failing to detect the deficiency may have resulted in premature termination of denosumab treatment. This case also highlights the extended timeframe in which such hypocalcaemia may present. Case-series literature describes hypocalcaemia manifesting at, on average, eight days post-infusion in patients with CKD-associated hyperparathyroidism. However we demonstrate here that extended lag times up to twelve weeks are possible; the patient was symptomatic with leg cramping at the time of clinic follow up. Future practice may benefit from establishing monitoring regimes for those with CKD and osteoporosis receiving denosumab, or bisphosphonates toward the lower end of permitted renal function. Key learning points Chronic kidney disease both limits available management options in osteoporosis, and increases the likelihood of complications from the remaining available agents – illustrated here with hypocalcaemia. Hypocalcaemia in a patient with chronic kidney disease and osteoporosis may be driven by several factors: hyperphosphataemia, vitamin D deficiency, and the effect of denosumab to prevent mobilisation of calcium from bone to serum can all be culprits. Calcium, phosphate, and vitamin D all need to be tightly monitored in medically complex patients on treatment for osteoporosis.

Transcutaneous bilirubin measured on protected skin during phototherapy in term and preterm neonates

BackgroundTranscutaneous bilirubin (TCB) measurement is a simple, painless, and time-saving alternative for the assessment of TSB (total serum bilirubin) levels. However, TCB measurements obtained during phototherapy can yield inaccurate results. We evaluated the effectiveness of TCB measurements obtained from protected skin areas in patients who underwent phototherapy. MethodsThis prospective study included neonates delivered at a gestational age of ≥340/7 weeks. TCB measurements were performed at the forehead and the lower end of the sternum using a JM-105 device. Simultaneously, blood samples were collected to determine TSB levels. During phototherapy, the forehead was covered with a photo-opaque patch. TSB and TCB were measured before, during, at the end of, and after phototherapy. ResultsIn total, 200 neonates, including 110 (55 %) term and 90 (45 %) late preterm infants, were enrolled. Of these neonates, 162 (81 %) were Turkish while 38 (19 %) were refugees from Syria and Iraq. Notably, no statistically significant differences were observed in the TSB and TCB values between the Turkish and refugee groups (p > 0.05). Bland–Altman analysis was conducted between the TCB values obtained from the covered forehead area and TSB values; the analysis revealed moderate, high, and excellent agreements for the first bilirubin measurement and at the end of phototherapy, before phototherapy, and for the second and rebound bilirubin measurements, respectively. Regarding intraclass correlation coefficients, values >0.95, 0.94–0.85, 0.84–0.70, and < 0.7 indicated perfect, high, moderate, and unacceptable compatibilities, respectively. Although a significant association was observed between pre-phototherapy TCB obtained from the sternum and TSB levels, no significant associations were observed during phototherapy. ConclusionsOur findings indicate that the consistency observed between TCB measurements obtained from the protected skin areas and TSB values can be used to monitor phototherapy effectiveness, particularly in late preterm/term infants and those with darker skin tones. Furthermore, this approach can aid in guiding decisions related to treatment termination, evaluating rebound bilirubin levels, minimizing costs, and providing a less invasive testing option.

P11.16.B THE MAYO CLINIC MULTIDISCIPLINARY NF2 CLINIC EXPERIENCE OF BEVACIZUMAB IN NEUROFIBROMATOSIS TYPE 2-RELATED SCHWANNOMATOSIS PATIENTS WITH VESTIBULAR SCHWANNOMAS

Abstract BACKGROUND Neurofibromatosis type 2-related schwannomatosis (NF2) is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS) as well as other nervous system tumors. Management decisions for NF2-related VS are typically predicated on tumor size, associated symptoms, patient age, and comorbidities. Observation, surgical resection, and stereotactic radiosurgery can be viable options. In patients with VS associated with NF2, vascular endothelial growth factor A (VEGF-A) inhibitor, bevacizumab, is a systemic treatment option. In this single institution study, we review our clinical experience in patients with NF2 who received bevacizumab for VS and evaluate the effect of bevacizumab treatment on VS growth and symptom progression. MATERIAL AND METHODS This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Three-dimensional volumetric data for VS were measured using manual segmentation with Visage PACS software under the direct supervision of a board-certified neuroradiologist. RESULTS Out of 76 patients with NF2 evaluated in the past 3 years, we identified 19 that received treatment with bevacizumab. Median age of NF2 diagnosis was 19 years (range 0.5-61) with a median NF2 phenotype severity score of 2 (range 1-3). Thirteen of these patients have discontinued bevacizumab, accounting for a median duration of 12.2 months (range 3.3-88 months) of bevacizumab treatment. Bevacizumab was discontinued due to hypertension (n=5), proteinuria and renal dysfunction (n=3), tumor progression (n=2), fatigue or other intolerance (n=2), or non-compliance (n=1). The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March 2023 (range 3.7-48.3 months). Fifteen patients had brain MRI data available to evaluate VS change during bevacizumab treatment, with partial response observed in 5 patients, stable disease in 8, and progression in 2. Ten of the 13 patients who stopped bevacizumab had MRI data to evaluate VS change following treatment termination. Within 6 months of bevacizumab discontinuation, 6 patients had rebound growth of their VS between 21-95% from their previous tumor volume, while 4 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. CONCLUSION Our single institution experience confirms that bevacizumab can slow progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.

Influence of oral microbiome on longitudinal patterns of oral mucositis severity in patients with squamous cell carcinoma of the head and neck.

This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck. OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit an average trend within each group and to assess the association between the longitudinal OM scores and longitudinal microbial abundances. Four latent groups (LGs) with differing patterns of OM severity were identified for 142 subjects. LG1 has an early onset of high OM scores. LGs 2 and 3 begin with relatively low OM scores until the eighth and 11th week, respectively. LG4 has generally flat OM scores. These LGs did not vary by treatment or clinical or demographic variables. Correlation analysis showed that the abundances of Bacteroidota, Proteobacteria, Bacteroidia, Gammaproteobacteria, Enterobacterales, Bacteroidales, Aerococcaceae, Prevotellaceae, Abiotrophia, and Prevotella_7 were positively correlated with OM severity across the four LGs. Negative correlation was observed with OM severity for a few microbial features: Abiotrophia and Aerococcaceae for LGs 2 and 3; Gammaproteobacteria and Proteobacteria for LGs 2, 3, and 4; and Enterobacterales for LGs 2 and 4. These findings suggest the potential to personalize treatment for OM. Oral mucositis (OM) is a common and debilitating after effect for patients treated for squamous cell carcinoma of the head and neck. Trends in the abundance of specific microbial features may be associated with patterns of OM severity over time. Our findings suggest the potential to personalize treatment plans for OM via tailored microbiome interventions.

Chronic exposure to cigarette smoke extract increases nicotine withdrawal symptoms in adult and adolescent male rats.

The aim of the current study was to determine whether non-nicotine constituents of cigarette smoke contribute to nicotine dependence in adolescent and adult male Sprague Dawley rats. For 10days animals were given three times daily intravenous injections of nicotine (1.5mg/kg/day) or cigarette smoke extract (CSE) containing an equivalent dose of nicotine. Both spontaneous and mecamylamine-precipitated withdrawal were then measured. Chronic treatment with CSE induced significantly greater somatic and affective withdrawal signs than nicotine in both adolescents and adults. Mecamylamine-precipitated somatic signs were similar at both ages. In contrast, animals spontaneously withdrawn from chronic drug treatment exhibited significant age differences: whereas adolescents chronically treated with nicotine did not show somatic signs, those treated with CSE showed similar physical withdrawal to those of adults. Mecamylamine did not precipitate anxiety-like behavior at either age. However, both adolescents and adults showed significant anxiety in a light-dark box test 18h after spontaneous withdrawal. Anxiety-like behavior was still evident in an open field test 1month after termination of drug treatment, with adolescents showing significantly greater affective symptoms than adults. Our findings indicate that non-nicotine constituents of cigarette smoke do contribute to dependence in both adolescents and adults and emphasize the importance of including smoke constituents with nicotine in animal models of tobacco dependence.

Eosinophil dynamics during chemo-radiotherapy correlate to clinical outcome in stage Ⅱ-Ⅳa nasopharyngeal carcinoma patients: Results from a large cohort study

Background and purposeWe investigated the dynamics of eosinophil depletion during definitive concurrent chemo-radiotherapy (CCRT) and their association with the prognosis of stage Ⅱ-Ⅳa nasopharyngeal carcinoma (NPC) patients. Materials and methodsFuzzy C-means algorithm (FCMA) assessed longitudinal trends in circulating eosinophil counts (CECs) of 1225 patients throughout the period of radical radiotherapy. The prognostic impact on patients’ survival was evaluated with Kaplan-Meier analysis and Cox proportional risk model was used to determine the hazard ratio for adverse prognostic effects in grades of eosinophil depletion. The interactive effect of pre-treatment CECs and CCRT on outcomes was evaluated using HRs within the framework of Cox regression models. ResultsThree grades of eosinophil depletion, as defined by the interaction between dynamic types of CECs in the period of treatment and the value of CECs at the termination of treatment, significantly stratified the poor prognosis in terms of progression-free survival (PFS), overall survival (OS), and distant metastasis-free survival (DMFS) [1.57-fold (P = 0.001), 1.69-fold (P = 0.007), and 1.51-fold (P = 0.019) for G1, 2.4-fold (P < 0.001), 2.76-fold (P < 0.001), and 2.31-fold (P < 0.001) for G2, as compared with G0]. Furthermore, high levels of pre-treatment CECs acted as the strongest protective factor against severe depletion grade (G0 vs. G2, HR = 0.20, P = 0.005; G1 vs. G2, HR = 0.14, P < 0.001). However, compared with radiotherapy alone, the benefit from CCRT was attenuated in patients with high pre-treatment CECs. ConclusionsCECs reduction after treatment in patients with NPC may be helpful in the clinical setting to aid in assessing the prognosis for standard treatment of NPC.

Chemotherapy compliance in elderly patients with solid tumors: a real-world clinical practice data

Introduction. Malignant tumors in elderly people are more than ten times more prevalent than in the younger population. The data on the compliance with chemotherapy in older cancer patients managed outside of clinical trials is scarce. Material and methods. We retrospectively assessed 181 consecutive cancer patients aged 65 years or more who received systemic chemotherapy. The study aimed to examine chemotherapy compliance in a large series of elderly patients managed in routine clinical practice. We also investigated the ability to complete chemotherapy in relation to selected factors, such as tumor type, treatment setting and line, type of chemotherapy, presence of comorbidities, body mass index (BMI), an expected glomerular filtration rate, hemoglobin level (Hb), a neutrophil- to-lymphocyte ratio, and Eastern Cooperative Oncology Group performance status (PS). Results. Thirty-three percent of patients did not complete an initially pre-defined chemotherapy plan. The main reasons were disease progression (20%) and unacceptable toxicity (10%). Independent factors related to premature treatment termination included a lower BMI, a lower Hb level, lower PS, and palliative (compared to currative) setting. Conclusions. In conclusion, premature chemotherapy termination not related to disease progression is relatively rare in elderly patients and may be predicted with routinely used clinical parameters.

Efficacy of Levetiracetam versus Phenytoin in Neonatal Seizure in Rural Area of Thailand

Background: Neonatal seizure is an emergency condition that affects neurodevelopment and mortality. The appropriate treatment and seizure termination is crucial. Previous studies determined the efficacy of different types of antiseizure medications (ASMs), but there is no consensus toward second-line ASMs in neonatal seizure. Objective: To compare the efficacy of second-line ASMs in neonatal seizure, compared between levetiracetam and phenytoin. Materials and Methods: The present study was a retrospective study. The author recruited patients with diagnosis of neonatal seizure admitted at Maharat Nakhon Ratchasima Hospital, Thailand, between January 1, 2018 and December 31, 2020. Patients who had clinical seizure refractory and were given first-line ASM (intravenous phenobarbital) and received second-line ASMs as intravenous levetiracetam or intravenous phenytoin were included. Etiologies of seizure, seizure types, and other demographic data were recorded. The efficacy of levetiracetam and phenytoin were determined by comparing the duration of seizure, the need for third-line ASMs, and morbidity as developmental outcome, diagnosis of cerebral palsy, and mortality rate. Results: Twenty-five patients (68% male) were recruited. Sixty-four percent were diagnosed with hypoxic ischemic encephalopathy (HIE). The most common seizure type was subtle seizure at 56%. Levetiracetam was given to 56% and phenytoin was given to 44% as second-line ASMs. The duration of seizure was significantly different at 28.12 minutes in levetiracetam and 42.72 minutes in phenytoin (p=0.01). The drug adherence was higher in the levetiracetam group. Regarding third-line ASMs, 28.7% of the levetiracetam group and 45.45% of phenytoin group needed third-line ASMs, but this was not statistically significant. Mortality was 20% and 48% were diagnosed as cerebral palsy. There was no significant difference in mortality and morbidity between the two groups. Conclusion: Levetiracetam had no superior efficacy than phenytoin in neonatal seizure. Keywords: Neonatal seizure; Levetiracetam; Phenytoin; Efficacy

Antibiotic stewardship

The spread of antimicrobial resistance (AMR) is one of the greatest threats to global health and causes very many deaths. Also in the context of sepsis-the severest complication of certain infectious diseases-does AMR play arole. Wise use of anti-infectives and application of antibiotic stewardship (AMS) principles can reduce the spread of AMR and improve the quality of management of patients with infectious diseases. Correct use of anti-infective agents includes the correct diagnostic approach and documentation of the (suspected) diagnosis, guideline-conform diagnostic workup and treatment selection, re-evaluation and tailoring during the course of treatment, afocus on treatment de-escalation depending on clinical response and microbiology results, dose optimization, and, if possible, conversion to oral therapy, and early termination of treatment if the suspected diagnosis is not confirmed. Particularly adherence to the guideline-conform treatment duration can reduce unnecessary use of anti-infectives. Prevention of infections via adherence to vaccination recommendations also contributes to areduction in the use of anti-infectives. Interdisciplinary collaboration with infectious diseases and AMS specialists, as recommended for sepsis, also improves treatment quality and patient outcomes. Particularly for complex infections such as endocarditis cases should be discussed in multidisciplinary teams including specialists in infectious diseases. In this manner, decisive steps against the spread of AMR and towards maintenance of the efficacy of available anti-infective drugs can be taken.

Costs and cost-effectiveness of Shamiri, a brief, layperson-delivered intervention for Kenyan adolescents: a randomized controlled trial

BackgroundLow- and middle-income countries (LMICs) have the highest socio-economic burden of mental health disorders, yet the fewest resources for treatment. Recently, many intervention strategies, including the use of brief, scalable interventions, have emerged as ways of reducing the mental health treatment gap in LMICs. But how do decision makers prioritize and optimize the allocation of limited resources? One approach is through the evaluation of delivery costs alongside intervention effectiveness of various types of interventions. Here, we evaluate the cost-effectiveness of Shamiri, a group– and school–based intervention for adolescent depression and anxiety that is delivered by lay providers and that teaches growth mindset, gratitude, and value affirmation.MethodsWe estimated the cost-effectiveness of Shamiri using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines for economic evaluations. Changes in depression and anxiety were estimated using the Patient Health Questionnaire (PHQ-8) and Generalized Anxiety Disorder questionnaire (GAD-7) at treatment termination and 7-month follow-up using two definitions of treatment benefit. Cost-effectiveness metrics included effectiveness-cost ratios and cost per number needed to treat.ResultsBase case cost assumptions estimated that delivering Shamiri cost $15.17 (in 2021 U.S. dollars) per student. A sensitivity analysis, which varied cost and clinical change definitions, estimated it cost between $48.28 and $172.72 to help 1 student in Shamiri, relative to the control, achieve reliable and clinically significant change in depression and anxiety by 7-month follow-up.ConclusionsShamiri appears to be a low-cost intervention that can produce clinically meaningful reductions in depression and anxiety. Lay providers can deliver effective treatment for a fraction of the training time that is required to become a licensed mental health provider (10 days vs. multiple years), which is a strength from an economic perspective. Additionally, Shamiri produced reliable and clinically significant reductions in depression and anxiety after only four weekly sessions instead of the traditional 12–16 weekly sessions necessary for gold-standard cognitive behavioral therapy. The school setting, group format, and economic context of a LMIC influenced the cost per student; however, broader conclusions about the cost-effectiveness of Shamiri have yet to be determined due to limited economic evaluations of mental health programs in LMICs.Trial registrationThis study was registered prior to participant enrollment in the Pan-African Clinical Trials Registry (PACTR201906525818462), registered 20 Jun 2019, https://pactr.samrc.ac.za/Search.aspx.

Successful management of adult hemophagocytic lymphohistiocytosis with an etoposide-containing regimen: Case report and literature review

Objective: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder characterized by a hyperimmune response. Although HLH is well described in the pediatric population, less is known about the appropriate management in adults. Despite the inclusion of etoposide in HLH society protocols, some clinicians refrain from using it due to its cytotoxicity and potential adverse effects. Case: We report here the case of a 43-year-old male presenting with fever and pancytopenia, who was diagnosed with HLH following further evaluation. The patient immediately started the HLH-2004 initial protocol, which consisted of dexamethasone, etoposide, cyclosporine, and IVIG. Symptoms improved after 2 weeks of treatment. Subsequent bone marrow biopsy showed normal results, and the patient achieved complete remission, leading to the termination of treatment in the 12th week of the protocol. At 8 months post-treatment, the patient remained recurrence-free with normal hematological and biochemical test results. Conclusion: This case underscores the importance of considering etoposide-containing regimens, particularly for medically fit patients.

Outcome analysis of pregnancy termination and expectant treatment in pregnant women with suspected invasive placenta accreta spectrum disorders in the second trimester

Objective: To investigate the maternal and fetal outcomes of expectant treatment and early termination of pregnancy in pregnant women with suspected invasive placenta accreta spectrum disorders (PAS) in the second trimester. Methods: A retrospective cohort study was performed on 51 pregnant women with suspected invasive PAS (ultrasound score ≥10) evaluated by ultrasound with gestational age <26 weeks and confirmed as invasive PAS by intraoperative findings or postoperative pathology in Peking University Third Hospital from January 2015 to January 2022. According to the informed choice of pregnant women and their families, they were divided into expectant treatment group (37 cases) and mid-term termination group (14 cases). The general clinical data and outcome indexes of the two groups were analyzed by χ2 test, Mann-Whitney U rank sum test, logistic regression and linear regression. Results: (1) General clinical data: among 51 pregnant women who were assessed as suspected invasive PAS by ultrasonography in the second trimester, invasive PAS was finally diagnosed by intraoperative findings and postoperative pathology, among which 46 cases (90%) were placenta percreta and 5 cases (10%) were placenta increta. (2) Outcome indicators: univariate analysis showed that there were no statistically significant differences in the intraoperative blood loss (median: 2 200 vs 2 150 ml), the proportion of blood loss >1 500 ml [73% (27/37) vs 9/14], the hysterectomy rate [62% (23/37) vs 8/14], the rate of intensive care unit (ICU) admission [78% (29/37) vs 9/14] between the expectant treatment group and the mid-term termination group (all P>0.05). Multivariate analysis showed that the rate of intraoperative blood loss >1 500 ml (aOR=0.481, 95%CI: 0.017-13.958; P=0.670), hysterectomy (aOR=0.264, 95%CI: 0.011-6.569, P=0.417) and ICU admission (aOR=1.327, 95%CI: 0.048-36.882, P=0.867) between the two groups showed no statistical differences. (3) Outcome analysis: all 37 cases in the expectant treatment group had live births and no early neonatal death. Five pregnant women (14%, 5/37) in the expectant treatment group underwent emergency cesarean section in the course of expectant treatment. In the mid-term termination group, all pregnancies were terminated by operation, including 9 cases of hysterectomy and 5 cases of placental hysterectomy. There was 1 fetal survival (gestational age of termination: 27+4 weeks) and 13 fetal death in the mid-term termination group. Conclusions: Pregnant women who are diagnosed as suspected invasive PAS, especially those with placenta percreta, have the risk of uterine rupture and emergency surgery in the course of expectant treatment. However, early termination of pregnancy does not reduce the risk of intraoperative blood loss and hysterectomy.

Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial.

In recent years, survival in patients with breast cancer has increased. Despite the improvement in outcomes of those patients, the risk of treatment-related cardiotoxicity remains high, and its presence has been associated with a higher risk of treatment termination and thus lower therapeutic efficacy. Prior trials demonstrated that a preventive initiation of heart failure drugs, including the renin-angiotensin-aldosterone inhibitors, might reduce the risk of treatment-related cardiotoxicity. However, to date, no study investigated the efficacy of sacubitril/valsartan, a novel antineurohormonal drug shown to be superior to the previous therapies, in the prevention of cardiotoxicity in patients with early-stage breast cancer, which is the aim of the trial. MAINSTREAM is a randomized, placebo-controlled, double-blind, multicentre, clinical trial. After the run-in period, a total of 480 patients with early breast cancer undergoing treatment with anthracyclines and/or anti-human epidermal growth factor receptor 2 drugs will be randomized to the highest tolerated dose of sacubitril/valsartan, being preferably 97/103mg twice daily or placebo in 1:1 ratio. The patients will be monitored, including routine transthoracic echocardiography (TTE) and laboratory biomarker monitoring, for 24months. The primary endpoint of the trial will be the occurrence of a decrease in left ventricular ejection fraction by ≥5% in TTE within 24months. The key secondary endpoints will be the composite endpoint of death from any cause or hospitalization for heart failure, as well as other imaging, laboratory, and clinical outcomes, including the occurrence of the cancer therapy-related cardiac dysfunction resulting in the necessity to initiate treatment. The first patients are expected to be recruited in the coming months, and the estimated completion of the study and publication of the results are expected in December 2027, pending recruitment. The MAINSTREAM trial will determine the efficacy and safety of treatment with sacubitril/valsartan as a prevention of cardiotoxicity in patients with early breast cancer (ClinicalTrials.gov number: NCT05465031).

Effect of on-site first aid for industrial injuries on healthcare utilization after medical treatment: a 4-year retrospective longitudinal study

BackgroundThe number of industrially injured workers (IIW) is increasing in Korea. However, little research has been conducted on whether first aid is performed at industrial sites or on the association between first aid for industrial injuries and the prognosis of IIW, including healthcare utilization.MethodsA total of 3,092 participants (2,562 males and 530 females) were analyzed during the 4-year study period, which contributed to 11,167 observations. Healthcare utilization was evaluated based on the number of outpatient visits, hospitalizations, and duration of hospitalization using a generalized estimating equation Poisson regression. Several time-varying socioeconomic characteristics and information about the injury were adjusted, and transfer time to the medical institutions was also considered.ResultsDuring 4-year after the termination of medical treatment, participants who had not receive first aid visited outpatient clinics 15.243 times per year, and those who had visited 13.928 times per year, which is 16.16% less (adjusted relative risk [aRR]: 0.838, 95% CI = 0.740–0.950). Participants who had received on-site first aid with less than a 0.5-hour transfer time to the medical institutions visited outpatient clinics 14.87% less per year than those who had not received first aid (aRR: 0.851, 95% CI = 0.750–0.966).ConclusionTo reduce the long-term outpatient utilization rate for IIW after medical treatment, on-site first aid must be provided in a timely manner. Employee education and first aid training are also necessary.

Socioeconomic status, psychotherapy duration, and return to work from disability due to common mental disorders

ABSTRACT Objective Low socioeconomic status (SES) is a risk factor for work disability due to common mental disorders (CMDs), one possible reason being inequal use of services. Psychotherapy is an evidence-based treatment for CMDs. This study examines socioeconomic and sociodemographic differences in psychotherapy attendance and an association of psychotherapy duration with return to work (RTW). Methods The study subjects (N = 12,263) were all Finnish citizens granted a disability pension (DP) due to CMDs in 2010–2012. Numbers of psychotherapy sessions (maximum 200) were collected from the nine-year interval around the DP grant. Socioeconomic and sociodemographic differences in psychotherapy duration (dependent variable) among DP recipients were studied using multinomial logistic regression models, likewise, the association between psychotherapy duration and RTW (dependent variable) among temporary DP recipients was examined. Results Higher SES, female gender, and younger age were positively associated with attending longer psychotherapies and surpassing the early treatment termination level (>10 sessions). Attending 11–60 psychotherapy sessions was positively associated with full RTW and partial RTW, whereas longer psychotherapies were not. Early termination was positively associated with partial RTW only. Conclusion This study demonstrates varying tendencies among CMD patients from different backgrounds to attend long rehabilitative psychotherapies, which may create inequalities in RTW.

Feasibility of a Career Development Intervention for Veterans in Vocational Rehabilitation: Protocol for a Pilot Randomized Controlled Trial

Background Veterans with psychiatric disorders want additional career development services to support their recovery and pursuit of meaningful employment. However, no career counseling programs have been designed for this specific population. We developed the Purposeful Pathways intervention to fill this need. Objective This study protocol aims to (1) evaluate the feasibility and acceptability of the Purposeful Pathways intervention for veterans living with psychiatric disorders and (2) explore preliminary clinical outcome data. Methods A total of 50 veterans who are participating in transitional work vocational rehabilitation services at a Veterans Affairs hospital will be randomized to either treatment as usual or the augmented treatment condition (treatment as usual plus Purposeful Pathways). Feasibility will be assessed via recruitment rates, clinician fidelity to treatment, retention rates, and acceptability of randomization procedures. Acceptability will be assessed via client satisfaction at treatment termination using quantitative and qualitative data collection. Preliminary clinical and vocational outcomes will be assessed at baseline, 6 weeks, 12 weeks (treatment termination), and a 3-month follow-up via quantitative measures assessing vocational functioning, vocational process, and mental and physical functioning. Results This pilot randomized controlled trial is beginning recruitment in June 2023 and is expected to continue through November 2025. Data collection is expected to be completed by February 2026, with full data analysis completed by March 2026. Conclusions Findings from this study will provide information on the feasibility and acceptability of the Purposeful Pathways intervention, as well as secondary outcomes related to vocational functioning, vocational process, and mental and physical functioning. Trial Registration ClinicalTrials.gov NCT04698967; https://clinicaltrials.gov/ct2/show/NCT04698967 International Registered Report Identifier (IRRID) PRR1-10.2196/47986

Patient-Specific Pharmacokinetics and Dasatinib Nephrotoxicity.

Dasatinib has been associated with nephrotoxicity. We sought to examine the incidence of proteinuria on dasatinib and determine potential risk factors that may increase dasatinib-associated glomerular injury. We examined glomerular injury through urine albumin-creatinine ratio (UACR) in 82 patients with chronic myelogenous leukemia who were on tyrosine-kinase inhibitor therapy for at least 90 days. t tests were used to compare mean differences in UACR, while regression analysis was used to assess the effects of drug parameters on proteinuria development while on dasatinib. We assayed plasma dasatinib pharmacokinetics using tandem mass spectroscopy and further described a case study of a patient who experienced nephrotic-range proteinuria while on dasatinib. Participants treated with dasatinib ( n =32) had significantly higher UACR levels (median 28.0 mg/g; interquartile range, 11.5-119.5) than participants treated with other tyrosine-kinase inhibitors ( n =50; median 15.0 mg/g; interquartile range, 8.0-35.0; P < 0.001). In total, 10% of dasatinib users exhibited severely increased albuminuria (UACR >300 mg/g) versus zero in other tyrosine-kinase inhibitors. Average steady-state concentrations of dasatinib were positively correlated with UACR ( ρ =0.54, P = 0.03) and duration of treatment ( P = 0.003). There were no associations with elevated BP or other confounding factors. In the case study, kidney biopsy revealed global glomerular damage with diffuse foot process effacement that recovered on termination of dasatinib treatment. Exposure to dasatinib was associated with a significant chance of developing proteinuria compared with other similar tyrosine-kinase inhibitors. Dasatinib plasma concentration significantly correlated with higher risk of developing proteinuria while receiving dasatinib. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000219.mp3.

Thromboelastography and Traditional Coagulation Testing in Non-ICU-Admitted Patients with Acute Kidney Injury: An Observational Cohort Study

Introduction: This study aimed to elucidate the coagulation disorders in non-ICU patients with acute kidney injury (AKI) and their contribution to clotting-related outcomes of intermittent kidney replacement therapy (KRT). Methods: We included non-ICU-admitted patients with AKI requiring intermittent KRT, clinically having a risk of bleeding and against systemic anticoagulant use during KRT between April and December 2018. The premature termination of treatment due to circuit clotting was considered a poor outcome. We analyzed the characteristics of thromboelastography (TEG)-derived and traditional coagulation parameters and explored the potential-affecting factors. Results: In total, 64 patients were enrolled. Hypocoagulability was detected in 4.7%–15.6% of patients by a combination of the traditional parameters, i.e., prothrombin time (PT)/international normalized ratio, activated partial PT, and fibrinogen. No patient had hypocoagulability observed on TEG-derived reaction time; only 2.1%, 3.1%, and 10.9% of patients had hypocoagulability on TEG-derived kinetic time (K-time), α-angle, and maximum amplitude (MA), respectively, which were also platelet-related coagulation parameters, despite 37.5% of the cohort having thrombocytopenia. In contrast, hypercoagulability was more prevalent, involving 12.5%, 43.8%, 21.9%, and 48.4% of patients on TEG K-time, α-angle, MA, and coagulation index (CI), respectively, although thrombocytosis was only in 1.5% of the cohort. Patients with thrombocytopenia showed lower fibrinogen level (2.6 vs. 4.0 g/L, p = 0.00), α-angle (63.5° vs. 73.3°, p = 0.00), MA (53.5 vs. 66.1 mm, p = 0.00), and CI (1.8 vs. 3.6, p = 0.00) but higher thrombin time (17.8 vs. 16.2 s, p = 0.00) and K-time (2.0 vs. 1.2 min, p = 0.00) than those with a platelet count over 100 × 10⁹/L. 41 patients were treated with heparin-free protocol, and 23 were treated with regional citrate anticoagulation (RCA). The premature termination rate was 41.5% on heparin-free patients, while 8.7% of patients underwent an RCA protocol (p = 0.006). Heparin-free protocol was the strongest adverse factor to poor outcomes. A heparin-free subgroup analysis found that the circuit clotting risk was increased by 61.7% with a 10 × 10⁹/L elevation in platelet count (odds ratio [OR] = 1.617, p = 0.049) and decreased by 67.5% following a second increase of PT (OR = 0.325, p = 0.041). No significant correlation was found between TEG parameters and premature circuit clotting. Conclusions: Most non-ICU-admitted patients with AKI had normal-to-enhanced hemostasis and activated platelet function based on TEG results, as well as a high rate of premature circuit clotting when receiving heparin-free protocol despite thrombocytopenia. Further studies are needed to better determine the use of TEG in respect to management of anticoagulation and bleeding complications in AKI patients with KRT.