Initial Phase Of Treatment Research Articles

Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression

BackgroundElectroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain.MethodsWe conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was −10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period.ResultsA total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test–Revised, −0.9±1.1 in the ketamine group vs. −9.7±1.2 in the ECT group; scores range from −300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation.ConclusionsKetamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis. (Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968.)

Postpartum Listeria Meningitis: A Case Report (P2-10.006)

<h3>Objective:</h3> n/a <h3>Background:</h3> Acute bacterial meningitis is a neurological emergency and fatal if left untreated. Here we present a case of bacterial meningitis, highlighting postpartum listeria monocytogenes infection. <h3>Design/Methods:</h3> <h3>Description:</h3> We present a case of 27 years-old woman with past medical history of migraine and hyperthyroidism, brought to the hospital with acute onset of reduced level of consciousness. A day prior to presentation, she woke up with a severe retro-orbital headache of 10/10 intensity along with nausea, vomiting, photophobia and phonophobia. Her symptoms further progressed to worsening confusion/somnolence with agitation. She had an uncomplicated vaginal delivery a month earlier. On admission, vitals were significant for high grade fever, hypotension, tachypnea and tachycardia. On examination, she was restless, combative, was not following any commands. No focal motor deficit. Nuchal rigidity and Babinski were negative. Labs showed mild anemia, leukocytosis, mild hyponatremia and lactic acidosis. MRI Brain showed faint diffuse leptomeningeal enhancement. CSF analysis showed WBC 732/Ul, SEG: 66%, protein&gt; 300mg/dl and CSF glucose &lt;20mg/dl. Meningitis panel and CSF culture were positive for listeria monocytogenes. Post CSF analysis, her broad spectrum antibiotics were deescalated to ampicillin for 21 days and gentamycin for 7 days for synergistic effects. During the initial treatment phase, she developed horizontal binocular diplopia and her exam showed isolated sixth nerve palsy. MRI brain revealed worsening diffuse leptomeningitis, involving the basal cisterns and the ependymal walls of the lateral ventricles. Eventually, she responded to the treatment and her symptoms resolved slowly. <h3>Results:</h3> n/a <h3>Conclusions:</h3> Listeria Monocytogenes can be a possible cause of postpartum meningoencephalitis due to the underlying transient immunosuppressive condition. Return to a normal immune response may take as long as up to one year after childbirth. Treatment should not be delayed in highly suspicion cases to avoid complications like rhombencephalitis, progressive neurological deficits and eventually death. <b>Disclosure:</b> Mr. Tang has nothing to disclose. Dr. Kausar has nothing to disclose. Dr. Rivera has nothing to disclose. The institution of Dr. Cruz-Flores has received research support from University of Texas System. Dr. Yerram has nothing to disclose.

Health services costs for ovarian cancer in Australia: Estimates from the 45 and Up Study.

There have been significant advancements in risk identification and treatment for ovarian cancer over the last decade. However, their impact on health services costs is unclear. This study estimated the direct health system costs (government perspective) for women diagnosed with ovarian cancer in Australia during 2006-2013, as a benchmark prior to opportunities for precision-medicine approaches to treatment, and for health care planning. Using cancer registry data, we identified 176 incident ovarian cancers (including fallopian tube and primary peritoneal cancer) in the Australian 45 and Up Study cohort. Each case was matched with four cancer-free controls on sex, age, geography, and smoking history. Costs were derived from linked health records on hospitalisations, subsidised prescription medicines and medical services to 2016. Excess costs for cancer cases were estimated for different phases of care relative to cancer diagnosis. Overall costs for prevalent ovarian cancers in Australia in 2013 were estimated based on 5-year prevalence statistics. At diagnosis, 10% of women had localised disease, 15% regional spread and 70% distant metastasis (5% unknown). The mean excess cost per ovarian cancer case was $40,556 in the initial treatment phase (≤12 months post-diagnosis), $9,514 per annum in the continuing care phase and $49,208 in the terminal phase (up to 12 months before death). Hospital admissions accounted for the greatest proportion of costs during all phases (66%, 52% and 68% respectively). Excess costs were higher for patients diagnosed with distant metastatic disease, particularly during the continuing care phase ($13,814 versus $4,884 for localised/regional disease). The estimated overall direct health services cost of ovarian cancer in 2013 was AUD$99million (4,700 women nationally). The excess health system costs of ovarian cancer are substantial. Continued investment in ovarian cancer research, particularly prevention, early detection and more effective personalised treatments is necessary to reduce the burden of disease.

Two cases of cardiomyopathy associated with phaeochromocytoma successfully managed with veno-arterial extracorporeal membrane oxygenation (V-A ECMO).

Phaeochromocytoma, a rare neuroendocrine tumour of chromaffin cell origin, is characterised by catecholamine excess. Clinical presentation ranges from asymptomatic disease to life-threatening multiorgan dysfunction. Catecholamine-induced cardiomyopathy is a dreaded complication with high lethality. While there is lack of evidence-based guidelines for use of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) in the management of this condition, limited to case reports and small case series, V-A ECMO has been reported as 'bridge to recovery' therapy, providing circulatory support in the initial period of stabilisation prior to surgery. We report on two patients presenting with catecholamine-induced cardiomyopathy and circulatory collapse who were successfully treated with V-A ECMO for 5 and 6 days, respectively, providing initial haemodynamic support. After stabilisation and introduction of alpha-blockade, both cases had favourable outcomes, with successful laparoscopic adrenalectomies on days 62 and 83 of admission, respectively. Our case reports provide further support for the use of V-A ECMO in the treatment of such gravely ill patients. Phaeochromocytoma should be considered in the diagnosis of patients presenting with acute cardiomyopathy. Management of catecholamine-induced cardiomyopathy is complex and requires multidisciplinary specialist input. Pre-operative management of phaeochromocytoma involves alpha-blockade; however, haemodynamic instability in the setting of cardiogenic shock can preclude alpha-blockade use. Veno-arterial extracorporeal membrane oxygenation is a life-saving intervention which may be considered in cases of acute catecholamine-induced cardiomyopathy and cardiogenic shock in order to provide the required haemodynamic support in the initial phase of treatment, enabling the administration of traditional pharmacological agents, including alpha-blockade.

Comparative Evaluation of Conventional Therapy With and Without Use of Diode Laser (DL) in the Treatment of Chronic Generalized Periodontitis: A Clinico-Microbiological Study.

Chronic periodontitis is caused by a persistent and expanding interaction between a subgingival pathogenic microbial biofilm and the host immune system. The host's reaction to local factors directly influences the inflammation and bone loss that result from these interactions. Depending on variables like the severity of soft tissue damage and bone loss, treatment options can range from nonsurgical to surgical. Nonsurgical treatments are frequently used as the first-line therapy for inflammatory periodontal disease. In fact, careful scaling and root planing (SRP), a nonsurgical treatment, has been extensively studied and shown to be a highly predictable and effective therapy. According to recent research, using a diode laser (DL) in addition to standard SRP may reduce bacterial count and reinfection significantly. Laser therapy could be helpful in treating periodontal disease because of its antibacterial and detoxifying effects. The goal of this study is to investigate whether using a DL in addition to conventional flap surgery enhances patient outcomes for those with chronic generalized periodontitis. The 12 participants in this split-mouth trial with chronic generalized periodontitis were the main subject of the study. All of them had probing pocket depths (PPDs) of at least 5 mm after the initial phase of treatment. Each patient in the control group (Group A) and test group (Group B) received a conventional flap after being randomly assigned to one of the groups. Group B underwent a conventional flap with a 980 nm DL, whereas those in Group A did not receive any DL therapy. Periodontal pockets in both groups were evaluated at baseline, 45 days, and 90 days after a sub-gingival plaque test. Quantitative real-time polymerase chain reactions were used to examine the presence of red complex organisms in the plaque sample. From baseline to 45 days and then to 90 days, clinical attachment loss (CAL), plaque index (PI), and gingival index (GI) all significantly decreased. However, results from 45 days to 90 days were statistically non-significant, with the exception of the GI, where Group B results were significantly different from Group A results from 45 days to 90 days. On the other hand, when a DL was combined with conventional flap surgery in the test group, the quantity of red complex bacteria was significantly decreased. When DL was used in conjunction with conventional flap surgery, the results showed that CAL, PI, and GI were all significantly reduced while the quantity of red complex bacteria was also significantly decreased.

ФАКТОРЫ РИСКА НЕУДАЧИ ЛЕЧЕНИЯ ТУБЕРКУЛЕЗА ОРГАНОВ ДЫХАНИЯ У ДЕТЕЙ И ПОДРОСТКОВ

Objective: to identify the major risk factors for treatment failure among children and adolescents with pulmonary TB. Materials and methods: aretrospective comparative study enrolled 141 patients aged 2–17 years with different forms of pulmonary TB. Upon completion of the main chemotherapy course consisting of the intensive and continuation phases, the patients were divided into two groups: group 1 – patients with treatment failure, group 2 – patients with treatment success. We compared the patients’ gender and age, social status of the families, the presence of medical or biological risk factors (the absence of anti-TB vaccination, concomitant chronic diseases, acute infectious diseases during the treatment, TB process at detection, drug resistance patterns in the patients and infection sources, the time of drug resistance development, the information about chemotherapy regimens and treatment administration, the occurrence and duration of treatment interruptions) in the groups. The obtained data were processed using binary logistic regression carried out by the SPSS 21.0 software. Results: we built a mathematical statistical model of the individual risk for treatment failure among children and adolescents with pulmonary TB. Conclusion: the major risk factors for treatment failure among children andadolescents with pulmonary TB were associated with inadequate chemotherapy: ignorance of drug resistance patterns on the initial treatment phase, defective use of chemotherapy potentials, wrong choice of treatment administration form. Late detection of TB (lung destruction, advanced TB process) was a more frequent factor in group 2 than group 1 but did not significantly influence treatment outcome.

EFFICACY OF USING TOPICAL L-LYSINE WITH DEBRIDEMENT IN CHRONIC NON-HEALING ULCERS – A PROSPECTIVE STUDY

INTRODUCTION Chronic non-healing ulceration is a common ailment that can be found all over the world Chronic wounds are those that have not undergone a timely and ordered reparative process to restore anatomic and functional integrity. Poor wound healing may be caused by a number of factors, including ischemia, infection, advanced age, malnutrition, diabetes, venous insufficiency, and renal disease. It has been demonstrated that L-lysine monohydrochloride, also known as L-lysine, is effective in promoting therapeutic angiogenesis in wound healing. MATERIALS AND METHODS STUDY POPULATION AND SAMPLE SIZE: All patients admitted with clinical diagnosis of “NON HEALING NON MALIGNANT ULCERS” under General Surgery care in SRM MEDICAL COLLEGE HOSPITAL AND RESEARCH CENTRE would be taken as Subjects for this study with a sample size of 84 with 42 in each group. All patients presenting with complaints of non-healing, non- malignant ulcers were randomly assigned to receive either Treatment A (topical L-lysine with mechanical debridement) or Treatment B (the control) (betadine with debridement) INCLUSION CRITERIA: Patients of any age or gender who are suffering from noncancerous ulcers that are chronic and do not heal, regardless of their socioeconomic. EXCLUSION CRITERIA: 1. Patients who are suffering from osteomyelitis, ischemic ulcers, and malignant ulcers 2. Patients who are currently receiving chemotherapy, Corticosteroids, or immunosuppressantS RESULTS The difference in mean of Wound dimension, Rate of granulation tissue formation between study group was statistically significant. (p value &lt;0.05). When compared to conventional care the rate of closure was three times faster with lysine gel treatment. DISCUSSION In our study, the graft failure was very minimal in both the groups The difference in mean of Wound dimension, Rate of granulation tissue formation between study groups was statistically significant. Majority of the patients did not develop complications in both the groups. However, Pain was the common complication in lysine group and infection was the common complication in conventional treatment group To achieve the best augmentation of the ulcer closure, treatment must start as soon as the initial wound is debrided CONCLUSION The use of topical l-lysine with debridement in chronic non-healing ulcers is effective treatment strategy in bringing better clinical outcomes, recommending its use from the initial phase of ulcer treatment. We recommend that lysine can be used over the conventional treatment which is beneficial in cosmetic wound appearance size and increased rate of granulation. This is also found to be useful in bypassing the complications of ulcers such as pain and infection. Therefore, we advise topic al lysine as an effective treatment in chronic non-healing ulcers

Spontaneous evolution of the quality of life of patients treated for breast cancer within three years after the end of treatments

ObjectiveThis article gives a description of the spontaneous evolution of organic parameters, quality of life and return to work of young patients treated for a breast cancer requiring an adjuvant chemotherapy. Material and methodsA prospective study of post-breast cancer rehabilitation for a working population of patients was organized in a single town in France. The inclusion criteria allowed to recruit patients immediately after their diagnosis up to three years after the end of their chemotherapy. VO2max, pain level, sleep quality, WHO performance status, abdominal obesity, level of physical activity, fatigability score, quality of life and metabolic parameters where registered at study entrance as base line data. ResultsThese data described the state of this population at variable temporal distance from the treatment within three years’ post-breast cancer before any rehabilitation action, thus describing the spontaneous evolution of this population. There has been an overall progressive improvement in the quality of life along with the spontaneous return to working activities. However, the physical status shows a lasting alteration, even after two years after treatment. ConclusionThis rather lasting disability justify an offer of rehabilitation cares immediately after the exit of initial treatment phase but also during the years following this exit.

Home Automation for Adults With Disability Following an Injury: Protocol for a Social Return on Investment Study

People with disability following a serious injury require long-term care. The most common injuries resulting in long-term disability are spinal cord and acquired brain injuries. While the long-term effects are difficult to predict and will vary between individuals, the costs of care and recovery span well beyond the initial treatment phase and include long-term care. Long-term care is changing with the availability and advances in cost and function of technologies, such as home automation. "Home automation" refers to technology that automates or remotely controls household functions. Home automation costs vastly differ, but home automation has the potential to positively impact the lives of people with disabilities. However, there is a dearth of evidence relating to the impact of home automation for people with a disability and few rigorous evaluations about the costs and return on investment. The purpose of this study is to describe the impact of home automation for people with long-term disability following a serious injury (such as a motor vehicle accident) using case studies, and by conducting an evaluation of the costs and outcomes for individuals, families, and the wider community using a Social Return on Investment (SROI) approach. SROI is a form of economic evaluation that develops a theory of change to examine the relationship among inputs, outputs, and outcomes and, in recent years, has gained popularity internationally, including in Australia. SROI has six phases: (1) identify scope and stakeholders, (2) map outcomes, (3) evidence outcomes and give them value, (4) establish impact, (5) calculate the SROI, and (6) report findings. Individuals with a disability who use home automation and key stakeholders will be interviewed. Stakeholders will be individuals involved in home automation for people with disabilities, such as allied health professionals, medical practitioners, equipment suppliers, engineers, and maintenance professionals. Users of home automation will be people who have a disability following a serious injury, have the capacity to provide consent, and have 1 or more elements of home automation. The impact of home automation will be established with financial proxies and appropriate discounts applied to avoid overestimating the social return. The SROI ratio will be calculated, and findings will be reported. The project was funded in November 2021 by the Lifetime Support Authority. Recruitment is underway, and data collection is expected to be completed by October 2022. The final results of the study will be published in March 2023. To our knowledge, this study represents the first study in Australia and internationally to employ SROI to estimate the social, personal, and community outcomes of home automation for people with a disability following a serious injury. This research will provide valuable information for funders, consumers, researchers, and the public to guide and inform future decision-making. DERR1-10.2196/42493.

QEEG Predictors of Treatment Response in Major Depressive Disorder- A Replication Study from Northwest India.

Background: Predicting treatment response with antidepressant is a challenging task for clinicians and researchers. An important limitation of an antidepressant trial is the increased time spent before an adequacy of trial can be decided. Quantitative Electroencephalography has shown some evidence in identifying early changes seen with antidepressants. No data has been reported from Indian population on its predictive capabilities. Aim: To examine whether early changes in frontal and prefrontal theta value in QEEG could predict antidepressant treatment response. Methods: Structured clinical assessments were conducted at baseline and after one week in a sample of treatment-seeking adults with major depressive disorder (n = 50). Patients were started on SSRI (Escitalopram, fluoxetine, paroxetine or sertraline) and followed for 8 weeks. QEEG recordings were carried out at baseline and week 1 and its parameters (relative theta power and cordance) were assessed to identify its predictive value for treatment response. Treatment response was assessed using Hamilton depression rating scale with 50% reduction after 8 weeks being considered as response. Results: Mean age of the sample was 39 ± 10 years and majority of them were females (64%). A significant reduction was found in relative frontal theta value (p = 0.021) from baseline to one week in responders. However, linear regression revealed that this change could not predict the treatment response (p = 0.37). Conclusions: QEEG changes are observed in initial phase of antidepressant treatment but these changes can't predict the treatment response.

Phase-Specific Costs of Care in Hematological Malignancies in Ontario, Canada

Background: Hematological malignancies contribute a significant economic burden to health care systems. Therefore, to improve health care system planning, this Canadian study analyzed real-world data to estimate phase-specific costs and health care resource utilization for patients with hematological malignancies. Methods: A cohort of adult patients diagnosed with hematological malignancies (diffuse large B-cell lymphoma [DLBCL], Hodgkin lymphoma [HL], follicular lymphoma [FL], chronic lymphocytic leukemia [CLL], multiple myeloma [MM], acute myeloid leukemia [AML], acute lymphocytic leukemia [ALL], and others) were identified between 2003-2014 from the Ontario Cancer Registry (OCR) and linked to treatment data from Cancer Care Ontario and other provincial administrative health care databases. Health system costs and resource utilization were determined for four defined phases of care in which index date was defined as the diagnosis date, including: pre-diagnosis (90 days prior to index date), initial treatment (index date to 6 months), follow-up (end of treatment phase to beginning of end-of-life or completion of cohort follow-up) and end-of-life (last 6 months of life for patients who died). Costs (Canadian dollars in 2014) and resource utilization were normalized to 30-days. Results: There were 35,556 individuals (45% females and 55% males) diagnosed with hematological malignancies. The median age of diagnosis was 64 (IQR: 53-74) years. The median follow-up was 1,874 (IQR: 1,232-2,814) days. At follow-up completion, 26,092 (73.4%) individuals were alive. The median survival time among those who died was 1,005 (568-1,682) days. The phase-specific costs were highest overall in AML and ALL for the initial treatment and end-of-life phases; the costs were $1,169 (±3,230) and $733 (±1,787) for pre-diagnosis, $12,424 (±8,181) and $10,565 (±9,823) for initial treatment, $4,051 (±6,152) and $3,033 (±5,991) for follow-up, as well as $11,815 (±13,973) and $13,484 (±12,039) for end-of-life for AML and ALL, respectively. The phase-specific costs of care for DLBCL and HL were $1,175 (±2,267) and $813 (±1,541) in the pre-diagnosis phase, $9,166 (±5,581) and $5,474 (±3,485) in the initial treatment phase, $1,462 (±2,757) and $895 (±1,619) in the follow-up phase, and $7,966 (±7,104) and $8,679 (±9,087) in the end-of-life phase. For MM, the costs were $1,537 (±3,011) in pre-diagnosis, $7,254 (±6,870) in initial treatment, $4,100 (±4,217) in follow-up, and $9,820 (±8,294) in end-of-life. In comparison, the costs of care for FL and CLL were less in the initial treatment phase but remained elevated in the end-of-life phase; the costs were $775 (±1,798) and $674 (±1,902) in pre-diagnosis, $3,884 (±3,997) and $1,610 (±3,345) in initial treatment, $1,253 (±1,744) and $1,010 (±1,827) in follow-up, and $7,310 (±6,852) and $6,189 (±6,413) in end-of-life phases. Across the phases, the key cost driver was inpatient care. In particular, the increased costs due to inpatient care for the initial treatment and end-of-life phases, respectively, were: $3,864 (±5,013) and $5,045 (±5,908) for DLBCL; $2,384 (±3,712) and $6,441 (±8,129) for HL; $2,131 (±3,502) and $5,146 (±5,612) for FL; $2,435 (±3,860) and $4,498 (±5,582) for CLL; $3,798 (±4,847) and $5,026 (±6,788) for MM; $9,330 (±6,985) and $7,941 (±9,063) for AML; and $8,133 (±8,178) and $10,144 (±10,780) for ALL. The second largest contributor to the cost of care, particularly in the initial treatment phase, was the cost of cancer treatment medication; $3,115 (±1,236) for DLBLC, $1,132 (±766) for HL, $2,851 (±1,755) for FL, $1,069 (±1,549) for CLL, $1,602 (±1,877) for MM, $843 (±1,429) for AML, and $494 (±756) for ALL. Of note, the cost of cancer treatment medication remains elevated for MM across the phases after diagnosis; $1,602 (±1,877) in initial treatment, $1,622 (±2,160) in follow-up, and $2,078 (±2,697) in end-of-life. Conclusions: In general, the mean total costs were highest in the initial treatment and end-of-life phases, and lowest in the pre-diagnosis and follow-up phases of care for all hematological malignancies, following a U-shaped pattern. Inpatient care was the cost driver across all phases. These findings can help allocate appropriate resources throughout the different phases of cancer care for hematological malignancies, with particular focus on improving access to palliative-care at end-of-life. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Correlation Amongst Scoring of Various Frailty Tools in Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Introduction: With the growing array of treatment options for multiple myeloma (MM) patients, it is important to individualize the approach at each point in the patient's treatment journey. Frailty scores such as the Revised Myeloma Comorbidity Index (R-MCI) can help match therapeutic intensity to patient fitness, particularly important in the elderly. The R-MCI has been prospectively validated in transplant patients and found to be predictive for PFS and OS outcomes. At our centre, we are enrolling patients deemed transplant-eligible by standard institutional criteria into a prospective study applying a variety of frailty tools, including objective measures of comorbidity/function and subjective measures based on patient self-assessment and physician opinion. These tools are applied at time of transplant clearance, not at diagnosis as previously studied, to take into consideration changes in frailty that occur during the initial treatment phase. The primary objective is to identify normative frailty scores at this timepoint and correlate with severity of transplant-related toxicity. In this analysis, we present data on the first 101 enrolled patients, reporting the various frailty scores and their inter-correlation. Patients and Methods: The first 101 consecutive MM patients preparing for autologous transplant (ASCT) and consented for the frailty study were included. Patients underwent comprehensive frailty assessments including: 1) objective measures of fitness [hand grip strength, 6-min walk test (6MWT), Timed Up and Go (TUG), 2) subjective measures of function (abbreviated Fried Frailty Phenotype Score (FFP), Rockwood Clinical Frailty Score, KPS, ECOG, HSCT-CI, ESAS), 3) scoring systems integrating both objective and subjective measures (R-MCI, International Myeloma Working Group geriatric assessment tool (IMWG-GAT), and 4) routine screening for organ function (creatinine clearance, serum albumin, hemoglobin, BNP, PFT, and cardiac imaging). Demographics including disease and treatment details were obtained from electronic medical records. Measures were evaluated with Chi-square/Fischer's exact test/Kruskal-Wallis test to assess the association between the various frailty scores. In addition, frailty scores were compared against R-MCI as baseline. All p values were 2-sided and p≥0.05 was considered statistically significant. Results: From Feb 2020 to July 2022, 101 patients consented for the frailty study and were included in this analysis. Patient characteristics and frailty scores are summarised in Table 1. ASCT was part of upfront treatment in 87 patients (86%), with 14 patients (14%) receiving salvage transplant at relapse. Median age was 63 years (35-75), with 9(9%) age 70 and above. In general, our transplant-eligible population tested well on most frailty scores, mostly falling within the fit or intermediate-fit categories, as expected. Notable exceptions were significantly poorer handgrip strength and 6MWT than observed in the literature. Only 2 of 101 patients in our analysis were able to walk >400 metres, a threshold for fitness cited in prior transplant studies. Most scoring systems in our analysis correlated in designating our cohort as "fit” or "intermediate fit". When using the transplant-validated R-MCI scores as our gold standard, we observed correlations with the IMWG-GAT and Rockwood scores (p=0.0014 and <0.0001 respectively). The simple-to-perform ECOG and HCT-CI indices also correlated highly with R-MCI.(Table 2) That said, the R-MCI lacked discrimination in our patient population, with almost all patients clustered into the fit or pre-fit categories (98/101; 98%). Conclusions: In this analysis of various frailty assessments applied at ASCT for MM, we report that most scoring systems correlated but generally lacked discrimination in this relatively fit cohort. Even the widely cited R-MCI which is validated in both myeloma and transplant, has limited utility in discriminating within this more homogeneously fit population. We will hence focus next on identifying scoring systems or individual tools that can further define the less fit or mildly frail within the "fit” category, allowing us to identify subgroups for medical optimization pre-ASCT. We also note that physical function testing such as handgrip and 6MWT may have limited utility in myeloma where disease-related disability may prevent full engagement. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Early Time Courses of Recurrent Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer

Introduction The CARAVAGGIO trial was a multinational, randomised, investigator initiated, open-label with blind outcome assessment, noninferiority trial which demonstrated noninferiority of apixaban to dalteparin for treatment of cancer related venous thromboembolism (VTE) without an increased risk of major bleeding. In patients with acute VTE, the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation (1). We sought to evaluate the efficacy and safety of apixaban during the initial high-risk phase of treatment in patients with cancer associated VTE. Specifically, we performed a pre-specified sub-analysis of the time courses of recurrence and bleeding, with the aim to determine the incidence after 7, 30 and 90 days of treatment with apixaban compared with dalteparin. Methods The study design and methods of the CARAVAGGIO trial (CARAVAGGIO; NCT03045406; https://clinicaltrials.gov/ct2/show/NCT03045406) have been described (2). Briefly, CARAVAGGIO compared the efficacy and safety of apixaban with dalteparin in consenting patients who had active cancer and a newly diagnosed symptomatic or incidental proximal lower-limb deep-vein thrombosis (DVT) or pulmonary embolism (PE). Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed VTE. The primary safety outcome was major and clinically relevant non-major (CRNM) bleeding. Results The CARAVAGGIO study enrolled 1170 patients from 119 centres in eleven countries from April 2017 through June 2019); 1155 patients were included in the modified intention-to-treat analysis. The demographic and clinical characteristics of the patients were similar in the two treatment groups. Of the 78 recurrent VTE events 11 (14.1%) occurred in the first 7 days, 35 (44.8%) in the first 30 days and 63 (80.7%) in the first 90 days. Recurrent events occurred in 6 (1.0%) in the apixaban group and 5 (0.9%) in the dalteparin group (RR 1.21; 95% CI 0.37-3.93) by day 7, 15 (2.6%) in the apixaban group and 20 (3.5%) in the dalteparin group (RR 0.75; 95% CI 0.39-1.46) by day 30, and in 27 (4.7%) in the apixaban group and 36 (6.2%) in the dalteparin group (RR 0.75; 95% CI 0.46-1.23) by day 90. By 6 months, recurrent events occurred in 32 (5.6%) in the apixaban group and 46 (7.9%) in the dalteparin group (RR 0.70; 95% CI 0.45-1.08). (Table 1). During the six months of treatment, major and CRNM bleeding occurred in 70 patients who received apixaban (12.2%) and in 56 patients who received dalteparin (9.7%) (RR 1.26; 95% CI 0.90-1.75). Of the total 126 bleeding events, 24 (19.0%) occurred during the first 7 days; 58 (46.0%) during the first 30 days, and 89 (70.6%) during the first 90 days. Bleeding events occurred in 14 (2.4%) in the apixaban group and 10 (1.7%) in the dalteparin group (RR 1.40; 95% CI 0.63-3.14) by day 7, 30 (5.2%) in the apixaban group and 28 (4.8%) in the dalteparin group (RR 1.08; 95% CI 0.65-1.78) by day 30, and in 46 (8.0%) in the apixaban group and 43 (7.4%) in the dalteparin group (RR 1.07; 95% CI 0.72-1.60) by day 90. The Kaplan-Meier plot of time to recurrent VTE and major and CRNM bleeding is shown in figure 1. Conclusion The results of this sub-analysis of the CARAVAGGIO trial demonstrate no difference of oral apixaban to subcutaneous dalteparin at all time points. Specifically, there was no increase in recurrent VTE or bleeding events at 7 days, 30 days, 90 days and 6 months. This supports early initiation of oral anticoagulation. Oral versus subcutaneous anticoagulation has the advantage of ease of administration and outpatient delivery which may improve patients’ quality of life - an important consideration in patients with cancer. Reference 1. Raskob GE, Gallus AS, Sanders P, Thompson JR, Agnelli G, Buller HR, et al. Early time courses of recurrent thromboembolism and bleeding during apixaban or enoxaparin/warfarin therapy. A sub-analysis of the AMPLIFY trial. Thrombosis and haemostasis. 2016;115(4):809-16. 2. Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. New England Journal of Medicine. 2020;382(17):1599-607. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Achieving Therapeutic Anti-Xa Levels Using Rivaroxaban for Venous Thromboembolism in a Morbidly Obese Patient with a BMI >70

Background: Anticoagulation (AC) is the cornerstone of treatment for venous thromboembolism (VTE). Direct oral anticoagulants (DOACs) have become the standard of care during the acute and extended phases of therapy for VTE, mostly due to their ease of use, efficacy, and safety profiles. There is a 9.2% prevalence of severe obesity (BMI>40) in Americans as of 2017-2020 with a 6.2-fold increased risk of VTE in obese individuals. The 2021 International Society on Thrombosis and Haemostasis (ISTH) guidelines recommend using standard dosages of DOACs in patients with a BMI >40 kg/m2 or weight >120 kg. Despite these recommendations, their use in severely obese individuals at extremes of weight like our patient with a BMI > 70 kg/m2 remains uncertain. Case Presentation Herein, we present a 38-year-old morbidly obese female with no significant past medical history who presented with an acute worsening of dyspnea on exertion saturating 60% on room air. The diagnosis of intermediate-high risk pulmonary embolism (PE) was made based on computed tomographic angiography (CTA) with right ventricular strain and elevated cardiac biomarkers. A concomitant proximal DVT from the left common femoral to the distal peroneal vein was also noted. The patient's weight was 243kg with a calculated BMI of 72.3 kg/m2. After the patient had received parenteral anticoagulation with heparin for 4 days, it was decided to switch to Rivaroxaban 15mg BID for 21 days followed by 20 mg daily. With a history of irregular menses, the patient developed heavy menstrual bleeding (HMB) following the initiation of rivaroxaban. Her hemoglobin remained stable with no blood transfusion requirements. However, this led to the decision to switch to rivaroxaban 20 mg PO daily earlier than planned due to a lack of improvement in menstrual bleeding which was considered to be clinically relevant non-major bleeding (CRNMB). Despite this switch, there was no effect on efficacy and the patient did not develop any signs or symptoms of VTE recurrence during her prolonged hospital stay with a significant improvement in her oxygenation levels and VTE symptomatology. In our patient, we demonstrated the use of rivaroxaban in a morbidly obese individual with a BMI>70 by achieving therapeutic anti-Xa levels. Figure 1 shows the therapeutic peak and trough anti-Xa levels throughout the patient's hospitalization. The highest Anti Xa level of 314 mcg/mL was reported on day 19 correlating with the patient's menorrhagia, which self-limited with the transition from rivaroxaban 15 mg twice daily to 20 mg daily. Discussion: Two pivotal clinical trials, the EINSTEIN-DVT/PE trials, where 14% of patients in both arms weighed >100 kg, showed that patients on rivaroxaban (15 mg BID for 3 weeks, followed by 20 mg once daily) vs those on enoxaparin followed by a vitamin K antagonist, had no significant difference in recurrence rates of VTE and bleeding rates [Moore KT, et Al. Influences of Obesity, Am J Med 2017]. A recent post-hoc analysis of the EINSTEIN DVT/PE trials also portrayed no correlation between weight/BMI and risk of recurrent VTE or bleeding in those who received rivaroxaban. Our case illustrates the attainment of therapeutic anti-Xa levels with no recurrent VTE in our morbidly obese patient. Despite her heavy menstrual bleeding, the bleeding was controlled once the switch to rivaroxaban 20mg daily was completed. Another study in which its heaviest participant at 172 kg, showed compelling evidence that morbid obesity has minimal influence on the safety and efficacy of rivaroxaban [Speed V, et al. Fixed dose rivaroxaban. JTH 2020]. This remains true for our patient at 243 kg. Conclusion: Our case demonstrates that standard doses of rivaroxaban for the treatment of DVT/PE in individuals with morbid obesity with BMI>70 kg/m2 can be effective, and safer for the initial phase of treatment for VTE and in prevention of VTE recurrence. It also portrays that increased dosages attempting to account for high bodyweight/fat can potentially result in major bleeding events. Despite the 2021 ISTH guidelines, further prospective studies and randomized controlled trials are warranted, to assess the safety and efficacy of DOACs in VTE, particularly in such challenging clinical scenarios like morbid obesity. Alongside clinical assessment, additional studies will be essential to evaluate the need for universal and external validation of anti-Xa levels in patients taking DOACs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

QOL-02. FACTORS INFLUENCING COMPLIANCE IN TTF TREATMENT – THE COMPTUNE STUDY

Abstract INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (nGBM). A crucial parameter for TTFields efficacy is compliance to treatment. In this prospective study, we assessed 5 psychological domains known to influence treatment compliance using a standardized interview in nGBM patients. The results of this psychological assessment were correlated to TTF compliance. METHODS A cohort of 49 nGBM patients (female 22; male 27, median age 62 years) were recruited. Most patients received a gross total resection (51%), the postsurgical treatment consisted of concomitant radiochemotherapy plus TTF in most cases (81%), only 2 patients received chemotherapy only, and 7 patients were additionally enrolled in clinical drug trials. The psychological assessment system consisted of 5 domains: Social support, confidence in treatment efficacy, communication status about treatment, anxiety, and depression. The interview was repeated every 8 weeks over a period of 8 months or if patients stopped treatment or developed second tumor progression. Additional phone interviews were conducted every 4 weeks. RESULTS Median and mean compliance was 98% and 81.6%, respectively (range 5%-100%), drops of compliance below 75%, which were classified as a threshold value, occurred 2259 times. Over-dispersed Poisson and multivariate negative binomial regression analysis revealed depression to be significantly correlated with the number of drops below 75% and with the mean compliance in the first 4 months of treatment. In addition, at later time points, confidence in treatment efficacy significantly correlated with the number of drops below 75%. All other domains did not appear to be associated with TTF treatment compliance. CONCLUSION Overall, compliance to TTF was high, however, drops below 75% of compliance occurred frequently during the measurement periods. In the initial treatment phase, depression was associated with these events, whereas confidence in treatment efficacy was correlated at later time points.

Transdiagnostic therapy for persistent physical symptoms: A mediation analysis of the PRINCE secondary trial

The PRINCE secondary trial did not find any evidence that transdiagnostic cognitive behavioural therapy (TDT-CBT) plus standard medical care (SMC) was more efficacious than SMC for patients with Persistent Physical Symptoms (PPS) for the primary outcome Work and Social Adjustment Scale (WSAS) at final follow-up (52 weeks). There was a significant treatment effect for TDT-CBT plus CBT compared with SMC for two secondary outcomes: WSAS at the end of active treatment (20 weeks) and symptom severity (Patient Health Questionnaire, PHQ-15) at 52 weeks.To understand mechanisms that lead to effects of TDT-CBT plus SMC versus SMC we performed a planned secondary mediation analysis. We investigated whether TDT-CBT treatment effects on these two secondary outcomes at the end of the treatment could be explained by effects on variables that were targeted by TDT-CBT during the initial phase of treatment. We pre-specified mediator variables measured at mid-treatment (9 weeks).Reductions in catastrophising and symptom focusing were the strongest mediators of TDT-CBT treatment effects on WSAS at the end of treatment. Improvements in symptom focusing also mediated the effect of TDT-CBT on PHQ-15.Future developments of the TDT-CBT intervention could benefit from targeting these mediators.

The Impact of Living with Clubfoot on Children and Their Families: Perspectives from Two Cultural Environments.

To study the physical, emotional and social impact of clubfoot on the lives of affected children and their families. A purposive sample ofchildren with treated idiopathic clubfoot and their parentswas recruited from two geographical locations-the United Kingdom (UK) and India. Children were divided into age groups of 5-7 and 8-11years. Questionnaires were administered separately to children and parents; the former comprised multiple-choice questions scored using an 'emoji' system, and the latter included open-ended questions divided intopre-defined themes of daily limitations, social life, general health, emotional barriers and family impact. Thirty-four children and parentsparticipated from UK; 96 children and parents participated from India. The majority of children (> 80%) reported no problems in daily activities, although 32.8% reported having pain. Difficulty finding appropriate footwear and limitation in sports were more common among UK children, whereas difficulty in squatting was more problematic for Indian children. Self and emotional perceptions regarding their appearance/condition were lower among older as compared to younger children in both countries. Parents' responses mirrored those of children; additionally they reported emotional and financial difficulties during initial treatment phase, and ongoing concerns about the future during the maintenance phase. Treated clubfoot continues to impact the lives of affected children and families. Perceptions of the condition and its impact vary between population groups; this needs to be appreciated when collecting and analysing outcomes.

Baseline Stimulability Predicts Patterns of Response to Traditional and Ultrasound Biofeedback Treatment for Residual Speech Sound Disorder.

This study aimed to identify predictors of response to treatment for residual speech sound disorder (RSSD) affecting English rhotics. Progress was tracked during an initial phase of traditional motor-based treatment and a longer phase of treatment incorporating ultrasound biofeedback. Based on previous literature, we focused on baseline stimulability and sensory acuity as predictors of interest. Thirty-three individuals aged 9-15 years with residual distortions of /ɹ/ received a course of individual intervention comprising 1 week of intensive traditional treatment and 9 weeks of ultrasound biofeedback treatment. Stimulability for /ɹ/ was probed prior to treatment, after the traditional treatment phase, and after the end of all treatment. Accuracy of /ɹ/ production in each probe was assessed with an acoustic measure: normalized third formant (F3)-second formant (F2) distance. Model-based clustering analysis was applied to these acoustic measures to identify different average trajectories of progress over the course of treatment. The resulting clusters were compared with respect to acuity in auditory and somatosensory domains. All but four individuals were judged to exhibit a clinically significant response to the combined course of treatment. Two major clusters were identified. The "low stimulability" cluster was characterized by very low accuracy at baseline, minimal response to traditional treatment, and strong response to ultrasound biofeedback. The "high stimulability" group was more accurate at baseline and made significant gains in both traditional and ultrasound biofeedback phases of treatment. The clusters did not differ with respect to sensory acuity. This research accords with clinical intuition in finding that individuals who are more stimulable at baseline are more likely to respond to traditional intervention, whereas less stimulable individuals may derive greater relative benefit from biofeedback. https://doi.org/10.23641/asha.20422236.

Alignment Efficiency of Nickel-Free Niobium–Titanium–Tantalum–Zirconium Compared to Nickel–Titanium Orthodontic Archwires during Initial Treatment Phase: A Randomized Controlled Trial

Abstract Objective This randomized controlled trial investigated the efficiency of nickel–titanium (NiTi) and nickel-free archwires during the initial leveling and alignment stage. Materials and Methods A total of 30 patients (mean age, 17.81 ± 1.96 years) were randomly grouped to receive either single-strand or niobium–titanium–tantalum–zirconium (nickel-free Gummetal), or multistrand NiTi archwires. All the patients had moderate anterior crowding and were treated via a nonextraction approach. Three-dimensional digital models were taken at baseline (T0) and 4-week intervals for three months (T1, T2, and T3). The amount and percentage variations in Little's Irregularity Index (LII) scores during the 3-month observation period were used to estimate alignment efficiency and rate. Statistical Analysis The Analysis of variance (ANOVA) and Kruskall–Wallis tests were used to test the differences between the three archwire groups. The difference between variables within each group at different measurement intervals was assessed using paired t-test. Results The LII scores were reduced in all the three archwire groups; however, there were insignificant differences in the scores between the tested archwire groups (p &lt; 0.05). For the single-strand NiTi group, the LII scores reduced by 2.15 mm (28.38%) after 4 weeks (T1) by 3.79 mm (47.93%) after 8 weeks (T2), and by 5.61 mm (73.98%) after 12 weeks (T3). The LII scores decreased by 1.90 mm (26.93%) after 4 weeks, 3.59 mm (50.84%) after 8 weeks, and 5.28 mm (74.85%) after 12 weeks with Gummetal archwire. Similar to the other groups, the LII scores for multistrand archwire reduced by 1.82 (27.83%), 3.34 (51.07%), and 4.54 mm (69.38%) at T1, T2, and T3, respectively. There was nonsignificant differences in the alignment rates (mm) and percentage (%) of changes among the groups at all measurement intervals (p &gt; 0.05). Conclusion All three tested archwires were equally effective for correcting moderate mandibular anterior crowding. Furthermore, all three archwires produced a comparable rate of alignment after 12 weeks of initiating orthodontic therapy.

Two Cases of Methemoglobinemia Caused by Prilocaine, A Local Anesthetic

In situations of methemoglobinemia, elevated amounts of methemoglobin decrease hemoglobin's ability to bind oxygen. Cases of methemoglobinemia may appear with a mild or severe presentation at emergency departments. This disorder can be inherited or acquired. In the initial phase of treatment, intravenous administration of methylene blue is preferable. This methemoglobinemia may be caused by prilocaine, one of the local anesthetics used for surgical procedures. This paper attempts to describe the examination, diagnostic, and treatment processes of two patients who presented to the emergency room with cyanosis and shortness of breath following the administration of local anesthetic. We aimed to contribute to the literature by explaining the importance of differential diagnosis, clinical findings, and treatment in methemoglobinemia.