Recommended Treatment Guidelines Research Articles

Atrial Fibrillation Surgery in Australia: Are We Doing Enough?

This study aimed to examine contemporary burden and treatment trends of atrial fibrillation (AF) in patients undergoing cardiac surgery in Australia and New Zealand. This allows comparison of contemporary practice with the Society of Thoracic Surgeons guideline recommendations for the surgical treatment of AF in patients undergoing cardiac surgery. A 10-year retrospective review of the Australian & New Zealand Society of Cardiac & Thoracic Surgeons National Cardiac Surgery Database was performed, examining all adult cardiac surgery patients from 2011 to 2021. Patients were grouped by the presence or absence of AF, and simple descriptive statistical analysis was performed to assess baseline demographics and premorbid condition of the patients. The incidence of AF was analysed by type of surgery. Trends for surgical treatment of AF were then analysed using simple descriptive statistics, examining isolated left atrial appendage ligation, isolated surgical ablation, and combined ligation and ablation. In the last 10 years, the Australian & New Zealand Society of Cardiac & Thoracic Surgeons database has recorded 140,680 patients who underwent cardiac surgery. Atrial fibrillation (AF) was present in 21,077 patients (14%). Patients with AF were generally older (72.25 vs 66.65 years; p<0.001). Among patients undergoing cardiac surgery, AF was more common in female than in male patients (18% vs 13%, respectively). Patients with AF more often had a higher classification of dyspnoea according to the New York Heart Association and lower ejection fractions compared with their AF-free counterparts. The incidence of AF as a comorbid condition was more frequent in patients undergoing mitral valve surgery or combined coronary artery bypass grafting and valve surgery (aortic, mitral, or both) compared with those undergoing isolated coronary or aortic surgery. Only 11.90% (n=2,509) of patients with AF received a combined ablation and left atrial appendage ligation, and 19.54% (n=693) of those received a Cox-Maze IV ablation. The burden of concomitant AF in patients undergoing cardiac surgery in Australia is higher than previously reported (14% vs 5%-11%). Despite strong recommendation for the surgical management of AF in patients undergoing cardiac surgery and clear evidence of its benefit, both left atrial appendage ligation and surgical ablation independently or concomitantly remain heavily underutilised in this cohort.

1-year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study.

In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge. Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions-Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI -0.026-0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change -0.12±0.22 versus -0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups. Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed.

KDIGO 2024 Clinical Practice Guideline for the management of lupus nephritis. Translated into Russian by E.V. Zakharova

The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Management of Lupus Nephritis represents a focused update of the Lupus nephritis chapter from the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. The aim is to assist clinicians caring for individuals with lupus nephritis. The update takes into consideration evidence from randomized controlled trials published since February 2022. As in 2021, the chapter follows the same template, providing guidance related to diagnosis, treatment, and special situations. Based on the evidence, this update is focused on guidance related to treatment of lupus nephritis. This guideline update followed an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the strength of recommendations and certainty of the evidence following the “Grading of Recommendations Assessment, Development and Evaluation” (GRADE) approach. Limitations of the evidence are discussed and areas of future research are presented.

Conventional versus high-dose salvage chemotherapy for relapsed testicular germ cell tumours

Since the introduction of cisplatin-based combination chemotherapy, patients with metastatic germ cell tumours achieve very high cure rates of >80%. Nevertheless, about 30% of patients relapse despite guideline-endorsed first-line treatment. Of these, again about 50% of patients can still achieve cure with platinum-based salvage chemotherapy and eventually post-chemotherapy residual mass resection.Salvage chemotherapy generally involves platinum-based combination chemotherapy, either as conventional dose cisplatin-based combinations again or as high-dose chemotherapy with subsequent autologous stem cell transplantation.To date, high level evidence from randomised trials supporting the use of salvage high-dose chemotherapy for all patients relapsing after first-line treatment remains lacking, but a large international retrospective registry study had shown a 15% overall survival benefit for patients undergoing salvage high-dose chemotherapy.In this article, we summarise the available literature on the different salvage treatment approaches and discuss these in the light of current treatment guideline recommendations for the management of testicular cancer.

The association between obesity, knee pain, and gait during stair descent in older adults with knee osteoarthritis

BackgroundObesity and knee osteoarthritis adversely affect activities of daily living in older adults. Together, the complexities of their interaction on mobility, including stair negotiation, are unresolved. The purpose of this study was to determine the relationship between obesity, pain, and stair negotiation in older adults with knee osteoarthritis. MethodsOlder adults with symptomatic knee osteoarthritis and overweight or obesity participated in the study (n = 28; age range = 57.0–78.0 yrs.; body mass index range = 26.6–42.8 kg•m−2). The Western Ontario and McMaster Universities Osteoarthritis Index pain subscale was used to measure knee pain. Measurements included a three-dimensional biomechanical analysis during descent on a set of force plate-instrumented stairs and a timed stair descent test. Pearson's r was used to determine associations between body mass index and pain, stair descent weight-acceptance phase vertical ground reaction force (vGRF) variables and lower extremity joint kinematics and kinetics, and timed stair descent performance. FindingsSignificant correlations existed between body mass index and pain (r = 0.41; p = 0.03), peak vGRF (r = 0.39; p = 0.04), vertical impulse (r = 0.49; p = 0.008), and peak ankle plantar flexor moments (r = 0.50; p = 0.007) in older adults with knee osteoarthritis. InterpretationGreater obesity in older adults with knee osteoarthritis was associated with greater knee pain and higher ankle joint loads during stair descent. These results support the recommendations of osteoarthritis treatment guidelines for weight-loss as a first-line of treatment for older adults with obesity and knee osteoarthritis.

A Practical Guide to Understanding and Treating Peripheral Artery Disease.

Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic morbidity after coronary heart disease and stroke yet is widely underdiagnosed and undertreated. Treatment of risk factors such as diabetes and cigarette smoking can benefit patients with PAD. Patients should have adequate blood pressure and lipid control to decrease clinical manifestations and symptoms of PAD. Use of antithrombotic medications should be individualized to the patient depending on the presence of symptoms, revascularization, and comorbidities. All patient care providers, including physicians, pharmacists, nurse practitioners, and physician assistants, should incorporate PAD screening in their at-risk patients to improve access for appropriate earlier diagnosis, initiation of guideline directed therapy, and risk factor modification to reduce both major adverse CV and limb outcomes. The purpose of this narrative review is to provide an overview of PAD and summarize clinical trial evidence and guideline recommendations for screening and treatment to increase awareness among health care providers to ultimately have a positive impact on patient care.

Analysis of guideline recommendations for treatment of asthma exacerbations in children: a Pediatric Emergency Research Networks (PERN) study

RationaleThere is significant practice variation in acute paediatric asthma, particularly severe exacerbations. It is unknown whether this is due to differences in clinical guidelines.ObjectivesTo describe and compare the content and...

Predictors of Long-Acting Injectable Antipsychotic Medication Use in Patients with Schizophrenia Spectrum, Bipolar, and Other Psychotic Disorders in a US Community-based, Integrated Health System.

Long-acting injectable (LAI) antipsychotics improve patient outcomes and are recommended by treatment guidelines for patients with limited medication adherence in schizophrenia spectrum, bipolar, and other psychotic disorders. Reports of LAI antipsychotic use in these disorders and if use aligns with treatment guidelines are lacking. This study aimed to report patient characteristics associated with LAI antipsychotic use in these disorders. Retrospective observational study of patients ≥18-years-old with bipolar or psychotic disorders at a large, integrated, community-based health system. Patient demographic and clinical characteristics served as exposures for the main outcome of adjusted odds ratio (aOR) for LAI versus oral antipsychotic medication use from January 1, 2017 to December 31, 2023. There were N = 2685 LAI and N = 31 531 oral antipsychotic users. Being non-white (aOR = 1.3-2.0; P < .0001), non-female (aOR = 1.5; P < .0001), from a high deprivation neighborhood (NDI, aOR = 1.3; P < .0007), having a higher body mass index (BMI, aOR = 1.3-1.7; P < .0009), having a schizophrenia/schizoaffective (aOR = 5.8-6.8; P < .0001), psychotic (aOR = 1.6, P < .0001), or substance use disorder (aOR = 1.4; P < .0001), and outpatient psychiatry (aOR = 2.3-7.5; P < .0001) or inpatient hospitalization (aOR = 2.4; P < .0001) utilization in the prior year with higher odds and age ≥40 (aOR = 0.4-0.7; P < .0001) or bipolar disorder (aOR = 0.9; P < .05) were associated with lower odds of LAI use. Non-white, non-female, age 18-39, and high NDI patients had higher LAI use regardless of treatment adherence markers. Smoking and cardiometabolic markers were also associated with LAI use. Demographic and clinical factors are associated with increased LAI use irrespective of treatment adherence. Research on utilization variation informing equitable formulation use aligned with treatment guideline recommendations is warranted.

Evaluating Antibiotic Treatment Guideline Adherence to Ongoing Antibiotic Stewardship in a Tertiary Care Setting: A Retrospective Observational Study.

Antimicrobial resistance (AMR) is widely regarded as an increasing threat to global public health. Antibiotic treatment guidelines have been increasingly recognized as an effective tool to guide appropriate prescriptions and help curtail antibiotic resistance. The present study aimed to assess physician's adherence to hospital antibiotic treatment guideline recommendations in Nepal and determine predictive variables with a significant association. This was a retrospective, monocentric observational review to investigate the adherence to endorsed guidelines using the medical records of adults admitted to the hospital with a diagnosis of urinary tract infection (UTI), pneumonia, or skin and soft tissue infection (SSTI) from January 2018 to December 2019. Of the 2,077 medical records that were reviewed (954 UTI, 754 pneumonia, and 369 SSTI), 354 (17%) met the study inclusion criteria, which included 87 UTI, 180 pneumonia, and 87 SSTI patients. Among eligible patients with antibiotic prescriptions, the following were adherent to guideline recommendations: 33 (37.9%) UTI, 78 (43.3%) pneumonia, and 23 (26.4%) SSTI. The overall extent of adherence to hospital antibiotic treatment guidelines for the use of antibiotics among adult inpatients diagnosed with these common infections was 37.9%. Patients who received ceftriaxone (OR = 2.09, 95% CI = 1.18-3.71, p=0.012) and levofloxacin (OR = 4.63, 95% CI = 1.30-16.53, p=0.018) had significantly higher adherence to treatment guidelines. This study revealed a low adherence rate despite the availability of updated guidelines for antibiotic prescriptions. The findings confer an urgent need to confront antibiotic prescription patterns in such tertiary care centers for tailored interventions to improve adherence to antibiotic guidelines.

Male-female differences in the natural history of ascending thoracic aortic aneurysms: insights from the dissexion study

Abstract Background The natural history of ascending thoracic aortic aneurysms (ATAAs) remains poorly understood, including potential male-female differences. Purpose Therefore, this study sought to evaluate the natural history and outcomes of patients with ATAAs, with an emphasis on aortic growth and male-female differences. Methods Adult patients who received diagnostic and/or follow-up imaging of an ATAA (≥40mm) in two academic centers between 2007-2021 were included. Aortic growth was modeled non-linearly through mixed-effects models using repeated measurements, including age and sex through interaction terms. Joint models were constructed to adjust for the effect of nonrandom dropout due to surgical intervention. Secondary outcomes were male-female differences in presentation, aneurysm characteristics, time to intervention, acute aortic syndromes and survival relative to the age- and sex-matched general Dutch population. Cox models were employed to evaluate predictors of intervention and survival. Results In total, 1,858 patients were included (31.6% female). Median clinical follow-up was 5.9 [IQR: 3.0-10.0] years. Median age was 65.4 years [53.4-71.7y] for females and 59.0 years [IQR: 49.3-68.0y] for males (p&amp;lt;0.001). Males had more bicuspid aortic valve (BAV) disease (male: 27.5%, female: 18.2%; p&amp;lt;0.001) and were more likely to have had a previous dissection or aneurysm in a major artery other than the thoracic aorta (male: 8.9%, female: 4.9%; p=0.004) before diagnosis. Maximum absolute aortic diameter at diagnosis did not differ between males (46.5mm) and females (45.0mm; p=0.388). Unadjusted 10-year survival was 76% (68%-78%) for females (relative survival: 68.8%) and 78% (75%-81%) for males (relative survival: 78.7%). For females, tubular ascending aortic growth was faster compared to males (p=0.005), particularly in the first 6 years after diagnosis. Contrarily, SoV growth was faster in males compared to females (p=0.002). Surgical intervention occurred more quickly after diagnosis in females (HR: 2.5 (1.2-5.2), corrected for BAV, diameter and age. Twenty-three type A dissections (TAD) occurred with an incidence rate ratio between females and males of 3.4 (95%CI:1.5-8.0, p=0.004). The last known aortic diameter before TAD was comparable between males (47.5mm [47.0-50.8]) and females (47.0mm [43.0-51.0]; p=0.416). Conclusions Ascending aortic aneurysms show a strikingly different growth pattern between males and females at the level of the SoV and tubular ascending aorta, suggesting that although females present at an older age, their aortic disease progresses faster and with more TAD compared to males, and warranting an even more careful follow-up. Absolute known aortic diameter before TAD was comparable between males and females. These insights can be used to fuel discussion about male-female specific follow-up and treatment recommendations in future clinical guidelines development.Ascending aortic growth (A) &amp; sinus (B)Freedom from intervention from diagnosis

An evaluation of the quality of ear health services for Aboriginal children living in remote Australia: a cascade of care analysis

BackgroundIn the Northern Territory (NT) the prevalence of otitis media (OM) in young Aboriginal children living in remote communities has persisted at around 90% over the last few decades. OM-associated hearing loss can cause developmental delay and adversely impact life course trajectories. This study examined the 5-year trends in OM prevalence and quality of ear health services in remote NT communities.MethodsA retrospective analysis was performed on de-identified clinical data for 50 remote clinics managed by the NT Government. We report a 6-monthly cascade analysis of the proportions of children 0–16 years of age receiving local guideline recommendations for surveillance, OM treatment and follow-up at selected milestones between 2014 and 2018.ResultsBetween 6,326 and 6,557 individual children were included in the 6-monthly analyses. On average, 57% (95%CI: 56–59%) of eligible children had received one or more ear examination in each 6-monthly period. Of those examined, 36% (95%CI: 33–40%) were diagnosed with some type of OM, of whom 90% had OM requiring either immediate treatment or scheduled follow-up according to local guidelines. Outcomes of treatment and follow-up were recorded in 24% and 23% of cases, respectively. Significant decreasing temporal trends were found in the proportion diagnosed with any OM across each age group. Overall, this proportion decreased by 40% over the five years (from 43 to 26%).ConclusionsThis cascade of care analysis found that ear health surveillance and compliance with otitis media guidelines for treatment and follow-up were both low. Further research is required to identify effective strategies that improve ear health services in remote settings.

Physician knowledge, practice patterns, and barriers encountered regarding guideline-concordant use of bone modifying agents for prostate cancer.

Guidelines recommend bone-modifying agents (BMAs) for patients with castrate-resistant prostate cancer (CRPC) and bone metastasis, but not for castrate-sensitive prostate cancer (CSPC). Physicians beliefs and practices regarding BMA therapy are poorly understood. This was a qualitative interview study with embedded Likert-scale elements. Study participants were physicians who treat prostate cancer, located within an academic cancer center or an affiliated community-based network. Participants were asked about their experiences and practice patterns regarding BMA therapy. Participants used Likert-scale items to identify the most common barriers to guideline-concordant BMA use and the most effective potential interventions. Participants were subsequently asked to rank the three most common barriers and the three most effective interventions to reduce underuse (for CRPC) and overuse (for CSPC). Nineteen physicians were invited and 15 participated; one physician did not answer some questions as outside of their practice scope. All were aware of the recommendation for BMAs in CRPC. 14% (2/14) were unaware of the recommendation against BMA use for CSPC; an additional 29% (4/14) believed that BMA use could be appropriate for CSPC depending on the metastatic disease burden. 36% (5/14) were unaware of recommendations for screening and treatment of low bone mineral density. The most common barriers (occurring "often" or "sometimes") were obtaining dental clearance (11/15) and insufficient clinic time (6/15). The interventions identified as most effective to reduce underuse were dental navigation (11/15) and electronic medical record (EMR)-based guidance (9/15). The interventions identified as most effective to reduce overuse were peer-to-peer education (14/15) and EMR-based guidance (13/15). Awareness of guideline recommendations for screening and treatment of low bone mineral density and against BMA use for CSPC was good, but not complete. Dental navigation, peer-to-peer education, and EMR-based guidance were preferred intervention strategies to improve guideline-concordant use.

Associations between baseline heart rate and blood pressure and time to events in HFrEF patients: data from the QUALIFY international registry.

A high resting heart rate (RHR) and low systolic blood pressure (SBP) are a risk factor and a risk indicator, respectively, for poor heart failure (HF) outcomes. This analysis evaluates the associations between baseline RHR and SBP with outcomes and treatment patterns in HF patients with reduced ejection fraction (HFrEF) in the QUALIFY international registry. Between September 2013 and December 2014, 7317 HFrEF patients with a previous HF hospitalization within 1-15 months were enrolled in the QUALIFY registry (Quality of Adherence to Guideline Recommendations for Life-Saving Treatment in Heart Failure Survey). Complete follow-up data were available for 5138 patients. The relationships between RHR and SBP and outcomes were assessed using a Cox proportional hazards model and were analyzed according to baseline values as high RHR (H-RHR) ≥ 75 vs. low RHR (L-RHR) < 75 bpm) and high SBP (H-SBP): ≥ 110 vs. low SBP (L-SBP): <110 mmHg and analyzed according to each of the following 4 phenotypes: (H-RHR/L-SBP, L-RHR/L-SBP, H-RHR/H-SBP and L-RHR/H-SBP (reference group). Compared to the reference group, H-RHR/L-SBP was associated with the worst outcomes for the combined primary endpoint of CV death and HF hospitalization (HR 1.83, CI 1.51-2.21, p<0.001), CV death (HR 2.7, CI 1.69-4.33, p <0.001), and HF hospitalization (HR 1.62, CI 1.30-2.01, p<0.001). Low-risk patients with L-RHR/H-SBP achieved more frequently >=50% of target doses of ACEIs and BBs than the other groups. However, 48% and 46% of low-risk patients were not well treated with ACEIs and BBs, respectively (<=50% of target dose or no treatment). In patients with HFrEF and recent hospitalisation, elevated RHR and lower SBP identify patients at increased risk for CV endpoints. While SBP and RHR are often recognized as barriers that deter physicians from treating with high doses of recommended drugs, they are not the only reason leaving many patients suboptimally treated. This article is protected by copyright. All rights reserved.

Efficacy and safety of pharmacological treatments for Lyme neuroborreliosis: an updated systematic review.

Evidence-based recommendations for treatment of Lyme neuroborreliosis (LNB) should rely on the available literature. As new data emerges, close review and evaluation of the recent literature is needed to build evidence-based recommendations to inform clinical practice and management of LNB. We performed an update of a previous systematic review on treatment of LNB. A systematic literature search of Medline and CENTRAL was performed for published studies from 2015-2023 to update a previous systematic review. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs, NRS were assessed using the ROBINS-I-tool. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Data was integrated in existing meta-analysis of the available literature. After screening 1530 records, 2 RCTs and 5 NRS with new and relevant data were additionally identified. Meta-analysis showed no statistically significant difference between doxycycline and beta-lactam antibiotics regarding residual neurological symptoms after 12 months. Meta-analysis showed no benefit of extended antibiotic treatment of LNB. Three NRS show no benefit for additional steroid use in LNB with facial palsy. Additional incorporated recent research corroborates existing guideline recommendations for treatment of LNB. New RCTs add to the certainty of previous analysis showing similar efficacy for doxycycline and beta-lactam antibiotics in LNB. Available evidence shows no benefit for extended antibiotic treatment in LNB. NRS do not suggest a role for steroids in facial palsy due to LNB.

Changing the role of pCR in breast cancer treatment - an unjustifiable interpretation of a good prognostic factor as a "factor for a good prognosis".

Pathologic complete response (pCR) after neoadjuvant systemic therapy (NAST) of early breast cancer (EBC) has been recognized as a good prognostic factor in the treatment of breast cancer because of its significant correlation with long-term disease outcome. Based on this correlation, pCR has been accepted by health authorities (FDA, EMA) as a surrogate endpoint in clinical trials for accelerated drug approval. Moreover, in recent years, we have observed a tendency to treat pCR in routine clinical practice as a primary therapeutic target rather than just one of the pieces of information obtained from clinical trials. These trends in routine clinical practice are the result of recommendations in treatment guidelines, such as the ESMO recommendation "…to deliver all planned (neoadjuvant) treatment without unnecessary breaks, i.e. without dividing it into preoperative and postoperative periods, irrespective of the magnitude of tumor response", because "…this will increase the probability of achieving pCR, which is a proven factor for a good prognosis…". We hypothesize that the above recommendations and trends in routine clinical practice are the consequences of misunderstanding regarding the concept of pCR, which has led to a shift in its importance from a prognostic factor to a desired treatment outcome. The origin of this misunderstanding could be a strong subconscious incentive to achieve pCR, as patients who achieved pCR after NAST had a better long-term outcome compared with those who did not. In this paper, we attempt to prove our hypothesis. We performed a comprehensive analysis of the therapeutic effects of NAST and adjuvant systemic therapy (AST) in EBC to determine whether pCR, as a phenomenon that can only be achieved at NAST, improves prognosis per se. We used published papers as a source of data, which had a decisive influence on the formation of the modern attitude towards EBC therapy. We were unable to find any evidence supporting the use of pCR as a desired therapeutic goal because NAST (reinforced by pCR) was never demonstrated to be superior to AST in any context.

50% Improvement

Background: The emphasis on symptom resolution in depression treatment research is at variance with the recommendations of official treatment guidelines and the results of surveys of depressed patients' views of the most important treatment goals. In the present study, we examined the interrelationship between response rates on various outcome domains and whether response on each domain was associated with patients' global rating of improvement (PGI) reported upon treatment completion. We also examined whether the PGI was associated with the number of domains on which the patients had achieved responder status and which domains were independent predictors of PGI response.Methods: Between January 2016 to April 2022, 844 patients with DSM-IV major depressive disorder completed the Remission from Depression Questionnaire (RDQ), a self-report measure that assesses 6 constructs considered by patients to be relevant to assessing treatment outcome. The patients completed the RDQ at admission and discharge from the treatment program. For each domain, response was defined as a 50% or greater reduction in scores. At discharge, the patients rated the PGI.Results: The patients significantly improved from admission to discharge on each of the 6 domains assessed on the RDQ (Cohen d range, 1.09-1.55). The responders on each domain reported significantly greater improvement on the global rating of improvement at discharge (all P values < .001). Responder status in one domain mostly co-occurred with responder status in another domain. In a logistic regression analysis, responses on all domains except nondepressive symptoms were independently associated with PGI response.Conclusions: The results of the present study are consistent with the results of multiple patient surveys which have suggested that focusing on symptom reduction is too narrow of an approach when measuring outcome in the treatment of depression. Expanding the assessment of outcome beyond symptoms and viewing nonsymptomatic outcome domains as critical composites of primary endpoints would be more consistent with a patient-centered approach toward the treatment of depression.

50% Improvement: Should Treatment Response Go Beyond Symptom Improvement When Evaluating the Treatment of Depression?

IntroductionThe emphasis on symptom resolution in depression treatment research is at variance with the recommendations of official treatment guidelines and the results of surveys of depressed patients’ views of the most important treatment goals.ObjectivesIn the present study, we examined the interrelationship between response rates on various outcome domains and whether response on each domain was associated with patients’ global rating of improvement (PGI) reported upon treatment completion. We also examined whether the PGI was associated with the number of domains on which the patients had achieved responder status and which domains were independent predictors of PGI response.MethodsEight hundred and forty-four patients with major depressive disorder completed the Remission from Depression Questionnaire (RDQ), a self-report measure that assesses 6 constructs considered by patients to be relevant to assessing treatment outcome. The patients completed the RDQ at admission and discharge from the treatment program. For each domain, response was defined as a 50% or greater reduction in scores. At discharge, the patients rated the PGI.ResultsThe patients significantly improved from admission to discharge on each of the 6 domains assessed on the RDQ. The responders on each domain reported significantly greater improvement on the global rating of improvement at discharge. Responder status in one domain mostly co-occurred with responder status in another domain. In a logistic regression analysis, responses on all domains, except nondepressive symptoms, were independently associated with PGI response.ConclusionsThe results of the present study are consistent with multiple surveys which have suggested that focusing on symptom reduction is too narrow of an approach when measuring outcome in the treatment of depression. Expanding the assessment of outcome beyond symptoms and viewing nonsymptomatic outcome domains as critical composites of primary endpoints would be more consistent with a patient-centered approach towards the treatment of depression.Disclosure of InterestNone Declared

Abstract P1-08-07: Educational Opportunities to Improve HER2 Testing and Use of Newer Therapies for HER2-Positive MBC Among Community Healthcare Professionals

Abstract Background: The management of HER2-positive (HER2+) metastatic breast cancer (MBC) has continued to evolve, with multiple FDA approvals of novel HER2-targeted agents since late 2019. Considering the growing HER2+ MBC treatment armamentarium and the emerging HER2-low MBC subtype, we undertook an analysis of the current implementation of guideline and expert recommendations for HER2 testing and treatment of HER2+ MBC with recently approved agents among oncology healthcare professionals (HCPs) participating in educational programs on these topics. Methods: Between January 2020 and April 2022, we conducted several expert-designed educational activities for HCPs focusing on recommended HER2 testing and treatment of HER2+ MBC. Polling questions on HCP knowledge, practice patterns, and confidence in the evaluation of HER2 status and the use of newer targeted therapies in the setting of HER2+ MBC were assessed across the activities and compared with expert recommendations. Results: Among 129 HCPs participating in 2 educational activities held from July 2020 to March 2021, 53% reported confidence to appropriately apply current HER2 testing guidelines to patient care. Similarly, among 407 HCPs who participated in 4 educational programs from May 2020 to January 2021, 24% reported confidence to incorporate recently approved drugs (including trastuzumab deruxtecan [T-DXd], neratinib, and tucatinib) into the care of patients with HER2+ MBC. The percentage of HCPs reporting confidence in the use of these new drugs remained low over this time period. Comparison of treatment recommendations for various HER2+ MBC case scenarios across 7 educational activities from January 2020 through April 2022 showed considerable discordance between experts and HCPs regarding the implementation of newly approved HER2-targeted regimens (Table 1). For patients with disease progression after 2 lines of therapy and no central nervous system (CNS) metastases, 27% to 57% of HCPs (n = 571) chose T-DXd in agreement with experts. For patients with disease progression after 2 lines of therapy with CNS metastases, 27% to 42% of HCPs (n = 597) chose a tucatinib-based regimen in agreement with experts. Treatment choice concurrence between HCPs and experts did not increase over the course of this study for either of these patient scenarios. Conclusions: These data suggest that some HCPs are challenged to optimally incorporate recommendations for HER2 testing and the implementation of novel HER2-targeted therapies in the care of patients with HER2+ MBC. Educational activities designed to improve the knowledge and confidence of HCPs would benefit patients with HER2+ MBC. A detailed analysis of trends over time and by role on the care team will be presented. Table 1. Expert and HCP Treatment Selections for Case Scenarios in HER2+ MBC. Citation Format: Ryan P. Topping, Rachael M. Andrie, Kristen Rosenthal, Timothy A. Quill. Educational Opportunities to Improve HER2 Testing and Use of Newer Therapies for HER2-Positive MBC Among Community Healthcare Professionals [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-08-07.

Barriers to guideline-concordant use of bone modifying agents for prostate cancer.

68 Background: NCCN Guidelines recommend the use of bone-modifying agents (BMAs) to prevent skeletal-related events (SRE) for patients with castrate-resistant prostate cancer (CRPC) and bone metastasis, but not for castrate-sensitive prostate cancer (CSPC). Prior studies have identified both underuse of BMAs for CRPC and overuse for CSPC, but the clinical circumstances underlying these apparent gaps in care are unknown. Methods: Qualitative interview study, with physicians who treat prostate cancer within an academic cancer center and an affiliated network of community-based practices. Using a semi-structured interview guide, an experienced moderator probed participants’ experiences and perceptions around NCCN Guidelines recommendations, guideline adherence and non-adherence, and barriers to adherence. Interviews also probed participants’ views of potential interventions to promote guideline-concordant BMA use. Participants used Likert-scale items to rate the likely effectiveness of each intervention in influencing BMA practice patterns. They also identified the 3 most helpful interventions for reducing BMA underuse and overuse separately. Results: 19 physicians were invited, of whom 15 agreed to participate; 1 physician did not respond to some questions as outside scope of practice. All were aware of the recommendation for use of BMAs in CRPC. 14% (2/14) were unaware of the recommendation against BMA use for CSPC; an additional 29% (4/14) believed that BMA use could be appropriate for CSPC depending on the burden of bony metastatic disease. 36% (5/14) were unaware of recommendations for baseline DEXA scan and BMA for patients with low bone mineral density. The most commonly reported barriers (occurring “often” or “sometimes”) to BMA use for CRPC were obtaining dental clearance (11/15) and insufficient time in clinic (6/15). The interventions perceived as most helpful to reduce underuse for CRPC were dental navigation (11/15) and EMR-based guidance (9/15). The interventions identified as most helpful to reduce overuse for CSPC were peer-to-peer education (14/15) and EMR-based guidance (13/15). Conclusions: Among physicians treating prostate cancer in our study, there was incomplete awareness of guideline recommendations for screening and treatment of low bone mineral density, and against BMA use for SRE prevention in CSPC. Dental navigation, peer-to-peer education, and EMR-based guidance were preferred implementation strategies to reduce underuse and overuse of BMAs.

Critical Appraisal of Current Acute LBP Management and the Role of a Multimodal Analgesia: A Narrative Review.

Acute low back pain (LBP) stands as a leading cause of activity limitation and work absenteeism, and its associated healthcare expenditures are expected to become substantial when acute LBP develops into a chronic and even refractory condition. Therefore, early intervention is crucial to prevent progression to chronic pain, for which the management is particularly challenging and the most effective pharmacological therapy is still controversial. Current guideline treatment recommendations vary and are mostly driven by expertise with opinion differing across different interventions. Thus, it is difficult to formulate evidence-based guidance when the relatively few randomized clinical trials have explored the diagnosis and management of LBP while employing different selection criteria, statistical analyses, and outcome measurements. This narrative review aims to provide a critical appraisal of current acute LBP management by discussing the unmet needs and areas of improvement from bench-to-bedside, and proposes multimodal analgesia as the way forward to attain an effective and prolonged pain relief and functional recovery in patients with acute LBP.