Changes In Treatment Of Patients Research Articles

Central nervous system pediatric multi-disciplinary tumor board: a single center experience

BackgroundThe Multidisciplinary Tumor Board (MTB) is a collaborative platform involving specialists in oncology, surgery, radiology, pathology, and radiotherapy, and aims to optimize diagnostics and treatments. Despite MTB’s widespread benefits, limited literature addresses its application in pediatric neuro-oncology. After a literature revision on pediatric neuro-oncology MTB, our study describes our institute’s pediatric neuro-oncology MTB, focuses on evaluating its impact and the neuroradiologist’s role in patient-centric approaches, considering recent genetic insights into pediatric brain tumors.Materials and methodsLiterature Review concerning pediatric neuro-oncology MTB from January 2002 to June 2024. Clinical Data: retrospective study of all patient files presented in the pediatric neuro-oncology MTB (pnMTB) between 2019 and 2022. Statistical analysis was mainly carried out by directly comparing the absolute or relative values of the respective parameters examined; qualitative variables compared mainly with the chi-square test, quantitative variables mainly with the t-test.ResultsLiterature Review: 7 papers encompass a multidisciplinary approach for the pediatric CNS tumors.Clinical dataA total of 236 discussions were analyzed representing 107 patients. Median age was 14,3 years (range: 6 months – 17 years). The requests for case evaluations primarily came from the pediatric oncologists (83%) and neurosurgeons (14.8%), and they were mainly addressed to the neuroradiologists (70.3%). Proposals during pnMTB mainly involved imaging follow-up (47.8%) and management with chemotherapy (34.7%). Changes in patient treatment (CPT) occurred in 115 cases, and pediatric neuroradiologist intervention contributed to 72.4% of these changes.ConclusionThanks to their multidisciplinarity, high number of cases discussed, and usual respect for their proposals, the pnMTB has made it possible to improve the coordination among specialties involved in patient management, to apply the recent protocols, and to exchange knowledge among teams managing pediatric CNS tumors.

Utility of Echocardiography Screening for Cancer Therapy-Related Cardiac Dysfunction

Availability of echocardiography resources in New Zealand is under pressure due to workforce shortages. This study examined real-world utility of echocardiogram (echo) as a screening tool for cancer therapy-related cardiac dysfunction (CTRCD), changes in patient treatment, and outcome because of CTRCD detected by echocardiography. A retrospective audit was undertaken of all patients dispensed with trastuzumab, pertuzumab, and/or doxorubicin chemotherapy, with serial echocardiography performed, at Lakes and Bay of Plenty District Health Boards between January 2018 and January 2021. Two-dimensional ejection fraction (EF), three-dimensional (3D) EF, and global longitudinal strain (GLS) were used to classify patients with CTRCD based on current guidelines. Changes in patient management were examined. A total of 407 echos were performed in 107 patients. Of 25 (23%) patients with CTRCD, 11 had a change in cancer treatment and seven started cardiac medications. Fifteen (60%) patients showed recovery in EF/GLS measurements over time and eight (32%) showed spontaneous recovery. Patients were more likely to have a change in cancer treatment based on a change in left ventricular ejection fraction than GLS (p<0.001). The use of 3D EF and GLS was limited by 43% of the population who were obese, which was performed in 14% and 62% of studies, respectively. Cancer therapy-related cardiac dysfunction was associated with mortality in univariate (p=0.02) but not multivariate (p=0.06) analysis. Detection of CTRCD remains a priority. However, echo screening requires many resources and did not result in consistent changes in management approach. It is worth examining whether the use of biomarkers would be effective and resource sparing.

Clinical and epidemiological correlates of treatment change in patients with NMOSD: insights from the CIRCLES cohort

ObjectiveNeuromyelitis optica spectrum disorders (NMOSD) represent rare autoimmune diseases of the central nervous system largely targeting optic nerve(s) and spinal cord. The present analysis used real-world data to identify clinical and epidemiological correlates of treatment change in patients with NMOSD.MethodsCIRCLES is a longitudinal, observational study of NMOSD conducted at 15 centers across North America. Patients with ≥ 60 days of follow-up and receiving on-study maintenance treatment were evaluated. The mean annual relapse rate (ARR) was estimated using negative binomial models; the likelihood of treatment change was estimated using Cox proportional hazards models. Relapses were included as time-varying covariates to estimate the relationship to treatment change.ResultsOf 542 patients included, 171 (31.5%) experienced ≥ 1 relapse on the study and 133 patients (24.5%) had ≥ 1 change in the treatment regimen. Two categories of variables significantly correlated with the likelihood of treatment change: (1) relapse: any on-study relapse (hazard ratio [HR] = 2.91; p < 0.001), relapse phenotypes (HR range = 2.15–5.49; p < 0.001), and pre-study ARR > 0.75 (HR 2.28; p < 0.001); 2) disease phenotype: brain syndrome only vs transverse myelitis involvement at onset (HR 2.44; p = 0.008), disease duration < 1 vs > 5 years (HR 1.66; p = 0.028), or autoimmune comorbidity (HR 1.55; p = 0.015). A subset of these factors significantly correlated with shorter time to first rituximab discontinuation.ConclusionsIn CIRCLES, relapse patterns and disease phenotype significantly correlated with changes in the maintenance treatment regimen. Such findings may facilitate the identification of patients with NMOSD who are likely to benefit from treatment change to reduce relapse risk or disease burden and enhance the quality of life.

Preliminary experience with a new institutional tumor board dedicated to patients with neuroendocrine neoplasms.

PurposeTo determine the decision patterns of a neuroendocrine neoplasm (NEN) tumor board (TB) and the factors behind those.MethodsWe retrospectively reviewed all NEN-TB recommendations from 07/2018 to 12/2021 and recorded patient characteristics, TB outcomes and associations between them.ResultsA total of 652 patient entries were identified. Median age of participants was 61 years and an equal number of men and women were presented. Most patients (33.4%) had tumors originating in the small bowel with 16.8% of high grade and 25.9% of pancreatic origin. Imaging was reviewed 97.2% of the time, with most frequently reviewed modalities being PET (55.3%) and CT (44.3%). Imaging review determined that there was no disease progression 20.8% of the time and significant treatment changes were recommended in 36.1% of patients. Major pathology amendments occurred in 3.7% of cases and a clinical trial was identified in 2.6%. There was no association between patient or disease presentation with the tumor board outcomes. There was a slight decrease in number of patients discussed per session, from 10.0 to 8.2 (p < 0.001) when the TB transitioned to a virtual format during the COVID-19 pandemic but all other factors remained unchanged.ConclusionNEN-TB relies heavily on image review, can impact significant treatment changes in patients with rare tumors like NENs, and was not affected by the switch to a virtual format. Finally, none of the examined factors were predictive of the tumor board recommendations.

Neuro-Oncology Multidisciplinary Tumor Board: The Point of View of the Neuroradiologist.

Background: The multi-disciplinary tumor board (MTB) is essential to quality cancer care and currently recommended to offer the best personalized clinical approach, but little has been published regarding MTBs in neuro-oncology (nMTBs). The aim of the present paper is to describe our nMTB, to evaluate its impact on clinical management decisions, and to assess the role of neuroradiologists. Methods: The retrospective evaluation of the cases discussed at our nMTB from March 2017 to March 2020. From the electronic records, we extracted epidemiological, clinical and other specific data of nMTB. From the radiological records, we calculated data relating to the number, time for revision, and other specifications of MRI re-evaluation. Statistical analysis was performed. Results: a total of 447 discussions were analyzed, representing 342 patients. The requests for case evaluations came from radiation oncologists (58.8%) and neurosurgeons (40.5%), and were mainly addressed to the neuroradiologist (73.8%). The most frequent questions were about the treatment’s changes (64.4%). The change in patient treatment was reported in 40.5% of cases, 76.8% of these were based on the neuroradiologic assessment. A total of 1514 MRI examinations were re-evaluated, employing approximately 67 h overall. The median of the MRI exams reviewed per patient was 3 (min–max 1–12). Conclusions: Our study supported that the multidisciplinary approach to patient care can be particularly effective in managing brain tumors. A review by an expert neuroradiologist impacts patient management in the context of nMTBs, but has costs in terms of the time and effort spent preparing for it.

Ambulatory Extracorporeal Membrane Oxygenation: Times Are Changing.

During the past century, medical technology has evolved to enhance quality and quantity of life. Medications, surgeries, and implantable devices have been developed and enhanced to reduce complications and improve patient outcomes. The use of extracorporeal membrane oxygenation is one of the most substantial advances in life-saving modalities. Extracorporeal membrane oxygenation has been widely used for patients with heart or lung failure across the lifespan. Expansion and simplifications of extracorporeal membrane oxygenation circuit designs have informed changes in patient treatment (from bed confinement to ambulatory) and shifted many clinical staffing structures (from cardiovascular perfusionist to nurse-managed care). Highly skilled registered nurses and advanced practice registered nurses are increasingly involved in managing extracorporeal membrane oxygenation in the critical care setting. The purpose of this article is to highlight the technological evolution of extracorporeal membrane oxygenation and the corresponding patient care that bedside registered nurses and advanced practice registered nurses provide.

Changes in Treatment of Patients with Incident ESKD during the Novel Coronavirus Disease 2019 Pandemic.

The COVID-19 pandemic caused major disruptions to care for patients with advanced CKD. We investigated the incidence of documented ESKD, ESKD treatment modalities, changes in eGFR at dialysis initiation, and use of incident central venous catheters (CVCs) by epidemiologic week during the first half of 2020 compared with 2017-2019 historical trends, using Centers for Medicare and Medicaid Services data. We used Poisson and logistic regression for analyses of incidence and binary outcomes, respectively. Incidence of documented ESKD dropped dramatically in 2020 compared with the expected incidence, particularly during epidemiologic weeks 15-18 (April, incidence rate ratio [IRR], 0.75; 95% CI, 0.73 to 0.78). The decrease was most pronounced for individuals aged ≥75 years (IRR, 0.69; 95% CI, 0.66 to 0.73). Pre-emptive kidney transplantation decreased markedly during weeks 15-18 (IRR, 0.56; 95% CI, 0.46 to 0.67). Mean eGFR at dialysis initiation decreased by 0.33 ml/min per 1.73 m2 in weeks 19-22; non-Hispanic Black patients exhibited the largest decrease, at 0.61 ml/min per 1.73 m2. The odds of initiating dialysis with eGFR <10 ml/min per 1.73 m2 were highest during weeks 19-22 (May, OR, 1.14; 95% CI, 1.05 to 1.17), corresponding to an absolute increase of 2.9%. The odds of initiating peritoneal dialysis (versus hemodialysis) were 24% higher (OR, 1.24; 95% CI, 1.14 to 1.34) in weeks 11-14, an absolute increase of 2.3%. Initiation with a CVC increased by 3.3% (OR, 1.30; 95% CI, 1.20 to 1.41). During the first wave of the COVID-19 pandemic, the number of patients starting treatment for ESKD fell to a level not observed since 2011. Changes in documented ESKD incidence and other aspects of ESKD-related care may reflect differential access to care early in the pandemic.

The effect of TEE on treatment change in patients with acute ischemic stroke.

Background and purposeIschemic stroke is a widespread disease carrying high morbidity and mortality. Transesophageal echocardiography (TEE) is considered an important tool in the work-up of patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients; its utility is limited by a semi-invasive nature. The purpose of this study was to evaluate the probability of treatment change due to TEE findings (yield) in the work-up of AIS and TIA patients.MethodsRetrospective data on patients with AIS or TIA who underwent TEE examination between 2000–2013 were collected from the institutional registry.ResultsThe average age of 1284 patients who were included in the study was 57±10.4, 66% of patients were male. The most frequent TEE findings included aortic plaques in 54% and patent foramen ovale (PFO) in 15%. TEE findings led to treatment change in 135 (10.5%) patients; anticoagulant treatment was initiated in 110 of them (81%). Most common etiology for switch to anticoagulation was aortic plaques (71 patients); PFO was second most common reason (26 patients). Significant TEE findings (thrombus, endocarditis, tumor) were found in 1.9% of patients, they were more common in young patients (<55; 56% of the patients).ConclusionsThe beginning of anticoagulation treatment in patients with thick and complicated plaques was found frequently in our study. Significant TEE findings, were infrequent, constituted an absolute indication for treatment change and were more common in younger patients.

Transjugular liver biopsy and hepatic venous pressure gradient measurement in patients with and without liver cirrhosis

Transjugular liver biopsy (TJLB) and hepatic venous pressure gradient (HVPG) measurement are diagnostic procedures for patients with acute and chronic liver diseases. Technical execution of TJLB and HVPG may be challenging in patients with advanced liver disease. We studied consecutive TJLB and HVPG procedures and investigated technical success, complications, quality of biopsies, indications and treatment changes in patients with and without liver cirrhosis. In the study period from 2010 to 2018, 575 consecutive TJLB and HVPG procedures were analyzed. Demographic characteristics, procedure-related and follow-up data were extracted from medical records. In total, 259 (45%) patients were diagnosed with liver cirrhosis whereas 316 (55%) patients had no evidence of advanced chronic liver disease. Technical success of TJLB was significantly higher in patients without liver cirrhosis (287; 92%) compared to patients with liver cirrhosis [184; 76.7% (P = 0.001)]. Technical success of HVPG measurement was not different between both groups (P = 0.553). Liver biopsy specimens were significantly shorter in patients with liver cirrhosis (P = 0.001). Medical therapy was adjusted in 163 (28.4%) patients. In patients with liver cirrhosis, results of TJLB led less frequently to therapy initiation or adjustment compared to patients without liver cirrhosis (P = 0.001). In multivariate analysis, liver cirrhosis (Exp(B) 1.866; P = 0.012), alanine aminotransferase (Exp(B) 0.248; P < 0.001) and INR (Exp(B) 0.583; P = 0.027) were independently associated with treatment change. Technical success and therapeutic decisions of TJLB are directly linked to presence or absence of liver cirrhosis.

Evaluation of Changes in Skin and Joint Outcomes and Associated Treatment Changes in Psoriatic Arthritis (PsA): Experience From the Corrona PsA/SpA Registry.

To characterize skin severity and joint activity outcomes and associated treatment changes in patients with psoriatic arthritis (PsA) through 12 months of follow-up after enrollment in the Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry. Patients ≥ 18 years of age with a diagnosis of PsA and a history of psoriasis between March 21, 2013, and September 30, 2016, were enrolled (n = 647). Demographics, clinical features, and treatment characteristics were collected and stratified by skin severity and joint activity. Change in joint and skin from enrollment to the 12-month visit was classified by change in category of Clinical Disease Activity Index (CDAI) or body surface area (BSA). Tests of association evaluated the relationship between changes in therapy and changes in skin severity and joint activity. Patients with improvement in both joint activity and skin severity saw the largest median reduction in both CDAI and BSA, while those who worsened in both had the greatest median increase in both CDAI and BSA. The majority of PsA patients (> 50%) had no change in skin severity regardless if they had reduced therapy (50%), no therapy changes (54%), or increased therapy (56%; P = 0.5875). However, there was a significant association between changes in therapy and changes in joint activity (P < 0.001). Patients who increased therapy were more likely to have improvement in joint activity (32%) compared to patients who reduced therapy (22%) or had no therapy changes (11%). The clinical implication for our findings suggests the assessment and incorporation of both skin and joint components may be advisable.

Abstract P2-17-01: Therapy of advanced breast cancer for patients with hormone receptor-positive/HER2-negative and HER2-positive tumors is changing in real life: First results from the prospective, national research platform OPAL for patients with advanced breast cancer in Germany

Abstract Introduction Tumor Registries give insight into routine treatment and complement the knowledge derived from randomized controlled trials (RCT), since characteristics of patients from RCTs often differ from those of patients in routine care. Furthermore, follow-up of patients in registries is generally longer which gives the possibility to analyze sequential treatments. Since 2007 the Tumor Registry Breast Cancer (TMK, NCT01351584) has prospectively collected data on treatment and outcome of patients with breast cancer in Germany. Among other topics, insights into “real-world” treatment and outcome and long-term observation of quality of life have been published. Since 2017 the registry platform OPAL (NCT03417115) has extended the work of the TMK by recruiting patients with advanced breast cancer (ABC) from all specialties (medical and gynecologic oncologists). The main aims are to observe the impact of novel treatments on patient outcome, and to identify areas for improvement of quality of care. Methods OPAL started in December 2017. Patients are prospectively recruited at start of their first systemic treatment for ABC. Follow-up continues until death or up to 5 years. There is no treatment specification. Detailed information on all (sequential) treatments, patient and tumor characteristics, physician-reported factors regarding treatment decision making, biomarker testing, outcomes (e.g. best response, progression-free and overall survival) are collected in a web-based data capture system with implemented checks for completeness and plausibility. Data are monitored by data management and on-site. Patient-reported outcomes (PROs) are collected at start of treatment and every 3 months thereafter. Patients can also give informed consent for their tumor samples to be used in future translational research (virtual biobank). All patient data remain in Germany. Here, first combined data from the TMK and OPAL (database as of 01.04.2019) are presented. Results Since 2007, 5076 patients have been recruited. Patients with ABC (n=2105, 434 since the start of OPAL) have a median age of over 60 years at start of treatment; about 60% have comorbidities. For patients with hormone-receptor positive (HRpos)/HER2 negative (HER2neg) ABC, first-line treatment has changed over the years. From 2007-11 (n=458) 60% of patients started with chemotherapy, decreasing to 48% in 2012-16 (n=528) and to 23% in 2018-19 (n=170) with 58% of patients now being treated with CDK4/6-inhibitor. First-line of HER2pos ABC has also changed from 79% of patients receiving trastuzumab (TRA) between 2007-12 (n=268) to 78% of patients receiving dual-blockade with TRA/pertuzumab in 2018-19 (n=97) and 10% receiving TRA only. About 25% of patients treated with TRA in 2018-19 received a biosimilar. Median overall survival (OS) of patients with start of first-line therapy between 2007-16 is currently 15 months for triple-neg (74% events), 34 months for HRpos/HER2neg (59% events), 40 months for HER2pos (52% events); median OS has not yet been reached for patients in OPAL. Conclusions For patients with HRpos/HER2neg ABC, a shift towards more endocrine therapy in the first-line setting, and a quick implementation of CDK4/6-inhibitors after their approval can be observed. In patients with HER2pos ABC, integration of trastuzumab biosimilars into routine care has started. Prognosis for patients with triple-negative ABC remains poor and new treatment options are urgently needed. OPAL together with TMK will allow to follow changes in treatment of patients with ABC in a “real world” setting in Germany, the application of sequential treatments, and their impact on clinical as well as patient-reported outcome. Citation Format: Elmar Stickeler, Nadia Harbeck, Marc Thill, Arnd Nusch, Marco Chiabudini, Lisa Kruggel, Martina Jänicke, Norbert Marschner, Mark-Oliver Zahn, Anja Welt, Achim Wöckel, Thomas Decker, OPAL Study Group. Therapy of advanced breast cancer for patients with hormone receptor-positive/HER2-negative and HER2-positive tumors is changing in real life: First results from the prospective, national research platform OPAL for patients with advanced breast cancer in Germany [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-01.

Analysis of the Cost-Effectiveness of Liquid Biopsy to Determine Treatment Change in Patients with Her2-Positive Advanced Breast Cancer in Colombia.

BackgroundBreast cancer is highly prevalent worldwide and leads to high health-care costs. HER2-positive subtype represents 30% of all breast cancers and is associated with a poor prognosis. Patients treated with anti-HER2 therapies frequently develop resistance and require pharmacological treatment change. Liquid biopsy is a minimally invasive and an easily accessible technique, with high sensitivity and specificity, to detect molecular treatment resistance even before the onset of clinical manifestations and can thus be used to reduce unnecessary anti-HER2 treatment costs.ObjectiveTo evaluate the cost-effectiveness of using liquid biopsy (ctDNA detection) to determine treatment change in women with HER2-positive advanced breast cancer in Colombia.MethodologyWe performed an economic evaluation using decision tree modeling and deterministic analyses based on literature search for first and second lines of treatment (trastuzumab, pertuzumab, docetaxel, and TDM1); resistance; outcomes; and sensitivity and specificity of tests detecting molecular resistance. The effectiveness was measured using quality-adjusted life year (QALY) score, and costs were obtained from databases with national validity, suppliers, the Colombian Drug Price Information System (SISMED), and local studies.ResultsThe use of liquid biopsy (ctDNA detection) with conventional treatment was more expensive and less effective than conventional treatment without liquid biopsy (US $177,985.35 and 0.533889206 QALY, respectively). The incremental cost with liquid biopsy was US $7,333.17 and the incremental effectiveness was 0.00042256 QALY relative to the conventional method.ConclusionIncluding liquid biopsy in the treatment of HER2-positive advanced breast cancer was considered currently inapplicable in Colombia because it was not cost effective. Our results open a window of opportunity to improve the development and implementation of ctDNA testing in Colombia, potentially reducing current costs. More evidence is required on the utility of this test, depending on the financial capacity of Colombia and other countries.

The Use of Chromogenic Factor VIII Assay Changes Treatment Approach in a Portion of Mild Hemophilia A Patients with Factor VIII Assay Discrepancy

Introduction Hemophilia A is an X-linked inherited bleeding disorder characterized by a deficiency of coagulation factor VIII (FVIII). FVIII assays used for diagnosis and classification of hemophilia are the widely used one-stage assay (OSA) and the chromogenic assay (CSA), a more costly and less commonly used test. The CSA has the advantages of improved precision and insensitivity to pre-activation effects of FVIII that can lead to erroneous results. In approximately one-third of mild hemophilia A cases, reliance on OSA can lead to overestimation of factor level in comparison to CSA, and this 'discrepancy' phenomenon is closely associated with the FVIII molecular abnormality. In mild or moderate hemophilia A, assay discrepancy can lead to misclassification or inappropriate treatment. The objectives of this retrospective study were to determine the proportion of patients with OSA/CSA discrepancies defined by OSA to CSA ratio of &amp;gt;1.5 or &amp;lt;0.5, to identify previously reported and new F8 gene mutations and to classify the impact of assay discrepancy on clinical treatment approach. Also, the study aimed to re-evaluate published discrepant OSA/CSA ratios to identify a ratio with the highest sensitivity to indicate that a change of treatment approach or intensity may be required. Methods We reviewed the charts of adult (&amp;gt;18 years old) patients with mild or moderate hemophilia A followed at the Adult British Columbia Hemophilia clinic with concomitant OSA and CSA results between January 2013 and March 2019. Data collected included patient age, disease severity classification, baseline OSA FVIII:C, and F8 gene mutation. Bleeding phenotype and impact of discrepancy on treatment approach was evaluated and determined independently by two individuals and was correlated with concomitant OSA and CSA. Gene mutation data was collected to determine whether OSA/CSA discrepancy has been previously reported in the international hemophilia A mutation database (www.factorviii-db.org). Descriptive data was reported as medians and ranges. Statistical analyses using Spearman's correlation, logistic regression and receiver operating characteristics (ROC) curve were performed using IBM SPSS v. 22.0. Results 98 patients were included in the study with median age of 53 years (18-88). 75 patients were classified by OSA at baseline as mild and 23 patients as moderate severity. Median FVIII:C by OSA was 15% (6%-40%) in the mild group and 3% (1%-5%) in the moderate severity group. Median FVIII:C using CSA was 13% (2%-66%) in the mild group and 4% (1%-7%) in the moderate group. Based on ratio alone, OSA/CSA discrepancy was detected in 51 (52%) patients out of which 3 (3%) were reverse discrepancies (CSA higher than OSA). Treatment approach was changed as a result of CSA introduction in 14 (27%) patients with OSA/CSA discrepancy (14% of the entire study population). OSA had overall good correlation with CSA (r = 0.84) and as expected, there was no correlation between age and OSA to CSA ratio (r = 0.03). In the patients with OSA/CSA discrepancies, neither age nor OSA/CSA predicted a change of treatment approach (OR 1.02 for age; 95% CI 0.99-1.06; p value 0.213 and OR 1.48 for OSA/CSA; 95% CI 0.96-2.28; p value 0.08). The OSA to CSA ratio of 1.8 to 3.5 demonstrated the highest area under the ROC curve and sensitivity for identification of requirement for treatment change in patients with OSA/CSA discrepancy (AUC 0.75; sensitivity 71%, negative predictive value 75%). Six F8 gene mutations with OSA/CSA discrepancies previously not reported in the database were identified. Conclusions OSA/CSA discrepancies were detected in 52% of the patients with mild or moderate hemophilia A and resulted in change of treatment approach in 27% of discrepant patients. Use of an adjusted OSA/CSA ratio between 1.8 to 3.5 was more likely to detect cases with a requirement for change of treatment approach and use of this ratio to indicate discrepancy may be more clinically meaningful. Six gene mutations associated with OSA/CSA discrepancies previously not described in the international hemophilia A mutation database were identified in the study population, highlighting the need for genotyping discrepant cases. Disclosures No relevant conflicts of interest to declare.

Describing medicine therapy management of type 2 diabetes mellitus at primary health care facilities in Cape Town.

BackgroundRational medicine use aims to optimise chronic disease management and prevent episodes of hospitalisation that economically burden the health care system. Diabetes mellitus is one of the most prevalent chronic diseases globally, yet more than 60% of patients with diabetes are not optimally managed according to their therapeutic glycaemic targets.AimTo describe the use of glycated haemoglobin (HbA1c) and fasting plasma glucose results in guiding treatment changes in patients with type 2 diabetes mellitus.SettingPublic sector primary health care facilities in the Cape Town Metropolitan Region in South Africa.MethodRetrospective, descriptive study design was employed. Data for an 18-month period were collected during 2014 and 2015. Data were collected from patient medical records and included baseline demographics, laboratory monitoring tests and the patients’ last three prescriptions.ResultsThe study consisted of 575 participants (64% female) with an average age of 57 (± 11.38) years. The average baseline HbA1c for 493 participants with at least one result was 8.78% (± 1.63), and only 28% of these participants reached the glycaemic target at consequent consultations. HbA1c levels were available to guide 245 prescription changes, of which 181 of these results were outside of the target range. Of these, 15.5% had appropriate therapy adjustments, 78.4% had no change or a lateral change in their follow-up prescriptions, and 6.1% had therapy adjustments opposite to what guidelines suggest.ConclusionGlycaemic monitoring indicated consistent suboptimal glycaemic control in more than 60% of participants. Medicine prescribing patterns did not align with the prescribed local guidelines, Society for Metabolism, Endocrinology and Diabetes of South Africa (SEMDSA). The appropriate use and interpretation of HbA1c at a clinic level should be emphasised to promote rational use of medicines that minimise acute hospitalisation episodes and optimise patients’ long-term health outcomes.

Graded histologic response after neoadjuvant chemotherapy is an optimal criterion for treatment change in patients with locally advanced gastric cancer.

The necessity for changing the postoperative therapy regimen for locally advanced gastric cancer after ineffective neoadjuvant chemotherapy and surgery is unclear because there are no criteria to determine which patients can benefit from this treatment. We assessed whether graded histologic regression of <50% could be the criterion for regimen modification. The study was designed as a matched-pair case-control investigation to minimize intergroup heterogeneity. Patients were stratified into two groups in which they either continued in the same course of treatment or changed the regimen to neoadjuvant chemotherapy. Thirty-six patients were stratified into two groups. The adjuvant chemotherapy regimen of 12 patients was changed, while 24 patients continued on the same regimen. During an average follow-up period of 36 months, there was no difference observed in overall survival in the two groups (median, 24.0 vs. 31.0 months, P=0.863). In a subgroup analysis, however, patients in the changed regimen group with ypTNM stage III disease tended to have superior overall survival, though this effect was not significant (median, 23.0 vs. 14.0 months, P=0.123). Post-therapy nodal status was associated with overall survival in the multivariate analysis (P=0.014, HR 12.503, 95% CI: 1.664-93.919). Most adverse events were categorized as grade 1 or 2, and all treatments were well tolerated. Changing treatment based on a graded histologic regression of <50% after neoadjuvant chemotherapy did not prolong overall survival in patients with gastric cancer. However, changing the adjuvant regimen did reveal a trend towards improved overall survival in the ypTNM stage III subgroup, which merits further investigation using a larger sample size.

Variations in Insurance Policies Regarding Adherence to the AGA Guideline for Therapeutic Drug Monitoring in IBD.

The American Gastroenterological Association (AGA) published guidelines on therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) in August 2017 recommending use of reactive TDM to guide treatment changes in patients with active IBD who are being treated with anti-tumor necrosis factor (anti-TNF) agents or thiopurines. We sought to determine if changes in national clinical practice guidelines result in changes in health care insurance policies within 6 months of publication. Using the National Association of Insurance Commissioners Market Share Reports of the top 125 insurance companies by market share in 2016, we reviewed the largest 50 companies for their publicly available online policies regarding TDM of anti-TNF and thiopurine in IBD. For those with available policies, we looked for whether proactive and/or reactive TDM was covered. Policies were also looked for genetic or enzymatic activity of thiopurine methyltransferase (TPMT) testing before use of thiopurine. All these policies were reviewed within the week of publication of the AGA guideline. They were reviewed again 1, 3, and 6 months later for evaluation of any policy changes after the published AGA guidelines. Fifty of the largest insurance company policies were included. With regards to TDM policy for anti-TNF, we did not find a difference between baseline and 6 months values (P=0.38). With regards to TDM policy for thiopurine, we did not find a difference between baseline and 6 months values (P=1.00). About half of the companies did not have a policy regarding TPMT testing for thiopurine use. Of those with available policies for TPMT testing, there was no difference between baseline and 6 months values (P=0.13). Even after publication of national guidelines, a large number of the largest health insurance companies do not have a policy regarding reactive TDM for anti-TNF and/or thiopurines. Majority of those with a policy, fail to meet the current standards set forth by the practice guidelines. A significant gap remains between the insurance policies and AGA guidelines. Further studies are needed to determine how to effectuate change to improve insurance company adherence to clinical practice guidelines.

Whole-Body CT after Motor Vehicle Crash: No Benefit after High-Energy Impact and with Normal Physical Examination.

Background Debate continues about the risks and benefits of systematic whole-body CT when no injury is clinically suspected. Risks of whole-body CT include high radiation exposure and iodine contrast agent, but its effectiveness in reducing mortality in low-risk motor vehicle crashes is unclear. Purpose To assess unsuspected injuries revealed at whole-body CT in patients following motor vehicle crash (MVC) meeting only kinetic elements of the Vittel criteria for the severity of trauma, with no evidence of trunk injury and a Glasgow Coma Scale score of 15. Materials and Methods This retrospective study included all consecutive adult patients who consulted an emergency department of a level 1 trauma center between August 2016 and July 2017 if they underwent whole-body CT for one or more kinetic elements of the Vittel criteria, had a normal examination of the trunk, and had a Glasgow Coma Scale score of 15. Data of the MVC mechanism and physical and biologic examinations were collected, as well as patient treatment data after whole-body CT. Whole-body CT examinations were read by two double-blinded readers to help detect unsuspected injuries. Results Ninety-three patients were included; 72 were men with a mean age of 30.8 years ± 12.0 (standard deviation). Sixty-nine patients were occupants of a car. Seventeen patients were hit by a car while on motorbikes, three while on bicycles, and four as pedestrians. Unsuspected injuries were depicted at 11 whole-body CT examinations: eight lung contusions, one acetabular fracture, one sternal fracture, and one adrenal hematoma. None of these injuries required a specific treatment. One patient with lung contusion of more than 30% of lung volume was followed without requiring further treatment. Conclusion In this population, whole-body CT did not lead to any change in patient treatment. These results suggest whole-body CT should not be systematically performed when no evidence of trunk injury is observed in patients following motor vehicle crash meeting only kinetic elements of Vittel criteria. © RSNA, 2019 See also the editorial by Munera and Durso in this issue.

Clinical assessment and ultrasonography in the follow-up of enthesitis in patients with spondyloarthritis: a multicenter ultrasound study in daily clinical practice.

ObjectivesThe aim of this study was to compare the clinical Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and an established ultrasound enthesitis score following treatment change in patients with spondyloarthritis and enthesitis with respect to the sensitivity to change and health-related quality of life.Materials and methodsAbout 145 patients with active ankylosing spondylitis (n=65), psoriatic arthritis without (n=66) or with (n=14) axial involvement undergoing intensification of their treatment were included in this multicenter study. At baseline, after 3 and 6 months, 13 entheses were scored by MASES, ultrasonography was performed for 14 entheses. Assessments of clinical, laboratory and patient-reported outcome measurements were performed.ResultsDuring 6 months of follow-up, MASES was reduced from 5.57 to 3.12 (P<0.001), which was similar to the reduction of the power Doppler sum score from 5.47 to 2.88 (P<0.001). Both MASES and power Doppler ultrasound were responsive at the 3-month follow-up visit, as indicated by a high sensitivity to change in patients initiating anti-tumor necrosis factor treatment (–0.96 for MASES and –0.74 for power Doppler ultrasound). Improvement of enthesitis did not correlate with patient-reported outcomes.ConclusionClinical assessment by MASES and power Doppler sonography as well reflects anti-tumor necrosis factor treatment response in patients with spondyloarthritis. Improvement of enthesitis did not correlate with changes in quality of life measures.

Characteristics Associated with Hydroxyurea Treatment Change in Patients with Polycythemia Vera: An Analysis from the Reveal Study

Introduction: Polycythemia vera (PV) is associated with increased blood cell counts, risk of thrombosis, and symptoms. Guidelines support the use of hydroxyurea (HU) in high-risk patients, or low-risk patients with an indication for cytoreductive therapy. However, a proportion of patients become resistant or intolerant to HU over time. The objective of this analysis is to describe patients with PV enrolled in REVEAL who changed from HU to an alternative treatment.Methods: REVEAL (NCT02252159) is a prospective, observational study of adult patients with PV in the US. Patients were observed over a 36-month period and clinical data were collected from usual care visits. In this analysis, an index date of 6 months prior to enrollment was determined for each patient. Patients who received other PV-related treatments prior to initiating HU, who never received HU prior to data cutoff, or who discontinued HU within 3 months of the data cutoff were excluded. Patients who initiated HU prior to their index date and continued through the index date and patients who initiated HU after the index date were included. This patient cohort was subdivided into 3 subgroups: patients who discontinued HU and did not initiate an alternative; patients who were still receiving HU at the time of data cutoff; and patients who started an alternative treatment after HU. For patients who initiated an alternative treatment, laboratory values (maximum values within the reporting period), number of phlebotomies, and symptoms were evaluated within 3 months prior to the treatment change. For patients who discontinued and for those who continued HU, data were evaluated within 3 months prior to discontinuation or data cutoff, respectively (time of evaluation).Symptom burden was assessed using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). All data were analyzed with descriptive statistics.Results: Of the 2,510 patients enrolled in REVEAL, 1,239 met the criteria for this analysis. Of these patients, 56 (4.5%) discontinued HU without initiating an alternative therapy, 1,059 (85.5%) continued HU, and 124 (10.0%) started an alternative cytoreductive treatment after HU. Patients who discontinued HU treatment were older, with a median age (range) of 74.0 (28.0-91.0) years compared with patients who continued HU or who started an alternative treatment (Table). A similar proportion of patients who discontinued HU had high-risk disease (89.3%) compared to those who continued HU (87.2%) or initiated an alternative treatment (83.1%). Among those who started an alternative treatment, ruxolitinib was the most common (102 patients, 82.3%), followed by anagrelide (17 patients, 13.7%), interferon (4 patients, 3.2%), and chlorambucil (1 patient, 0.8%).Patients who initiated an alternative treatment for PV had higher mean blood counts and more frequent phlebotomy procedures compared with those who discontinued HU and with those who continued (Table).Patients who initiated an alternative treatment had higher mean HU dose at the time of treatment change (968.6 mg/d) compared with those who discontinued HU (707.1 mg/d at the time of discontinuation) or those who continued (811.2 mg/d at the time of data cutoff). Similarly, the maximum HU dose received since index was higher for those who initiated an alternative treatment compared with those who discontinued HU or continued HU (1072.9, 803.6, and 891.9 mg/d, respectively).Patients who initiated an alternative treatment following HU had a higher mean TSS, both at the time of treatment change and at enrollment (29.8 and 25.9) compared with those who discontinued HU (at the time of discontinuation, 22.5 and 20.4) and those who continued HU (at the time of data cutoff, 20.8 and 16.8).A higher proportion of patients who discontinued HU had a history of nonhematological adverse events (12.5%) compared with those who started another alternative treatment (8.1%) or those who continued HU (5.9%).Conclusion: Patients with PV who received HU demonstrated variation with respect to HU management. Patients who started alternative treatments after HU were younger, had higher counts, more frequent phlebotomies, and higher symptom burden before changing treatment. These data support current criteria for HU resistance/intolerance. [Display omitted] DisclosuresMesa:Promedior: Research Funding; Novartis: Consultancy; UT Health San Antonio - Mays Cancer Center: Employment; Pfizer: Research Funding; NS Pharma: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Incyte Corporation: Research Funding; Gilead: Research Funding; CTI Biopharma: Research Funding. Colucci:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Grunwald:Celgene: Consultancy; Pfizer: Consultancy; Agios: Consultancy; Merck: Consultancy; Janssen: Research Funding; Forma Therapeutics: Research Funding; Genentech: Research Funding; Cardinal Health: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Research Funding.

Association of Amyloid Positron Emission Tomography With Changes in Diagnosis and Patient Treatment in an Unselected Memory Clinic Cohort

Previous studies have evaluated the diagnostic effect of amyloid positron emission tomography (PET) in selected research cohorts. However, these research populations do not reflect daily practice, thus hampering clinical implementation of amyloid imaging. To evaluate the association of amyloid PET with changes in diagnosis, diagnostic confidence, treatment, and patients' experiences in an unselected memory clinic cohort. Amyloid PET using fluoride-18 florbetaben was offered to 866 patients who visited the tertiary memory clinic at the VU University Medical Center between January 2015 and December 2016 as part of their routine diagnostic dementia workup. Of these patients, 476 (55%) were included, 32 (4%) were excluded, and 358 (41%) did not participate. To enrich this sample, 31 patients with mild cognitive impairment from the University Medical Center Utrecht memory clinic were included. For each patient, neurologists determined a preamyloid and postamyloid PET diagnosis that existed of both a clinical syndrome (dementia, mild cognitive impairment, or subjective cognitive decline) and a suspected etiology (Alzheimer disease [AD] or non-AD), with a confidence level ranging from 0% to 100%. In addition, the neurologist determined patient treatment in terms of ancillary investigations, medication, and care. Each patient received a clinical follow-up 1 year after being scanned. Primary outcome measures were post-PET changes in diagnosis, diagnostic confidence, and patient treatment. Of the 507 patients (mean [SD] age, 65 (8) years; 201 women [39%]; mean [SD] Mini-Mental State Examination score, 25 [4]), 164 (32%) had AD dementia, 70 (14%) non-AD dementia, 114 (23%) mild cognitive impairment, and 159 (31%) subjective cognitive decline. Amyloid PET results were positive for 242 patients (48%). The suspected etiology changed for 125 patients (25%) after undergoing amyloid PET, more often due to a negative (82 of 265 [31%]) than a positive (43 of 242 [18%]) PET result (P < .01). Post-PET changes in suspected etiology occurred more frequently in patients older (>65 years) than younger (<65 years) than the typical age at onset of 65 years (74 of 257 [29%] vs 51 of 250 [20%]; P < .05). Mean diagnostic confidence (SD) increased from 80 (13) to 89 (13%) (P < .001). In 123 patients (24%), there was a change in patient treatment post-PET, mostly related to additional investigations and therapy. This prospective diagnostic study provides a bridge between validating amyloid PET in a research setting and implementing this diagnostic tool in daily clinical practice. Both amyloid-positive and amyloid-negative results had substantial associations with changes in diagnosis and treatment, both in patients with and without dementia.