Routine Clinical Care Of Patients Research Articles

Liquid Biopsy in Colorectal Cancer: Quo Vadis? Implementation of Liquid Biopsies in Routine Clinical Patient Care in Two German Comprehensive Cancer Centers.

ObjectivesThe use of liquid biopsies (LB) in patients with solid malignancies enables comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) and has the potential to guide therapy stratification and support disease monitoring. To examine clinical uptake of LB in a real-world setting, LB implementation was analyzed at two German cancer centers (LMU Munich and Charité - Universitätsmedizin Berlin) between 2017 and 2021, with focus on colorectal cancer (CRC) patients.MethodsIn this retrospective analysis, all patients who received a LB between January 2017 and December 2021 as part of routine clinical management were included. To provide adequate context, we collected disease characteristics and technical specifications of the LB methods applied. Additionally, we examined the concordance of RAS status in tumor tissue and LB. Finally, we discuss the potential of LB as a diagnostic tool to drive personalized treatment in CRC patients and how to implement LB in clinical routine.ResultsIn total, our cohort included 86 CRC patients and 161 LB conducted in these patients between 2017 and 2021. In 59 patients, comparison between tissue-based and liquid-based molecular diagnostics, revealed a divergence in 23 (39%) of the evaluable samples.ConclusionOur real-world data analysis indicates that the possibilities of LB are not yet exploited in everyday clinical practice. Currently, the variety of methods and lack of standardization, as well as restricted reimbursement for liquid based CGP hinder the use of LB in clinical routine. To overcome these issues, prospective clinical trials are needed to provide evidence driving the implementation of LB into the management of CRC patients and to support their implementation into clinical guidelines.

Utilization and findings of out-patient EEG in routine clinical care of patients with acute symptomatic seizure concern after acute stroke (P14-8.006)

Utilization and findings of out-patient EEG in routine clinical care of patients with acute symptomatic seizure concern after acute stroke (P14-8.006)

Monitoring of Disease Activity With a Smartphone App in Routine Clinical Care in Patients With Axial Spondyloarthritis.

To investigate the performance of a health app with respect to usability, adherence, and equivalence of data in daily care of patients with axial spondyloarthritis (axSpA). Consecutive patients with axSpA were asked to export patient-reported outcomes (PRO) electronically with the AxSpA Live App regularly every 2 weeks over a period of 6 months. The first clinical visit was followed by 2 further personal visits after 3 and 6 months. Patients completed paper-based PRO at every visit; they also completed the Mobile App Rating Scale and the System Usability Scale after 3 and 6 months. Of 103 patients with axSpA, 69 agreed to participate (67.0%): age 41.5 (11.3) years, 58.0% male, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 4.3 (2.0), and 76.8% treated with biologic disease-modifying antirheumatic drugs. Patients' adherence to regular app exports was 29.0% and 28.4% after 3 and 6 months, respectively. Significant predictors for good adherence were high disease activity (P = 0.02) and older age (P = 0.04). No systematic differences between digital and paper-based BASDAI scores were found (intraclass correlation coefficients 0.99 [95% CI 0.98-0.99]). Performance of the app was rated as good. Collection of digital PROs by AxSpA Live App may be successfully used in patients with axSpA with high disease activity. Our study showed equivalence of digital data, but adherence to the app after 6 months was poor. Higher disease activity and older age resulted in increased adherence to the app. This suggests that the use of health apps like this should concentrate on more severely affected patients.

Electronic Patient-Reported Outcome Measures in Burn Scar Rehabilitation: A Guide to Implementation and Evaluation

In burn scar rehabilitation, electronic patient-reported outcome measures (ePROMs) are increasingly being used in research and clinical settings as part of patient- and family-centred care. These measures can identify patients’ needs and monitor the therapeutic progress of both adults and children. The feedback of information from ePROMs to clinicians treating patients with scarring and psychosocial issues may have therapeutic benefits. However, testing the effectiveness of ePROMs used in the routine clinical care of patients with burn scarring is in its infancy, and one of the greatest challenges remains the implementation of ePROMs in real-world clinical settings. The aim of this paper is to provide a guide for clinicians and researchers involved in burn scar rehabilitation to assist in implementing ePROMs in clinical settings. The guide outlines strategies, processes, and considerations for ePROM implementation and the accompanying resources. Two real-world case studies of ePROM implementation are presented in burn scar clinics in Belgium and Australia. Additionally, ten recommendations for the implementation of ePROMs are provided based on research evidence and the lessons learned by the authors. The information provided should pave the way forward for using and testing these ePROMs in research and practice.

A Study Protocol for Validation and Implementation of Whole-Genome and -Transcriptome Sequencing as a Comprehensive Precision Diagnostic Test in Acute Leukemias.

BackgroundWhole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed.Methods and AnalysisThe study comprises four phases (i.e., retrospective, prospective, real-time validation, and follow-up) including approximately 700 adult and pediatric Swedish AML and ALL patients. Results of WGS for tumor (90×) and normal/germline (30×) samples as well as WTS for tumors only will be compared to current standard of care diagnostics. Primary study endpoints are diagnostic efficiency and improved diagnostic yield. Secondary endpoints are technical and clinical feasibility for routine implementation, clinical utility, and health-economic impact.DiscussionData from this national multi-center study will be used to evaluate clinical performance of the integrated WGTS diagnostic workflow compared with standard of care. The study will also elucidate clinical and health-economic impacts of a combined WGTS strategy when implemented in routine clinical care.Clinical Trial Registration[https://doi.org/10.1186/ISRCTN66987142], identifier [ISRCTN66987142].

Targeting PSMA Revolutionizes the Role of Nuclear Medicine in Diagnosis and Treatment of Prostate Cancer.

Simple SummaryImaging plays a crucial role in the accurate staging of prostate cancer. Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells, and targeting the PSMA protein for diagnostic purposes has become of great clinical value. Another valuable feature of PSMA is its opportunity to serve as a target for delivering radionuclide therapy to cancer cells. PSMA-ligands can be labeled with various radionuclides, such as alpha and beta-emitters. This review offers an overview of the literature on recent developments in nuclear medicine regarding PSMA in prostate cancer diagnostics and targeted radionuclide therapy.Targeting the prostate-specific membrane antigen (PSMA) protein has become of great clinical value in prostate cancer (PCa) care. PSMA positron emission tomography/computed tomography (PET/CT) is increasingly used in initial staging and restaging at biochemical recurrence in patients with PCa, where it has shown superior detection rates compared to previous imaging modalities. Apart from targeting PSMA for diagnostic purposes, there is a growing interest in developing ligands to target the PSMA-protein for radioligand therapy (RLT). PSMA-based RLT is a novel treatment that couples a PSMA-antibody to (alpha or beta-emitting) radionuclide, such as Lutetium-177 (177Lu), to deliver high radiation doses to tumor cells locally. Treatment with 177Lu-PSMA RLT has demonstrated a superior overall survival rate within randomized clinical trials as compared to routine clinical care in patients with metastatic castration-resistant prostate cancer (mCRPC). The current review provides an overview of the literature regarding recent developments in nuclear medicine related to PSMA-targeted PET imaging and Theranostics.

Medical cannabis use by rheumatology patients in routine clinical care: results from The Ontario Best Practices Research Initiative.

Medical cannabis is often used to alleviate common symptoms in patients with chronic conditions. With cannabis legalisation in Canada and easier access, it is important that rheumatologists understand its potential impact on their practice. Among patients attending rheumatology clinics in Ontario we assessed: the prevalence of medical cannabis use; symptoms treated; rheumatologists' perceptions. Eight rheumatology clinics recruited consecutive adult patients in a 3-part medical cannabis survey: the first completed by rheumatologists; the second by all patients; the third by medical cannabis users. Student's t-test and Chi-square test were used to compare medical cannabis users to never users. 799 patients participated, 163 (20.4%) currently using medical cannabis or within <2 years and 636 never users; most had rheumatoid arthritis (37.8%) or osteoarthritis (34.0%). Compared to never users, current/past-users were younger; more likely to be taking opioids/anti-depressants, have psychiatric/gastrointestinal disorders, and have used recreational cannabis (p<0.05); had higher physician (2.9 vs. 2.1) and patient (6.0 vs. 4.2) global scores, and pain (6.2 vs. 4.7) (p<0.0001). Pain (95.5%), sleeping (82.3%) and anxiety (58.9%) were the most commonly treated symptoms; 78.2% of current/past-users reported medical cannabis was at least somewhat effective. Most rheumatologists reported being uncomfortable to authorise medical cannabis, primarily due to lack of evidence, knowledge, and product standardisation. Medical cannabis use among rheumatology patients in Ontario was two-fold higher than that reported for the general population of similar age. Use was associated with more severe disease, pain, and prior recreational use. Reported lack of research, knowledge, and product standardisation were barriers for rheumatologist use authorisation.

Neoadjuvant pertuzumab in non‑metastatic HER2‑positive breast tumors: Multicentric study in Peru (NeoHer)

Several clinical trials have demonstrated the benefit of adding pertuzumab to trastuzumab plus neoadjuvant chemotherapy in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The comparison of outcomes between nonrandomized groups of patients who received similar treatments in routine practice remains difficult. The present study aimed to evaluate the pathological complete response (pCR) rates achieved with pertuzumab among patients in routine clinical care in Peru using real-world data. The definition of pCR used was the absence of residual invasive cancer from the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. A total of 44 patients with non-metastatic HER2-positive breast cancer (stages II and III) treated with pertuzumab in the neoadjuvant setting and who underwent surgery at three private clinics in Lima (Peru) were retrospectively evaluated. The pCR was the efficacy endpoint and it was determined and compared with the results from other clinical trials. Furthermore, safety data were described. The median age was 44 years (interquartile range, 39.5-50.5 years) and 65.9% of patients were premenopausal. Regarding the clinical stage, 56.8% were IIA/IIB and 36.4% were IIIA/IIIB/IIIC. All treatment schemes included concurrent trastuzumab. The patients' treatment comprised neoadjuvant therapy of docetaxel/trastuzumab/pertuzumab (THP) with a median of 4 cycles in 30 patients (68.2%) or docetaxel/trastuzumab/pertuzumab/carboplatin (THPCarb) with a median of 6 cycles in 14 patients (31.8%). In total, 70.5% of patients experienced pCR; among hormone receptor-negative cases, 75.0% achieved pCR and in tumors expressing hormone receptors, the rate of pCR was 66.7%. Of those patients subjected to neoadjuvant treatment with THP, 66.7% (20/30) achieved pCR, whereas 78.6% (11/14) of patients who received THPCarb had a pCR. The incidence of drug-related adverse events was 59.1% and in none of the patients, administration was discontinued due to toxicity. The present results of Peruvian patients with HER2 breast cancer treated according to clinical routine demonstrated that dual blockade of HER2 with trastuzumab and pertuzumab in the neoadjuvant setting achieved high rates of pCR even in hormone receptor-positive patients. These results are consistent with those of randomized controlled trials, with a good safety profile.

Effect of Complementary and Integrative Treatments on Fatigue Symptoms in Hemodialysis Patients: A Systematic Review.

Although hemodialysis treatment is one of the main treatment methods in chronic kidney failure, it also causes many health problems. A variety of complementary and integrative therapies are used to relieve or minimize hemodialysis symptoms. Fatigue (60%-97%) is also one of these problems. Therefore, we have conducted a systematic review to determine the effect of complementary and integrative therapies on fatigue in hemodialysis patients. Relevant studies published from 2005 to 2019, in PubMed, EBSCOhost, ScienceDirect, and Cochran Library databases have been reviewed. In the study, initially, 21 039 pieces of data were obtained, and then 14 randomized controlled studies meeting the inclusion criteria were reviewed. The methodological qualities of the articles included in the study were determined by using the quality evaluation checklist in Jadad randomized controlled studies. In the literature, acupressure, aromatherapy, reflexology, massage, and yoga practice were found to be applied to hemodialysis patients and be effective in reducing pain and anxiety as well as improving sleep quality. It is recommended that these methods be included in the routine clinical care of patients receiving hemodialysis.

Geriatric Assessment Predicts Non-Fatal Toxicities and Survival for Intensively Treated Elderly Acute Myeloid Leukemia: A Prospective Study

IntroductionGeriatric assessment (GA) typically refers to a multidimensional evaluation designed to evaluate an older person's functional ability, physical health, cognition, psychological health, nutritional status, and social support. The purpose of GA is to develop time-efficient and straightforward tools to evaluate multiple patient characteristics, which may be predictive of treatment outcomes of elderly acute myeloid leukemia (eAML) patients treated with intensive chemotherapy. Given that there have been few prospective studies with conflicting results, we performed a single-center prospective observational cohort study (#KCT0002172) investigating the prognostic value of multiparameter GA domains for eAML patients' tolerance and survival outcomes after intensive chemotherapy.Patients and methodsNewly diagnosed eAML patients aged over 60 years who received intensive chemotherapy (n=105) were prospectively enrolled between November 2016 and December 2019. The median age was 64 years (range, 60-75), and they were all considered fit for intensive chemotherapy, with adequate performance and organ function. All the enrolled patients were administered various questionnaires for pretreatment GA and functional evaluation, which included evaluation for social and nutritional support, cognition, depression, distress, and physical function.ResultsOf the 105 enrolled patients, 93% had an Eastern Cooperative Oncology Group performance score of 1 and received intensive chemotherapy. Among them, between 32.4% and 69.5% of patients met the criteria for impairment on each GA domain. Physical impairment measured by the Short Physical Performance Battery (SPPB) was significantly associated with non-fatal toxicities of Grade III-IV severe infection (odds ratio (OR) 3.000, 95% confidence interval (CI), 1.159-7.788, p=0.024) and acute renal failure (OR 3.891, 95% CI, 1.329-11.39, p=0.013). Cognitive dysfunction measured by the Mini-Mental Status Examination- Korean version of CERAD Assessment Packet was significantly associated with a higher risk of Grade III-IV infection (OR 2.667, 95% CI, 1.025-6.939, p=0.044) and prolonged hospitalization (OR 4.208, 95% CI, 1.485-4.229, p=0.005). Reduced physical function measured by the SPPB and depressive symptoms measured by the Korean version of Short form Geriatric Depressive Scale (SGDS-K) were predictive of worse overall survival (OS; hazard ratio (HR) 1.917, 95% CI, 1.074-3.420, p=0.027 and HR 1.902, 95% CI, 1.005-3.602, p=0.048). SPPB impairment was also significantly related to higher treatment-related mortality (TRM; HR 2.023, 95% CI, 11.057-3.874, p=0.033). Furthermore, gait or sit-and-stand speed, a component of SPPB, was the single most powerful tool to predict survival outcomes of both OS (HR 2.766, 95% CI, 1.471-5.200, p=0.002 and HR 3.615, 95% CI, 1.868-6.999, p<0.001) and TRM (HR 2.461, 95% CI, 1.233-4.913, p=0.011 and HR 3.814, 95% CI, 1.766-8.237, p<0.001). We reconfirmed the prognostic value of preexisting survival prediction models, Wheatley index scores, and web-based AML scores, contrasting to the lack of significance of Ferrara criteria. The addition of SPPB/SGDS-K or gait (or sit-and-stand) speed/SGDS-K improved the predictability of the Wheatley index and web-based AML scores with 69% and 90% relative increases in predictive power for survival, respectively.ConclusionsWe prospectively demonstrated the prognostic value of physical and psychological assessment by GA for survival outcomes in intensively treated eAML patients. Gait or sit-and-stand speed was the single most powerful tool to identify frailty and predict survival outcomes. The prognostic value of preexisting survival prediction models, Wheatley index scores, and AML scores was reconfirmed.. The addition of measures for physical function and depression improved the predictability of those prediction models for survival. Cognitive and physical impairment were able to identify non-fatal toxicities during intensive chemotherapy in eAML patients. Our data will facilitate the incorporation of GA measures into validated survival prediction models to determine initial treatment for eAML patients in routine clinical care and clinical trials. Further studies are warranted to determine the best ways to adjust the care provided for frail patients to improve treatment tolerance and outcomes. DisclosuresKim: Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; ILYANG: Research Funding; Takeda: Research Funding. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria.

Transdiagnostic and functional predictors of depression severity and trajectory in the Penn state psychiatry clinical assessment and rating evaluation system (PCARES) registry

BackgroundTimely, accurate diagnosis and subsequent identification of risk factors for depression that is difficult-to-treat can aid in decreasing the burden of depressive illness and reducing probability of future disability. We aimed to identify sociodemographic, clinical, and functional factors that predict depression severity over one year in a real-world, naturalistic, transdiagnostic clinical sample. A subset sample with moderate depression was examined to determine the magnitude of improvement. MethodsThe Penn State Psychiatry Clinical Assessment and Rating System (PCARES) Registry houses data from systematically-structured patient-reported outcomes and clinical data from an Electronic Medical Record (EMR) gathered during routine clinical care of patients seeking mental health care at a mid-Atlantic clinic. Self-report symptom and functional measures were obtained, and sociodemographic features and clinical diagnoses were extracted from the EMR from 1,766 patients between 2/6/2016 to 9/30/2019. The Patient Health Questionnaire 9 (PHQ-9) depression scale was obtained at each visit. Using a discrete mixture clustering model, the study population was divided into five longitudinal trajectory groups, termed depression severity groups, based on intra-individual PHQ-9 score trajectories over one year. Multinomial logistic regression models were estimated to evaluate associations between characteristics and the likelihood of depression severity group membership. To determine the magnitude of improvement, predictors of the slope of the PHQ-9 trajectory were examined for patients with moderate depression. ResultsThe strongest predictors of high depression severity over one year were poor functioning, high transdiagnostic DSM-5 Level 1 crosscutting symptom score, diagnosis of Post-Traumatic Stress Disorder (PTSD), public/self-pay insurance, female gender, and non-White race. Among the subset of patients with moderate depression, strong predictors of improvement were commercial insurance and exposure to trauma; the strongest predictors of worsening were high functional impairment, high transdiagnostic Level 1 symptom score, diagnosis of PTSD, diagnosis of bipolar disorder, and marital status of single or formerly married; depression-specific symptom measures were not predictive. LimitationsLimitations include inferring education and income status from zip code level-data, the non-random missingness of data, and the use of diagnoses collected from the electronic medical record. ConclusionFunctional impairment, transdiagnostic measures of symptom burden, and insurance status are strong predictors of depression severity and poor outcome.

PCSK9 inhibitor therapy and guideline treatment targets for cardiovascular disease and familial hypercholesterolaemia

Abstract Background Updated trial data on the benefits of low-density lipoprotein cholesterol (LDL-C) reduction on cardiovascular outcomes have been incorporated into 2019 ESC/EAS guidelines and 2020 UK-based NICE guidance. Treatment targets for secondary cardiovascular disease (CVD) prevention are LDL-C &amp;lt;1.4mmol/L (ESC/EAS) and non-high-density lipoprotein &amp;lt;2.5mmol/L (equates to LDL-C &amp;lt;1.8mmol/L; NICE). Guidelines also recommend ≥50% LDL-C reduction in patients with CVD or Familial Hypercholesterolaemia (FH). Targets are often not achieved with oral statin +/− ezetimibe due to reduced efficacy or tolerability, warranting a switch to PCSK9 inhibitor therapy. However, there is limited data on whether this achieves LDL-C targets for both CVD and FH in real world clinical practice. Purpose To assess attainment of LDL-C treatment targets using PCSK9 inhibitor mono- or combination therapy in routine clinical care for patients with FH or CVD. Methods Observational study in a single specialist lipid clinic, using retrospective case note review of patients prescribed PCSK9 inhibitor therapy according to NICE guidelines until February 2021. Anonymised clinical, demographic and biochemical data before and after commencement of PCSK9 inhibitor therapy were collected. Primary outcomes were attainment of guideline-defined LDL-C treatment targets: LDL-C &amp;lt;1.8 mmol/L, LDL-C &amp;lt;1.4mmol/L and ≥50% LDL-C reduction. Results A total of 55 patients (mean age 60.8±12.9 years, 58% male) on PCSK9 inhibitor therapy (98% alirocumab, 2% evolocumab; mean treatment duration 1.7±1.3 years) were identified. PCSK9 inhibitor therapy was commenced due to drug intolerance to statins (89%), ezetimibe (36%) and fenofibrate (25%). In patients with FH (n=18), 78%, 56% and 33% of patients achieved targets of ≥50% LDL-C reduction, LDL-C &amp;lt;1.8 mmol/L and LDL-C &amp;lt;1.4 mmol/L on treatment, respectively. In CVD patients (n=49), 84%, 51% and 27% achieved the same targets respectively (Table 1). In patients on PCSK9 inhibitor monotherapy (n=19), 21% and 5% achieved LDL-C targets &amp;lt;1.8 mmol/L and &amp;lt;1.4 mmol/L respectively, whereas in those on PCSK9 inhibitor + two or more additional oral lipid-lowering therapies, 87% and 60% achieved the same targets respectively (Table 2). Conclusions Most patients with FH or CVD achieve an LDL-C reduction of ≥50% from baseline with PCSK9 inhibitor therapy, however fewer achieve the LDL-C targets of &amp;lt;1.8 mmol/L or &amp;lt;1.4 mmol/L. Patients on PCSK9 inhibitor monotherapy are unlikely to reach LDL-C &amp;lt;1.8 mmol/L and &amp;lt;1.4mmol/L targets, whereas PCSK9 inhibitor combination therapies are more likely to do so. Additional lipid-lowering drugs are required with PCSK9 inhibitor therapy in most patients to reach guideline LDL-C targets. Funding Acknowledgement Type of funding sources: None.

MAJOR DEPRESSIVE DISORDER IS ASSOCIATED WITH TYPE 2 DIABETES IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION.

Major depressive disorder (MDD) is commonly reported in patients with chronic hepatitis C (CHC); however, the factors behind the co-occurrence of these conditions have not been completely clarified yet. We aimed to evaluate the frequency of mental disorders in CHC patients and to investigate variables associated with MDD. CHC patients (n=151) attending a referral Centre for hepatitis were evaluated using the Mini-International Neuropsychiatry Interview and the Cut-Annoyed-Guilty-Eye (CAGE) Questionnaire. Multivariate analysis was used to evaluate independent covariates associated with current MDD. Seventy-six (50.3%) patients had, at least, one current psychiatric diagnosis with MDD (33.1%) being the most common. Current MDD was independently associated with age (≤50 yr.) (OR=2.57; 95%CI=1.25-5.29; P=0.01) and type 2 diabetes mellitus (OR=2.80, 95%CI=1.17-6.70; P=0.02). Cirrhosis was associated with type 2 diabetes mellitus (OR=5.09; 95%CI=1.73-15.04; P=0.03) and current alcohol abuse/dependence (OR=2.54; 95%CI=1.04-6.22; P=0.04). MDD is associated with type 2 diabetes in CHC patients. Even in the direct-acting antivirals (DAAs) era, characterized by great perspectives for the first ample cure of a chronic viral infection, we should ensure that the screening for psychiatric disorders takes place in the course of routine clinical care of patients chronically infected with hepatitis C virus.

48. A PHENOTYPIC SPECTRUM OF AUTISM IS ATTRIBUTABLE TO THE COMBINED EFFECTS OF RARE VARIANTS, POLYGENIC RISK AND SEX

Timely, accurate diagnosis and subsequent identification of risk factors for depression that is difficult-to-treat can aid in decreasing the burden of depressive illness and reducing probability of future disability. We aimed to identify sociodemographic, clinical, and functional factors that predict depression severity over one year in a real-world, naturalistic, transdiagnostic clinical sample. A subset sample with moderate depression was examined to determine the magnitude of improvement.The Penn State Psychiatry Clinical Assessment and Rating System (PCARES) Registry houses data from systematically-structured patient-reported outcomes and clinical data from an Electronic Medical Record (EMR) gathered during routine clinical care of patients seeking mental health care at a mid-Atlantic clinic. Self-report symptom and functional measures were obtained, and sociodemographic features and clinical diagnoses were extracted from the EMR from 1,766 patients between 2/6/2016 to 9/30/2019. The Patient Health Questionnaire 9 (PHQ-9) depression scale was obtained at each visit. Using a discrete mixture clustering model, the study population was divided into five longitudinal trajectory groups, termed depression severity groups, based on intra-individual PHQ-9 score trajectories over one year. Multinomial logistic regression models were estimated to evaluate associations between characteristics and the likelihood of depression severity group membership. To determine the magnitude of improvement, predictors of the slope of the PHQ-9 trajectory were examined for patients with moderate depression.The strongest predictors of high depression severity over one year were poor functioning, high transdiagnostic DSM-5 Level 1 crosscutting symptom score, diagnosis of Post-Traumatic Stress Disorder (PTSD), public/self-pay insurance, female gender, and non-White race. Among the subset of patients with moderate depression, strong predictors of improvement were commercial insurance and exposure to trauma; the strongest predictors of worsening were high functional impairment, high transdiagnostic Level 1 symptom score, diagnosis of PTSD, diagnosis of bipolar disorder, and marital status of single or formerly married; depression-specific symptom measures were not predictive.Limitations include inferring education and income status from zip code level-data, the non-random missingness of data, and the use of diagnoses collected from the electronic medical record.Functional impairment, transdiagnostic measures of symptom burden, and insurance status are strong predictors of depression severity and poor outcome.

Underascertainment of Clinically Meaningful Symptoms During Prostate Cancer Radiation Therapy-Does This Vary by Patient Characteristics?

It is well known that physicians underascertain chemotherapy-related toxicity compared with patient self-report. However, symptom underascertainment in radiation therapy and characterization of patient groups at increased risk for underascertainment have not been examined. As part of routine clinical care, 7 urinary and gastrointestinal symptoms were prospectively collected with both patient-report outcomes (PROs) using the validated Prostate Cancer Symptom Indices and physician-graded symptoms using Common Terminology Criteria for Adverse Events (CTCAE) for 544 consecutive patients from 2010 to 2018 who received intensity modulated radiation therapy to the prostate or prostate bed. Data from weekly treatment visits and the first posttreatment follow-up were analyzed. Underascertainment was defined as an occurrence when a clinically meaningful symptom was indicated on PROs but not physician CTCAE assessment. Univariate and multivariable logistic regression examined characteristics associated with underascertainment. Overall, 85.3% of patients had underascertainment of at least 1 symptom. Per PRO, 16.9% of assessments reported clinically meaningful symptoms, in contrast to only 3.4% per CTCAE, representing an approximate 5-fold difference. Multivariable analysis showed underascertainment was more common in patients who were unmarried (odds ratio [OR] 1.28; 95% confidence interval [CI], 1.18-1.38), lived in rural regions (OR 1.10; 95% CI, 1.01-1.21), incarcerated (OR 1.58; 95% CI, 1.36-1.84), retired/unemployed (OR 1.29; 95% CI, 1.18-1.40), received prostate gland (vs prostate bed) treatment (OR 1.43; 95% CI, 1.31-1.58), and received concurrent hormone therapy (OR 1.16; 95% CI, 1.04-1.29). Patients age >70 years were less likely to have underascertainment compared with those age <60 years (OR 0.82; 95% CI, 0.73-0.92). This is the first study to show underascertainment of clinically meaningful symptoms in radiation therapy patients in routine clinical care and further to demonstrate that certain patient groups are especially vulnerable to underascertainment. These results highlight the importance of incorporating PROs in the clinical care of radiation therapy patients. If PROs are not routinely used, vulnerable patient groups may need additional attention during cancer treatment to ensure accurate toxicity assessment and management.

Performance evaluation of scoring systems for predicting post-operative hypertension cure in primary aldosteronism.

Hypertension cure following adrenalectomy in unilateral primary aldosteronism is not guaranteed. Its likelihood is associated with pre-operative parameters, which have been variably combined in six different predictive scoring systems. The relative performance of these systems is currently unknown. The objective of this work was to identify the best performing scoring system for predicting hypertension cure following adrenalectomy for primary aldosteronism. Retrospective analysis in a single tertiary referral centre. Eighty-seven adult patients with unilateral primary aldosteronism who had undergone adrenalectomy between 2004 and 2018 for whom complete data sets were available to calculate all scoring systems. Prediction of hypertension cure by each of the six scoring systems. Hypertension cure was achieved in 36/87 (41.4%) patients within the first post-operative year, which fell to 18/71 (25.4%) patients at final follow-up (median 53months, P=.002). Analysis of receiver operating characteristic area under the curves for the different scoring systems identified a difference in performance at early, but not late, follow-up. For all systems, the area under the curve was lower at early compared with late follow-up and compared to performance in the cohorts in which they were originally defined. No single scoring system performed significantly better than all others when applied in our cohort, although two did display particular advantages. It remains to be determined how best such scoring systems can be incorporated into the routine clinical care of patients with PA.

Performance of the UCLA Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 instrument as a clinical decision aid in the routine clinical care of patients with systemic sclerosis

Background and objectivesThe University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA GIT 2.0) is validated to capture gastrointestinal (GI) tract morbidity in patients with systemic sclerosis (SSc). The aims of this study were to determine in a large SSc cohort if the UCLA GIT 2.0 is able to discriminate patients for whom a rheumatologist with experience in SSc would recommend an esophago-gastro-duodenoscopy (EGD), and if it could identify patients with endoscopically proven esophagitis or with any pathologic finding on EGD.MethodsWe selected patients fulfilling the ACR/EULAR 2013 criteria for SSc from our EUSTAR center having completed at least once the UCLA GIT 2.0 questionnaire, and we collected data on gastrointestinal symptoms and EGD from their medical charts. We analyzed by general linear mixed effect models several parameters, including UCLA GIT 2.0, considered as potentially associated with the indication of EGD, as well as with endoscopic esophagitis and any pathologic finding on EGD.ResultsWe identified 346 patients (82.7% female, median age 63 years, median disease duration 10 years, 23% diffuse cutaneous SSc) satisfying the inclusion criteria, who completed UCLA GIT 2.0 questionnaires at 940 visits. EGD was recommended at 169 visits. In multivariable analysis, UCLA GIT 2.0 and some of its subscales (reflux, distention/bloating, social functioning) were associated with the indication of EGD. In 177 EGD performed in 145 patients, neither the total ULCA GIT 2.0 score nor any of its subscales were associated with endoscopic esophagitis, nor with any pathologic EGD findings.ConclusionsIn a real-life setting, the UCLA GIT 2.0 and its reflux subscale were able to discriminate patients with SSc who had an indication for EGD, but did not correlate with findings in EGD. We conclude that, while using the UCLA GIT 2.0 in the routine care of patients with SSc may help the rheumatologist to better understand the burden of GI symptoms in the individual patient, it should not be used as a stand-alone instrument to identify an indication of EGD.

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4.

BackgroundClinical laboratory reference intervals (RIs) are essential for diagnosing and managing patients in routine clinical care as well as establishing eligibility criteria and defining adverse events in clinical trials, but may vary by age, gender, genetics, nutrition and geographic location. It is, therefore, critical to establish region-specific reference values in order to inform clinical decision-making.MethodsWe analyzed data from a prospective observational HIV incidence cohort study in Kombewa, Kenya. Study participants were healthy males and females, aged 18–35 years, without HIV. Median and 95% reference values (2.5th percentile to 97.5th percentile) were calculated for laboratory parameters including hematology, chemistry studies, and CD4 T cell count. Standard Deviation Ratios (SDR) and Bias Ratios (BR) are presented as measures of effect magnitude. Findings were compared with those from the United States and other Kenyan studies.ResultsA total of 299 participants were analyzed with a median age of 24 years (interquartile range: 21–28). Ratio of males to females was 0.9:1. Hemoglobin range (2.5th—97.5th percentiles) was 12.0–17.9 g/dL and 9.5–15.3 g/dL in men and women respectively. In the cohort, MCV range was 59-95fL, WBC 3.7–9.2×103/μL, and platelet 154–401×103/μL. Chemistry values were higher in males; the creatinine RI was 59–103 μmol/L in males vs. 46–76 μmol/L in females (BRUL>.3); and the alanine transferase range was 8.8–45.3 U/L in males vs. 7.5–36.8 U/L in females (SDR>.3). The overall CD4 T cell count RI was 491–1381 cells/μL. Some parameters including hemoglobin, neutrophil, creatinine and ALT varied with that from prior studies in Kenya and the US.ConclusionThis study not only provides clinical reference intervals for a population in Kisumu County but also highlights the variations in comparable settings, accentuating the requirement for region-specific reference values to improve patient care, scientific validity, and quality of clinical trials in Africa.

Effect of applying inclusion and exclusion criteria of phase III clinical trials to multiple sclerosis patients in routine clinical care

Background: Newly approved, drug-modifying therapies are associated with still unknown adverse events, although clinical trials leading to approval have strict inclusion and exclusion criteria and analyse safety and efficacy. Objectives: The aim of this study was to analyse the eligibility of multiple sclerosis (MS) patients treated in routine care into the phase III clinical trial of the respective drug. Methods: In total, 3577 MS patients with 4312 therapies were analysed. Patients with primary-progressive MS were excluded. Inclusion and exclusion criteria of phase III clinical trials in relapsing–remitting MS were adopted and subsequently applied. A comparison in clinical and sociodemographic characteristics was made between patient who met the criteria and those who did not. Results: 83% of registered patients would not have been eligible to the respective phase III clinical trial. Relapse was the single most frequent criterion not fulfilled (74.7%), followed by medication history (21.2%). Conclusion: The majority of MS patients treated in routine care would not have met clinical trials criteria. Thus, the efficacy and safety of therapies in clinical trials can differ from those in the real world. Broader phase III inclusion criteria would increase their eligibility and contribute to a better generalizability of the results in clinical trials.

Prevalence of smooth muscle dysfunction among children with Duchenne muscular dystrophy.

Smooth muscle dysfunction in Duchenne muscular dystrophy (DMD) has been rarely studied. A cross-sectional study was conducted to estimate the prevalence of smooth muscle dysfunction (vascular, upper gastrointestinal, and bladder smooth muscle) in children with DMD using questionnaires (Pediatric Bleeding Questionnaire, Pediatric Gastroesophageal Symptom Questionnaire, and Dysfunctional Voiding Symptom Score). Investigations included bleeding time estimation, nuclear scintigraphy for gastroesophageal reflux, and uroflowmetry for urodynamic abnormalities. Ninety-nine subjects were included in the study. The prevalence of vascular, upper gastrointestinal, and bladder smooth muscle dysfunction was 27.2%. Mean bleeding time was prolonged by 117.5 seconds. The prevalence of gastroesophageal reflux was 21%. Voided volume/estimated bladder capacity over 15% and abnormal flow curves on uroflowmetry were seen in 18.2% and 9.7% of the subjects, respectively. Our study highlights the need for addressing issues related to smooth muscle dysfunction in the routine clinical care of patients with DMD.