Need For Individualized Treatment Research Articles

Correction of Severe Pterygium Colli with a Staged, Double, Posterior and Lateral Approach: A Case Report

AbstractPterygium colli is a rare congenital disorder characterized by excessive skin in the lateral and posterior neck, often associated with genetic syndromes such as Turner's syndrome or Klippel–Feil syndrome. Severe presentations present special challenges for surgeons since its diagnosis is not always evident and its treatment often results in important scaring. Surgical correction of the typical cases mostly involves a lateral approach, but in this “special” case, we used a double, posterior and lateral approach. A 15-month-old girl with prenatal diagnosis of a cystic lesion in the posterior neck presented with massive neck webbing at birth. Genetic studies ruled out chromosomal disorders and RASA 1 mutations. Surgical correction involved a modified posterior approach combined with a lateral approach 1 year later. The cervical tissue redundancy was successfully reduced achieving a good aesthetic outcome with very acceptable scars. At 1 year of follow-up, the patient continues with good neck appearance and mobility. The goal of surgical treatment of pterygium colli is achieving a harmonious neck contour with good function and minimal scarring while minimizing complications and sequelae. No consensus exists on the optimal approach for its correction, emphasizing the need for individualized treatment considering patient-specific characteristics, particularly in the severe cases.

Phenotypes of patients with lupus-associated pulmonary hypertension in the Chinese Han population: a cluster analysis.

Pulmonary hypertension (PH) is a severe complication of systemic lupus erythematosus (SLE). This study investigated the clinical features of patients with SLE-PH in China based on disease manifestations and organ involvement to define precise treatment of SLE and early prevention of complications. In total, 205 SLE-PH patients were included in this study. A cluster analysis was applied according to six clinical and serological variables to define different subgroups of patients. The survival rates of SLE-PH patients and risk factors that influenced prognosis were also compared and a clinical prediction model was developed for the diagnosis of associated lupus nephritis (LN). Patients were clustered in five groups. Patients in cluster 1 had severe renal damage (all patients had LN and had the highest creatinine and urea nitrogen and the lowest eGFR levels). Patients in cluster 2 had mild renal damage (more than half of the patients had associated LN and 87.5% had increased urinary protein levels but presented a lower degree of renal damage than those in the first group. Patients in cluster 3 had low-grade proteinuria (all patients had 24h urinary protein < 0.5g). Patients in cluster 4 had hematuria or urinary tubular damage (26% of patients had associated LN, but none of the patients had proteinuria. In cluster 5, patients barely had any major organ involvement. The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies > 364.64IU/mL and neutrophil-to-leukocyte ratio (NLR) > 5.55. Our findings provide evidence indicating that SLE-PH presents varying clinical phenotypes and the treatment varies accordingly, suggesting the need for individualized treatment. Key Points • Clustered grouping of patients with SLE-PH is associated with renal injury. • This may be because PH and LN share a common pathogenesis. • The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies >364.64 IU/mL and NLR >5.55.

A Case Report on Paradoxical Emboli

Venous Thromboembolism (VTE) is a major public health concern, affecting approximately 900,000 people annually in the United States. In rare cases, a Patent Foramen Ovale (PFO) may allow a venous thrombus to cross into the arterial circulation, causing a paradoxical embolism. This case report presents a 46-year-old male who developed left renal artery stenosis after a paradoxical embolism, likely triggered by a prolonged flight and binge alcohol consumption. The patient was found to have a moderate-sized PFO and renal infarction, confirmed by imaging studies. Despite initial anticoagulation therapy and a planned stenting procedure, intraoperative findings revealed only mild stenosis, leading to cancellation of the stent placement. The patient ultimately underwent PFO closure with an Amplatzer Talisman device. This case underscores the diagnostic challenges in managing paradoxical embolism and the need for individualized treatment, particularly concerning anticoagulation duration, the decision for PFO closure, and post-procedural antithrombotic therapy. Further research is required to establish optimal management strategies for cryptogenic embolic events.

Predictors of improvement in disease activity in childhood and adolescent Crohn’s disease: an analysis of age, localization, initial severity and drug therapy — data from the Saxon Registry for Inflammatory Bowel Disease in Children in Germany (2000–2014)

The escalating worldwide prevalence of Crohn’s disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants.Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn’s disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment.

Exploring the potential of thyroid hormone therapy: Recent advancements and controversies

This article provides an overview of the recent advancements in thyroid hormone therapy for treating hypothyroidism and other thyroid disorders. The traditional thyroid hormone replacement therapy using levothyroxine has been effective, but recent advancements have led to a more individualized approach to treatment. The article discusses the development of new formulations and dosages of thyroid hormone replacement therapy, as well as the exploration of new combination therapies using both levothyroxine and liothyronine. Additionally, recent developments in the guidelines for thyroid hormone replacement therapy have emphasized the need for individualized treatment based on the patient’s specific needs and physiology. The article also highlights recent advancements in thyroid hormone therapy for depression, cardiovascular disease, and non-thyroidal illness syndrome. Overall, the article shows that recent advancements in thyroid hormone therapy have provided clinicians with more options for treating patients with thyroid disorders, improving their lives.

Evaluating adherence to American Diabetes Association standards of care in diabetes and impacts of social determinants of health on patients at two nurse practitioner-owned clinics.

The COVID-19 pandemic created barriers in the management of type 2 diabetes mellitus (T2DM) and worsened social determinants of health (SDOH). A New Hampshire primary care office worked to adhere to T2DM standards of care and began screening for SDOH. This project assessed adherence to quality metrics, hemoglobin A1C, and SDOH screening as telehealth utilization decreased. A1C values have increased at the practice, especially since COVID-19. The practice also began screening for SDOH at every visit, but there was need to assess how needs were being documented and if/how they were addressed. A retrospective chart review of patients with T2DM was performed. Demographic data and T2DM metrics were collected and compared with previous years and compared new versus established patients. Charts were reviewed to evaluate documentation of SDOH and appropriate referral. The practice transitioned from an increased utliization of telehealth back to prioritizing in-office visits. The practice also began routinely screening for SDOH in 2020; however, this process had not been standardized or evaluated. Adherence to nearly all quality metrics improved. Glycemic control improved after a year of nurse practitioner (NP) care, especially in new patients. All patients were screened for SDOH, but documentation varied, and affected patients had higher A1Cs, despite receiving comparable care. Nurse practitioners at this practice are adhering to American Diabetes Association guidelines, and A1C values improve under their care. Social determinants of health continue to act as unique barriers that keep patients from improving glycemic control, highlighting the need for individualized treatment of SDOH in T2DM care.

“Be All That You Can Be”: The Role of Identity, Pro‐Social Labeling, and Narratives in Veterans Treatment Courts*

Veterans Treatment Courts (VTCs) are one of the ever‐developing brands of specialty or problem‐solving courts that have emerged in recent decades. These courts recognize that the criminal behavior stems from a variety of issues, and that punishment should represent a therapeutic jurisprudential approach in its strategies. As such, VTCs treat substance abuse and mental health issues and address criminality in a manner that recognizes a need for individualized treatment and accountability in structure. This research provides an in‐depth institutional ethnography of one Southern California VTC (SC VTC). To understand the powerful transformative tools of identity and narrative, this research utilized over 3 years of non‐participant observation at 117 court sessions in the SC VTC, and 23 in‐depth interviews with both current court participants and graduates and a judge, exploring participants' experiences with and perceptions of the SC VTC. This study demonstrates the utility of identity‐based narratives to navigate legal systems and potentially desist from crime. These mechanisms of narrative and identity provide a powerful illumination of these courts that have ramifications for successful reintegration into society post‐criminal justice interaction.

Anatomical Variations in the Posterior Tibial Slope in the North Indian Population: A Hospital-Based Study.

The measurement of the posterior tibial slope (PTS) angle is crucial for various knee surgeries such as total knee replacement, high tibial osteotomy, and anterior cruciate ligament reconstruction. This hospital-based study aimed to determine the average PTS angle in the knee joints of the North Indian population and provided valuable data to aid knee surgeries in this region. An analysis of 200 plain X-ray films, specifically the true lateral view of both knees in 20-degree flexion, was conducted on participants who exhibited skeletal maturity with no arthritis, tumours, or previous knee surgeries. The PTS measurements were performed manually. The data were analyzed statistically by matching them with variables such as gender, age, laterality, and body mass index (BMI). The study revealed the following findings for the posterior tibial slope in a section of the North Indian population: there was no significant laterality difference (right knee: 12.76±2.35°, left knee: 12.55±2.46°); no notable sexual dimorphism (males: right knee - 12.79±2.65°, left knee - 12.25±2.65°, females: right knee - 12.73±2.11°, left knee - 12.77±2.30°). However, as age advanced, there were significant differences observed (PTS: 14.27±1.28° and 13.84±1.80° in the 18-40 years age group, 11.36±1.76° and 11.31±1.97° in the 41-60 years age group, 10.32±2.82° and 10.56±3.04° in the >60 years age group for the right and left knee, respectively). No significant correlation was found with BMI (PTS: 13.12±3.13° and 12.59±3.14° for BMI <25, 12.88±2.15° and 12.80±2.34° for BMI 25-30, 12.00±2.09° and 11.66±2.99° for BMI >30 in the right and left knee, respectively). The study demonstrated significant variations in the posterior tibial slope based on age, emphasizing the need for individualized treatment in knee surgeries. The research provided valuable insights into normal PTS values specific to the North Indian population, offering regional data to inform knee surgery procedures.

Managing Vulvodynia with Central Sensitization: Challenges and Strategies.

Background: Vulvodynia is defined as a chronic idiopathic vulvar pain condition. This study aimed to investigate the effect of central sensitization on the prognosis of neuromodulator treatment for vulvodynia. Method: A total of 105 patients with vulvodynia who underwent pelvic mapping pain exploration were included and scored according to the Convergence PP Criteria for pelvic pain and central sensitization. The patients were treated according to chronic pelvic pain guidelines, and their response to treatment was evaluated. Results: A total of 35 out 105 patients (33%) with vulvodynia had central sensitization, which was associated with comorbidities, dyspareunia, pain with micturition, and pain with defecation. Dyspareunia and pain with defecation were independent prognostic factors for central sensitization. Patients with central sensitization experienced more pain during intercourse, urination, or defecation, had more comorbidities, and responded worse to treatment. They required more treatment, with a longer response time (over 2 months). Patients with localized vulvodynia were treated with physiotherapy and lidocaine, while patients with generalized vulvodynia were treated with neuromodulators. Amitriptyline was effective in treating patients with generalized spontaneous vulvodynia and dyspareunia. Conclusions: Overall, this study highlights the importance of considering central sensitization in the diagnosis and treatment of vulvodynia and the need for individualized treatment based on the patient's symptoms and underlying mechanisms. Vulvodynia patients with central sensitization had more pain during intercourse, urination, or defecation, and responded worse to treatment, requiring more time and medication.

The clinical feasibility of circulating tumor DNA alterations in patients with advanced hepatocellular carcinoma.

4110 Background: Need for individualized treatment based on tumor attributes is being reinforced with the rapid development of targeted therapies and immune checkpoint inhibitors for hepatocellular carcinoma (HCC). Lack of mandatory tissue biopsy for the diagnosis of HCC, continues to be a challenge for development of precision medicine for HCC compared to other solid tumors. Liquid biopsy enables comprehensive genomic profiling of circulating tumor DNA (ctDNA) shed from tumors into the circulation. This could compensate for the lack of tissue-based analysis in HCC providing a non-invasive and safer option for genomic profiling. This study aims to address the concordance between commercially available ctDNA and tissue genomic profiling in patients with advanced HCC and to assess the feasibility of liquid biopsy in the treatment of patients with HCC. Methods: Patients subjected to tissue-based next-generation sequencing (NGS) before systemic therapy for advanced HCC at CHA Bundang Medical Center from June 2020 to October 2022 and also had sufficient plasma samples available for ctDNA analysis were included. Oncomine Comprehensive Assay (OCA) ThermoFisher was used for tissue-based NGS and Guardant360 for ctDNA based NGS. For the concordance assessment for the same patient, paired samples of ctDNA and tumor tissue, we investigated the common targeted regions across both the panels. Results: Out of hundred thirty patients included in this study, 98% percent of ctDNA samples for these patients were successfully sequenced; ctDNA were detected in 88% of the samples. For the assessment of concordance between intra-patient ctDNA and tumor tissues, we investigated only clinically important (AMP/ASCO/CAP guidelines tier 1 or 2) variants. When we considered the variants detected in tissues as true positive, the concordance between the mutations detected from ctDNA and tissue samples indicated 68.9% sensitivity and 63.1% positive predictive value (PPV). In ctDNA, targetable alterations were detected in 16.9% of samples, such as ARID1A mutations (7.7%), PTEN mutations (6.9%), PIK3CA hotspot mutations (1.5%), RAS mutations (1.5%), and one RET fusion (0.8%). Regarding the concordance between ctDNA and tumor tissue, the sensitivity for mutation was high for RAS mutation (100.0%), PTEN mutations (100.0%), and ARID1A mutations (75.0%) but low for PIK3CA hotspot mutations (0.0%). One RET fusion was identified only in ctDNA. Conclusions: ctDNA-based genotyping demonstrated clinically acceptable concordance with tissue genomic profiling in patients with advanced HCC. Thus, liquid biopsy using ctDNA help address any challenges associated with the limited use of tissue-based genomic profiling in HCC. Investigation of time between blood and tissue collection and the impact it has on concordance is ongoing.

Presenting symptoms as prognostic measures of mental health recovery among service members with concussion.

Comorbid mental illness may negatively impact recovery from concussion. This study evaluated whether the level of symptom clusters at clinic intake contribute to poor mental health recovery in concussed patients during treatment, which may in turn serve as a target intervention. The objective of this study is to examine the association between the level of initial symptoms and mental health symptoms among service members with concussion. Data were obtained from 483 active duty service members treated in interdisciplinary treatment programs for traumatic brain injury, all of which were concussions. Pre-treatment symptom clusters included self-reported hyperarousal, dissociation/depression, cognitive dysfunction/headache and neurological symptoms. The outcomes, clinically-relevant decreases in depressive symptoms (assessed by the 8-item Patient Health Questionnaire, PHQ-8) and PTSD symptoms (assessed by the PTSD Checklist for DSM-5, PCL-5), were defined as a decrease in PHQ-8 > 5 and PCL-5 > 7, respectively. Poisson regression with robust error variance was used to evaluate the relationship between the level of each symptom cluster and clinically-relevant decrease in outcomes. Participants with higher (vs. lower) levels of pre-treatment hyperarousal and dissociation/depression symptom cluster were less likely to improve in depressive and PTSD symptoms during treatment. The level of cognitive/headache and neurological symptom clusters were not significantly associated with any symptom changes. These findings support the need for individualized treatment for symptoms identified and treated after determining concussion history, with particular attention to high levels of hyperarousal and dissociation/depression prior to treatment.

Like a Game of Chess, Every Move Matters: The Role of Antibodies in the Myasthenia Gravis Treatment Landscape.

Symptoms and disease pathophysiology of myasthenia gravis (MG) vary considerably with each patient, and their individual preferences and priorities add to the need for individualized treatment of this autoimmune disease. Research in MG has grown substantially in recent years. New treatments have the potential of being both effective and well tolerated, addressing the trade-off of choosing either efficacy or tolerability when selecting treatments. Promising investigational treatments that may become available in the future may allow more patients than ever before to achieve an asymptomatic state, with the ultimate goal being to turn off abnormal antibody production.

User perspectives on systematic data collection regarding back pain managed in general practice – a qualitative study

BackgroundBack pain is a main driver of disability and the most prevalent reason why people in Demark visit a general practitioner (GP). However, little is known about back pain management in primary care. For new strategies to be sustainable and to accommodate the recommendations for evidence-based practice, patients’ perspectives are paramount to complement clinical expertise and research evidence.This study aimed to identify recommendations for systematic data collection in a nationwide cohort regarding the management of back pain in general practice from the perspectives of GPs and patients.MethodWe applied an adapted exploratory sequential design using focus groups and individual interviews. Seven GPs and ten patients with back pain participated, and four focus groups and seventeen individual interviews were conducted. Data were analyzed using abductive reasoning.ResultsBoth GPs and patients with back pain found that 1) recruitment to a cohort should take place through the GPs, 2) the heterogeneity of patients with back pain and their need for individualized treatment and care should be considered, and 3) data from the cohort should feed into a flowchart or guideline to illustrate a generic patient pathway and visually assist both the patient and GP to obtain an overview and, thus, structure the patient pathway.ConclusionGPs and patients with back pain both considered the nationwide cohort with the overall aim to investigate back pain management as being extremely relevant in relation to improve t the patient pathway. User perspectives should be explored and integrated into health care interventions.

Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia

ABSTRACT Objectives This review aims to see the progress of several clinically-used monoclonal antibodies in treating ALL patients and how they improved patients' outcomes. Methods We searched Web of Science, Elsevier and PubMed for relevant published studies, and summarized eligible evidence on the management of newly-diagnosed and relapsed or refractory ALL with monoclonal antibodies. Ongoing trials were identified from ClinicalTrials.gov. Results Rituximab, an anti-CD20 monoclonal antibody, prolonged patients' complete remission duration and overall survival when combined with hyper-CVAD regimen. Another anti-CD20 monoclonal antibody, Ofatumumab, was reported to have similar benefits. Blinatumomab allows endogenous CD3-positive cytotoxic T cells to target and eliminate CD19-positive blasts. FDA has approved its efficacy in patients with R/R B-ALL and eliminating minimal residual disease (MRD). It serves as a bridge to eradicate MRD before transplantation, and may also be a new choice for patients unable to undergo transplantation. An anti-CD22 monoclonal antibody named Inotuzumab Ozogamicin showed great improvement in patients' outcome, but its toxicity to liver is also worthy of our attention. Conclusion Monoclonal antibodies are proven to be a promising immunotherapeutic strategy to improve ALL patients' outcome in the long term. There's still a need for individualized treatment with effective and well-tolerated medicines. Trial registration: ClinicalTrials.gov identifier: NCT01363128. Trial registration: ClinicalTrials.gov identifier: NCT01466179. Trial registration: ClinicalTrials.gov identifier: NCT02013167. Trial registration: ClinicalTrials.gov identifier: NCT02000427. Trial registration: ClinicalTrials.gov identifier: NCT01564784. Trial registration: ClinicalTrials.gov identifier: NCT03677596. Trial registration: ClinicalTrials.gov identifier: NCT01363297. Trial registration: ClinicalTrials.gov identifier: NCT02981628. Trial registration: ClinicalTrials.gov identifier: NCT03094611. Trial registration: ClinicalTrials.gov identifier: NCT01371630. Trial registration: ClinicalTrials.gov identifier: NCT04224571. Trial registration: ClinicalTrials.gov identifier: NCT02458014. Trial registration: ClinicalTrials.gov identifier: NCT04546399. Trial registration: ClinicalTrials.gov identifier: NCT02879695. Trial registration: ClinicalTrials.gov identifier: NCT03913559. Trial registration: ClinicalTrials.gov identifier: NCT03441061. Trial registration: ClinicalTrials.gov identifier: NCT03739814. Trial registration: ClinicalTrials.gov identifier: NCT02877303. Trial registration: ClinicalTrials.gov identifier: NCT03698552. Trial registration: ClinicalTrials.gov identifier: NCT04601584. Trial registration: ClinicalTrials.gov identifier: NCT04684147. Trial registration: ClinicalTrials.gov identifier: NCT04681105.

Cytochrome P450 3A5 polymorphism affects the metabolism of sorafenib and its toxicity for hepatocellular carcinoma cells in vitro.

Cytochrome P450 3A5 (CYP3A5) is a highly polymorphic gene and the encoded protein variants differ in catalytic activity, leading to inter-individual variation in metabolic ability. The aim of the current study was to investigate the effects of seven allelic variants on the ability of CYP3A5 to metabolize sorafenib in vitro and further explore the impacts of CYP3A5 polymorphism on the proliferation and apoptosis of hepatocellular carcinoma cell line (HepG2) induced by sorafenib. Wild-type and variant CYP3A5 enzymes were expressed in Spodoptera frugiperda insect cells using a baculovirus dual-expression system, and protein expression was checked by western blot. The enzymes were incubated with sorafenib at 37°C for 30 min, and formation of the major metabolite sorafenib N-oxide was assayed using ultra-performance liquid chromatography and tandem mass spectrometry. Intrinsic clearance values (Vmax/Km) were calculated for each enzyme. Additionally, recombinant HepG2 cells transfecting with CYP3A5 variants were used to investigate the effects of sorafenib on the proliferation of HepG2 cells. Intrinsic clearance of the six variants CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 was 26.41-71.04% of the wild-type (CYP3A5*1) value. In contrast, the clearance value of the variant CYP3A5*6 was significantly higher (174.74%). Additionally, the decreased ATP levels and cell viability and the increased cell apoptosis in HepG2 cells transfected with CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 were observed, whereas, the increased ATP levels and cell viability and the reduced cell apoptosis in HepG2 cells transfected with CYP3A5*6 were also investigated when compared to CYP3A5*1. Our results suggest that CYP3A5 polymorphism influences sorafenib metabolism and pharmacotherapeutic effect in hepatic carcinomas. These data may help explain differential response to drug therapy for hepatocellular carcinoma, and they support the need for individualized treatment.

What Recovery Means to Postpartum Women in Treatment for Opioid Use Disorder.

Introduction: Opioid overdose has become a leading cause of pregnancy-associated deaths, particularly in the 1st year postpartum, highlighting the need to better understand how to promote recovery for postpartum women. This mixed-methods study aims to investigate how postpartum women receiving medication for opioid use disorder (MOUD) define recovery and factors associated with recovery progression or inhibition.Methods: Women receiving MOUD 2–6 months postpartum were recruited from an outpatient perinatal addiction clinic. Participants completed electronic measures including the Brief Assessment of Recovery Capital (BARC-10, total score range: 6–60) and semistructured individual interviews. Substance Abuse and Mental Health Services Administration (SAMHSA)'s recovery framework served as the conceptual model for interview guide development. Descriptive statistics were generated for survey responses. A qualitative descriptive approach was used to analyze and report the interview data.Results: On average, participants (n = 8) were 28.6 years old and taking 19.5 mg/day buprenorphine (range 8–24). Fifty percent identified as white and 37.5% as black. All participants identified as currently in recovery, with mean BARC-10 score 52.5 (standard deviation 4.8). Recovery goals included no use of drugs or alcohol (62.5%), being a better partner/spouse (87.5%), and improving finances (87.5%). Interviews generated themes including recovery as transformative, building resilience, and transforming one's health, relationships, and environment through recovery.Conclusions: Participants defined recovery as a dynamic transformative process, including nonabstinence-based goals consistent with SAMHSA domains coupled with reduced substance use. Central to recovery for our postpartum participants was the sense of self reinforced throughout their recovery journey. Women highlighted the key role of MOUD in their recovery process. Findings underscore the need for individualized treatment for postpartum women with opioid use disorder based on their personal goals and will inform development of a validated, gender-informed measure of patient-reported recovery outcomes tailored for this population.

Cytochrome P450 3A5 polymorphism affects the metabolism of sorafenib and its toxicity for hepatocellular carcinoma cells in vitro.

Cytochrome P450 3A5 (CYP3A5) is a highly polymorphic gene and the encoded protein variants differ in catalytic activity, leading to inter-individual variation in metabolic ability. The aim of the current study was to investigate the effects of seven allelic variants on the ability of CYP3A5 to metabolize sorafenib in vitro and further explore the impacts of CYP3A5 polymorphism on the proliferation and apoptosis of hepatocellular carcinoma cell line (HepG2) induced by sorafenib. Wild-type and variant CYP3A5 enzymes were expressed in Spodoptera frugiperda insect cells using a baculovirus dual-expression system, and protein expression was checked by western blot. The enzymes were incubated with sorafenib at 37°C for 30 min, and formation of the major metabolite sorafenib N-oxide was assayed using ultra-performance liquid chromatography and tandem mass spectrometry. Intrinsic clearance values (Vmax/Km) were calculated for each enzyme. Additionally, recombinant HepG2 cells transfecting with CYP3A5 variants were used to investigate the effects of sorafenib on the proliferation of HepG2 cells. Intrinsic clearance of the six variants CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 was 26.41-71.04% of the wild-type (CYP3A5*1) value. In contrast, the clearance value of the variant CYP3A5*6 was significantly higher (174.74%). Additionally, the decreased ATP levels and cell viability and the increased cell apoptosis in HepG2 cells transfected with CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 were observed, whereas, the increased ATP levels and cell viability and the reduced cell apoptosis in HepG2 cells transfected with CYP3A5*6 were also investigated when compared to CYP3A5*1. Our results suggest that CYP3A5 polymorphism influences sorafenib metabolism and pharmacotherapeutic effect in hepatic carcinomas. These data may help explain differential response to drug therapy for hepatocellular carcinoma, and they support the need for individualized treatment.

Assessing Self-reported Recovery in a Community Psychiatry Setting.

This study examined demographic and diagnostic characteristics associated with self-reported recovery in patients with serious mental illness. Patient demographics and diagnoses were obtained from a retrospective review of charts from 981 patients attending a community psychiatry outpatient program between January 2015 and December 2016. All patients completed the Recovery Assessment Scale-Revised (RAS-R), a self-report recovery questionnaire consisting of 5 subscales, approximately every 6 months. Generalized estimating equation models were used to assess change in RAS-R scores over time and to test for associations with demographic characteristics, clinical diagnoses, and appointment adherence. RAS-R scores increased among all demographic and diagnostic groups during the study period. A primary diagnosis of a psychotic disorder (including schizophrenia) was associated with higher 2-year average RAS-R total scores and scores on the Personal Confidence and Hope, Goal and Success Orientation, and Not Dominated by Symptoms subscales. African American race was associated with higher 2-year average scores on the Personal Confidence and Hope subscale. Increasing age was associated with higher total RAS-R scores and multiple subscale scores. No significant associations were found between sex or appointment adherence and RAS-R total scores or any of the subscale scores. While certain demographic and diagnostic groups were associated with higher RAS-R scores, study results suggest that time in treatment is itself associated with higher self-reported recovery among all demographic groups. Age, race, and diagnosis were all associated with higher scores on the Personal Confidence and Hope subscale, highlighting the need for individualized treatment that takes multiple patient characteristics into account.

Key Determinants of Health-Related Quality of Life Among Advanced Lung Cancer Patients: A Qualitative Study in Belgium and Italy.

Background: The lung cancer (LC) treatment landscape has drastically expanded with the arrival of immunotherapy and targeted therapy. This new variety of treatment options, each with its own characteristics, raises uncertainty regarding the key aspects affecting patients’ health-related quality of life (HRQL). The present qualitative study aimed to investigate how LC patients perceive their HRQL and the factors that they consider to be most influential in determining their HRQL. Methods: This qualitative research incorporates four focus group discussions, with six LC patients in each group. In total, 24 stage III and IV LC patients were included in the discussions, with Italian (n = 12) and Belgian (n = 12) patients, age range: 42–78, median age = 62 (IQR = 9.3 years), SD = 8.5; 62% men. Using thematic analysis, transcripts and notes from the FGDs were analyzed using NVivo software (edition 12). Results: Three main themes capturing determinants of HRQL were identified. First, patients agreed on the importance of physical aspects (symptoms and side-effects) in determining their HRQL. In particular, skin conditions, nausea, fatigue, risk of infections, sensory abnormalities, pain, and changes in physical appearance were highlighted. Second, patients worried about psychological aspects, negatively impacting their wellbeing such as uncertainties regarding their future health state, and a lower degree of autonomy and independence. Third, patients underlined the importance of social aspects, such as communication with healthcare providers and social interaction with friends, family and peers. Conclusion: This study demonstrates that physical, psychological, and social aspects are key factors driving LC patients’ HRQL. Gaining a better understanding of how LC patients perceive their HRQL and how it is affected by their illness and therapy will aid patient-centric decision-making across the drug life cycle, by providing stakeholders (drug developers, regulators, reimbursement bodies, and clinicians) insights about the treatment and disease aspects of importance to LC patients as well as the unmet needs LC patients may have regarding available treatment modalities. Finally, this study underscores a need for individual treatment decision-making that is considerate of uncertainties among LC patients about their future health state, and ways for improving communication between healthcare providers and patients to do so.

SY1.7. Rewiring pain through non-invasive brain stimulation

Chronic pain occurs when pain in an injured tissue persists beyond the normal recovery time. This crippling condition causes significant burden to the individual and to society. Despite years of research, treatments for chronic pain are largely ineffective, which may in part be due to a lack of understanding of the mechanisms that underpin chronic pain. There is increasing evidence that chronic musculoskeletal pain is associated with sensorimotor dysfunction, and that targeting the mechanisms associated with this dysfunction using non-invasive brain stimulation may alleviate symptoms of pain. This presentation will highlight studies investigating the manifestation of sensorimotor neuroplasticity in a range of musculoskeletal pain conditions such as low back pain, persistent elbow pain and persistent patellofemoral pain. These studies have used transcranial magnetic stimulation and electromyography methodologies and have shown that the organisation of the sensorimotor cortical representation of the pain afflicted muscle is altered. Novel treatment studies will then be reviewed. These studies have attempted to “rewire” pain by targeting sensorimotor cortical organisation using ‘top-down’ (non-invasive brain stimulation) and “bottom-up” approaches (trans-spinal stimulation, peripheral electrical stimulation and exercise). The potential limitations of these approaches will then be discussed including the large variation in responsiveness to treatment, and the need for individualized treatment. Indeed, our work using transitional pain models in healthy human subjects has shown that inter-individual differences in sensorimotor function in a pain free state and during persistent pain, can predict the severity of pain. It will be argued that tailoring treatment in accordance with an individual’s sensorimotor function in the early stages of pain may facilitate the diagnosis, prevention and treatment of pain. A planned project will be presented which will focus on modulating pain in accordance with these individual differences using non-invasive brain stimulation.