Treatment Pathways For Patients Research Articles

Utilisation of disease modifying treatment and diversity of treatment pathways in relapsing remitting multiple sclerosis

BackgroundThere is minimal information on the utilisation of Disease Modifying Treatment (DMTs) for multiple sclerosis. The appropriate and safe use of medicines is informed by utilisation studies. Outcomes can inform health interventions to improve appropriate use of medicines and post marketing surveillance activities to improve safety. ObjectiveTo evaluate utilisation and treatment patterns of disease modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS). MethodsA representative sample of the Australian pharmaceutical benefits scheme data were analysed (2006–2016). Demographics of incident users and trends in incident and prevalent users were determined. Individual patient treatment pathways were determined by sequential initiation of medicines in two different periods (2006–2013 and 2014–2019). ResultsThere were 20,660 patients with at least one dispensing of a DMT for RRMS during the study period (median age 41 years, 75% female). Incident and prevalent use increased by 20% and 88%, respectively. The market was responsive to 13 new listings of DMTs over the study period. Sequential treatment was found for 66% of initiators in 2006–2013 and 28.5% of initiators in 2014–2019. Diverse treatment pathways were found, with 278 and 93 unique sequences in 2006–2013 and 2014–2019, respectively. ConclusionThe availability of new DMTs has influenced both initial treatment choice and prevalence of users. Individualised treatment patterns and exposure to multiple medicines over time will challenge traditional pharmacovigilance systems.

Real-World Study of the Treatment Patterns of Patients Diagnosed with Therapy-Related AML or AML-MRC in England between 2013 and 2020 Using the Cancer Analysis System Database

Introduction: Patients with therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) are a known high-risk AML subgroup with historically poor outcomes. In December 2018, CPX-351 (Vyxeos ® Liposomal) received a positive reimbursement decision in England for the treatment of adults with newly diagnosed t-AML or AML-MRC. The objective of this retrospective study was to utilize the Cancer Analysis System (CAS) database available through the National Cancer Registration and Analysis Service (NCRAS) to describe the demographics, clinical characteristics, and treatment pathways for patients with t-AML or AML-MRC in England from 2013 to 2020, including the use of CPX-351.Methods: The NCRAS systematically collects and curates population-level data about cancer diagnoses, treatments, and outcomes across England. Adults (aged ≥18 years) diagnosed with t-AML or AML-MRC between January 2013 and March 2020 were identified either directly using International Classification of Diseases for Oncology, Third Edition(ICD-O-3) codes or indirectly using non-specific ICD-O-2, ICD-O-3, or ICD-10 AML codes in combination with a record of prior systemic anticancer therapy or radiotherapy (t-AML) or a prior diagnosis of MDS or CMML (AML-MRC; other AML-MRC subtypes could not be distinguished from de novo AML). First-line and second-line treatments identified included clinical trials, intensive chemotherapy (IC) treatments (CPX-351; daunorubicin plus cytarabine [DA]; fludarabine, cytarabine, idarubicin and granulocyte-colony stimulating factor [FLAG-Ida]; or “other IC” consisting of mitoxantrone-based therapy or high-dose cytarabine alone), or less-intensive therapies (azacitidine, low-dose cytarabine [LDAC], or hydroxycarbamide alone). Patients who did not receive active systemic therapy (ie, those who received best supportive care alone) were not included.Results: A total of 2,891 patients with t-AML or AML-MRC were identified. Most patients were male (62%), white (91%), and aged ≥60 years (80%). Overall, 590 (20%) patients received first-line treatment in a clinical trial, 1,474 (51%) received less-intensive therapy, and 827 (29%) received an IC regimen. Patients aged ≥60 years at diagnosis were less likely than those aged <60 years to either enter a clinical trial (18% vs 32%, respectively) or receive IC (22% vs 54%). In patients treated with IC, those who received CPX-351 were slightly older (mean [standard deviation] age: 63.9 years [8.3]) than those who received DA (60.5 years [11.4]) or FLAG-Ida (55.6 years [12.6]); 28% of patients treated with CPX-351 were aged <60 years compared to 37% for DA and 55% for FLAG-Ida.When treatment patterns were analyzed per annum, utilization of less-intensive therapies remained stable over time (Figure 1A). Azacitidine was the most common less-intensive therapy both overall (64%) and across all yearly time points, followed overall by LDAC (22%) then hydroxycarbamide alone (14%). In contrast, the IC treatment patterns were more dynamic over time (Figure 1B). DA chemotherapy was the most common IC overall (48%), followed by FLAG-Ida (23%) and other ICs (18%). However, CPX-351 uptake started in 2018 (5% of all IC) and by the end of 2019 had displaced DA chemotherapy as standard-of-care IC (40% vs 22%, respectively). Excluding patients who were alive but had not received subsequent therapy (ie, censored), most patients who received front-line azacitidine or LDAC died without receiving salvage therapy (89% and 92%, respectively). In comparison, non-censored patients who received front-line DA chemotherapy or FLAG-Ida were more likely to receive salvage treatment (52% and 34%, respectively). Key salvage treatments following DA included azacitidine alone and FLAG-based therapy. Key salvage treatments following front-line CPX-351 included FLAG-Ida or DA ± hematopoietic cell transplant and azacitidine.Conclusions: This large population-level, retrospective analysis of CAS data provides a detailed overview of the management of patients with t-AML and AML-MRC. Historically, a high proportion of these high-risk patients have received less-intensive treatment. Since 2018, CPX-351 has been rapidly adopted into the IC treatment pathway, displacing DA chemotherapy. These analyses will be repeated after the CAS database has been updated to determine the impact of COVID-19. [Display omitted] DisclosuresLegg: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Muzwidzwa: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Adamson: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Wilkes: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Medalla: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.

Finding common (research) ground between general practitioners and neuroscientists: the vital role of knowledge circulation in closing the evidence-to-practice gap

BackgroundIt may take 15 years or longer before research evidence is integrated into clinical practice. This evidence-to-practice gap has deleterious effects on patients as well as research and clinical processes. Bringing clinical knowledge into the research process, however, has the potential to close the evidence-to-practice gap. The NEUROTRANS-Project attempts to bring research and practice together by focusing on two groups that usually operate separately in their communities: general practitioners and neuroscientists. Although both groups focus on dementia as an area of work, they do so in different contexts and without opportunities to share their expertise. Finding new treatment pathways for patients with dementia will require an equal knowledge exchange among researchers and clinicians along with the integration of that knowledge into research processes, so that both groups will benefit from the expertise of the other.MethodsThe NEUROTRANS-Project uses a qualitative, multi-stage research design to explore how neuroscientists and general practitioners (GPs) approach dementia. Using a grounded theory methodology, it analyzes semi-structured interviews, case vignettes, focus groups with GPs in Saxony-Anhalt, Germany, and informal conversations with, and observations of, neuroscientists from the German Center for Neurodegenerative Diseases in Magdeburg.ResultsThe NEUROTRANS-Project identified a clear division of labor between two highly specialized professional groups. Neuroscientists focus abstractly on nosology whereas general practitioners tend to patient care following a hermeneutic approach integrating the patients’ perspective of illness. These different approaches to dementia create a barrier to constructive dialogue and the capacity of these groups to do research together with a common aim. Additionally, the broader system of research funding and health care within which the two groups operate reinforces their divide thereby limiting joint research capacity.ConclusionsOvercoming barriers to research collaboration between general practitioners and neuroscientists requires a shift in perspective in which both groups actively engage with the other’s viewpoints to facilitate knowledge circulation (KC). Bringing ‘art into science and science into art’, i.e. amalgamating the hermeneutic approach with the perspective of nosology, is the first step in developing joint research agendas that have the potential to close the evidence-to-practice gap.

Rate of malignancy for thyroid nodules with AUS/FLUS cytopathology in a tertiary care center \u2013 a retrospective cohort study

BackgroundThyroid nodules are stratified through fine-needle aspiration (FNA) and are often categorized using The Bethesda System for Reporting Thyroid Cytopathology, which estimates the risk of malignancy for six cytopathological categories. The atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS) categories have varying malignancy rates reported in the literature which can range from 6 to 72.9%. Due to this heterogeneity, we assessed the malignancy rate and effectiveness of repeat FNA (rFNA) for AUS/FLUS thyroid cytopathology at our institution.MethodsElectronic health records of patients with AUS/FLUS thyroid cytopathology on FNA at our center since the implementation of the Bethesda System on May 1, 2014–December 31, 2019 were retrospectively reviewed. Patient demographics, treatment pathway, and pathology results were collected. The treatment pathway of the nodules, the rFNA results, and the malignant histopathology results were reported. Malignancy rates were calculated as an upper and lower limit estimate.ResultsThis study described 182 AUS/FLUS thyroid nodules from 177 patients. In total, 24 thyroid nodules were deemed malignant upon histopathology, yielding a final malignancy rate of 13.2–25.3%. All of the malignancies were variants of papillary thyroid carcinoma. The malignancy rate of the nodules which underwent resection without rFNA (21.5%) was lower than the malignancy rate of the nodules which underwent resection after rFNA (43.8%). 45.5% of the rFNA results were re-classified into more definitive categories.ConclusionThe malignancy rate of AUS/FLUS thyroid cytopathology at our center is in line with the risk of malignancy stated by the 2017 Bethesda System. However, our malignancy rate is lower than some other Canadian centers and approximately half of our rFNAs were re-classified, highlighting the importance of establishing center-specific malignancy and rFNA re-classification rates to guide treatment decisions.

OAB-016: Treatment pathways for patients with multiple myeloma: a real-life study based on the French National Claim database from 2014 to 2019

<h3>Background</h3> Multiple Myeloma (MM) disease course is a succession of remissions and relapses, which define lines of treatment. For each line, several regimens can be used. This study provides a comprehensive overview of the evolution through treatment lines of MM patients, based on the nationwide French National Health Insurance (NHI) databases, called SNDS ("Système National des Données de Santé"). These databases include hospital records, primary and secondary care, and death records of 66 million people. <h3>Methods</h3> This is a retrospective observational cohort study including all cases of multiple myeloma from 2014 to 2019 identified through the French NHI databases (SNDS). Cases were detected using a validated algorithm which was expanded to consider recent evolution of MM therapeutic management. Incident patients of 2014 and 2015 were extracted and followed up until December 31st, 2019. Treatment lines were reconstructed from 2014 to 2019 through ATLAS, an artificial intelligence algorithm adapted from the Smith-Waterman alignment sequence. Time To Next Treatment (TTNT) for each line has been estimated with a Kaplan Meier method. <h3>Results</h3> 40,747 prevalent treated patients with MM were identified in the SNDS from 2014 to 2019. This analysis involved more specifically 7,118 of these patients, including 3,557 incident patients from 2014 and 3,561 from 2015. Patients were followed until December 31st, 2019, or death. For the frontline treatment, 76% [N=5,409] had a frontline without transplant (L1 NTE) and 24% [N=1,709] had a frontline with transplant (L1 TE). Among patients with L1 NTE (resp. TE), 15% [N=827] (resp. 33% [N=560]) stayed in frontline until the end of the follow-up, 31% [N=1,682] (resp. 4% [N=71]) died after their frontline, and 54% [N=2,900] (resp. 63% [N=1,078]) switched to L2. Among patients with a L1 NTE (resp. TE) and a L2, 26% [N=764] (resp. 35% [N=378]) stayed in L2 until the end of the follow-up, 29% [N=841] (resp. 12% [N=124]) died after their L2, and 45% [N=1,295] (resp. 53% [N=576]) switched to L3. Among patients with a L1 NTE (resp. TE) and a L3, 24% [N=316] (resp. 28% [N=159]) stayed in L3 until the end of the follow-up, 28% [N=367] (resp. 19% [N=111]) died after their L3, and 47% [N=612] (resp. 53% [N=306]) switched to L4. The median TTNT for L1 NTE (resp. TE) was 2.4 (resp. 3.3) years. The overall survival rate at 5 years for patients with a L1 NTE (resp. TE) was 41% (resp. 75%). Regarding treatment sequencing, the main course of patients was as follows: frontline: V-based regimen (VMP for NTE, VTd for TE); L2: Rd; L3: Pom-dex; L4: Dara mono. <h3>Conclusions</h3> This study shows the flow of patients from frontline to L4+ and their survival rates. The study also showed that real-world data are a powerful tool to study treatment lines at a national scale and lead the way to more precise analyses of optimal therapeutic sequences, including their impact on the overall survival.

A Fully Remote Diagnostic and Treatment Pathway in Patients with Obstructive Sleep Apnoea during the COVID-19 Pandemic: A Single Centre Experience.

The COVID-19 pandemic led to significant delays in the diagnostic and management pathway of patients with obstructive sleep apnoea (OSA). During the first wave of COVID-19, our department adopted a fully remote diagnostic (home cardiorespiratory polygraphy) and treatment (autoset continuous positive airway pressure, CPAP) approach. As a novel mode of service delivery, our aim was to evaluate our pathway and analyse factors associated with adherence to CPAP. We analysed the first 300 patients (51 ± 13 years, 48% men) who were set up on remote CPAP between 20 May 2020 and 11 September 2020. The associations between CPAP usage at 90 days and age, gender, body mass index, disease severity, Epworth Sleepiness Scale and comorbidities were investigated with linear and logistic regression analyses. A total of 124 patients (41.3%) were fully-adherent to CPAP therapy, defined as CPAP usage ≥ 4 h on ≥ 70% of the days. Only driving status was associated with adherence to CPAP. Patients who were adherent at 28 days were more likely to stay adherent at 90 days (3.77 odd ratio /3.10–4.45/ 95% confidence interval). We have shown that a fully remote diagnostic and treatment pathway for patients with OSA can be successfully delivered, and our preliminary outcomes of adherence to CPAP are comparable with published data.

Expression of ITG β-1, MMP9 and Vimentin in Oral Squamous Cell Carcinoma – A Real Time PCR Based Approach

Background: Oral Squamous Cell Carcinoma (OSCC) is the most common malignancies which accounts for 90% of oral cancer worldwide. The 5 year survival rate of OSCC is not more than 60% due to tumor metastasis and subsequent recurrence.&#x0D; Aim: To compare the gene expression of ITG β-1, MMP9 and Vimentin in OSCC tissue samples and normal tissue samples and to correlate the expression levels of these molecules with the pathological grading and survival in OSCC patients. This would facilitate the understanding of EMT in OSCC progression thereby targeting this pathway for treatment of OSCC patients in near future.&#x0D; Materials and Methods: 10 OSCC samples as well as normal healthy samples were collected and RNA isolation was done using TRIR kit, and then subjected to cDNA synthesis using ITG β-1, MMP9 and Vimentin primers. Real time PCR was performed using gene specific primers at 40 cycles. The results were retrieved, tabulated and analyzed.&#x0D; Results: The current research results revealed that there were up regulation of mRNA expression in ITG β-1, MMP9 and Vimentin in OSCC patients than in healthy individuals. On comparison, MMP9 showed highest mRNA expression levels than ITG β-1 and Vimentin&#x0D; Conclusion: Over expression of ITG B-1, MMP9, Vimentin plays a crucial role in progression of oral cancer and targeting EMT molecules could be an effective targeted approach for OSCC.

Antineutrophil cytoplasmic antibody (ANCA) vasculitis: pathophysiology, diagnosis, and the evolving treatment landscape.

The antineutrophil cytoplasmic antibody (ANCA) vasculitides include several closely related, often severe, multisystem autoimmune diseases characterized by antibodies against serine proteinase 3 (PR3) or myeloperoxidase. Loss of tolerance to these antigens triggers a cascade of events, beginning with the priming of neutrophils by proinflammatory cytokines and complement activation, translocation of ANCA-specific antigens to the plasma membrane, neutrophil hyperactivation, and further activation of the alternative complement pathway, leading to tissue damage and the clinical manifestations of ANCA vasculitis. Due to the heterogeneity in presentation of these diseases, diagnosis is often substantially delayed, leading to poor outcomes. The current treatment pathway for most patients involves induction with cyclophosphamide or rituximab in combination with glucocorticoids, followed by a maintenance phase with rituximab, azathioprine, or methotrexate, during which time glucocorticoids are tapered. Current therapies are often effective in inducing and maintaining remission but are associated with a range of toxicities. Several new therapies are in development for ANCA vasculitis. Avacopan, an orally administered inhibitor of the complement fragment 5a (C5a) receptor, has been assessed in a phase 3 clinical trial and may play a role in reducing the cumulative glucocorticoid dose. Preliminary data suggest that cluster of differentiation (CD) 80 and CD86 blockade with abatacept may also have a role in the management of ANCA vasculitis. There is an unmet need for additional therapeutic options for patients with these diseases.

A single-centre ten-year retrospective cohort study of malignant small bowel obstruction.

Management of malignant small bowel obstruction (mSBO) is challenging. The decision to perform an operation evaluates the perceived chance of success against a patient's fitness for operation. The aim of this study was to characterise the mSBO patient population in a tertiary UK centre and assess the patient's treatment pathway including use and effects of palliative surgery, total parenteral nutrition (TPN), Gastrografin and dexamethasone as well as preoperative stratification. Patients were included if they had mSBO confirmed on computed tomography imaging due to a primary or metastatic neoplasm. Data were collected on pathway and management, and Cox proportional hazard methods were utilised to observe effects on survival. Ninety-four patients were included, with 104 inpatient episodes. Mean age was 67.4 (SD 13.7), with 57 (60.6%) females. Most (89.4%) had only one admission for mSBO. Eighty-four (89.4%) patients died over the ten-year period, 18 (17.3%) within 30 days of admission. Fifty patients (53.1%) underwent operative management: 70% bypass, 24% stoma formation and 6% open-close laparotomies. Log rank testing of survival probability analysis was significant (p = 0.00018), with 50% survival probability at 107.32 days for operative management and 47.87 days for non-operative. Operative management forms part of the treatment pathway for a significant proportion of patients with mSBO, offering a survival benefit, though quality of survival is not known. Case selection is good, with few open-close laparotomies. Trials of non-operative interventions such as Gastrografin and dexamethasone are not utilised fully.

Artificial Intelligence: Guidance for clinical imaging and therapeutic radiography professionals, a summary by the Society of Radiographers AI working group

IntroductionArtificial intelligence (AI) has started to be increasingly adopted in medical imaging and radiotherapy clinical practice, however research, education and partnerships have not really caught up yet to facilitate a safe and effective transition. The aim of the document is to provide baseline guidance for radiographers working in the field of AI in education, research, clinical practice and stakeholder partnerships. The guideline is intended for use by the multi-professional clinical imaging and radiotherapy teams, including all staff, volunteers, students and learners. MethodsThe format mirrored similar publications from other SCoR working groups in the past. The recommendations have been subject to a rapid period of peer, professional and patient assessment and review. Feedback was sought from a range of SoR members and advisory groups, as well as from the SoR director of professional policy, as well as from external experts. Amendments were then made in line with feedback received and a final consensus was reached. ResultsAI is an innovative tool radiographers will need to engage with to ensure a safe and efficient clinical service in imaging and radiotherapy. Educational provisions will need to be proportionately adjusted by Higher Education Institutions (HEIs) to offer the necessary knowledge, skills and competences for diagnostic and therapeutic radiographers, to enable them to navigate a future where AI will be central to patient diagnosis and treatment pathways. Radiography-led research in AI should address key clinical challenges and enable radiographers co-design, implement and validate AI solutions. Partnerships are key in ensuring the contribution of radiographers is integrated into healthcare AI ecosystems for the benefit of the patients and service users. ConclusionRadiography is starting to work towards a future with AI-enabled healthcare. This guidance offers some recommendations for different areas of radiography practice. There is a need to update our educational curricula, rethink our research priorities, forge new strong clinical-academic-industry partnerships to optimise clinical practice.Specific recommendations in relation to clinical practice, education, research and the forging of partnerships with key stakeholders are discussed, with potential impact on policy and practice in all these domains. These recommendations aim to serve as baseline guidance for UK radiographers. Implications for practiceThis review offers the most up-to-date recommendations for clinical practitioners, researchers, academics and service users of clinical imaging and therapeutic radiography services. Radiography practice, education and research must gradually adjust to AI-enabled healthcare systems to ensure gains of AI technologies are maximised and challenges and risks are minimised. This guidance will need to be updated regularly given the fast-changing pace of AI development and innovation.

Clinical nutrition as part of the treatment pathway of pancreatic cancer patients: an expert consensus

PurposeMalnutrition is a common problem among pancreatic cancer (PC) patients that negatively impacts on their quality of life (QoL) and clinical outcomes. The main objective of this consensus is to address the role of Medical Nutrition Therapy (MNT) into the comprehensive therapeutic management of PC patients.MethodsA Spanish multidisciplinary group of specialists from the areas of Medical Oncology; Radiation Oncology; Endocrinology and Nutrition; and General Surgery agreed to assess the role of MNT as part of the best therapeutic management of PC patients.ResultsThe panel established different recommendations focused on nutritional screening and nutritional screening tools, MNT strategies according to PC status, and MNT in palliative treatment.ConclusionsThere is an unmet need to integrate nutritional therapy as a crucial part of the multimodal care process in PC patients. Health authorities, health care professionals, cancer patients, and their families should be aware of the relevance of nutritional status and MNT on clinical outcomes and QoL of PC patients.

A Multidisciplinary Approach to Rectal Cancer Treatment in Ulcerative Colitis Results in High Rate of Restorative Minimally Invasive Surgery.

Few recent studies focus on the treatment of rectal cancer in patients with ulcerative colitis. We report treatment options and results for this subset of patients with a multimodal approach at two European referral centres. Ulcerative colitis patients diagnosed with rectal cancer arising at less than 15 cm from the anal verge between January 2010 and December 2020 were analysed. Demographics, clinical data, and details of medical and surgical treatment were retrieved from prospectively collected institutional databases. Of 132 patients with ulcerative colitis and concomitant colorectal cancer, rectal cancer was diagnosed in 46. The median time between disease onset and rectal cancer diagnosis was 17.5 years; 21/46 were preoperatively staged as early tumours [cT1-T2/N0]. Eleven patients received neoadjuvant chemoradiotherapy for locally advanced extraperitoneal adenocarcinoma, and the rest underwent surgery first. Over two-thirds of the procedures were restorative [68%]; a minimally invasive approach was used in 96% of patients, with no conversion to open. The median follow-up was 44 months. Local recurrence occurred in three patients [6%]. The cumulative 3-year cancer-specific survival rate was 94% [and the 3-year disease-free rate was 86%]. Rectal cancer in ulcerative colitis is a very complex condition. Our results show that surgery for rectal cancer can be delivered with excellent oncological and functional outcomes in patients with ulcerative colitis. A multidisciplinary discussion among surgeons, gastroenterologists, and medical oncologists is key to ensure the appropriate treatment pathway for individual patients.

CHRONIC PAIN AND DEPRESSION – ARBITRARINESS OR CONSECUTION OF THE PATIENT'S DIAGNOSTIC AND TREATMENT ROUTE

Unrecognized depression among patients with chronic pain is a common medical problem, highlighting the need for targeted search and identification of depression-related symptoms. Purpose: The aim of the present study is to investigate the trends in the diagnostic and treatment pathway of comorbid patients with depression and chronic pain. Materials and Methods: 110 psychiatrists and 119 neurologists were interviewed through an anonymous, randomized survey in Bulgaria. Results: Referrals of the patients with chronic pain to neurologists and psychiatrists are not routine practice. The general practitioners are the main group, referring the patients with chronic pain to a consultation with a neurologist (89.10%) and a psychiatrist (68.20%). The patients themselves seek help more often from a neurologist (77.20%) than from a psychiatrist (44.50%). The most common reason for neurologists to consult their patients with a psychiatrist issuicidal ideation and intentions (50.42%) and the least common –insomnia (15.96%). According to psychiatrists, chronic pain patients seek help from them for other symptoms like somatic – vegetative ones (97.8%), anxiety (78.20%), insomnia (55.50%) and depressed mood (54.50%). More than 1/4 (29%) of them have had suicidal thoughts and intentions, which suggests a long history of depressive symptoms. Conclusions: The diagnostic and treatment processes of patients with chronic pain and depression are performed randomly rather than following a certain logical sequence. The creation of an algorithm for general practitioners and pain specialists aimed at early detection of symptoms of depression and related predictors of suicidal behavior is needed.

Patient treatment pathways of multidrug-resistant tuberculosis cases in coastal South India: Road to a drug resistant tuberculosis center

Background: Delays in initiating multidrug-resistant tuberculosis (MDR TB) treatment adds risk to individual patients and the community due to disease progression, and on-going transmission. The Government of India offers free TB diagnosis and treatment, however many presumptive MDR TB patients wander within the Indian healthcare system and delay accessing the programme. To improve access to care, it is imperative to understand the treatment pathways taken by MDR TB patients. We aimed to describe the diagnostic and treatment pathway taken by presumptive MDR TB patients registered under Programmatic Management of Drug-resistant TB Program. Methods: We conducted a cross-sectional study amongst patients registered during August 2016 – April 2017 at one District Drug Resistance Tuberculosis centre of Dakshina Kannada district in Karnataka, India. A semi-structured questionnaire was used to collect the number, type (private and public sector), and dates of healthcare facilities (HCFs) visits prior to the initiation of MDR TB treatment. Delays in pathway were measured in days and summarised as median and interquartile range (IQR), from the date of onset of illness until the initiation of MDR TB treatment. Results: We found that patients preferred private HCFs; however, due to lack of treatment and unaffordability they shifted to public HCFs. Median delay to register under the program was more in private HCFs (180 days) in comparison with public HCFs (120 days). We also found that the detection rates were much higher in public HCFs (80%). Conclusion: The present study found that there was substantial patient delay and total delay in diagnosis and treatment of MDR TB patients. Private HCF was first point of contact for most of the patients; however those visited public HCF diagnosed earlier as compared to others. The government should involve private HCFs to provide standard diagnostics and treatment to the patients seeking a private facility.

Antimicrobial Stewardship-Driven Monoclonal Antibody Treatment Program for COVID-19 Patients in the Bronx, New York

Background: In November 2020, bamlanivimab received emergency use authorization (EUA) to treat patients with early, mild-to-moderate COVID-19 who are at high risk of progression. Montefiore Medical Center serves an economically underserved community of &gt;1.4 million residents in the Bronx, New York. Montefiore’s antimicrobial stewardship team (AST) developed a multidisciplinary treatment pathway for patients meeting EUA criteria: (1) outpatients and hospital associates and (2) acute-care patients (EDs or inpatient). Methods: The Montefiore AST established a centralized process for screening high-risk COVID-19 patients 7 days a week. Referrals were sent by e-mail from occupational health, primary care practices, specialty practices, emergency departments, and urgent care centers. Patients were screened in real time and were treated in the ED or a newly established infusion center within 24 hours. After infusion, all patients received phone calls from nurses and had an infectious diseases televisit. Demographics, clinical symptoms, subsequent ED visit or hospital admission, and timing from infusion to ED or hospitalization were obtained from the electronic health record. Results: In total, 281 high-risk patients (median age, 62 years; 57% female) received bamlanivimab at the infusion center or in the acute-care setting between December 2, 2020, and January 27, 2021 (Table 1). The number of treated patients increased weekly (Figure 1). Also, 62% were Hispanic or black, and 96% met EUA criteria. Furthermore, 51 (18%) were referred from occupational health, 205 (73%) were referred from the community, and 25 (9%) were inpatients (https://www.fda.gov/media/143605/download). All patients were successfully infused without adverse reactions. In addition, 23 patients (8.2%) were hospitalized and 6 (2.1%) visited EDs within 30 days of treatment. The average number of days between symptom onset and infusion was 4.9. The median age of admitted versus nonadmitted patients was 68 years versus 61.5 years (P = .07). Conclusions: An AST-coordinated bamlanivimab treatment program successfully treated multiple high-risk COVID-19 patients and potentially reduced hospitalizations. However, the effort, personnel, and resources required are significant. Dedicated hospital investment is necessary for maximal success.Funding: NoDisclosures: None

Hepatitis B Virus Induces Microtubule Stabilization to Promote Productive Infection through Upregulating Microtubule-associated Protein 1S.

Background and AimsContinuous release and transmission of hepatitis B virus (HBV) is one of the main factors leading to chronic hepatitis B (CHB) infection. However, the mechanism of HBV-host interaction for optimal viral transport is unclear. Hence, we aimed to explore how HBV manipulates microtubule-associated protein 1S (MAP1S) and microtubule (MT) to facilitate its transport and release.MethodsThe expression of MAP1S or acetylated MT was investigated by immunofluorescence, RT-PCR, immunoblotting, and plasmid transfection. MAP1S overexpression or knockdown was performed by lentiviral infection or sh-RNA transfection, respectively. HBV DNA was quantified using q-PCR.ResultsSignificantly higher level of MAP1S in HepG2215 cells compared with HepG2 cells was detected using RT-PCR (p<0.01) and immunoblotting (p<0.001). Notably, stronger MAP1S expression was observed in the liver tissues of patients with CHB than in healthy controls. MAP1S overexpression or knockdown demonstrated that MAP1S promoted MT acetylation and reduced the ratio of HBV DNA copies inside to outside cells. Further, transfection with the hepatitis B virus X protein (HBx)-expressing plasmids induced significantly higher level of MAP1S than that in controls (p<0.0001), whereas HBVX− mutant-encoding HBV proteins (surface antigen, core protein, and viral DNA polymerase) hardly affected its expression.ConclusionsThese results demonstrate that HBx induces the formation of stable MTs to promote the release of HBV particles through upregulating MAP1S. Thus, our studies delineate a unique molecular pathway through which HBV manipulates the cytoskeleton to facilitate its own transportation, and indicate the possibility of targeting MAP1S pathway for treatment of patients with CHB.

Patient Goal-directed Care in an Orthopaedic Spine Specialty Clinic.

Using health-related goals to direct care could improve quality and reduce cost of medical care; however, the effect of these goals for patients with spinal pathologies is not well understood. The purpose of this study was to describe patient-reported goals by provider type and to evaluate the effect of patient-provider goal awareness on patient satisfaction and treatment pathway. A pilot program was instituted in which all new or existing patients scheduled with either a single spine surgeon or a nonsurgical spine nurse practitioner were asked to complete a paper survey instrument regarding their goals of care before their visit. The patient goals were then discussed between the provider and the patient. Univariate and multivariate analyses were performed to evaluate relationships between patient goals, provider seen, diagnosis, and treatment recommendations. There were 703 respondents to the survey, of whom 416 were included for subgroup analysis. Patient-reported goals varied by provider type. When examining rates of recommended interventions by patient goals, notable differences were observed for 7 of the 13 goal categories. Significant differences in intervention recommendations by provider type existed for physical therapy, medications, MRI, and surgery (all P < 0.001). After controlling for other variables, seeing a surgeon, thoracolumbar pathology, and goals of "return to activity or social events I enjoy," and "learn about spine surgery" were significant independent predictors of recommendation for surgery (all odds ratio > 3 and P < 0.05). This model generated an area under the curve of 0.923 (95% confidence interval, 0.861 to 0.986), indicating outstanding discrimination in predicting recommendation for surgery. Patient satisfaction scores rose from 91.5% to 92.2%, but this difference was not statistically significant (P = 0.782). Specific patient-reported goals vary by provider type and are associated with specific diagnosis and treatment recommendations. Goal-directed care may improve the design of treatment pathways and the overall patient experience.

PRS26 Comparison of Guidelines on Diagnostic Criteria and Recommended Treatment Pathways for COPD Patients in Latin America – A Systematic Review

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines periodically review recommended practices for diagnosing and treating chronic obstructive pulmonary disease (COPD). Country-specific COPD guidelines are available; however, there are differences regarding optimum diagnostic and treatment strategies. This systematic review aimed to map and compare guidance on diagnostic criteria and recommended treatment pathways for COPD patients in Latin America (LA), using GOLD as the standard. Electronic searches for guidelines, consensus, or protocols for COPD across 20 LA countries were conducted in October 2019 across seven databases (MEDLINE via Pubmed, BVS, LILACS, ScIELO, Scopus, Web of Science, Embase), websites of medical societies, and government agencies of each country. 14 guidelines were included, 2 regional and 12 country-specific (Argentina, Brazil, Chile, Colombia, El Salvador, Mexico, and Peru). Half were from government agencies and 4 were from medical societies. For diagnosis, 8 guidelines included risk factors or signs/symptoms as diagnostic criteria. Ten guidelines recommended spirometry for COPD diagnosis, in line with GOLD recommendations. Seven guidelines had instructions for diagnosing an exacerbation, while 6 contained guidance for classifying exacerbation severity, with the main strategies including an increase in symptom occurrence and the characteristics of the required treatment. Recommended treatment for COPD was defined through disease severity in 11 guidelines, similar to GOLD guidelines. For bronchodilation strategies, 9 guidelines recommend dual therapy, whilst only 5 recommend triple therapy (long-acting β2 agonist – long-acting muscarinic antagonist – inhaled corticosteroid) for symptomatic patients. Four guidelines specifically recommend triple therapy for exacerbating patients. COPD guidelines were not available in some LA countries. Few of the available guidelines recommended triple therapy as a treatment strategy. Identifying these characteristics enable better understanding of current clinical practices and highlight an urgent need for further standardization in COPD guidelines in LA, especially for patients with symptomatic/severe disease.

X-ray and UV Radiation Damage of dsDNA/Protein Complexes.

Simple SummaryOne of the most common diseases in the world is cancer. The development of an appropriate treatment pathway for cancer patients seems to be crucial to fight this disease. Therefore, solving the problem that affects more and more people in an aging society is crucial. The study presents the results of radiation and photochemical damage to DNA interacting with proteins (specifically/non-specifically). The obtained results of the analysis of photoliths and radiolites by means of the LC-MS technique allowed to identify possible mechanisms of degradation of DNA interacting with proteins. Results suggest the protective action of protein against hydroxyl radicals or solvated electrons and increased damaging effect when sensitized DNA is irradiated by UV light (280 or 320 nm) compared to the DNA alone (without protein interaction).Radiation and photodynamic therapies are used for cancer treatment by targeting DNA. However, efficiency is limited due to physico-chemical processes and the insensitivity of native nucleobases to damage. Thus, incorporation of radio- and photosensitizers into these therapies should increase both efficacy and the yield of DNA damage. To date, studies of sensitization processes have been performed on simple model systems, e.g., buffered solutions of dsDNA or sensitizers alone. To fully understand the sensitization processes and to be able to develop new efficient sensitizers in the future, well established model systems are necessary. In the cell environment, DNA tightly interacts with proteins and incorporating this interaction is necessary to fully understand the DNA sensitization process. In this work, we used dsDNA/protein complexes labeled with photo- and radiosensitizers and investigated degradation pathways using LC-MS and HPLC after X-ray or UV radiation.

Primary biliary cholangitis: assessment and management strategies

Primary biliary cholangitis (PBC) is an autoimmune disease resulting in permanent damage to the bile ducts in the liver, often leading to symptoms including fatigue and itch that significantly impair patient quality of life. PBC is often diagnosed in its early stages and can generally be treated effectively with first-line treatment. Patients who do not respond to this should be referred to the hub centre of their local operational delivery network for assessment and prescription of second-line treatment. These patient treatment pathways are based on national guidance. This supplement summarises the key components of the guidance on the assessment, diagnosis and treatment of patients with PBC.