Zeitschriftenartikel zum Thema „Fueling diagnosis“

Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs.Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. Diabetic ketoacidosis is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with significant fluid and electrolyte loss. DKA occurs mostly in type 1 diabetes mellitus (DM). It causes nausea, vomiting, and abdominal pain and can progress to cerebral edema, coma, and death. DKA is diagnosed by detection of hyperketonemia and anion gap metabolic acidosis in the presence of hyperglycemia. Treatment involves volume expansion, insulin replacement, and prevention of hypokalemia. Diabetic ketoacidosis (DKA) is a rare yet potentially fatal hyperglycemic crisis that can occur in patients with both type 1 and 2 diabetes mellitus. Due to its increasing incidence and economic impact related to the treatment and associated morbidity, effective management and prevention is key. Elements of management include making the appropriate diagnosis using current laboratory tools and clinical criteria and coordinating fluid resuscitation, insulin therapy, and electrolyte replacement through feedback obtained from timely patient monitoring and knowledge of resolution criteria. In addition, awareness of special populations such as patients with renal disease presenting with DKA is important. During the DKA therapy, complications may arise and appropriate strategies to prevent these complications are required. DKA prevention strategies including patient and provider education are important. This review aims to provide a brief overview of DKA from its pathophysiology to clinical presentation with in depth focus on up-to-date therapeutic management.

Gliomas are the most common CNS tumors in children and adolescents, and they show an extremely broad range of clinical behavior. The majority of pediatric gliomas present as benign, slow-growing lesions classified as grade I or II by the WHO classification of CNS tumors. These pediatric low-grade gliomas (LGGs) are fundamentally different from IDH-mutant LGGs occurring in adults, because they rarely undergo malignant transformation and show excellent overall survival under current treatment strategies. However, a significant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classified as WHO grade III or IV high-grade gliomas (HGGs). Despite all therapeutic efforts, they remain largely incurable, with the most aggressive forms being lethal within months. Thus, the intentions of neurosurgeons, pediatric oncologists, and radiotherapists to improve care for pediatric patients with glioma range from increasing quality of life and preventing long-term sequelae in what is often a chronic, but rarely life-threatening disease (LGG), to uncovering effective treatment options to prolong patient survival in an almost universally fatal setting (HGG). The last decade has seen unprecedented progress in understanding the molecular biology underlying pediatric gliomas, fueling hopes to achieve both goals. Large-scale collaborative studies around the globe have cataloged genomic and epigenomic alterations in gliomas across ages, grades, and histologies. These studies have revealed biologic subgroups characterized by distinct molecular, pathologic, and clinical features, with clear relevance for patient management. In this review, we summarize hallmark discoveries that have expanded our knowledge in pediatric LGGs and HGGs, explain their role in tumor biology, and convey our current concepts on how these findings may be translated into novel therapeutic approaches.

In neuropsychiatric tradition, Alzheimer's disease (AD) is a clinical diagnosis that requires demonstration of a progressive memory-predominant type of dementia and exclusion of alternative causes. This simple set of criteria is neither sensitive for early clinical stages of AD since amnestic dementia only arises when the underlying neurodegeneration is fairly advanced, nor is it specific because it also occurs in other brain disorders involving the medial temporal lobe and cannot be easily distinguished from AD on clinical grounds. Efforts to identify AD before full-blown amnestic dementia develops, i.e. at a prodromal or even asymptomatic stage, and to treat the driving components of the pathology rather than its end products, are fueling the search for diagnostic indicators that unveil the neurodegeneration independently of its typical clinical manifestation. Such indicators are termed biomarkers in current technical parlance.

Abstract Background: Jod-Basedow phenomenon is a rare cause of thyrotoxicosis due to excess iodine intake. Herbal supplements containing sea-moss have high iodine amount which may precipitate thyrotoxicosis in patients with underlying Grave’s disease or autonomous thyroid nodules. Clinical Case: A seemingly healthy 28-year-old female presented to the ED with chief complaint of fatigue with associated anxiety, palpitations and weight loss. On admission her temperature was 100.4 F, pulse 126 bpm and blood pressure 116/56 mmHg. Exam was unremarkable for thyroid goiter or orbitopathy. Labs revealed WBC count 3.4 x103/µL (ref range 4.0-11.0) with neutropenia, hemoglobin 4.3 g/dL (11.7-15.7), platelet 49 x103/µL (150-450). Liver transaminases (AST, ALT, and alkaline phosphatase) were elevated with levels up to 4 times the upper limit of normal. She was diagnosed with hemolytic anemia secondary to severe Vitamin B12 deficiency due to pernicious anemia. TSH was <0.01 mIU/L (0.27-4.20), free T4 2.46 ng/dL (0.8-1.9) and total T3 139 ng/dL (76-181). The patient subsequently endorsed remote history of hyperthyroidism diagnosed 7 years ago however she could not recall the underlying etiology or the name of medication she was treated with. She reportedly stopped this medication after 1 month due to developing goiter. She also endorsed intermittent use of store-bought supplement of Irish sea moss and bladderwrack in last 2 years. Further workup revealed elevated TSI and TBII antibody titers establishing diagnosis of Grave’s disease. Thyroid ultrasound showed normal sized heterogeneous hypervascular gland with no nodules. I-123 thyroid uptake and scan showed diffuse moderately elevated radioiodine uptake of 16.8% and 40.8% at 4 and 24 hours, respectively. Thionamide therapy was withheld due to concern of neutropenia and transaminitis. She was treated with beta-blocker after which her vital signs normalized. Labs 1 week after stopping sea moss showed TSH 0.01 mIU/L and free T4 1.4 ng/dL. Conclusion: Irish sea moss is a readily available herbal supplement with high, variable amounts of iodine. Despite little scientific evidence, it is often marketed to improve goiter amongst other health benefits. The recommended daily iodine intake per the FDA is 150 mcg. Higher amounts are expected to initially cause a short-lived suppression of thyroid function; the Wolff-Chaikoff effect, followed by “escape” and accelerated production of thyroid hormone in abnormal thyroid gland, known as Jod-Basedow phenomenon. In our case, the patient unknowingly worsened her underlying Grave’s disease due to the Jod-Basedow effect. Of note, apparantly she had a longer than expected course of Wolff-Chaikoff effect preceding the thyrotoxic state due to sporadic irregular intake of sea moss. Discontinuing sea moss led to clinical and biochemical improvement of hyperthyroidism without requiring thionamide therapy.

Opioid prescribing has dramatically increased in the United States (US) over the past two decades, fueling the current crisis of opioid-related adverse events and deaths.1 Understanding the potential contributors to this increased prescribing is paramount to developing effective strategies for preventing propagation. In this issue of the Journal of Hospital Medicine, Burden et al. report the results of a cross-sectional observational study investigating the rates of opioid receipt, patient satisfaction with pain control, and other perceptions of pain management in a sample of patients from geographically diverse US hospitals compared with patients hospitalized in seven other countries.2 Although cultural influences on pain perceptions have been demonstrated by others previously, this is the first study to measure opioid receipt and patient satisfaction with pain control across an international sample of hospitalized patients.

Surgery is one of the mainstays of head and neck cancer treatment, and aims at radical resection of the tumor with 1 cm tumor-free margins to obtain locoregional control. Surgical margins are evaluated by histopathological examination of the resection specimen. It has been long an enigma that approximately 10–30% of surgically treated head and neck cancer patients develop locoregional recurrences even though the resection margins were microscopically tumor-free. However, the origins of these recurrences have been elucidated by a variety of molecular studies. Recurrences arise either from minimal residual disease, cancer cells in the surgical margins that escape detection by the pathologist when examining the specimen, or from precancerous mucosal changes that may remain unnoticed. Head and neck tumors develop in mucosal precursor changes that are sometimes visible but mostly not, fueling research into imaging modalities such as autofluorescence, to improve visualization. Mostly unnoticed, these precancerous changes may stay behind when the tumor is resected, and subsequent malignant progression will cause a local relapse. This led to a clinical trial of autofluorescence-guided surgery, of which the results were reported in 2020. This review focuses on the most recent literature of the improved diagnosis of the resection margins of surgically treated head and neck cancer patients, the pathobiological origin of recurrent disease, and relevant biomarkers to predict local relapse. Directions for further research will be discussed, including potential options for improved and personalized treatment, based on the most recently published data.

Today, tuberculosis (TB) is still one of the major threats to humankind, being the first cause of death by an infectious disease worldwide. TB is a communicable chronic disease that every year affects 10 million people and kills almost 2 million people in the world. The main key factors fueling the disease are the progressive urbanization of the population and poverty-related socioeconomic factors. Moreover, the lack of effective tools for TB diagnosis, prevention, and treatment has decisively contributed to the lack of an effective model to predict TB spread. In Nigeria, the rapid urbanization along with unprecedented population growth is causing TB to be endemic. This paper proposes a mathematical model to evaluate TB burden in Nigeria by using data obtained from the local TB control program in the community. This research aims to point out effective strategies that could be used to effectively reduce TB burden and death due to TB in this country at different levels. The study shows that efforts should be oriented to more active case finding rather than increasing the treatment effectiveness only. It also reveals that the persistence of the disease is related to a large number of latently infected individuals and quantifies the lives that could be saved by increasing the notification rate using active case finding strategy. We conclude that undiagnosis is the bottleneck that needs to be overcome in addition to the incorporation, improvement, and/or strengthening of treatment management and other essential TB control measures in Nigeria.

Abstract Diffuse Large B-cell Lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. It is a heterogeneous disease in which one third of patients either do not respond to treatment or relapse within five years after chemotherapy. It is unclear whether epigenetic alterations are responsible for B cell lymphomas relapse phenotypes, such as increased aggressiveness and chemoresistance. To investigate how the B cell lymphoma epigenome evolves upon chemotherapy, we used Enhanced Reduced Representation Bisulfite Sequencing (ERRBS) to profile DNA methylation genome-wide in primary matched diagnosis-relapse DLBCL samples. We interrogated 13 pairs of DLBCL diagnosis tumors and their matched relapse samples. In addition, we performed methylation profiling of normal tonsilar B cell subsets (Naïve and germinal center B cells) from two healthy human individuals. ERRBS provided DNA methylation levels at 3-4M CpG sites. When combining methylation levels from all interrogated CpG sites, we observed increased DNA methylation levels at CpG-islands (CGIs; p=3.5e-9, t-test) in DLBCLs compared to normal B cells, and stable or slightly decreasing methylation levels outside of CGIs (>10 kb away from known CGIs; p=0.057, t-test). There was no significant change in average DNA methylation levels from diagnosis to relapse either at CGIs or outside of CGIs. However, when we investigated DNA methylation changes at gene promoters, we identified 107 consistently differentially methylated promoters between diagnosis and relapse (> 10% DNA methylation alteration and p < 0.05, paired t-test). Pathway analysis of the corresponding genes using iPAGE identified several pathways and processes associated with either hyper or hypo-methylated genes in relapse, demonstrating that methylation changes associated with relapse are functionally coherent. For example, several genes with TGF-beta receptor activity displayed lower DNA methylation in relapse. Taking advantage of single CpG resolution and high coverage provided by ERRBS, we then sought to investigate the extent of allele-specific methylation (ASM) levels in normal tissues and DLBCL patients. We found increased ASM levels in DLBCLs compared to normal tissues (p=0.0011, t-test) confirming observations in solid tumors. There was no significant change in ASM levels from diagnosis to relapse (p=0.24, t-test). These results suggest that methylation changes associated with lymphomagenesis might frequently involve one allele only, perhaps due to differential nuclear localization of individual chromosomes. However allele-specific methylation may not play a key role in lymphoma progression. Finally, we investigated whether intra-tumor methylation heterogeneity at diagnosis would predict whether a DLBCL patient would relapse. We quantified intra-tumor methylation heterogeneity using a statistical approach based on the probability that two randomly sampled DNA molecules from the tumor cell populations differ from each other in their methylation pattern. We found decreased intra-sample methylation heterogeneity in DLBCLs compared to normal germinal center B cells (p=1.9e-4, t-test), consistent with the clonal origin of tumors. 12 out of 13 pairs also displayed decreased methylation heterogeneity from diagnosis to relapse, which is also consistent with clonal selection upon chemotherapy treatment. We then performed ERRBS on primary tumors from 8 DLBCL patients who have not relapsed five years after treatment. We found that non-relapse patients displayed significantly lower intra-tumor methylation heterogeneity as compared to that of the relapsed patients (p=0.047, t-test), which suggests that increased epigenetic diversity within a population of tumor cells at diagnosis might fuel the Darwinian evolutionary process underlying relapse. We also looked at genetic clonal heterogeneity based on next-generation sequencing of somatic hypermutation profiles in IGH VDJ sequences, but found no differences between relapsed and not relapsed patients (p=0.22, Wilcoxon test). This suggests that epigenetic heterogeneity plays a more substantial role than clonal heterogeneity in fueling the relapse phenotype. In summary, this study provides the first comprehensive characterization of aberrations in DNA methylation in relapse DLBCLs and identified epigenetic diversity in DLBCLs as a potential predictor of relapse. Disclosures: No relevant conflicts of interest to declare.

Context: The female athlete triad (Triad) and relative energy deficiency in sport (RED-S) specify the consequences of energy imbalance. Athletic trainers (ATs) are positioned to identify athletes who are fueling themselves inadequately and experiencing related health and performance consequences. Objective: To assess the knowledge of collegiate ATs about the Triad and RED-S and to examine variability in related screening and referral behaviors among National Collegiate Athletic Association divisions. Design: Cross-sectional study. Setting: Collegiate athletic training departments. Patients or Other Participants: Head ATs at National Collegiate Athletic Association member institutions (n = 285, response rate = 33%). Main Outcome Measure(s): An electronic survey was administered. The number of Triad components that were correctly identified and screening and referral behaviors related to Triad components were measured. Results: Nearly all respondents (98.61% [n = 281]) had heard of the Triad; a smaller proportion (32.98% [n = 94]) had heard of RED-S. On average, respondents correctly identified 2 components of the Triad. We observed differences by sex, with women correctly identifying more components than men (U = 12.426, P = .003). More than half (59.93% [n = 163]) indicated that athletes at their institutions were screened for eating disorders. Nearly three-quarters (70.55% [n = 115]) of respondents indicated that all female athletes at their institutions were screened annually for menstrual dysfunction. More comprehensive referral behaviors for athletes identified as experiencing menstrual dysfunction or a bone injury (eg, athlete referred to a nutritionist, dietitian, or counselor) occurred at Division I institutions than at Division II and III institutions. Conclusions: Continuing education for ATs about the Triad and RED-S may encourage a more comprehensive approach to referral and screening after a diagnosis of menstrual dysfunction or bone-stress injury. Using institutional opportunities, such as preparticipation screening, for identifying components of the Triad or RED-S and specifying protocols for referring athletes who screen positive for 1 of these components should also be explored.

Gynaecological malignancy is a major challenge in women’s health worldwide. Cervical cancer (CC) is a particularly common type affecting the female reproductive system through an uncontrolled cell propagation causing cervical tissue injury in women. The advent of new technologies empowers research into the discovery and development of novel markers for early diagnosis, as well as therapy evaluation and monitoring. Despite manifold attempts to unravel the molecular mechanisms of CC, its pathogenesis remains largely unclear. The study of putative CC predictors is key to the invention of effective alleviating treatments. Systems biology enabled with high-throughput methods currently provides routes to tackle this problem. Unlike a traditional approach, it generates a wealth of data on prognostic biomarkers and therapeutic targets in cervical cancer, fuelling the search for novel high-sensitive and specific molecular markers. This approach will help improve the early diagnosis and treatment efficacy at a lower relapse rate. This review presents the currently on-stage and emerging biomarkers in cellular and molecular research into cervical cancer detection and prognosis.

Abstract Purpose Orthorexia nervosa (ON) is a proposed new eating disorder, used to describe a pathological obsession with healthy or ‘clean’ eating. Although some quantitative research has been carried out in ON, very little qualitative work has been published to date to explore individual experiences of ON. Thus, this study aimed to explore individuals’ personal experiences of ON, as described in online blogs. Methods Fifteen women bloggers, who self-identified as having ON, consented for their blog entries to be analysed in this study. Forty pre-existing blog entries describing the first-person experiences of ON were analysed using thematic analysis. Results Three key themes were discussed: (1) initial motivations for a healthier lifestyle, (2) fuelling the problem—social influences, and: (3) when healthy becomes unhealthy. Bloggers described the role of social messages, comparison with others around ideas of ‘healthiness’, as well as confusion around diagnosis as factors influencing their disordered eating. They also described the exacerbating impact of perfectionism and perceived control, as well as a confirmatory cycle of fear and avoidance. For some bloggers, increased physical symptoms in response to feared foods provided confirmation for these fears, further exacerbating food avoidance. Conclusion Whilst the debate around the diagnosis of ON continues, these bloggers’ accounts suggest that ON is experienced as a legitimate, debilitating disorder, worthy of clinical and research investigation. This study provides evidence of some of the potential triggers and maintaining factors for this disordered eating style. Level of evidence Level V, qualitative descriptive study.

In Morocco, the prevalence of multidrug resistant tuberculosis (MDR-TB) continues to increase especially within previously treated cases; these MDR cases may evolve to extensively drug resistant tuberculosis (XDR-TB) raising major concern to TB control programs. From an epidemiological window, scarce informations are available about the genetic diversity of Mycobacterium tuberculosis (MTB) strains fueling these forms of resistance. The aim of this study was to assess to genetic diversity of MDR-MTB strains. Hence, this prospective study was conducted on patients diagnosed with MDR-TB at Pasteur Institute of Casablanca from 2010 to 2013. A total of 70 MDR-MTB isolates were genotyped by spoligotyping and 15-loci MIRU-VNTR methods. Spoligotyping generated four orphan patterns, five unique profiles whereas 61 strains were grouped in nine clusters (2 to 25 strains per cluster), the clustering rates being 87.1%. Subtyping by 15 loci MIRU-VNTR splitted all clusters already established by spoligotyping and generated 70 unique profiles not recognized in SITVIT2 database; clustering rate was equal to zero. HGDI analysis of 15 loci MIRU demonstrated that eight out of 15 loci were highly discriminant. Of note, all pre-XDR strains belongs to many clades, meaning that there no association between gyrA mutants and particular clade. Overall, the data generated by this study (i) describe the population structure of MDR MTBC in Morocco which is highly homogenous, (ii) confirm that TB in Morocco is almost exclusively transmitted by modern and evolutionary lineages with high level of biodiversity seen by MIRU, and (iii) validate the use of optimized 15-loci MIRU-VNTR format for future investigations in Morocco.

Background: Colposcopy has a key role in the diagnostic work-up and management of abnormal cervical cytology, but it might generate negative feelings of mainly anxiety and pain to the patients undergoing such examination. These feelings are interrelated, with the anxiety fueling the painful sensations. The aim of our study was to investigate the effects of preliminary administration in terms of pain and anxiety relief that the preliminary administration of paracetamol would have on patients undergoing diagnostic colposcopy. Materials & Methods: We conducted a single center prospective study which enrolled 112 patients with diagnosed or suspected cervical pathology who were examined at the Outpatient Colposcopy Clinic of Patras University Hospital, over a 7-months period. Patients were randomly assigned to one of the two groups. The interventional group received 1gr of paracetamol (acematiminofen) in pill form, 30 to 60 minutes before colposcopic assessment; the control group received no medication. At the end of consultation, all participants completed a 2-page questionnaire. Results: More patients of the interventional arm did not experience any pain at all during colposcopy compared with the control group. However, this difference was statistically not significant, probably because of the small number of patients. Moreover, there were no differences in mild and moderate pain rates between the interventional and control groups. Severe pain was only experienced by patients in the control group. Further data analysis from the first time as and for repeat colposcopy patients showed similar findings regarding pain intensity rates in the interventional and control group. When considering anxiety levels, no differences were observed between the two groups. Conclusion: The preliminary administration of low dose paracetamol in a pilot sample of colposcopy patients did not illustrate significant benefits in terms of experienced pain and anxiety levels.

IntroductionWorldwide, attention deficit hyperactivity disorder (ADHD) diagnosis rates in children and adolescents have been increasing consistently over the past decades, fuelling a debate about the underlying reasons for this trend. While many hypothesise that a substantial number of these additional cases are overdiagnosed, to date there has been no comprehensive evaluation of evidence for or against this hypothesis. Thus, with this scoping review we aim to synthesise published evidence on the topic in order to investigate whether existing literature is consistent with the occurrence of overdiagnosis and/or overtreatment of ADHD in children and adolescents.Methods and analysisThe proposed scoping review will be conducted in the context of a framework of five questions, developed specifically to identify areas in medicine with the potential for overdiagnosis and overtreatment. The review will adhere to the Joanna Briggs Methodology for Scoping Reviews. We will search Medline, Embase, PsycINFO and the Cochrane Library electronic databases for primary studies published in English from 1979 onwards. We will also conduct forward and backward citation searches of included articles. Data from studies that meet our predefined exclusion and inclusion criteria will be charted into a standardised extraction template with results mapped to our predetermined five-question framework in the form of a table and summarised in narrative form.Ethics and disseminationThe proposed study is a scoping review of the existing literature and as such does not require ethics approval. We intend to disseminate the results from the scoping review through publication in a peer-reviewed journal and through conference presentations. Further, we will use the findings from our scoping review to inform future research to fill key evidence gaps identified by this review.

e19235 Background: New developments in oncology therapy continue to grow in complexity, fueling a dramatically rising cost of care. Traditional care models present opportunities to streamline plan sponsor management efforts, expedite therapy, and improve health outcomes. Studies suggest adherence to evidence-based standards results in higher quality care. Current plan sponsor management platforms match medical policy to individual drugs, not to combination therapy regimens and lack real-time access to standard treatment guidelines. 70% of precertification requests are submitted via antiquated, cumbersome methods such as paper and fax. Methods: CVS Health/Aetna developed a comprehensive oncology solution featuring an enterprise web-based clinical decision support prior authorization tool (Novologix) at the regimen level to reduce administrative burden and support quality care. Novologix regimens were updated via collaboration with the National Comprehensive Cancer Network (NCCN) evidence-based guidelines. Groups also entered a value-based payment (VBP) model to help support quality of care by promoting adherence to NCCN guidelines when clinically appropriate and tool utilization. Eligible members were Commercial, fully-insured members newly diagnosed with breast, colorectal, or lung cancer. Providers were offered dedicated, individual training sessions to provide education on the Novologix tool. NCCN-aligned regimens requested through the platform were automatically certified. Any non-NCCN aligned regimens received accelerated medical review by a board-certified medical oncologist with the option for an external peer-to-peer review upon denial. Providers received ongoing quality and cost of care reporting. Results: Primary in progress. N of precertification requests submitted via Novologix ( 28 requests as of 1/23/2020) - (will include graph displaying N of requests by month). N of regimens submitted via Novologix that were automatically certified (46% as of 1/23). Avg turnaround times for modified regimen requests requiring clinical review (TBD). Avg % adherence to NCCN guidelines (100% as of 1/23/20) Secondary: Total cost of care (preliminary/other leading indicator). Conclusions: By engaging oncology practices through an enhanced payer-provider collaboration and implementing an automated regimen-level precertification process we can facilitate higher-quality oncology care. Future studies will be needed to measure the impact of this program on total cost of care.

Abstract Background With globalisation fuelling the fire for infectious diseases, it’s important for general physicians to be aware of the tropical infections presenting to hospitals. Malaria, with over 400,000 deaths annually worldwide, has an Irish notification rate of 1.2 per 100,000 of the population, the seventh highest incidence rate of imported malaria globally. This analysis aims to examine the demographics and outcomes of Irish patients with malaria over a four year period. Methods A retrospective analysis of all patients with malaria admitted to Irish hospitals between January 1st 2016 and December 31st 2019 was performed. Data was obtained from the National Quality Assurance Improvement System (NQAIS), a national electronic database that collates data from hospital admissions. This was analysed using STATA. Patient demographics, hospital length of stay and documented malaria subspecies are described. Results Between January 1st 2016 and December 31st 2019 there were 289 cases of malaria admitted to Irish hospitals, 13/289 (4.5%) requiring high dependency care. 197/289 (68%) were male. The mean age was 35 years (95% CI 33.3 – 37). 220/289 (76%) of all cases resulted from Plasmodium falciparum infection, 16/289 (5.5%) Plasmodium ovale, 11/289 (3.8%) Plasmodium vivax and 2/289 (0.7%) Plasmodium malariae, while 40/289 (13.8%) were unspecified. The median length of stay was 3 days (IQR 1-4 days) and 72/289 (25%) were admitted under an Infectious Diseases team, although this had no significant impact in length of stay (3.1 days versus 3.4 days, p=0.68). 117/289 (40%) were admitted in the months of August and September. There were no reported deaths. Conclusion This report gives a clinical context to the 2016 – 2019 NQAIS data, particularly with regards to inpatient length of stay, malaria species diagnosed and numbers requiring critical care. The majority of all cases in the four year period were P. falciparum, reflective of the dominant African region of exposure in most cases. Interestingly, 43% of all cases were from hospitals outside of the Dublin City catchment area, reflecting a diversification of travel and population demographics in Ireland. This highlights the importance of malaria awareness in all regions in Ireland, not simply the major urban centres. Disclosures All Authors: No reported disclosures

Abstract Abstract 1317 Introduction: Allogeneic stem cell transplantation offers potentially curative therapy for selected patients with hematopoietic malignancies or bone marrow failure states. Only 20–25% of transplantation candidates have compatible related donors, and thus the majority of patients require stem cells from unrelated individuals matching their human leukocyte antigen (HLA) genes. Unrelated donor transplantation (NMUDT) is associated with higher rate of acute and chronic graft versus host disease (aGVHD and cGVHD, respectively) resulting in significant treatment related morbidity and mortality. Severe aGVHD (grade III/IV) occurs in 30–40% of patients and many of these patients eventually die from the complications. The incidence of cGVHD following unrelated transplantation was reported to occur up to 80%. Treatment-related mortality in the first 100–180 days post-transplant ranges from 30–60% depending on the patient/donor age, disease status at time of transplant and HLA mismatch. This compares to a treatment-related mortality of approximately 20–30% for patients receiving sibling-donor transplants. More aggressive conditioning including total body irradiation is believed to result in severe organ toxicities fueling subsequent GVHD in the NMUDT patients. In this study we evaluated chemotherapy only based preparative therapy (busulfan and fludarabine) and tacrolimus plus methotrexate as the GVHD prophylaxis. Also the donors and recipients were matched with strict HLA compatibility. Patients and Method: Thirty-five patients meeting eligibility criteria for NMUDT were prospectively enrolled. Diagnoses included:14 AML, 6 NHL, 6 MDS, 5 ALL, 2 MPD, 2 CML. The median age was 46 years (18-61); 20 males and 15 females. Preparative therapy consisted of Fludarabine (F) 30mg/m2 daily for 5 doses, Busulfan (Bu) 0.8mg/kg IV q6 hrs for 16 doses. All patients received stem cells from allele-matched unrelated donors; 7/8 (n=1), 8/10 (n=1), 9/10 (n= 7) or 10/10 (n= 26) at HLA A, B, C, DR and DQ. 9 patients received bone marrow and 26 patients received G-CSF mobilized peripherial blood stem cells. All patients received TAC (target 5–10 ug/L), MTX (5mg/m2 d1,3,6,11) for GVHD prophylaxis. Infectious disease prophylaxis included; G-CSF, acyclovir, anti-bacterials, voriconazole, and CMV pre-emptive therapy. Results: The engraftment was documented as follows: ANC >1.0 median: day 12 (SD3.5), Plt >50×10e9/L median: day 16 (SD 7.2), Plt >100×10e9/L median: day 20 (SD 40.7). The frequent (>20%) toxicities included bone marrow suppression (grade 4 100%) mucositis (gr≥1 91%), enteritis (gr≥1 43%); elevated AST (gr 1 27%), elevated total bilirubin (gr 1 20%) and alkaline phosphatase (gr1 40%). Other significant toxicities (gr ≥3) included neutropenic fever (20%), bacteremia (11%), infections (including pneumonia, fungal pneumonia, CMV viremia) (26%), enteritis 6%, ARF 9%, rash 9%, respiratory failure 14%. The incidence of aGVHD (Gr II-IV) was 43%. The incidence of cGVHD was 60% (90% extensive cGVHD). The 100 day non-relapse mortality (NRM) was 9% (2 GVHD, 1 VOD). The late TRM (beyond 100 days) was 11% (3 GVHD, 1 infection). Cumulative relapse related mortality was 17% at 6 months, 26% at 9 months and 31% at 24 months. Overall mortality at 1 year was 44%. Overall survival is currently 40% with median follow-up of 4.4 years. Conclusions: In this prospective study of 35 patients undergoing matched unrelated donor transplantation, the busulfan/fludarabine preparative regimen is safe and resulting in reasonably low TRM and comparable GVHD rates. Disease relapse remains the most significant cause of death. Disclosures: No relevant conflicts of interest to declare.

Abstract Malignant plasma cell (PC) disorders are clonal diseases based on their immunoglobulin variable region sequence signature. However, intratumor phenotypic, genetic, and morphologic heterogeneity is often observed, fueling the notion that a subpopulation of the malignant PC clone may have extensive self-renewal properties whereas others may not. Little information exists regarding the relationship between these putative tumor subpopulations that is instrumental to our understanding of the growth, progression and therapeutic targeting of PC disorders. We recently described establishment of two novel cell lines from one patient initially diagnosed with primary amyloidosis (ALMC-1), who eventually progressed to a combination of AL and symptomatic multiple myeloma (MM; ALMC-2). Although both cell lines are clonally related, they exhibit a number of intriguing differences, including a marked variability in their makeup of mononuclear (MoN) and multinuclear cells (2 − &gt;10 nuclei; MuN). The ALMC-1 cell line consistently displays a much larger fraction of MuN cells (~50%) than the ALMC-2 cell line (~20%). By contrast, the growth rate of the ALMC-2 cells is significantly higher than ALMC-1 cells suggesting an inverse relationship between growth rate and fraction of MuN cells. It has been demonstrated that MoN plasmablastic morphology is a predictor of poor survival in MM, however the clinical significance of MuN PCs, which are frequently observed in bone marrow biopsies, has yet to be determined. We therefore used the ALMC-1 and ALMC-2 cell lines to begin to test the hypothesis that the MoN fraction in both cell lines contains cells with extensive self-renewal properties whereas the MuN cells are no longer capable of cell division. The central questions become by what mechanism are MuN PCs generated and how are MoN PCs maintained? Two hypotheses that can explain the dual persistence of both types of cells are: random cell fusion; regulated or sporadic cell division of MoN cells into 2 daughter cells, one of which divides normally and the other one fails to undergo cytokinesis. To address the first possibility, each cell line was transfected with GFP or YFP. Single positive (GFP or YFP) cells were then mixed and cocultured for assessing the frequency of dual positive cells by flow cytometry at various time points. However, studies to date suggest this mechanism does not occur. To begin to address the second possibility and determine whether extrinsic factors, e.g., cytokines, may regulate the rate of generation of MuN PCs, we cultured both cell lines +/− IL-6 and IGF-I and assessed numbers of MoN and MuN PCs. Initial analyses suggest that IL-6, but not IGF-I, increases the proportion of MoN PCs in both cell lines. To address the hypothesis that MuN PCs are no longer capable of growth, cells were labeled with bromodeoxyuridine (BrDU) to assess the capability of MuN cells to synthesize DNA. We observed that MuN PCs incorporating BrDU did so uniformly in each nucleus present in the cell. We then assessed the ability of cell division of MuN cells by quantitating normal vs abnormal metaphases in both cell lines and observed that &gt;90% of metaphases were present in MoN PCs, suggesting that MoN PCs largely give rise to MuN PCs and the latter are likely compromised in cytokinesis. As centrosomes play a critical role in regulating cell division and centrosome abnormalities have been noted in MM by others, we next used gamma-tubulin immunofluorescence to detect centrosomes. MoN PCs exhibited uniformly normal centrosome numbers and positioning while MuN PCs showed clear centrosomal abnormalities including accumulation of centrosomes, centrosome clustering, and multiple directional centrosome polarization, suggesting a mechanism by which the MuN cells may be generated. In summary, our data suggest that MuN PCs lack growth potential and that intrinsic and/or extrinsic factors may drive accumulation of these cells. These observations support the possibility that patients with a larger proportion of MuN PCs may have differences in clinical outcome from those patients with largely MoN PCs. To test this, we have begun hematopathological analysis of a large series of patients diagnosed with various plasma cell disorders. Knowledge of the signals that regulate the balance between MoN and MuN cells could lend itself toward identification of therapeutic modalities that may maximize differentiation of tumor cells into end-stage cells.

Background: Negative attitude and stigma against leprosy patients constrain them to resort to concealing their status thus resulting in delayed detection, treatment, complications and perpetuation of the condition in the locality. This study was aimed at finding out the prevailing attitude and stigma toward leprosy in the community with a view to addressing the fueling factors. Materials and Methods: It was descriptive cross sectional study. Semi-structured interviewer administered questionnaires were used for data collection. Explanatory Model Interview Catalogue (EMIC), was used to grade stigma against leprosy amongst participants. Answers to questions in the questionnaire were assigned scores which were summed up into percentage breakpoints. A respondent was interpreted as having favorable or unfavorable attitude to leprosy depending on his or her percentage sum of score. Stigma was categorized based on the sum of an individual’s EMIC score as high, moderate or low level of stigma. Data were analyzed using SPSS version 20. Results: The study revealed that only 44(15%) of respondents had favorable attitude towards leprosy whereas 250(85%) had unfavorable attitude towards this group. Attitude to leprosy was observed to be significantly related to age and sex of respondent, religion and ethnicity, p-value< 0.05. EMIC profile of the study respondents revealed that 47(16%) demonstrated low stigma, 81(28%) demonstrated moderate stigma and 166(56%) demonstrated high stigma towards leprosy. There was no statistically significant relationship between stigma and socio-demographic variables. Conclusion: Misunderstanding and misconceptions about leprosy and leprosy patients is still well rooted in the norms and culture of the people of Ikun, breeding negative attitude and stigma toward leprosy. Vigorous leprosy awareness programs structured along the lines of attitude-stigma influencing socio-demographic variables, with emphasis on the cause, transmission, diagnosis and treatment of leprosy will help to stem the tide of myths and misconceptions.

ObjectiveTo evaluate whether dried blood spot (DBS) testing improves diagnostic uptake in Vientiane Capital City province, Lao People's Democratic Republic (PDR) compared to conventional diagnostic techniques (venous blood by venepuncture) during syndromic surveillance from 2016-17. To also explore reasons for low blood sampling uptake via quantitative results and qualitative responses from health care workers; in addition to the perceived acceptance of DBS compared to venepuncture.IntroductionThe Lao PDR is aiming for measles elimination despite ongoing outbreaks of the disease. Outbreak detection in the country relies on recognising cases meeting a set “fever and rash” case definition incorporated into the syndromic surveillance system run by the National Center for Laboratory and Epidemiology (NCLE). Suspected cases are passively identified by presentations at health care facilities, with information forwarded to the NCLE's Early Alert and Response Network (EWARN) along with event-based reported data1. World Health Organization (WHO) measles surveillance guidelines require ≥80% of “fever and rash” cases be sampled for testing; currently only 20% sampling occurs in Laos2,3. Sampling using DBS has been proposed as an alternative to conventional venepuncture in facilitating suspected measles case detection. In this study, DBS was proposed to improve blood uptake of syndromic cases, by evaluating whether it increased ascertainment compared to conventional venepuncture. It also analysed reasons for poor diagnostic uptake among healthcare personnel involved in syndromic surveillance.MethodsA mixed methods study involving a cross-sectional study and a qualitative survey was undertaken in Vientiane Capital City Province. Nine district and central hospitals were included to represent the general provincial population composition. Surveillance data were provided through routine surveillance staff review of hospital logbooks and community health centres together with case investigation forms forwarded to the NCLE's EWARN. A sample size of 166 was calculated with 80% power to detect a 20% difference in uptake in syndromic surveillance between DBS and venepuncture. A 1:1 matching of venepuncture and DBS notifications was set. A randomly selected sample of 105 from a total of 204 notifications of “fever and rash” from June-September 2016 during routine venepuncture-based surveillance was compared with a preliminary 13 collected notifications from a proposed 100 in June-September 2017 following introduction of DBS to routine use. Resource limitations in 2017 restricted the DBS samples (n=13) analysed at this preliminary stage.Reasons for baseline poor sampling uptake using 2016 venepuncture data (n=204) were separately explored according to categories including demographics, hospital, provisional diagnosis and measles immunisation. Microsoft Excel 2007 and STATA v14.0 were used for descriptive, univariate and multivariate analyses of explanatory variables.Qualitative questionnaires were physically administered to personnel at each hospital according to their involvement in syndromic surveillance in July-September 2016-17. Given time constraints, a limited sample of surveillance personnel involved in the study (n=7) completed qualitative questionnaires. Questionnaires explored reasons for poor uptake using a framework analysis of five themes focused on demographics, aetiology of reasoning, venous and DBS acceptance, and sampling preference. Patterns were correlated with quantitative data.ResultsBaseline characteristics were similar across both study periods. A high frequency of "fever and rash" cases was detected among those 0-9 years (71.19%) in the study periods analysed. Blood samples were obtained from 25.77% of "fever and rash" notifications using conventional venepuncture, reflecting current poor diagnostic uptake. Direct comparison of 2016 and 2017 periods was underpowered at the time of analysis (n=105 vs n=13). But preliminary results indicated DBS had no difference in improving diagnostic uptake (23.07% vs 25.77%; OR 0.83; CI 0.14-3.41) compared to baseline venepuncture.Exploration of baseline 2016 venepuncture data (n=204) revealed only three "fever and rash" notifications were forwarded to the EWARN from hospitals involved in this study period. Hospitals also varied in blood sampling. Presenting at Nasaithong district hospital was less associated with uptake than not presenting there (OR 0.15; CI 0.003-0.99). Those presenting at Xaythany district (OR 4.53; CI 1.66-12.56) and Settathirath central (OR 3.09; CI 1.39-6.77) hospitals had greater odds of blood sampling than those who did not. Logistic regression indicated a borderline increased odds of 1.02 (CI 1.00-1.05) for having bloods taken with each year of increased age. With provisional diagnoses, there were six suspected measles cases, with only three suspected cases being tested. Measles diagnosis was not associated with blood uptake (OR 2.35; CI 0.69-7.55). Varicella diagnosis was less associated with uptake than not having varicella (OR 0.06; CI 0.001-0.39), even after multivariable analysis.Qualitative results described staff concerned with competing demands from clinical workloads and fulfilling syndromic surveillance reporting requirements. A common theme was in neglecting the syndromic case definition in lieu of the clinical case definition, fueling misunderstanding of reporting requirements. Patient cultural beliefs were identified as being associated with altered blood sampling rates. Respondents were equally split on patient preference between DBS and venepuncture techniques.ConclusionsResults for DBS and venepuncture analysis were limited by data collection. However, this is one of the first studies to analyse the use of DBS in syndromic surveillance. Preliminary results revealed no difference in diagnostic uptake between DBS and venepuncture, indicating poor blood ascertainment regardless of technique. Collected data reflected current diagnostic uptake trends in the Lao PDR and was representative of Vientiane Capital City Province. Quantitative and qualitative analyses of uptake indicate weaknesses in syndromic surveillance, varying by institution, cultural beliefs and understanding of case definitions. Completion of DBS data collection will be expected to corroborate current findings. Further studies exploring diagnostic uptake limitations and DBS viability in low resource settings may build on this data and inform syndromic surveillance opinion on using DBS.References1. World Health Organization. Hidden varicella outbreak, Luang Prabang Province, the Lao People's Democratic Republic, December 2014 to January 2015. Western Pacific Surveillance and Response Journal. 2016; 7(1):1-5.2. World Health Organization. WHO-recommended standards for surveillance of selected vaccine-preventable diseases. In: Department of Vaccines and Biologicals. Geneva, Switzerland: World Health Organization. 2003; 1-59.3. Musto J. Measles epidemiology in Lao People's Democratic Republic. (Unpublished data). 2017.

Recurrent abdominal pain accounts for a significant proportion of attenders and high impact users in the emergency department. Due to the heterogeneity of presentation and the broad spectrum of possible causes, abdominal pain presents as a significant clinical challenge within the emergency department, particularly as distress and pain are commonly elevated. Patients in this group are routinely prescribed opiate-based interventions and repeated investigations in a ‘better safe than sorry’ culture which saturates the field of persistent physical symptoms. This approach is contributing to the growing problem, and fuelling a cycle of repeated attendance and failure to resolve. This article reviews the current clinical and psychophysiological understanding of recurrent abdominal pain, critiquing guidelines and approaches to diagnosis and management. We offer an alternative evidence-based biopsychosocial approach using the mnemonic ‘ERROR’, recommending five steps to assessment and clinical management of recurrent abdominal pain in the emergency department.

Current experiences of tuberculosis policy and care among Indigenous people are interpreted and understood in light of the past colonial violence and cultural genocide. The expressed reluctance to seek health care was often grounded in experiences of colonial violence and racism, pointing toward colonial and racist practice in health care as an important driver of tuberculosis stigma. The ongoing presence of anti-Indigenous racism in Canada’s health care systems underscores the ways that these worries are not confined to historical events but manifest in the interactions across individuals and systems today. For tuberculosis stigma in the context of migration, tuberculosis policies and programs targeting migrant persons or racialized groups were seen as fuelling discriminatory and exclusionary views and practices toward these groups in the wider society and exacerbating tuberculosis stigma. Migrant detention centres were 1 of the sites where tuberculosis stigma was amplified through isolation when diagnosed. Further, the twining of immigration policy with tuberculosis policy led to worries among migrant persons about one’s tuberculosis status and its impact on one’s immigration status, and subsequently a reluctance to access health care. These findings ask us to consider the ways that tuberculosis policy, in concert with immigration policy, can generate tuberculosis stigma. Tuberculosis stigma differs across contexts. It can be both a determinant of, and determined by, other forms of discrimination. Moreover, it requires close attention to the specific setting where tuberculosis stigma is sought to be addressed. The implications of this for tuberculosis policy and care are that a universal, one-size approach to addressing tuberculosis stigma is unlikely to be successful. Rather, program-specific approaches are likely needed that engage with questions as to how different forms of tuberculosis stigma play out in the context of care. Cutting across this review findings were widespread experiences of racism in health care. These findings suggest that, in as much as tuberculosis stigma is a barrier to the uptake of tuberculosis screening and treatment, racism against Indigenous people and racialized migrants remains endemic in Canada’s health care system and may in some cases overshadow the role or experience of tuberculosis stigma. In light of these findings, and again, depending on the particular setting, engaging with anti-racist efforts and challenging white supremacy remain necessary and urgent.