tbuckley/cabot-search huggingface dataset:
FRI0239 Pain therapy of failed back surgery syndrome patients (fbss): successful long-term treatment with fentanyl tts
Authors: H Haentzschel, S Schwalen, J Kraemer, T Theodoridis
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Patients with a FBSS suffer from chronic severe back pain. Most of these patients have had a postlaminectomy in the lumbosacral region. 10% of patients with a postlaminectomy develop chronic pain after the surgery. The percentage of positive outcomes after a re-surgery amount about 30–75%. In general the outcome of these patients is unfavourable. At present pain therapy with opioids is not generally recommended in patients with FBSS. <h3>Objectives</h3> Documentation of long-term efficacy and safety of fentanyl TTS treatment for patients who have had at least one surgical intervention for chronic back pain and who continue to suffer from severe back pain. <h3>Methods</h3> Subgroup analysis of an open, international, multi-centre study (FEN-INT-13) with a duration of 12 months. 85 patients (mean age 50 years; 46 women; mean pain duration 9 years) with failed back surgery syndrome received fentanyl TTS in an initial dosage of equivalent analgesic strength to prior opioid therapy. The dose was subsequently adjusted to provide optimum pain therapy. Visits have been scheduled day 1, week 1, month 1–12. The primary target parameter was the subjective weekly assessment of pain control (very good, good, moderate, poor, very poor). In addition the treatment preference with regard to the prior analgesic treatment and the quality of life (SF-36) has been documented. Regarding the safety unexpected events and vital parameters have been documented. <h3>Results</h3> 59% of the patients were treated for 12 months, 41% discontinued treatment earlier (5% because of inadequate effect, the rest for other reasons). The primary target parameter of subjective weekly assessment of pain control was consistently rated very good to moderate (50 to 80%). 77% of patients preferred fentanyl TTS to the former opioid therapy. There was a significant improvement in SF-36 (quality of life) after 12 months in terms of physical pain, mental health, average pain intensity and pain frequency. The mean fentanyl TTS dose was 67 μg/h in month 1, 90 μg/h in months 6 and 97 μg/h in month 12. The most frequently reported adverse reactions caused by fentanyl TTS (&gt;10%) were nausea, vomiting, headache, increased perspiration, constipation, drowsiness, fatigue, dizziness and depression. <h3>Conclusion</h3> In this trial patients with chronic, therapy-resistant back pain showed benefit of a treatment with fentanyl TTS. There was not only pain reduction but also improvement in quality of life over a period of one year. At the same time the dosage of fentanyl remained stable. The success of this pain therapy may offer the possibility to initiate a causal therapy like physiotherapy. Fentanyl TTS offer stable pain control for failed back surgery syndrome patients and improves their quality of life. It is safe and well tolerated.
PB2036 EFFECTS OF DIFFERENT IRON FORMULATION SUPPORT ON SELECTION OF SOME PATHOGENS IN HUMAN GUT FLORA: MONOCENTRIC STUDY
Authors: G. Giordano, A. Lucchesi, M. magri, G. niro, M. gasperi
Journal: HemaSphere (2019)

Background: Food and micronutrients support modify the composition of our intestinal flora. Aims: Aim of this study is to see how different iron formulations used in human iron support are able to expand gut pathogen flora. Methods: 36 female patients (6 per group) with sideropenic anemia due to hypermenorrhea received 60 mg/day of different iron formulations: sulphate, Sucrosomial®, heminic bisglycinated, bisglycinated chelated, micronized encapsulated. Median age of patients was 30y (R20‐38). A stool culture test was performed in each patient at start of treatment and one month after. If at time 0 a culture was positive for a pathogen, patient was excluded from the study. Cultural stool test were performed for E. coli enteropathogen, enterohemorragic, salmonella, shigella, clostridium, yersinia entherocolica. Results: Before treatment: 1 patient receiving iron sulphate had a yersinia positivity and 1 receiving heminic bisglycinated iron showed an E. coli. After treatment: 2 patients receiving heminic bisglycynated iron showed positivity for E. coli enteropathogenic, 1 for shigella; 4 patients receiving iron sulphate showed positivity for E. coli enteropathogenic; 2 patients receiving micronized encapsulated iron and 2 with bisglycinated chelated iron showed positivity for E. coli enteropathogenic, 1 with Sucrosomial® iron showed positivity for yersinia enterocolica. Summary/Conclusion: Different type of iron supplements differently affect pathogen gut flora selection. Molecular complexes iron carriers probably influence differently pathogen selection. The most represented selected pathogen flora is E. coli entheropathogenic.
A Discrete Dorsal Raphe to Basal Amygdala 5-HT Circuit Calibrates Aversive Memory
Authors: Ayesha Sengupta, Andrew Holmes
Journal: Neuron (2019)

Highlights•Fear learning selectively engages the anatomically distinct DRN→BA 5-HT pathway•The DRN→BA 5-HT pathway bidirectionally modulates fear learning and extinction•The DRN→BA 5-HT pathway sculpts fear-associated neuronal activity in the BA•The DRN→BA 5-HT pathway expresses VGluT3 but drives fear via BA 5-HT1A/2A receptorsSummaryDespite a wealth of clinical and preclinical data implicating the serotonin (5-HT) system in fear-related affective disorders, a precise definition of this neuromodulator's role in fear remains elusive. Using convergent anatomical and functional approaches, we interrogate the contribution to fear of basal amygdala (BA) 5-HT inputs from the dorsal raphe nucleus (DRN). We show the DRN→BA 5-HT pathway is engaged during fear memory formation and retrieval, and activity of these projections facilitates fear and impairs extinction. The DRN→BA 5-HT pathway amplifies fear-associated BA neuronal firing and theta power and phase-locking. Although fear recruits 5-HT and VGluT3 co-expressing DRN neurons, the fear-potentiating influence of the DRN→BA 5-HT pathway requires signaling at BA 5-HT1A/2A receptors. Input-output mapping illustrates how the DRN→BA 5-HT pathway is anatomically distinct and connected with other brain regions that mediate fear. These findings reveal how a discrete 5-HT circuit orchestrates a broader neural network to calibrate aversive memory.Graphical abstract
Abstract 14994: Association Between Low Socio-Economic Status and Risk of Incident Atrial Fibrillation
Authors: Satish Ramkumar, Hong Yang, Ying Wang, Nicholas D'Elia, Ayame Ochi, Henry West, Mark Nolan, Kazuaki Negishi, Thomas H. Marwick
Journal: Circulation (2017)

Background: Low socio-economic status is associated with an increased risk of metabolic syndrome. The Socio-Economic Indexes for Areas(SEIFA) released by the Australian Bureau of Statistics has thr...
What's hot that the other lot got
Authors: Akanksha Mimi Malhotra
Journal: Thorax (2019)

The use of e-cigarettes has rapidly increased. A UK based randomised trial by Hajek et al ( NEJM 2019;380:629) evaluated the effectiveness of e-cigarettes versus nicotine replacement therapy (NRT) as a tool for smoking cessation. Adults attending National Health Service smoking cessation services not currently using NRT or e-cigarettes were eligible. Participants had to agree to not use the non-assigned treatment for at least 4 weeks post quit date. 886 adults already attending stop smoking services were randomised to receive either refillable e-cigarettes (439/886) or a range of NRT (447/886) of their choice. Behavioural support was offered to both groups. NRT was offered for 12 months (~£120 for 3-month supply) or a starter e-cigarette pack with one liquid refill (~£30.25) and encouragement to purchase additional refills themselves. Sustained abstinence was defined as no more than five cigarettes 2 weeks following the quit date and exhaled CO <8 ppm at 52 weeks. Those in the e-cigarette group were statistically more likely to achieve abstinence at each timepoint analysed (4 weeks, 26 weeks and 26–52 weeks) including the primary outcome at 1 year (18.0% vs 9.9%, relative risk (RR) 1.83; 95% CI 1.30 to 2.58). The side effect profile was also investigated. Participants in the NRT arm were more likely to suffer from nausea (37.9% vs 31.3%) and ongoing cough with …
Association of Sexting With Sexual Behaviors and Mental Health Among Adolescents
Authors: Camille Mori, Jeff R. Temple, Dillon Browne, Sheri Madigan
Journal: JAMA Pediatrics (2019)

Sexting is the exchange of sexual messages, photographs, or videos via technological devices and is common and increasing among youth. Although various studies have examined the association between sexting, sexual behaviors, and mental health, results are mixed.To provide a meta-analytic synthesis of studies examining the associations between sexting, sexual behavior, and mental health using sex, age, publication date, and study methodological quality as moderators.Electronic searches were conducted in April 2018 in MEDLINE, PsycINFO, Embase, and Web of Science, yielding 1672 nonduplicate records.Studies were included if participants were younger than 18 years and an association between sexting and sexual behaviors or mental health risk factors was examined.All relevant data were extracted by 2 independent reviewers. Random-effects meta-analyses were used to derive odds ratios (ORs).Sexual behavior (sexual activity, multiple sexual partners, lack of contraception use) and mental health risk factors (anxiety/depression, delinquent behavior, and alcohol, drug use, and smoking).Participants totaled 41 723 from 23 included studies. The mean (range) age was 14.9 (11.9-16.8) years, and 21 717 (52.1%) were female. Significant associations were observed between sexting and sexual activity (16 studies; OR, 3.66; 95% CI, 2.71-4.92), multiple sexual partners (5 studies; OR, 5.37; 95% CI, 2.72-12.67), lack of contraception use (6 studies; OR, 2.16; 95% CI, 1.08-4.32), delinquent behavior (3 studies; OR, 2.50; 95% CI, 1.29-4.86), anxiety/depression (7 studies; OR, 1.79; 95% CI, 1.41-2.28), alcohol use (8 studies; OR, 3.78; 95% CI, 3.11-4.59), drug use (5 studies; OR, 3.48; 95% CI, 2.24-5.40), and smoking behavior (4 studies; OR, 2.66; 95% CI, 1.88-3.76). Moderator analyses revealed that associations between sexting, sexual behavior, and mental health factors were stronger in younger compared to older adolescents.Results of this meta-analysis suggest that sexting is associated with sexual behavior and mental health difficulties, especially in younger adolescents. Longitudinal research is needed to assess directionality of effects and to analyze the mechanisms by which sexting and its correlates are related. Educational campaigns to raise awareness of digital health, safety, and security are needed to help youth navigate their personal, social, and sexual development in a technological world.
PB2363 AUTOLOGOUS STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA: A SINGLE INSTITUTE OUTCOME ANALYSIS
Authors: T. Sui Keat, T. Ching Soon, G. Ai Sim, C. Teng Keat, C. Su Kien
Journal: HemaSphere (2019)

Background: High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is now considerd as standard therapy for young patients (&lt; 65 years) with multiple myeloma (MM). Aims: Although myeloma is the 3rd commonest hematological malignancy, only a few centres in Malaysia offer ASCT service for this group of patients. We hereby, share our 9 year's experience in Penang General Hospital. Methods: Clinical data of patients with MM who were transplanted in Penang General Hospital between 2008 to 2017 were collected retrospectively and analysed using SPSS IBM version 22.0. The patients were followed up from the time of transplant until 28 February 2018. The variables assesed included demographics, MM subtypes, remission status, induction chemotherapy pre‐transplant and maintenance therapy post‐transplant. Results: A total of 41 patients (18 males, 23 females) were evaluated. The median age at transplant was 54 years (ranged 33‐65 years). There were 19 Malays (46.3%), 15 Chinese (36.6%) and 7 Indian patients (17.1%). 73% had IgG Kappa subtype. 41.5% presented with ISS II, 34.1% ISS III and 24.4% ISS I. 61% of patients were transplanted with at least a very good partial response (VGPR) compared with 39% with partial response (PR). Majority of patients (75%) received Bortezomib based induction therapy prior to transplant. 58% patients received maintenance treatment post‐ASCT. The median follow‐up was 35 months (range 3‐103 months). The 5 years overall survival (OS) and progression‐free survival (PFS) was 70% and 44.3% respectively. There was no transplant related mortality. Median PFS of patients with ISS III was only 11 months compared with 53 months for ISS I‐II (p &lt; 0.001). Patients who received maintenance had longer PFS (65 months versus 12 months, p = 0.032). Multivariate analysis revelaed ISS III as an independent risk factor for survival in our cohort (PFS hazard ratio (HR), 4.76;95% CI 1.81 to 12.49;p = 0.002). Other variables evaluated did not affect survival. Summary/Conclusion: ASCT improves survival in patients with multiple myeloma and is safe in patients below 65 years. ISS III is an independent risk factor of PFS.
PS1430 INTEGRATION OF FOUR COLOUR FLOW TO PREDICT RELAPSE/PROGRESSION AND TIME TO NEXT TREATMENT IN MULTIPLE MYELOMA AFTER UPFRONT AUTOLOGOUS STEM CELL TRANSPLANT
Authors: P. Chorão, T. Maia, R. Bergantim, E. Aguiar, J. Cancela Pires, F. Trigo, J.E. Guimarães
Journal: HemaSphere (2019)

Background: Four colour multiparameter flow cytometry (4MFC) is widely available and easier to apply than conventional minimal residual disease methods, although less sensitive. Aims: Our objective was to integrate 4MFC results in a clinical model to predict relapse/progression free survival (R/PFS) and time to next treatment (TNT) after upfront autologous stem cell transplant (ASCT) in a resource limited setting. Methods: Single center retrospective review of 146 consecutive MM patients with 4MFC bone marrow (BM) evaluation at day 100 after upfront ASCT with melphalan conditioning between 2008 and 2016. The 4MFC panel included CD38, CD138, CD45, CD19 and CD56. CD38+, CD138+ plasmocytes (PC) with (CD45 ± )CD19‐CD56+ or CD45‐CD19‐(CD56 ± ) were considered abnormal. Baseline PC 4MFC was only available in 50% of patients and was not considered for this analysis. Multivariate Cox regression analysis was performed to elect statistically significant variables to integrate R/PFS (either biochemical or clinic) and TNT clinical models at 3 years (y) after ASCT. Results: Median follow‐up after ASCT was 43 months (interval 2–126). At diagnosis, median age was 58y (interval 36–70), 56% were male, 23% had hypercalcemia, 15% renal insufficiency, 41% anemia, 67% lytic lesions and 33% plasmacytomas. Induction regimens included a proteasome inhibitor (PI) in 62%, immunomodulator (IMiD) in 6%, IP and IMiD in 24% and neither in 8%. At day 100 after ASCT, 57% had a complete remission, 32% a very good partial remission (VGPR) and 11% had &lt;VGPR. BM evaluation at day 100 detected a median of 0.3% PC, with 17% of patients having abnormal PC. For all follow‐up, relapse/progression was documented in 75%, 69% was biochemical and 31% clinic. In multivariate analysis, kidney insufficiency at diagnosis, &gt;0.25% BM PC at day 100 and detection of abnormal BM PC at day 100 impacted on R/PFS at 3y. Different risk groups for relapse/progression were defined according to the presence of 0, 1 or &gt;1 of these characteristics (median R/PFS not reached versus (vs) 24 vs 14 months, respectively; p &lt; 0.001; Figure 1A). In multivariate analysis, the three characteristics above and also age &gt;58y impacted on TNT at 3 years. Three groups with distinct timings for second line treatment were defined according to the presence of 0–1, 2 or &gt;2 of these risk factors (median TNT not reached vs 24 vs 16 months, respectively; p &lt; 0.001; Figure 1B). Summary/Conclusion: The addition of BM 4MFC PC analysis at day 100 after upfront ASCT to clinical characteristics identifies subgroups of MM patients with increased risk for relapse/progression and need for second line treatment, which may require different post‐ASCT observation. Further efforts are needed in order to validate and integrate affordable end of treatment disease burden evaluation in resource limited settings. image
Ledipasvir‐Sofosbuvir for 12 Weeks in Children 3 to &lt;6 Years Old With Chronic Hepatitis C
Authors: Kathleen B. Schwarz, Philip Rosenthal, Karen F. Murray, Jonathan R. Honegger, Winita Hardikar, Rosie Hague, Naveen Mittal, Benedetta Massetto, Diana M. Brainard, Chia‐Hsiang Hsueh, Jiang Shao, Bandita Parhy, Michael R. Narkewicz, Girish S. Rao, Suzanne Whitworth, Sanjay Bansal, William F. Balistreri
Journal: Hepatology (2019)

For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event "abnormal drug taste." The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.
Evaluating the impact of healthcare interventions using routine data
Authors: Geraldine M Clarke, Stefano Conti, Arne T Wolters, Adam Steventon
Journal: BMJ (2019)

What you need to knowAssessing the impact of healthcare interventions is critical to inform future decisions Compare observed outcomes with what you would have expected if the intervention had not been implementedA wide range of routinely collected data is available for the evaluation of healthcare interventionsInterventions to transform the delivery of health and social care are being implemented widely, such as those linked to Accountable Care Organizations in the United States, 1 or to integrated care systems in the UK. 2 Assessing the impact of these health interventions enables healthcare teams to learn and to improve services, and can inform future policy. 3However, some healthcare interventions are implemented without high quality evaluation, in ways that require onerous data collection, or may not be evaluated at all. 4 A range of routinely collected administrative and clinically generated healthcare data could be used to evaluate the impact of interventions to improve care.However, there is a lack of guidance as to where relevant routine data can be found or accessed and how they can be linked to other data.A diverse array of methodological literature can also make it hard to understand which methods to apply to analyse the data.This article provides an introduction to help clinicians, commissioners, and other healthcare professionals wishing to commission, interpret, or perform an impact evaluation of a health intervention.We highlight what to consider and discuss key concepts relating to design, analysis, implementation, and interpretation.
PB1869 PERSISTENT COMPLEMENT ACTIVATION IS PROVOKED BY IGG‐AGGREGATES IN A SUB‐POPULATION OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
Authors: R. Michelis, T. Tadmor, M. Barhoum, M. Shehadeh, L. Shvidel, A. Aviv, G. Stemer, N. Dally, N. Rahimi‐Levene, M. Yuklea, A. Braester
Journal: HemaSphere (2019)

Background: Therapeutic monoclonal antibodies used in Chronic lymphocytic leukemia (CLL) act through complement‐mediated cytotoxicity and other mechanisms, and thus depend on the complement (C) availability and activity. Recently we showed abnormal Western analysis pattern of the C5 component in some CLL patients, that was associated with high basal levels of C activation markers, and decreased activity of the classical pathway (CP). We hypothesized that the CP may be constantly activated, and thus exhausted, in a sub‐group of CLL patients, identified by the abnormal appearance of C5. Aims: The aim was to study the circulating abnormal C5 and its association with the observed decrease in CP activity, and to search for potential CP‐activating factors in CLL plasma. Methods: Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). Activities of the CP and of the CP C5‐convertase were studied. C5, C5a and C5b were studied by Western blot analysis. The presence of high molecular weight (HMW) protein complexes, such as IgM or hexameric‐IgG, as potential CP activators was assessed by sera fractionation (gel‐filtration chromatography) followed by C activation with the obtained HMW, and low molecular weight (LMW) fractions. The levels of IgM were measured. Data from patients with abnormal C5 was compared to normal NC subjects and to patients with normal C5. Results: In patients with abnormal C5, activities of the CP and of the CP C5‐convertase were decreased, compared to NC subjects and to patients with normal C5. The abnormal C5 was identified as a complex of immunoglobulin with C5a (Ig‐C5a). In agreement, the high levels of C activation markers showed negative and significant correlation with activity of the CP, but not with the alternative pathway. The data on C activation by the HMW fraction indicated the presence of IgG‐aggregates, and not IgM, as the C activating factor in sera. Summary/Conclusion: In some CLL patients, factors such as IgG‐aggregates that are present in sera constantly trigger the activation of the CP. This constant activation results in the release of activation products, such as C5a, that form the complex Ig‐C5a. Another result is the exhaustion of the CP and the inability to exert CP activity that is comparable to normal subjects. The data provides a potential prognostic tool that may personalize therapy by identifying a sub‐group of CLL patients who display Ig‐C5a and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity.