tbuckley/cabot-search huggingface dataset:
Monitoring latent tuberculosis infection diagnosis and management in the Netherlands
Authors: Connie G.M. Erkens, Erika Slump, Maurits Verhagen, Henrieke Schimmel, Gerard de Vries, Frank Cobelens, Susan van den Hof
Journal: European Respiratory Journal (2016)

Targeted diagnosis and treatment of latent tuberculosis (TB) infection (LTBI) among persons with a high risk of exposure to TB or of developing TB when infected has been performed and monitored routinely in the Netherlands since 1993. We describe trends in target groups, diagnostic methods and treatment regimens, and explore determinants for treatment initiation, treatment completion and adverse events. In total, 37 729 persons were registered with LTBI from 1993 to 2013, of whom 28 931 (77%) started preventive treatment; 82% of those completed preventive treatment and 8% stopped preventive treatment due to adverse events. Two-thirds of the notified cases were detected through contact investigation. Increasing numbers of persons with immunosuppressive disorders, elderly persons and foreign-born persons were notified in recent years, due to policy changes and the introduction of the interferon-γ release assay. Children (96%) and the immunosuppressed (95%) were more likely to start preventive treatment. Children (93%) were also more likely to complete preventive treatment, as were persons treated with rifampicin or rifampicin/isoniazid regimens (91% and 92%, respectively). The latter groups were also 40% less likely to stop preventive treatment due to adverse events. Under these operational conditions, the estimated risk reduction on incident TB in the target population for LTBI management is 40–60%.
Frequency and Dynamics of Leukemia-Initiating Cells during Short-term <i>Ex Vivo</i> Culture Informs Outcomes in Acute Myeloid Leukemia Patients
Authors: Emmanuel Griessinger, Fernando Anjos-Afonso, Jacques Vargaftig, David C. Taussig, François Lassailly, Thomas Prebet, Véronique Imbert, Marielle Nebout, Norbert Vey, Christian Chabannon, Andrew Filby, Frederic Bollet-Quivogne, John G. Gribben, Jean-François Peyron, Dominique Bonnet
Journal: Cancer Research (2016)

Abstract Acute myeloid leukemia (AML) is sustained by a subpopulation of rare leukemia-initiating cells (LIC) detected in the xenograft assay by their capacity to self-renew and to generate non-LICs in vivo. The xenotransplantation model captures functional properties of LICs that have clinical prognostic value. However, the long duration of this in vivo assay has hampered its use as a prognostic tool. Here, we show, using an ex vivo coculture system, that intermediate and poor risk AML patient samples at diagnosis have a 5 to 7 times higher frequency of leukemic long-term culture-initiating cells (L-LTC-IC) compared with the good risk group. We defined a fluorescence dilution factor (FDF) parameter that monitors sample proliferation over 1 week and established a strong correlation of this parameter with the L-LTC-IC frequency. A higher FDF was found for poor prognostic AMLs or for samples capable of engrafting NSG mice compared with good risk AMLs or nonengrafters. Importantly, FDF could classify normal karyotype intermediate risk patients into two groups with a significant difference in their overall survival, thus making this nongenetic and non-in vivo approach a new clinically relevant tool for better diagnosis of AML patients. Cancer Res; 76(8); 2082–6. ©2016 AACR.
Ontario Child Health Study: suicidal behavior in youth age 12-16 years
Authors: R T Joffe, D R Offord, M H Boyle
Journal: American Journal of Psychiatry (1988)

The authors report on the prevalence and correlates of suicidal behavior in youth age 12-16 years. The data, from a community prevalence survey, show that 5%-10% of the male and 10%-20% of the female youth reported suicidal behavior within a 6-month period. Suicidal behavior in youth appeared to be related to psychiatric disorder in general as well as to family dysfunction and parental arrest.
No increase in serious asthma events occurs with fluticasone plus salmeterol, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Patients with asthma who were treated with a fixed dose combination of the long acting beta-agonist (LABA) salmeterol plus the inhaled glucocorticoid fluticasone had no higher risk of asthma related death or hospital admission than those on fluticasone alone,1 shows a randomised study that provides some reassurance after previous safety concerns.

But an accompanying editorial warned that the findings may not apply to patients with the most severe and unstable disease—the patients that guidelines say should be treated with LABAs plus inhaled glucocorticoid as first line therapy—because they were excluded from the study. …
Fluid Accumulation During The Early Phases Of Hematopoietic Stem Cell Transplantation (HSCT) Is Associated With An Increased Risk Of Mortality and Complications
Authors: Erika MM Costa, Fernanda NC Santos, Erika Abdon Oliveira, Juliano Cordova Vargas, Karine Sampaio Nunes Barroso, Alessandro de Moura Almeida, Jose Mauro Kutner, Juliana F Fernandes, Andreza Alice Feitosa Ribeiro, Iracema Esteves, Guilherme Fleury Perini, Paulo Vidal Campregher, Jairo Sobrinho, Fabio R. Kerbauy, Nelson Hamerschlak, Fabio P S Santos
Journal: Blood (2013)
Poor leadership is blamed for failure to reshape Scotland’s health service
Authors: Bryan Christie
Journal: BMJ (2016)

Ambitious plans to reshape healthcare in Scotland to provide more care at home are being jeopardised by a lack of effective leadership from the Scottish government, says a report from Audit Scotland.1

Ministers set out a vision for transformational change in 2011, but the system has remained largely the same, said the report, as the hospital sector continues to be funded more generously than community based services.

Changes that have taken place have mostly been small …
Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis
Authors: Robert J Boyle, Despo Ierodiakonou, Tasnia Khan, Jennifer Chivinge, Zoe Robinson, Natalie Geoghegan, Katharine Jarrold, Thalia Afxentiou, Tim Reeves, Sergio Cunha, Marialena Trivella, Vanessa Garcia-Larsen, Jo Leonardi-Bee
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease. <b>Design</b>&nbsp;Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool. <b>Data sources</b>&nbsp;Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015. <b>Eligibility criteria for selecting studies</b>&nbsp;Prospective intervention trials of hydrolysed cows’ milk formula compared with another hydrolysed formula, human breast milk, or a standard cows’ milk formula, which reported on allergic or autoimmune disease or allergic sensitisation. <b>Results</b>&nbsp;37 eligible intervention trials of hydrolysed formula were identified, including over 19 000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows’ milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I<sup>2</sup>=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I<sup>2</sup>=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I<sup>2</sup>=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could prevent allergy to cows’ milk. <b>Conclusion</b>&nbsp;These findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants. <b>Review registration</b>&nbsp;PROSPERO CRD42013004252.
Patient-Reported Outcomes After Choice for Contralateral Prophylactic Mastectomy
Authors: E. Shelley Hwang, Tracie D. Locklear, Christel N. Rushing, Greg Samsa, Amy P. Abernethy, Terry Hyslop, Dunya M. Atisha
Journal: Journal of Clinical Oncology (2016)

Purpose The rate of contralateral prophylactic mastectomies (CPMs) continues to rise, although there is little evidence to support improvement in quality of life (QOL) with CPM. We sought to ascertain whether patient-reported outcomes and, more specifically, QOL differed according to receipt of CPM. Methods Volunteers recruited from the Army of Women with a history of breast cancer surgery took an electronically administered survey, which included the BREAST-Q, a well-validated breast surgery outcomes patient-reporting tool, and demographic and treatment-related questions. Descriptive statistics, hypothesis testing, and regression analysis were used to evaluate the association of CPM with four BREAST-Q QOL domains. Results A total of 7,619 women completed questionnaires; of those eligible, 3,977 had a mastectomy and 1,598 reported receipt of CPM. Women undergoing CPM were younger than those who did not choose CPM. On unadjusted analysis, mean breast satisfaction was higher in the CPM group (60.4 v 57.9, P &lt; .001) and mean physical well-being was lower in the CPM group (74.6 v 76.6, P &lt; .001). On multivariable analysis, the CPM group continued to report higher breast satisfaction (P = .046) and psychosocial well-being (P = .017), but no difference was reported in the no-CPM group in the other QOL domains. Conclusion Choice for CPM was associated with an improvement in breast satisfaction and psychosocial well-being. However, the magnitude of the effect may be too small to be clinically meaningful. Such patient-reported outcomes data are important to consider when counseling women contemplating CPM as part of their breast cancer treatment.
AB0865 Hydroxychloroquine in the Symptomatic Control of Erosive Hand Osteoarthritis: Table 1
Authors: N. Cid Boza, J.L. Marenco de la Fuente, E. Rejόn Gieb
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Erosive hand OA is considered a subtype of hand OA characterized by a marked inflammatory component, more aggressive disease and in most cases a major functional impairment in patients of middle age. Despite this, so far now we do not have a treatment option that had shown to be effective in clinical management of this disease. <h3>Objectives</h3> The aim of this study is to evaluate the effectiveness of Hydroxychloroquine (HCQ) in the symptomatic control of erosive hand osteoartritis after 24 weeks of treatment. <h3>Methods</h3> We performed a prospective open study. Consecutive patients with symptomatic hand OA despite NSAIDs/analgesics treatment fulfilling the American College of Rheumatology (ACR) criteria, with at least one erosion on hands radiography and pain VAS ≥40 mm without contraindication to HCQ treatment were included. Demographics data, hypertension, diabetes, dyslipidemia, and clinical presentation, were collected. Joint tenderness and swelling basal and after 24 weeks were assessed. Pain, joint stiffness and disability were assessed by the Australian/Canadian OA hand index (AUSCAN visual analog scale version) and HAQ. Tolerance and side effects was also registered. <h3>Results</h3> A total of 10 patients were included between July 2012 and July 2013 and all completed a 24 weeks follow up. There was a marked female predominance of 100% (even greater than expected) with a mean age of 57,7±9,2 and a mean disease duration of 6,5±6,17 years. Attending to cardiovascular risk factors, we found a prevalence of 60% hypercholesterolemia, 50% of hypertension, and no case of type II diabetes. With regard to clinical presentation we found 40% hands and feet OA, 20% generalized and 40% hands limited. Basal and after 24 weeks treatment clinical data are given in table 1. There was no major side effects. A 50% of patients reached a reduction of at least 20% of pain assessment by AUSCAN pain domain but only 36% of patiente reported to be better after 24 weeks of treatment. <h3>Conclusions</h3> Our results suggest that hydroxychloroquine may decrease inflammatory activity in erosive hands OA and thus functional impairment after 24 weeks of treatment but seems to have limited effect on global pain. Hydroxychloroquine was well tolerated and no major side effects were observed. <h3>Disclosure of Interest</h3> None declared
sCD48 is anti-inflammatory in<i>Staphylococcus aureus</i>Enterotoxin B-induced eosinophilic inflammation
Authors: R. S. Gangwar, F. Levi-Schaffer
Journal: Allergy (2016)

Background Staphylococcus aureus, one of the most important pathogens, is heavily associated with allergy. S. aureus and its toxins interact with eosinophils through CD48, a GPI-anchored receptor important in allergy mainly as expressed by the eosinophils (mCD48). CD48 can exist in a soluble form (sCD48). Our aim was to investigate SEB-induced regulation of eosinophil CD48 and the possible formation and role of sCD48 in SEB-mediated eosinophil activation in vitro and in vivo. Methods Human peripheral blood eosinophils were activated by SEB with or without inhibitors for phospholipases (PL) (-C or -D), or cycloheximide, or brefeldin A. We evaluated eosinophil activation (CD11b expression or EPO/IL-8 release), mCD48 (flow cytometry), sCD48 (ELISA), SEB binding to sCD48 (ELISA), and chemotaxis toward SEB. C57BL/6 mice were pre-injected (ip.) with sCD48, and then, peritonitis was induced by SEB injection; peritoneal lavages were collected after 48 h and analyzed by flow cytometry and ELISA. Results SEB-activated human eosinophils formed sCD48, directly correlating with CD11b expression, through cell-associated PL-C and -D. mCD48 remained stable due to up-regulation in CD48 transcription and cellular trafficking. sCD48 bound to SEB and down-regulated SEB stimulatory effects on eosinophils as assessed by EPO and IL-8 release and eosinophil chemotaxis toward SEB. sCD48 showed anti-inflammatory activity in a SEB-induced mouse peritonitis model. Conclusions SEB regulates CD48 dynamics on eosinophils. Our data indicate sCD48 as a SEB-induced 'decoy' receptor derived from eosinophil and therefore as a potential anti-inflammatory tool in S. aureus-induced eosinophil inflammation often associated with allergy.
N9741: FOLFOX (oxaliplatin(Oxal)/ 5-fluorouracil (5-FU)/ leucovorin (LV) or reduced dose R-IFL (CPT-11 + 5-FU/LV) in advanced colorectal cancer (CRC): Final efficacy data from an intergroup study
Authors: R. M. Goldberg, D. J. Sargent, R. F. Morton, C. Fuchs, R. K. Ramanathan, S. K. Williamson, B. P. Findlay, H. R. Pitot, S. R. Alberts
Journal: Journal of Clinical Oncology (2004)

3621 Background: After reducing doses of CPT-11 from 125 to 100 (doses in mg/m2) and 5FU from 500 to 400 (LV unchanged, 20 ) due to increased toxicity & early mortality (Rothenberg, JCO 2001), Intergroup N9741 concurrently randomized 355 of a planned 600 patients (pts) with CRC to FOLFOX-4 or R-IFL. Randomization was terminated early due to superior results on FOLFOX. Methods: The regimens were: FOLFOX 4 (Oxal 85 d 1 + LV 200/5-FU 400 bolus + 600 as a 22 hour infusion d 1,2 q 2 week); R-IFL (CPT-11 100 + LV 20/5FU bolus 400 weekly x 4, q 6 week. Results: Pts/arm were: FOLFOX-154, R-IFL-151. 60 day all-cause mortality was FOLFOX 2.0%, R-IFL 2.7%. Common grade ≥3 toxicities are below. With median follow-up of 18.0 months, median time to progression (TTP) (primary endpoint) for FOLFOX is significantly better than for R-IFL: 10.1 vs 6.5 months (mo) respectively (Logrank p<0.0001). The median survival (OS) is significantly greater for FOLFOX than R-IFL: 20.5 vs 16.3 mo (p = 0.026). Confirmed response rates (RR) were improved for FOLFOX vs. R-IFL (47% vs 32%, p=0.007). Sixty-five percent of pts received second line Rx with 75% in each arm receiving the agent not used in their first line treatment (in contrast to earlier phases of the study when access to Oxal was limited by availability). Conclusions: R-IFL lessens the toxicity burden of IFL, and results in efficacy similar to full dose IFL (median TTP 6.9 mo, RR 32%, median OS 15 months (Goldberg, JCO 2004)). FOLFOX improves RR, TTP, and OS compared to R-IFL. These results suggest that R-IFL, while not the best primary treatment option, retains activity with less toxicity than IFL, and may have utility as a platform for adding targeted therapies to IFL. Supported by NIH Grant CA25224, Pharmacia and Sanofi-Synthelabo. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacia/Pfizer; Sanofi-Synthelabo Sanofi-Synthelabo Pharmacia/Pfizer; Sanofi-Synthelabo; NCI Sanofi-Synthelabo
Back pain, tendons, Tiger Woods: all grist for the mill for sports medicine clinicians
Authors: Gavan White
Journal: British Journal of Sports Medicine (2016)

Sports Doctors Australia is proud to be in its fourth year as one of BJSM 's 23 member societies. This issue will touch a chord—pleasant or unpleasant—with most primary care practitioners. Clinicians are well aware of the inability to change the course of chronic low back pain in many people. When yet another patient comes in with persisting back pain, it may trigger a heart-sinking response or be seen as a challenge.

For a long time, we clinicians have tried to attack this problem through the reductionist model, believing that the more we understand about the cause of the pain, the more likely we were to improve the outcomes. Jorgen Jevne ( see page 198 ) editorialises where we have gone wrong in our approach to finding a structural cause to treat to help these people. It is time for us to stand back and take a more holistic approach to managing back pain.

Fleshing out this point—that some long-held recommendations may not be based on …
Inaccurate Reporting of Insulin Reimbursement
Authors: Jenny Bryant
Journal: JAMA Internal Medicine (2016)

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Sixty seconds on . . . meldonium
Authors: Nigel Hawkes
Journal: BMJ (2016)

Yes, definitely a double fault for the Russian tennis star.

Meldonium (also known as mildronate) is a drug made in Latvia used for treating heart failure, angina, and myocardial infarction. It isn’t licensed in the United States or Europe.

We don’t know, but it seems unlikely. She has said that she had magnesium …
Phase II trial of sunitinib maintenance therapy after platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (ES SCLC).
Authors: B. J. Schneider, S. M. Gadgeel, N. Ramnath, A. J. Wozniak, G. K. Dy, S. Daignault, G. P. Kalemkerian
Journal: Journal of Clinical Oncology (2010)

e18041 Background: The prognosis for patients (pts) with ES SCLC is poor, with a median progression-free (PFS) and overall survival (OS) of 5 mo. and 9 mo., respectively. This trial was designed to evaluate the efficacy/toxicity of maintenance sunitinib after platinum-based chemotherapy in pts with ES SCLC. Methods: Treatment consisted of cisplatin 75 mg/m2 IV or carboplatin AUC 5 on day 1 plus etoposide 100 mg/m2 IV on days 1-3 every 21 days for 4 cycles. If no evidence of disease progression was identified, sunitinib was given at 50 mg orally QD for 4 wks of a 6-wk cycle continuously until disease progression or unacceptable toxicity. The primary endpoint was proportion of pts progression-free 4 mo. after starting sunitinib. Treatment was deemed not interesting if the 4-mo. PFS rate after starting sunitinib was < 35%; target enrollment of 21 pts in first stage. Results: 16 pts were enrolled: median age 66 yrs (range 34-80); 8 men: 8 women; PS 0/1/2 = 5/10/1. Responses to platinum/etoposide were CR/PR/SD = 3/11/2. Median number of wks on sunitinib was 3.7 (range 1.4-20). Reasons for discontinuation of sunitinib were disease progression (8), toxicity (4), decline in PS (1) and patient request (3). Median PFS from the start of sunitinib was 2.6 mo. (range 0.5-8.7) with a 4 mo. PFS rate of 13% (95% CI 2-38%). Further accrual would fail to reach the 35% PFS rate threshold, so the study was terminated. There were no objective responses to sunitinib, but 4 pts (25%) had SD for 15, 15, 17 and 20 wks. Median PFS and OS from the start of chemotherapy was 6.3 mo. (range 1.6-12.4) and 8.9 mo. (range 4.7-24.6+), respectively, with 6 pts alive at 10–25 mo. Grade 3-4 toxicity for sunitinib included thrombocytopenia 31%, fatigue 19%, weakness 13%, hypothyroidism 13%, hand-foot syndrome 13% and hypertension 13%. 13% and 6% of pts required 1 or 2 dose reductions, respectively. Conclusions: Sunitinib did not appear to maintain disease stability after response to chemotherapy. Sunitinib was discontinued in half of pts due to toxicity or request to stop therapy. Although disease stability with sunitinib was noted in 4 pts, this approach does not appear to warrant further clinical study. Supported in part by Pfizer, Inc. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer