The "NUTS" statistic: Applying an EBM disease model to defensive medicine.

Physicians believe that malpractice concerns result in unnecessary testing, and many emergency physicians state that avoiding malpractice is a contributing factor to ordering medically unnecessary tests. Unfortunately, defensive medicine does not come without possible harm to patients who may be subject to non-beneficial, downstream testing, procedures, and hospitalizations. We submit a novel statistic, "NUTS" or "Number of Unnecessary Tests to avoid one Suit. " We calculated a NUTS of 4737 for troponin testing in ED patients with suspected myocardial infarction, meaning a clinician will need to order 4737 medically unnecessary troponin tests to avoid one missed myocardial infarction lawsuit. The NUTS framework offers us an evidence-based lens to examine defensive medicine less superstitiously and more based on currently available data.AMSUNY DownstateEmergency MedicineN/

Decreased thermal tolerance under recurrent heat stress conditions explains summer mass mortality of the blue mussel Mytilus edulis

Extreme events such as heat waves have increased in frequency and duration over the last decades. Under future climate scenarios, these discrete climatic events are expected to become even more recurrent and severe. Heat waves are particularly important on rocky intertidal shores, one of the most thermally variable and stressful habitats on the planet. Intertidal mussels, such as the blue mussel Mytilus edulis, are ecosystem engineers of global ecological and economic importance, that occasionally suffer mass mortalities. This study investigates the potential causes and consequences of a mass mortality event of M. edulis that occurred along the French coast of the eastern English Channel in summer 2018. We used an integrative, climatological and ecophysiological methodology based on three complementary approaches. We first showed that the observed mass mortality (representing 49 to 59% of the annual commercial value of local recreational and professional fisheries combined) occurred under relatively moderate heat wave conditions. This result indicates that M. edulis body temperature is controlled by non-climatic heat sources instead of climatic heat sources, as previously reported for intertidal gastropods. Using biomimetic loggers (i.e. 'robomussels'), we identified four periods of 5 to 6 consecutive days when M. edulis body temperatures consistently reached more than 30 °C, and occasionally more than 35 °C and even more than 40 °C. We subsequently reproduced these body temperature patterns in the laboratory to infer M. edulis thermal tolerance under conditions of repeated heat stress. We found that thermal tolerance consistently decreased with the number of successive daily exposures. These results are discussed in the context of an era of global change where heat events are expected to increase in intensity and frequency, especially in the eastern English Channel where the low frequency of commercially exploitable mussels already questions both their ecological and commercial sustainability.Funding Agency French Ministere de l'Enseignement Superieur et de la Recherche Region Hauts-de-France European Funds for Regional Economical Development Pierre Hubert Curien PESSOA Felloswhip Fundacao para a Ciencia e Tecnologia (FCT-MEC, Portugal) IF/01413/2014/CP1217/CT0004 National Research Foundation - South Africa 64801 South African Research Chairs Initiative (SARChI) of the Department of Science and Technology National Research Foundation - South Africainfo:eu-repo/semantics/publishedVersio

P433 Sex-based differences in response to tumor necrosis factor inhibitor induction therapy for ulcerative colitis: a pooled analysis of individual patient-level clinical trials data

Abstract Background There are increasing data on sex-based differences in IBD epidemiology, phenotype and outcomes. The purpose of this study was to characterize sex-based differences in response to tumor necrosis factor inhibitor (TNFi) therapies in patients with ulcerative colitis (UC). Methods We conducted a pooled analysis of individual-level data from randomized clinical trials (RCTs) on induction therapy with infliximab and golimumab, accessed through the Yale University Open Data Access platform. We analyzed patients in the treatment and placebo arms separately. Using multivariable logistic regression modeling, we compared the primary outcome of clinical remission, and secondary outcomes of clinical response and mucosal healing, according to clinical trial definitions, between male and female patients with UC at week 6 (golimumab) or week 8 (infliximab) of induction therapy. Effect estimates were expressed as adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results We included 1639 patients (696, 42.5% were women, Table) from two trials using infliximab (ACT-1 and 2) and one trial using golimumab (PURSUIT). Male patients were older than female patients in the treatment arm of the overall cohort [mean age (standard deviation) 31.31 (16.53) years and 29.34 (15.19) years, respectively). All other baseline characteristics, such as sex, race, Mayo score at screening, and concomitant systemic corticosteroid and immunomodulator use were comparable. Compared to female patients, male patients were significantly less likely to achieve clinical remission in both treatment and placebo arms (aOR 0.55, 95% CI 0.31, 0.97 and 0.34, 95% CI 0.15, 0.82, respectively, Figure). Compared to female patients, male patients were significantly less likely to achieve mucosal healing and clinical response in the treatment arm (aOR 0.47, 95% CI 0.27, 0.83 and 0.51, 95% CI 0.29, 0.90, respectively), but there was no significant difference in these secondary outcomes by sex in the placebo arm. Conclusion Based on this analysis of pooled data from RCTs, we demonstrate that clinical remission, response and mucosal healing with TNFi induction therapies are less likely in male patients compared to female patients with UC. Clinical remission is also less likely in male patients on placebo. These finding may lead to further research on sex-based differences in treatment outcomes, including mechanistic studies. </jats:sec

Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer

Abstract High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous marrow support, time to engraftment, antibiotic days, transfusion requirements, and lengths of hospital stay were all significantly improved for the patients receiving PBPCs. Thus, autologous PBPCs can be efficiently collected during mobilization by chemotherapy and GM-CSF and are an attractive alternative to marrow for hematopoietic support after high-dose therapy. The enhanced speed of recovery may reduce the morbidity, mortality, and cost of high-dose treatment. Furthermore, PBPC support may enhance the effectiveness of high-dose therapy by facilitating multiple courses of therapy.</jats:p

Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer

High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous marrow support, time to engraftment, antibiotic days, transfusion requirements, and lengths of hospital stay were all significantly improved for the patients receiving PBPCs. Thus, autologous PBPCs can be efficiently collected during mobilization by chemotherapy and GM-CSF and are an attractive alternative to marrow for hematopoietic support after high-dose therapy. The enhanced speed of recovery may reduce the morbidity, mortality, and cost of high-dose treatment. Furthermore, PBPC support may enhance the effectiveness of high-dose therapy by facilitating multiple courses of therapy.</jats:p

Clarithromycin, lenalidomide and dexamethasone combination therapy as primary treatment of multiple myeloma

7545 Background: Lenalidomide (Revlamid [R]) is the leading clinical compound in a new group of drugs called IMiDs. Our group demonstrated that clarithromycin (Biaxin [Bi]) augments tumor mass reduction and improves responses in patients (pts) receiving low-dose thalidomide and/or dexamethasone (D). We report the results of the combination of Bi plus R plus D (BiRD) in newly diagnosed MM. Methods: A phase II trial designed to accrue 50 pts. A 2-stage design rejects a CR rate of &lt; 10% (alt &gt;30%). Between Nov. 2004 and Jan. 2006, 46 pts have been accrued of which 40 pts are eligible for evaluation. R is given po at 25 mg daily on days 1–21 of a 28-day cycle. D is given po at 40 mg once weekly. Bi is given po at 500 mg bid. Pts receive low dose aspirin (ASA)(81mg) qd as thrombosis (TE) prophylaxis. Responses are defined according to modified EBMTR criteria. Analysis is by intent-to-treat. Patient Selection: Median age: 62.5 years (36–80), Male/Female 25/15, Hgb: 10.6 g/dL (7.2–15.1), Plt 234 k/uL (51–526), β2m: 3 mg/L (0.8–12.8), CRP: 0.6 mg/dL (0.12–14.2), creat: 1.1 mg/dL (0.6–3.1), albumin 3.5 g/dL (2.3–4.9). SD stage IIIa: 48%, stage IIIb: 10% and IIa: 42%. ISS stage I: 50%, stage II: 25% and stage III: 25%. Cytogenetics and FISH: trisomy 11 (10 pts), tetrasomy 11 (3 pts), del13q14 (14 pts), t (4,14) (1pt), t (11,14) (3 pts). Results: Of the 40 evaluable pts, 38 (95%) have achieved an objective response (&gt;PR) within 3–4 months of Rx with the remaining pts continuing to respond. Seventeen pts (43%) had a &gt;90% reduction of the initial paraprotein. Nearly one third of pts have achieved either a CR (10/40) or a nCR (2/40-continuing on Rx). CR has been confirmed in all pts by normalization of free light chain levels and ratio. The remaining 26 pts (65%) achieved a PR. Of those pts who achieved a PR, 5/26 pts (19%) had &gt;90% reduction in the initial paraprotein. Nineteen pts have experienced grade ≥3 adverse events. Heme toxicities: anemia (11%), neutropenia (9%) and thrombocytopenia (9%). Non-heme toxicities (NHT) include TE in 7 patients (15%) 2 of them fatal. Four of the TE events were while off ASA. Other NHT include myopathy (6%), GI (4%), and mood (4%). Conclusions: BiRD therapy is a safe and highly effective primary therapy for symptomatic, treatment-naïve MM. [Table: see text] </jats:p