tbuckley/cabot-search huggingface dataset:
Managing in flight emergencies
Authors: C. L Gwinnutt, P. A Driscoll
Journal: BMJ (1995)

Emergency kit will now contain fatal dose of lignocaine

EDITOR,--While we admire the way in which W Angus Wallace and T Wong dealt with a tension pneumothorax under the adverse circumstances of a long haul flight, some comments have left us confused and concerned.1

The inability of both clinicians to …
A Successful Failure: Missing the MDG4 Target for Under-Five Mortality in South Africa
Authors: Peter Byass, Chodziwadziwa W. Kabudula, Paul Mee, Sizzy Ngobeni, Bernard Silaule, F. Xavier Gómez-Olivé, Mark A. Collinson, Aviva Tugendhaft, Ryan G. Wagner, Rhian Twine, Karen Hofman, Stephen M. Tollman, Kathleen Kahn
Journal: PLoS Medicine (2015)

Points• Millennium Development Goal (MDG) "success" is based on relatively arbitrary targets
Phase II Study of Liposomal Doxorubicin in Platinum- and Paclitaxel-Refractory Epithelial Ovarian Cancer
Authors: Alan N. Gordon, C.O. Granai, Peter G. Rose, John Hainsworth, Ana Lopez, Charles Weissman, Rosemary Rosales, Timothy Sharpington
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Stealth liposomal doxorubicin (Alzal Corp, Palo Alto, CA) has a slower clearance rate than free doxorubicin, resulting in sustained serum levels. Liposomal encapsulation also leads to increased concentration of drug in tumor tissue. Meta-analysis of previous studies has shown that doxorubicin has activity in epithelial ovarian cancer. The current study was developed to examine the activity of Stealth liposomal doxorubicin in platinum- and paclitaxel-refractory ovarian cancer. PATIENTS AND METHODS: Patients had epithelial ovarian cancer that either progressed on or recurred within 6 months of completion of platinum and paclitaxel chemotherapy. All patients had measurable disease. Stealth liposomal doxorubicin was administered at 50 mg/m 2 every 4 weeks as a 1-hour infusion. RESULTS: Eighty-nine patients were treated and included in an intent-to-treat analysis. There were 82 patients who were platinum and paclitaxel refractory and met all study criteria. There was one complete response and 14 partial responses, for a total response rate of 16.9% (95% confidence interval [CI], 9.1% to 24.6%). For platinum- and paclitaxel-refractory patients, the response rate was 18.3% (95% CI, 9.9% to 26.7%). Median time to progression was 19.3 weeks for the entire population. Ten patients (11.2%) withdrew because of adverse events related to the drug (palmar-plantar erythrodysesthesia [PPE], n = 3; asthenia, n = 2; cardiac, n = 2; neutropenia, n = 1; stomatitis, n = 1; and edema, n = 1). There were no drug-related fatal events. There were only eight grade 4 adverse events attributable to the drug. Stomatitis, PPE, and skin lesions were managed with dose reductions and delays in most cases. CONCLUSION: Stealth liposomal doxorubicin has activity in refractory epithelial ovarian cancer. PPE and stomatitis can usually be managed by dose adjustment. The ease of administration makes this an attractive agent.
Estradiol-stimulated nitric oxide release in human granulocytes is dependent on intracellular calcium transients: evidence of a cell surface estrogen receptor
Authors: George B. Stefano, Patrick Cadet, Christophe Breton, Yannick Goumon, Vincent Prevot, Jean Paul Dessaint, Jean-Claude Beauvillain, Ann S. Roumier, Ingeborg Welters, Michel Salzet
Journal: Blood (2000)
Novel organic arsenic molecule darinaparsin: Development of IV and oral forms
Authors: I. Lossos, M. D. Craig, M. S. Tallman, R. V. Boccia, P. R. Conkling, C. Becerra, P. B. Komarnitsky, B. L. Hamilton, J. Lewis, W. H. Miller
Journal: Journal of Clinical Oncology (2009)

8501 Background: Darinaparsin (ZIO-101) is a novel organic arsenical active against diverse cancers in vitro, and in vivo. Darinaparsin i.v. activity in lymphoma is being evaluated in a phase II study. Darinaparsin is orally bioavailable; the oral form is being investigated in two phase I studies in patients with advanced malignancies. Methods: Phase II trial is being conducted in patients diagnosed with advanced lymphomas who had ≥ 1 prior therapy. Patients receive 300 mg/m 2 /day of darinaparsin i.v. for 5 consecutive days every 28 days. Efficacy and safety are evaluated by standard criteria. Phase I oral dose escalation studies are being conducted in patients with advanced malignancies and explore safety, MTD, DLTs and preliminary efficacy of continuous and intermittent dosing schedules. Starting continuous dose is 100 mg BID for 3 weeks with 1 week rest, starting intermittent dose is 300 mg twice weekly for 3 weeks followed by 1 week rest. Results: The phase II study has accrued 28 lymphoma patients (21 non-Hodgkin's, 7 Hodgkin's); median age at baseline 61 years, ECOG ≤2, median number of prior therapies 3. Seventeen subjects have received at least 2 cycles of darinaparsin and are evaluable for efficacy. Of these, 1 subject (PTCL) has achieved a complete response, 3 - partial responses (2 marginal zone, 1 Hodgkin's), and 4 stable disease (2 PTCL, 1 DLBCL, 1 Hodgkin's). A total of 63 cycles of darinaparsin have been administered to subjects with lymphoma. No Gr. 3 or higher drug-related AEs were reported. Two SAEs were considered possibly drug-related (fall; neutropenic fever). Phase I studies accrued 35 patients; median age at baseline 58 years, ECOG ≤2, median number of prior therapies 3. Predominant tumor types include: colorectal (17), pancreatic (3), NHL (3). Current darinaparsin dose levels: continuous 200 mg BID, 2× weekly 900 mg. Of 18 patients evaluable for efficacy, 10 demonstrate SD ≥ 3 cycles. Oral darinaparsin bioavailability is 58%. Drug-related AEs include nausea/vomiting, fatigue, decreased appetite/anorexia. Conclusions: Darinaparsin is active in heavily pretreated patients with advanced lymphoma and has been very well tolerated. Oral darinaparsin is also well tolerated, and shows early activity. [Table: see text]
1,2-Dimethylhydrazine-Induced Nuclear Aberrations in A/J and C57BL/6J Mouse Colonic Crypts
Authors: L T Glickman, M K Senterman, D M Fleiszer
Journal: JNCI Journal of the National Cancer Institute (1987)

A single exposure to 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8] produces several forms of aberrant nuclei in the crypts of the murine colon. The frequency of nuclear aberrations (NAs) was examined in the distal colonic crypts in DMH-sensitive A/J mice and relatively DMH-resistant C57BL/6J mice before and after a single exposure to DMH. NAs, mitotic figures, and crypt column heights were scored for all animals as a function of time following administration of DMH. In both strains there was a significant increase in the absolute and relative frequency of NAs by 12 hours, with a corresponding drop and subsequent overshoot in the mitotic index by 48 hours after DMH. The temporal changes in crypt column height correlate closely with the temporal changes in frequency of NAs in both strains. The results showed that both inbred strains respond to acute DMH exposure in a similar and parallel fashion over time. It was concluded that the NA index assay is a sensitive method for detecting early DMH exposure. However, this assay does not relate to ultimate outcome after chronic DMH exposure and should not be used as a predictor of eventual neoplastic transformation of colonic mucosa with this carcinogen.
Outdoor exposure to formaldehyde is associated with increased DNA damage and respiratory symptoms in children
Authors: Paolo Girardi, Maria Enrica Fracasso, Alessandro Marcon, Denise Doria, Linda Guarda, Pierpaolo Marchetti, Giancarlo Pesce, Vanda Pironi, Giorgio Siliprandi, Paolo Ricci, Roberto de Marco
Journal: European Respiratory Journal (2012)

Background: Exposure to air pollutants emitted by industrial sources may be a health hazard for children living nearby.  Objectives: to evaluate whether residential outdoor exposure to formaldehyde was associated with DNA damage and with respiratory symptoms in children who lived in the largest chipboard manufacturing area in Northern Italy (Viadana).  Methods: In 2010, randomly selected children (6-12 years) living in the Viadana district were surveyed through a parental questionnaire on respiratory symptoms. A score was devised to evaluate the presence/intensity of asthma-like symptoms. DNA strand breaks and nuclear abnormalities of the oral mucosa cells were analyzed by the comet and micronucleus assays respectively. Passive samplers (n=63) were installed in the area to monitor formaldehyde both in winter and summer 2010. Kriging interpolation was used to estimate the concentration of formaldehyde of each child. Appropriate regression models were fitted to the data.  Results: 417 out of 656 eligible children (64%) took part in the study. Children living near ( 85th centile) had an increased risk of asthma like symptoms (OR=2.1; 1.1-4.2).  Conclusions: Exposure to pollutants emitted by chipboard industries statistically significantly increased DNA damage and asthma-like symptoms in children.
Results of invasive cervical cancer patients undergoing inadvertent hysterectomy followed by salvage radiotherapy
Authors: A. Goel, V. Goel, J. K. Singh
Journal: Journal of Clinical Oncology (2006)

15034 Background: Ca cervix is the leading gynecologic malignancy in India. Conventional treatment consists of radical hysterectomy or primary radiotherapy. Due to inadequate preop workup, invasive ca cervix has been incidentally found in surgical specimens after simple hysterectomy. Extrafascial hysterectomy is not curative as paracervical, paravaginal soft tissues &amp; vaginal cuff are not removed. It is technically difficult to perform adequate radical surgery after a previous simple hysterectomy. It is critical that these patients receive postop RT immediately after surgery; otherwise the prognosis is much worse. Methods: Retrospective analyses of 68 patients of ca cervix referred to our Institute after simple hysterectomy for presumed benign or preinvasive cervical disease was done. The median age was 44 yrs (35–65). 18 pts (26.5%) were pre menopausal while 50 (73.5%) were post menopausal. Exact postop staging was not possible; however 40 pts (59%) had residual growth at vault, 4 had involvement of vagina and in 18 cases parametrial infiltration was evident. Postop USG showed median tumor size of 4.4 cm, hydronephrosis in 17.6% &amp; bladder infiltration in 5.8% pts. Histopathology was squamous cell carcinoma in 97% cases. Results: All patients were treated with EBRT to whole pelvis (dose 50 Gy/25 Fr to 50.4 Gy/28 Fr) over 5-weeks, followed by central vaginal surface HDR brachytherapy (Dose 21 Gy/3 Fr). At an average follow up of 18 to 24 months post RT residual disease was present in 2 (2.9%), local recurrence in 6 (8.6%), scar recurrence in 2 (2.9%) and distant failures in 4 patients (5.8%). Radiation proctitis developed in 2, SAIO in 2, RVF in one and VVF in one patient. All local and distant failures were seen in patients with residual disease before starting RT. Poor response to RT was seen in patients elder than 40 years and when OTT was more than 75 days. No significant correlation was seen between local response rate and type or grade of tumor. Conclusion: Survival for patients with no residual cancer after simple hysterectomy is favorable; &amp; poor for those with gross disease at the start of post hysterectomy treatment. EBRT combined with one or two fractions of intravaginal brachytherapy in the immediate postop period can achieve satisfactory disease control. No significant financial relationships to disclose.
Balloon Angioplasty Versus New Device Intervention: Clinical Outcomes
Authors: Spencer B. King, Wanlin Yeh, Richard Holubkov, Donald S. Baim, George Sopko, Patrice Desvigne-Nickens, David R. Holmes, Michael J. Cowley, Martial G. Bourassa, James Margolis, Katherine M. Detre
Journal: Journal of the American College of Cardiology (1998)
Comparison of respiratory virus shedding by conventional and molecular testing methods in patients with haematological malignancy
Authors: L. Richardson, J. Brite, M. Del Castillo, T. Childers, A. Sheahan, Y.-T. Huang, E. Dougherty, N.E. Babady, K. Sepkowitz, M. Kamboj
Journal: Clinical Microbiology and Infection (2015)
Incidence and prevalence of non tuberculous mycobacteria [NTM] in adult CF population: A large adult CF centre experience
Authors: Arunesh Kumar, Christine Etherington, D.G. Peckham
Journal: European Respiratory Journal (2013)

Introduction 

Incidence of Non Tuberculous Mycobacterial [NTM] pulmonary infection has been increasing among Cystic Fibrosis patients reflecting the increase in longevity of such patients as well as the environmental exposure to various species of mycobacteria and possible association with antibiotics use.

Aims 

To find out the incidence and prevalence of different non tuberculous mycobacteria in patients with cystic fibrosis.

Patients and methods 

All Patients with Adult cystic fibrosis who are in clinic follow up were included. We searched our CF database to get information on the sputum microbiology on different culture positive NTM between 2007 and 2012. We also looked for type and frequency of different NTM cultured over this period.

Results 

A total of 403 patients were included, male 226[56%] and female 177[44%]. The overall prevalence of NTM in our CF population is 62 out of 403[ 15.38%] increasing from 18 out of 335[5.37%] in 2007.Among NTM, M.Avium Complex[MAC] is most common with prevalence of 27 out of 62 [43%], followed by M.abscessus 22 out of 62[35%]. M.Chelonae accounts for 19/62[30%], M.Kansasi 2/62[3%] and M.Fortuitum 1/62[1.62%]. Incidence of M.Abscessus infection has doubled from 1.49 % in 2007 to 2.72% in 2012 but the incidences of all other NTM have reduced.

Conclusion 

Co-infection with NTM is emerging as a significant problem in adult CF Population. Incidence of M.abscessus infection is increasing, posing a management challenge for pulmonary exacerbations in CF population.
Abstract 3699: Efficacy and Safety of Colesevelam HCl in Pediatric Patients with Heterozygous Familial Hypercholesterolemia
Authors: Evan A Stein, David Marais, Tamas Szamosi, Frederick Raal, Daniel Schurr, Elaine M Urbina, Paul N Hopkins, Sulekha Karki, Jianbo Xu, Michael Melino
Journal: Circulation (2008)

Heterozygous familial hypercholesterolemia (heFH) is a genetic disorder resulting in elevated LDL-C, which confers a high risk for a coronary event. Colesevelam HCl (COL), a non-absorbable bile acid sequestrant, is approved to lower LDL-C in adults with primary hypercholesterolemia. This is the first data demonstrating the efficacy and safety of COL in pediatric pts with heFH. This 32wk multicenter, randomized, double-blind (DB), placebo (PLA)-controlled study included: a 4wk PLA run-in (to measure compliance); an 8wk DB period (pts randomized 1:1:1 to PLA, 1.875 g/d COL, or 3.75 g/d COL); an 18wk open-label (OL) treatment to goal (LDL-C &lt;110 mg/dL) wherein all pts received COL 3.75 g/d (and were eligible to receive a statin); and a 2wk follow-up. Males and females, aged 10 –17yrs, with either genetic diagnosis of heFH or history of untreated LDL-C &gt;160 mg/dL combined with familial dyslipidemia in a first degree relative, who had a baseline LDL-C &gt;160 mg/dL (if naíve to lipid-lowering therapy) or &gt;130 mg/dL (if on a statin [≥6wks]) and following a NCEP step 1 diet were included. Additional inclusion criteria were TG &lt;250 mg/dL, ≥Tanner stage 2, and compliance ≥75% during the PLA run-in. Primary efficacy parameter was % change in LDL-C from baseline/Day 1 to Wk 8. The ITT population (randomized pts with a baseline and ≥1 post-baseline measurement) was used to evaluate efficacy parameters. Of the 194 pts randomized, 95.9% and 89.2% completed the DB and OL periods, respectively. Approximately 25% were on a statin at entry into the DB period; a further 10% added a statin during the OL period. At wk 8, LDL-C, TC, and apoB significantly decreased while HDL-C and apoA-I significantly increased with COL 3.75 g/d ( P &lt;0.01 vs PLA for all; Table ). Adverse events were as expected; no choking was recorded. No effects were noted on growth, sexual maturation, hormone levels, absorption of fat-soluble vitamins, or clotting parameters. In summary, COL lowered LDL-C and was well tolerated in pediatric pts.
Government’s U turn on custodial healthcare will endanger vulnerable people, says BMA
Authors: Adrian O’Dowd
Journal: BMJ (2015)

The UK government’s decision to drop plans to transfer police custodial healthcare commissioning to the NHS in England has been criticised by the BMA, which fears that it will put vulnerable people at risk of harm.

Currently, individual police forces provide healthcare for people in custody, who often include people with mental illness and drug and alcohol addictions. The BMA has previously raised concern about variation in care provided in these circumstances across the United Kingdom and …
The 3‐month readmission rate remains unacceptably high in a large North American cohort of patients with cirrhosis
Authors: Jasmohan S. Bajaj, K. Rajender Reddy, Puneeta Tandon, Florence Wong, Patrick S. Kamath, Guadalupe Garcia‐Tsao, Benedict Maliakkal, Scott W. Biggins, Paul J. Thuluvath, Michael B. Fallon, Ram M. Subramanian, Hugo Vargas, Leroy R. Thacker, Jacqueline G. O'Leary
Journal: Hepatology (2015)

In smaller single-center studies, patients with cirrhosis are at a high readmission risk, but a multicenter perspective study is lacking. We evaluated the determinants of 3-month readmissions among inpatients with cirrhosis using the prospective 14-center North American Consortium for the Study of End-Stage Liver Disease cohort. Patients with cirrhosis hospitalized for nonelective indications provided consent and were followed for 3 months postdischarge. The number of 3-month readmissions and their determinants on index admission and discharge were calculated. We used multivariable logistic regression for all readmissions and for hepatic encephalopathy (HE), renal/metabolic, and infection-related readmissions. A score was developed using admission/discharge variables for the total sample, which was validated on a random half of the total population. Of the 1353 patients enrolled, 1177 were eligible on discharge and 1013 had 3-month outcomes. Readmissions occurred in 53% (n = 535; 316 with one, 219 with two or more), with consistent rates across sites. The leading causes were liver-related (n = 333; HE, renal/metabolic, and infections). Patients with cirrhosis and with worse Model for End-Stage Liver Disease score or diabetes, those taking prophylactic antibiotics, and those with prior HE were more likely to be readmitted. The admission model included Model for End-Stage Liver Disease and diabetes (c-statistic = 0.64, after split-validation 0.65). The discharge model included Model for End-Stage Liver Disease, proton pump inhibitor use, and lower length of stay (c-statistic = 0.65, after split-validation 0.70). Thirty percent of readmissions could not be predicted. Patients with liver-related readmissions consistently had index-stay nosocomial infections as a predictor for HE, renal/metabolic, and infection-associated readmissions (odds ratio = 1.9-3.0).Three-month readmissions occurred in about half of discharged patients with cirrhosis, which were associated with cirrhosis severity, diabetes, and nosocomial infections; close monitoring of patients with advanced cirrhosis and prevention of nosocomial infections could reduce this burden. (Hepatology 2016;64:200-208).
A double blind placebo controlled study to assess the effect of roflumilast in addition to LABA/LAMA/ICS treatment in COPD patients using novel biomarkers
Authors: Jan De Backer, Wim Vos, Cedric Van Holsbeke, Rita Claes, Annemie Hufkens, Veronique Verplancke, Lieven Bedert, Wilfried De Backer
Journal: European Respiratory Journal (2014)

Rationale   Recently Roflumilast (PDE4 inhibitor, Daxas®, Takeda) has been added as therapeutic option for severe COPD patients. The current study aims to 1) assess the mode of action 2) identify responder type of Roflumilast as add-on to LABA/LAMA/ICS therapy in severe COPD patients.   Methods   41 patients were randomized to Roflumilast or placebo. At baseline and after 6m of treatment PFT, exercise tolerance tests (ETT) and functional respiratory imaging (FRI) were performed and patient reported outcomes (PRO) were measured.   Results   FEV1 did improve by 66±120ml (p=0.01) after Roflumilast as compared to baseline. Response was driven by a subset (n=8) of patients with a change in FEV1 g120ml (= measurement error of FEV1). Responders experienced worse dynamic hyperinflation during exercise at baseline compared to non-responders. FRI indicated regional changes in hyperinflation after Roflumilast leading to an improvement in PFT, PRO and ETT.   Conclusions   Roflumilast seems to reduce inflammation in the smaller airways resulting in reduced hyperinflation and changing internal airflow distribution (IAD). Changed IAD enhances deposition of LABA/LAMA/ICS leading to clinical improvements. Patients with dynamic hyperinflation tend to benefit from Roflumilast. These findings are relevant because 1) this is the first study to report effects of PDE4 inhibitor on top of ICS/LABA/LAMA; 2) sensitive, image-based endpoints provide insights in the mode of action of anti-inflammatory compounds and a basis for responder phenotyping. The current study provides hypotheses that need to be confirmed in larger clinical trials.  This study was funded by Takeda.
Injuries at the Whistler Sliding Center: a 4-year retrospective study
Authors: C A Stuart, D Richards, P A Cripton
Journal: British Journal of Sports Medicine (2015)

Background The Whistler Sliding Centre (WSC) in British Columbia, Canada, has played host to many events including the 2010 Winter Olympics. This study was performed to better understand sliding sport incident (crash, coming off sled, etc) and injury prevalence and provide novel insights into the effect of slider experience and track-specific influences on injury risk and severity. Methods Track documentation and medical records over 4 years (2007 track inception to 2011) were used to form 3 databases, including over 43 200 runs (all sliding disciplines). Statistics were generated relating incident and injury to start location, crash location and slider experience as well as to understand injury characteristics. Results Overall injury rate was found to be 0.5%, with more severe injury occurring in &lt;0.1% of the total number of runs. More frequent and severe injuries were observed at lower track locations. Of 2605 different sliders, 73.6% performed 1–29 runs down the track. Increased slider experience was generally found to reduce the frequency of injury. Lacerations, abrasions and contusions represented 52% of all injuries. A fatality represented the most severe injury on the track and was the result of track ejection. Conclusions By investigating the influence of start location, incident location and slider experience on incident and injury frequency and severity, a better understanding has been achieved of the inherent risks involved in sliding sports. Incident monitoring, with particular focus on track ejection, should be an emphasis of sliding tracks.