Effects of erythropoiesis-stimulating agents on fatigue- and anaemia-related symptoms in cancer patients: systematic review and meta-analyses of published and unpublished data.

Background:Erythropoiesis-stimulating agents (ESAs) reduce the need for red blood cell transfusions; however, they increase the risk of thromboembolic events and mortality. The impact of ESAs on quality of life (QoL) is controversial and led to different recommendations of medical societies and authorities in the USA and Europe. We aimed to critically evaluate and quantify the effects of ESAs on QoL in cancer patients.Methods:We included data from randomised controlled trials (RCTs) on the effects of ESAs on QoL in cancer patients. Randomised controlled trials were identified by searching electronic data bases and other sources up to January 2011. To reduce publication and outcome reporting biases, we included unreported results from clinical study reports. We conducted meta-analyses on fatigue- and anaemia-related symptoms measured with the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and FACT-Anaemia (FACT-An) subscales (primary outcomes) or other validated instruments.Results:We identified 58 eligible RCTs. Clinical study reports were available for 27% (4 out of 15) of the investigator-initiated trials and 95% (41 out of 43) of the industry-initiated trials. We excluded 21 RTCs as we could not use their QoL data for meta-analyses, either because of incomplete reporting (17 RCTs) or because of premature closure of the trial (4 RCTs). We included 37 RCTs with 10 581 patients; 21 RCTs were placebo controlled. Chemotherapy was given in 27 of the 37 RCTs. The median baseline haemoglobin (Hb) level was 10.1 g dl(-1); in 8 studies ESAs were stopped at Hb levels below 13 g dl(-1) and in 27 above 13 g dl(-1). For FACT-F, the mean difference (MD) was 2.41 (95% confidence interval (95% CI) 1.39-3.43; P<0.0001; 23 studies, n=6108) in all cancer patients and 2.81 (95% CI 1.73-3.90; P<0.0001; 19 RCTs, n=4697) in patients receiving chemotherapy, which was below the threshold (⩾3) for a clinically important difference (CID). Erythropoiesis-stimulating agents had a positive effect on anaemia-related symptoms (MD 4.09; 95% CI 2.37-5.80; P=0.001; 14 studies, n=2765) in all cancer patients and 4.50 (95% CI 2.55-6.45; P<0.0001; 11 RCTs, n=2436) in patients receiving chemotherapy, which was above the threshold (⩾4) for a CID. Of note, this effect persisted when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy. There was some evidence that the MDs for FACT-F were above the threshold for a CID in RCTs including cancer patients receiving chemotherapy with Hb levels below 12 g dl(-1) at baseline and in RCTs stopping ESAs at Hb levels above 13 g dl(-1). However, these findings for FACT-F were not confirmed when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy.Conclusions:In cancer patients, particularly those receiving chemotherapy, we found that ESAs provide a small but clinically important improvement in anaemia-related symptoms (FACT-An). For fatigue-related symptoms (FACT-F), the overall effect did not reach the threshold for a CID.British Journal of Cancer advance online publication, 17 April 2014; doi:10.1038/bjc.2014.171 www.bjcancer.com.

Risk factors associated with the longevity of multi-rooted teeth. Long-term outcomes after active and supportive periodontal therapy

AIM To investigate risk factors for the loss of multi-rooted teeth (MRT) in subjects treated for periodontitis and enrolled in supportive periodontal therapy (SPT). MATERIAL AND METHODS A total of 172 subjects were examined before (T0) and after active periodontal therapy (APT)(T1) and following a mean of 11.5 ± 5.2 (SD) years of SPT (T2). The association of risk factors with loss of MRT was analysed with multilevel logistic regression. The tooth was the unit of analysis. RESULTS Furcation involvement (FI) = 1 before APT was not a risk factor for tooth loss compared with FI = 0 (p = 0.37). Between T0 and T2, MRT with FI = 2 (OR: 2.92, 95% CI: 1.68, 5.06, p = 0.0001) and FI = 3 (OR: 6.85, 95% CI: 3.40, 13.83, p < 0.0001) were at a significantly higher risk to be lost compared with those with FI = 0. During SPT, smokers lost significantly more MRT compared with non-smokers (OR: 2.37, 95% CI: 1.05, 5.35, p = 0.04). Non-smoking and compliant subjects with FI = 0/1 at T1 lost significantly less MRT during SPT compared with non-compliant smokers with FI = 2 (OR: 10.11, 95% CI: 2.91, 35.11, p < 0.0001) and FI = 3 (OR: 17.18, 95% CI: 4.98, 59.28, p < 0.0001) respectively. CONCLUSIONS FI = 1 was not a risk factor for tooth loss compared with FI = 0. FI = 2/3, smoking and lack of compliance with regular SPT represented risk factors for the loss of MRT in subjects treated for periodontitis.

Measurement of isolated-photon pair production in pp collisions at sqrts=7 TeV with the ATLAS detector

The ATLAS experiment at the LHC has measured the production cross section of events with two isolated photons in the final state, in proton-proton collisions at root s = 7 TeV. The full data set collected in 2011, corresponding to an integrated luminosity of 4.9 fb(-1), is used. The amount of background, from hadronic jets and isolated electrons, is estimated with data-driven techniques and subtracted. The total cross section, for two isolated photons with transverse energies above 25 GeV and 22 GeV respectively, in the acceptance of the electromagnetic calorimeter (vertical bar eta vertical bar < 1.37 and 1.52 < vertical bar eta vertical bar 2.37) and with an angular separation Delta R > 0.4, is 44.0(-4.2)(+3.2) pb. The differential cross sections as a function of the di-photon invariant mass, transverse momentum, azimuthal separation, and cosine of the polar angle of the largest transverse energy photon in the Collins-Soper di-photon rest frame are also measured. The results are compared to the prediction of leading-order parton-shower and next-to-leading-order and next-to-next-to-leading-order parton-level generators.

Long-term outcome of elderly patients with severe aortic stenosis as a function of treatment modality

OBJECTIVE To assess long-term clinical outcomes of consecutive high-risk patients with severe aortic stenosis according to treatment allocation to transcatheter aortic valve implantation (TAVI), surgical aortic valve replacement (SAVR) or medical treatment (MT). METHODS Patients with severe aortic stenosis were consecutively enrolled into a prospective single centre registry. RESULTS Among 442 patients (median age 83 years, median STS-score 4.7) allocated to MT (n=78), SAVR (n=107), or TAVI (n=257) all-cause mortality amounted to 81%, 37% and 43% after a median duration of follow-up of 3.9 years (p<0.001). Rates of major adverse cerebro-cardiovascular events were lower in patients undergoing SAVR or TAVI as compared with MT (SAVR vs MT: HR 0.31, 95% CI 0.21 to 0.46) (TAVI vs MT: HR 0.34, 95% CI 0.25 to 0.46), with no significant difference between SAVR and TAVI (HR 0.88, 95% CI 0.62 to 1.25). Whereas SAVR (HR 0.39, 95% CI 0.24 to 0.61), TAVI (HR 0.37, 95% CI 0.26 to 0.52), and female gender (HR 0.72, 95% CI 0.53 to 0.99) were associated with improved survival, body mass index ≤20 kg/m(2) (HR 1.60, 95% CI 1.04 to 2.47), diabetes (HR 1.48, 95% CI 1.03 to 2.12), peripheral vascular disease (HR 2.01, 95% CI 1.44 to 2.81), atrial fibrillation (HR 1.74, 95% CI 1.28 to 2.37) and pulmonary hypertension (HR 1.43, 95% CI 1.03 to 2.00) were identified as independent predictors of mortality. CONCLUSIONS Among high-risk patients with severe aortic stenosis, long-term clinical outcome through 5 years was comparable between patients allocated to SAVR or TAVI. In contrast, patients with MT had a dismal prognosis.

Additional surgical procedure is a risk factor for surgical site infections after laparoscopic cholecystectomy

PURPOSE: Surgical site infections (SSI) are associated with increased costs and length of hospital stay, readmission rates, and mortality. The aim of this study was to identify risk factors for SSI in patients undergoing laparoscopic cholecystectomy. METHODS: Analysis of 35,432 laparoscopic cholecystectomies of a prospective multicenter database was performed. Risk factors for SSI were identified among demographic data, preoperative patients' history, and operative data using multivariate analysis. RESULTS: SSIs after laparoscopic cholecystectomy were seen in 0.8 % (n = 291) of the patients. Multivariate analysis identified the following parameters as risk factors for SSI: additional surgical procedure (odds ratio [OR] 4.0, 95 % confidence interval [CI] 2.2-7.5), age over 55 years (OR 2.4 [1.8-3.2]), conversion to open procedure (OR 2.6 [1.9-3.6]), postoperative hematoma (OR 1.9 [1.2-3.1]), duration of operation >60 min (OR 2.5 [1.7-3.6], cystic stump insufficiency (OR 12.5 [4.2-37.2]), gallbladder perforation (OR 6.2 [2.4-16.1]), gallbladder empyema (OR 1.7 [1.1-2.7]), and surgical revision (OR 15.7 [10.4-23.7]. SSIs were associated with a significantly prolonged hospital stay (p < 0.001), higher postoperative mortality (p < 0.001), and increased rate of surgical revision (p < 0.001). CONCLUSIONS: Additional surgical procedure was identified as a strong risk factor for SSI after laparoscopic cholecystectomy. Furthermore, operation time >60 min, age >55 years, conversion to open procedure, cystic stump insufficiency, postoperative hematoma, gallbladder perforation, gallbladder empyema, or surgical revision were identified as specific risk factors for SSI after laparoscopic cholecystectomy.

Risk factors for depressed mood amongst a community dwelling older age population in England: cross-sectional survey data from the PRO-AGE study.

BACKGROUND The Quality and Outcomes Framework in the United Kingdom (UK) National Health Service previously highlighted case finding of depression amongst patients with diabetes or coronary heart disease. However, depression in older people remains under-recognized. Comprehensive data for analyses of the association of depression in older age with other health and functional measures, and demographic factors from community populations within England, are lacking. METHODS Secondary analyses of cross-sectional baseline survey data from the England arm of a randomised controlled trial of health risk appraisal for older people in Europe; PRO-AGE study. Data from 1085 community-dwelling non-disabled people aged 65 years or more from three group practices in suburban London contributed to this study. Depressed mood was ascertained from the 5-item Mental Health Inventory Screening test. Exploratory multivariable logistic regression was used to identify the strongest associations of depressed mood with a previous diagnosis of a specified physical/mental health condition, health and functional measures, and demographic factors. RESULTS Depressed mood occurred in 14% (155/1085) of participants. A previous diagnoses of depression (OR 3.39; P < 0.001) and poor vision as determined from a Visual Function Questionnaire (OR 2.37; P = 0.001) were amongst the strongest factors associated with depressed mood that were independent of functional impairment, other co-morbidities, and demographic factors. A subgroup analyses on those without a previous diagnosis of depression also indicated that within this group, poor vision (OR 2.51; P = 0.002) was amongst the strongest independent factors associated with depressed mood. CONCLUSIONS Previous case-finding strategies in primary care focussed on heart disease and diabetes but health-related conditions other than coronary heart disease and diabetes are also associated with an increased risk for depression. Complex issues of multi-morbidity occur within aging populations. 'Risk' factors that appeared stronger than those, such as, diabetes and coronary heart disease that until recently prompted for screening in the UK due to the QOF, were identified, and independent of other morbidities associated with depressed mood. From the health and functional factors investigated, amongst the strongest factors associated with depressed mood was poor vision. Consideration to case finding for depressed mood among older people with visual impairment might be justified.

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at √s=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of √s = 8TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4 (stat.) +3.2 −2.9 (syst.) ±1.2 (lumi) fb for a Higgs boson of mass 125.4 GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations.

Measurement of the inclusive isolated prompt photons cross section in pp collisions at s √ =7 TeV with the ATLAS detector using 4.6 fb −1

A measurement of the cross section for the production of isolated prompt photons in pp collisions at a center-of-mass energy s √ =7  TeV is presented. The results are based on an integrated luminosity of 4.6  fb −1 collected with the ATLAS detector at the LHC. The cross section is measured as a function of photon pseudorapidity η γ and transverse energy E γ T in the kinematic range 100≤E γ T <1000  GeV and in the regions |η γ |<1.37 and 1.52≤|η γ |<2.37 . The results are compared to leading-order parton-shower Monte Carlo models and next-to-leading-order perturbative QCD calculations. Next-to-leading-order perturbative QCD calculations agree well with the measured cross sections as a function of E γ T and η γ .

Risk factors for Clostridium difficile nosocomial diarrhea in patients at the Michael E. Debakey Veterans Affairs Medical Center, Houston, Texas

Background. Clostridium difficile is the leading cause of hospital associated infectious diarrhea and colitis. About 3 million cases of Clostridium difficile diarrhea occur each year with an annual cost of $1 billion. ^ About 20% of patients acquire C. difficile during hospitalization. Infection with Clostridium difficile can result in serious complications, posing a threat to the patient's life. ^ Purpose. The aim of this research was to demonstrate the uniqueness in the characteristics of C. difficile positive nosocomial diarrhea cases compared with C. difficile negative nosocomial diarrhea controls admitted to a local hospital. ^ Methods. One hundred and ninety patients with a positive test and one hundred and ninety with a negative test for Clostridium difficile nosocomial diarrhea, selected from patients tested between January 1, 2002 and December 31, 2003, comprised the study population. Demographic and clinical data were collected from medical records. Logistic regression analyses were conducted to determine the associated odds between selected variables and the outcome of Clostridium difficile nosocomial diarrhea. ^ Results. For the antibiotic classes, cephalosporins (OR, 1.87; CI 95, 1.23 to 2.85), penicillins (OR, 1.57; CI 95, 1.04 to 2.37), fluoroquinolones (OR, 1.65; CI 95, 1.09 to 2.48) and antifungals (OR, 2.17; CI 95, 1.20 to 3.94), were significantly associated with Clostridium difficile nosocomial diarrhea Ceftazidime (OR, 1.95; CI 95, 1.25 to 3.03, p=0.003), gatifloxacin (OR, 1.97; CI 95, 1.31 to 2.97, p=0.001), clindamycin (OR, 3.13; CI 95, 1.99 to 4.93, p<0.001) and vancomycin (OR, 1.77; CI 95, 1.18 to 2.66, p=0.006, were also significantly associated with the disease. Vancomycin was not statistically significant when analyzed in a multivariable model. Other significantly associated drugs were, antacids, laxatives, narcotics and ranitidine. Prolong use of antibiotics and an increased number of comorbid conditions were also associated with C. difficile nosocomial diarrhea. ^ Conclusion. The etiology for C. difficile diarrhea is multifactorial. Exposure to antibiotics and other drugs, prolonged antibiotic usage, the presence and severity of comorbid conditions and prolonged hospital stay were shown to contribute to the development of the disease. It is imperative that any attempt to prevent the disease, or contain its spread, be done on several fronts. ^

Evaluation of epidemiological and clinical factors in survival of patients with de novo myelodysplastic syndrome at the University of Texas MD Anderson cancer center

Little is known about epidemiological markers that are associated with survival of patients with myelodysplastic syndromes (MDS). We conducted a secondary case-based analysis of 465 de novo MDS patients from the University of Texas MD Anderson Cancer Center (UTMDACC). We investigated the association between demographic as well as occupational exposure markers and survival while incorporating known clinical markers of prognosis. In our patient population, 60.6% were men and the majority were white (93.1%). The distribution of MDS subtypes by the French–American–British (FAB) classification was 81 (19%) refractory anemia (RA), 46 (9.9%) refractory anemia with ringed sideroblasts (RARS), 57 (12.3%) chronic myelomonocytic leukemia (CMML), 173 (37.2%) RA with excess blasts (RAEB), and 86 (18.5%) RAEB in transformation (RAEBT). We found that those older at diagnosis (> 60 years of age) (HR = 1.68, CI = 1.26-2.25) were at a higher risk of dying compared to younger patients. Similarly, high pack years of smoking (>= 30 pack years of smoking) (HR = 1.34, CI = 1.02-1.74), and agricultural chemical exposure (HR = 1.61, CI = 1.05-2.46) were significantly associated with overall lower survival when compared to patients with none or medium exposures. Among clinical markers, greater than 5% bone marrow blasts (HR = 1.81 CI = 1.27-2.56), poor cytogenetics (HR = 3.20, CI = 2.37-4.33)), and platelet cytopenias (<100000/ul) (HR = 1.46, CI = 1.11-1.92) were also significantly associated with overall MDS survival.^ The identification of epidemiological markers could help physicians stratify patients and customize treatment strategies to improve the outcome of MDS based on patient lifestyle information such as smoking exposure and agrochemical exposure. We hope that this study highlights the impact of these exposures in MDS prognosis.^

Geochemistry at DSDP Legs 36 and 71 Holes

For Middle Jurassic to Pleistocene times, clay mineralogical and geochemical data provide information on the evolution of continental and marine paleoenvironments. They are a source of information on marginal instability, on the continental and shallow marine environments related to the development of the Southern Ocean during the Middle and Late Jurassic, and on tectonic relaxation of the continental margins at the end of the Late Jurassic. They also provide evidence for the influences of the South Atlantic opening and the movement of the Falkland Plateau in a reduced marine environment until Aptian-Albian times, and the transition to an open marine environment during Albian time; the influences of the Albian-Turonian and Coniacian-Santonian Andean deformations in an open marine environment; the limited tectonic effects and strong influence of marine currents at the Cretaceous/Tertiary boundary; the influences of the global climatic cooling and inferred bottom water circulation during the late Eocene and Oligocene; the widening of the South Atlantic Ocean during Oligocene time, which was accompanied by an increased influence of the biogenic components on sedimentation; increased carbonate dissolution from late Oligocene to early Miocene, related to the deepening of the ocean; limited mineralogical and important geochemical modifications when the Drake Passage opened in the early Miocene; the influence of the late Miocene development of the Antarctic ice-sheet; the major Antarctic cooling and Patagonian glaciation during Pliocene time; and the change in the Antarctic Bottom Water circulation at the Pliocene/Pleistocene boundary.