Measuring the severity of upper gastrointestinal complaints: does GP assessment correspond with patients' self-assessment?

BACKGROUND: Questionnaires are frequently used to measure the severity of gastrointestinal (GI) complaints. These questionnaires can either be filled out by the physicians or by the patients, but it is not clear whether these scores correspond. This study aimed to investigate the interrater agreement between physician-reported severity and patient-reported severity concerning the patients' upper GI complaints. METHODS: In a prospective observational study, the severity of eight GI complaints was registered by both patients and GPs independently on a seven-point scale (n = 316) before and after treatment with esomeprazole. Weighted kappa values for the agreement on the severity and simple kappa values for the agreement on the absence or presence of symptoms were calculated. RESULTS: The weighted kappa values ranged from 0.14 to 0.68 indicating poor to moderate agreement. The agreement on the presence or absence of symptoms was similar. Several systematic differences in scoring were found: the GPs tended to underestimate the severity of belching, nausea, early satiety, vomiting and upper and lower abdominal pain. Furthermore, the treatment effect for belching and lower abdominal pain was more often overestimated, while the treatment effect for nausea was more often underestimated by the GP. CONCLUSION: The agreement between GP and patient is low. The differences in scoring should be kept in mind when comparing physician-reported outcomes with patient-reported outcomes.     

Prothrombin and factor X are elevated in multiple sclerosis patients

Animal models have implicated an integral role for coagulation factors in neuroinflammatory diseases such as multiple sclerosis (MS) beyond their role in hemostasis. However, their relevance in humans requires further elucidation. This study aimed to determine whether levels of coagulation factors differ between patients with neuroimmunological disorders and respective controls. Individuals suffering from relapsing–remitting and secondary progressive MS had significantly higher prothrombin and factor X levels than healthy donors, whereas levels were unchanged in primary progressive MS and neuromyelitis optica patients. Our study demonstrates that coagulation factors may be key mediators in neuroinflammation and may therefore provide future targets for therapeutic strategies. Ann Neurol 2016;80:946–951     

Amsacrine containing induction therapy in elderly AML patients: comparison to standard induction regimens in a matched-pair analysis

Many elderly patients with newly diagnosed acute myeloid leukemia (AML) present with cardiac comorbidity precluding the use of anthracycline containing chemotherapy regimens. Amsacrine, a topoisomerase II inhibitor, has been proposed as possible alternative to anthracyclines. Here, we report about the combination of amsacrine (210 mg/m(2)), in replacement for daunorubicin (DNR), with standard dose cytarabine and thioguanine (TAA) to elderly patients (>or=60 years of age) with impaired cardiac function. The outcome of 16 patients with a median age of 66 years treated between 1997 and 2003 was compared with standard treatment regimens of the AMLCG study group in a matched-pair analysis. There were no statistically significant differences in response rate, relapse free survival or overall survival between TAA treated patients or standard therapy. In conclusion, replacing anthracyclines with amsacrine for induction therapy of AML patients with significant cardiac comorbidities represents a treatment option without compromising the potential curability of the disease.     

Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma: A subgroup analysis of the PETAL trial

The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV_41max) and SUV₄ thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUV_max approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)-positive lymphoma were analyzed separately from patients with ALK-negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression-free survival, with thresholds best dichotomizing the population, of 232 cm³ using SUV_41max and 460 cm³ using SUV₄. For iPET response, the respective thresholds were 46.9% SUV_max reduction and Deauville score 1-4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV_41max and SUV₄, and 29% and 25% for iPET response by ΔSUV_max and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135-4.624) for SUV_41max and 3.206 (1.524-6.743) for SUV₄. At iPET, it was 3.910 (1.891-8.087) for ΔSUV_max and 4.371 (2.079-9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651-22.336]). Due to small numbers and events, PET did not predict survival in ALK-positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK-negative T-cell lymphoma for early allogeneic transplantation or innovative therapies.     

Impact of persistent antiphospholipid antibodies on risk of incident symptomatic thromboembolism in children: a systematic review and meta-analysis

The aim of this study was to estimate the impact of antiphospholipid (aPL) antibodies on the risk of incident thromboembolism (TE; arterial and venous) in children via meta-analysis of published observational studies. A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1966 to 2010 was conducted using keywords in combination both as MeSH terms and text words. Two authors independently screened citations and those meeting the a priori defined inclusion criteria were retained. Data on year of publication, study design, country of origin, number of patients/controls, ethnicity, TE type, and frequency of recurrence were abstracted. Heterogeneity across studies was evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using either fixed-effects or random-effects models. Of 504, 16 pediatric studies met the inclusion criteria. In total 1403 patients and 1667 population-based controls ≤18 years were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. Thus, data from arterial and venous TE were analyzed together. In addition, meta-regression analysis did not reveal statistically significant differences between site of TE, age at first TE, country, or publication year. A statistically significant association with a first TE was demonstrated for persistent aPL antibodies, with an overall summary ORs/CI of 5.9/3.6-9.7 (arterial 6.6/3.5-12.4; deep vein thrombosis 4.9/2.2-10.9). The present meta-analysis indicates that detection of persistent aPL is clinically meaningful in children with, or at risk for, TE and underscores the importance of pediatric thrombophilia screening programs.     

Prognostic significance of vessel architecture and vascular stability in non-small cell lung cancer

To evaluate characteristics and prognostic impact of different structure types of intratumoural blood vessels, tissue samples of 72 patients with primary stages I and II non-small cell lung cancer (NSCLC) were analysed. Performing immunohistochemistry, 45 of 56 analysed tumours (80%) demonstrated an obvious alveolar vascular pattern with tight coverage with perivascular cells in at least parts of the sample. After an overall median follow-up of 139 months for surviving patients, tumours with an alveolar vascular pattern showed a significantly better overall survival (OS) compared to those with an entirely angiogenic vascular pattern (108 months versus 63 months; p<0.05). Furthermore, high expression of angiopoietin-1 (Ang-1) correlated with OS (p<0.05). In contrast, expression of Ang-2 or vascular endothelial growth factor was not significantly associated with survival. Collectively, alveolar vessel architecture and angiopoietin expression appear to be common phenomenons in early stage NSCLC and may serve as prognostic factors.     

The effect of fluoxetine on anxiety and depression symptoms in cancer patients

Little has been done to study the effectiveness of antidepressants in controlling anxiety/depression in a population of cancer patients. A double-blind placebo-controlled study was therefore designed to assess the effectiveness of 20 mg fluoxetine. Of 115 cancer patients who fulfilled entry criteria for levels of distress, 45 patients were randomized to a fluoxetine treatment group (FA) and 46 patients to a placebo group (PA) after a 1-week placebo period designed to exclude placebo responders. The Montgomery and Asberg Depression Scale (MADRS), the Hamilton Anxiety Scale (HAS), the Hospital Anxiety and Depression Scale (HADS), the Revised Symptom Checklist (SCL90-R) and the Spitzer Quality of Life Index (SQOLI) were used to assess the efficacy of fluoxetine. The response rate, defined by a HADS score lower than 8 after 5 weeks of treatment, was not significantly higher in the FA group (11%) compared to the PA group (7%). Compared to the PA group, patients in the FA group showed a significantly greater decrease in SCL90-R mean total score after 5 weeks, but not a greater decrease in HADS mean score. No difference between the two groups was found in observer-reported assessments (MADRS, HAS and SQOLI). Significantly more drop-outs were observed in the FA group (n=15) than in the PA group (n=7), although the frequencies of side-effects were not significantly different.     

Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients

Septic shock and multiple organ failure may be associated with coagulation activation, disseminated fibrin formation, and consumption of coagulation inhibitors such as antithrombin III. We have evaluated prospectively coagulation measurements in patients with severe chemotherapy-induced neutropenia. This group of patients was chosen because of their high risk of developing severe septic complications, thus allowing serial prospective coagulation testing before and during evolving sepsis or septic shock. Sixty-two patients with febrile infectious events were accrued to the study. Of these, 13 patients progressed to severe sepsis and 13 additional patients to septic shock as defined according to standard diagnostic criteria. At the onset of fever, factor (F) VIIa activity, FVII antigen and antithrombin III (AT III) activity decreased from normal baseline levels and were significantly lower in the group of patients who progressed to septic shock compared with those that developed severe sepsis (medians: 0.3 v 1.4 ng/mL, 21 v 86 U/dL and 45% v 95%; P < .001). The decrease of these measurements in septic shock was accompanied by an increase in prothrombin fragment 1+2 (median: 3.6 v 1.4 nmol/L; P = .05), a marker of thrombin generation. These differences were sustained throughout the septic episode (P < .0001). FVIIa and AT III levels of < 0.8 ng/mL and < 70%, respectively, at onset of fever predicted a lethal outcome with a sensitivity of 100% and 85%, and a specificity of 75% and 85%, respectively. In contrast, FXIIa-alpha antigen levels were not different between groups at onset of fever but increased modestly during the course of septic shock (P = .001). Thus, septic shock in neutropenic patients is associated with increased thrombin generation. Furthermore, both FVIIa and AT III measurements are sensitive markers of an unfavorable prognosis.