Quality of life in melanoma patients during adjuvant treatment with pegylated interferon-α2b: patients' and doctors' views

Treatment of malignant melanoma with IFN-α has been associated with significant side-effects. The aim of this retrospective monocentric non-randomized study was first to evaluate the impact on quality of life (QOL) in 30 melanoma patients treated with once weekly 2?μg/kg PEG-IFN-α2b for 18 months, and second to examine whether there is a difference in patients' and physicians' perception of QOL. Data on QOL were collected by means of the EORTC QLQ-C30 questionnaire completed by the patient before consultation at baseline and every three months during treatment. A second questionnaire was filled out independently by the physician, based on the consultation and patient file. All data were routinely collected in an outpatient care unit. At baseline, patients had more favorable mean values on almost all dimensions of the EORTC QLQ-C30 than follow-up assessments. In comparison to published low-dose IFN-α2a data, once weekly 2?μg/kg PEG-IFN-α2b was associated with stronger impairment in most QOL single dimensions but with almost no differences regarding the global health status. QOL documented by physicians was significantly higher than QOL from the patients' questionnaires in all QOL dimensions (p<0.05). PEG-IFN-α2b has measurable effects on QOL. Measuring QOL based only on physicians' patient files without explicitly determining patients' assessments leads to a profound underestimation of impairment of QOL.     

Role of negative pressure wound therapy in total hip and knee arthroplasty

Negative-pressure wound therapy(NPWT) has been a successful modality of wound management which is in widespread use in several surgical fields. The main mechanisms of action thought to play a role in enhancing wound healing and preventing surgical site infection are macrodeformation and microdeformation of the wound bed, fluid removal, and stabilization of the wound environment. Due to the devastating consequences of infection in the setting of joint arthroplasty, there has been some interest in the use of NPWT following total hip arthroplasty and total knee arthroplasty. However, there is still a scarcity of data reporting on the use of NPWT within this field and most studies are limited by small sample sizes, high variability of clinical settings and end-points. There is little evidence to support the use of NPWT as an adjunctive treatment for surgical wound drainage, and for this reason surgical intervention should not be delayed when indicated. The prophylactic use of NPWT after arthroplasty in patients that are at high risk for postoperative wound drainage appears to have the strongest clinical evidence. Several clinical trialsincluding single-use NPWT devices for this purpose are currently in progress and this may soon be incorporated in clinical guidelines as a mean to prevent periprosthetic joint infections.     

Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer

Background and purpose

To compare the linear-quadratic (LQ) and the LQ-L formalism (linear cell survival curve beyond a threshold dose d_T) for modeling local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC).

Materials and methods

This study is based on 395 patients from 13 German and Austrian centers treated with SBRT for stage I NSCLC. The median number of SBRT fractions was 3 (range 1–8) and median single fraction dose was 12.5 Gy (2.9–33 Gy); dose was prescribed to the median 65% PTV encompassing isodose (60–100%). Assuming an α/β-value of 10 Gy, we modeled TCP as a sigmoid-shaped function of the biologically effective dose (BED). Models were compared using maximum likelihood ratio tests as well as Bayes factors (BFs).

Results

There was strong evidence for a dose–response relationship in the total patient cohort (BFs > 20), which was lacking in single-fraction SBRT (BFs < 3). Using the PTV encompassing dose or maximum (isocentric) dose, our data indicated a LQ-L transition dose (d_T) at 11 Gy (68% CI 8–14 Gy) or 22 Gy (14–42 Gy), respectively. However, the fit of the LQ-L models was not significantly better than a fit without the d_T parameter (p = 0.07, BF = 2.1 and p = 0.86, BF = 0.8, respectively). Generally, isocentric doses resulted in much better dose–response relationships than PTV encompassing doses (BFs > 20).

Conclusion

Our data suggest accurate modeling of local tumor control in fractionated SBRT for stage I NSCLC with the traditional LQ formalism.     

Adaptive Designs for Two Candidate Primary Time-to-Event Endpoints

In clinical trials, the choice of an adequate primary endpoint is often difficult. Besides its clinical relevance, the endpoint must be measurable within reasonable time and must allow differentiating between the treatments. Often, the most relevant endpoint is ‘’time-to-death,” but if the overall survival prognosis is good, only a few deaths are observed during the study duration. A possible solution is to use surrogate endpoints instead. However, various examples from the literature demonstrate that surrogates do not always perform as intended. Sometimes, the surrogate effect is smaller than for the original endpoint, or the latter shows a higher effect than anticipated so using the surrogate is not reasonable. In this work, different adaptive design strategies for two candidate endpoints are proposed to solve these problems. The idea is to base the efficacy proof on the significance of at least one endpoint. At an interim analysis, both candidates are evaluated. If it is not possible to stop the study early, the sample size is recalculated based on the more promising endpoint. The new methods are illustrated by a clinical study example and compared in terms of power and sample size using Monte Carlo simulations. The software code is provided as supplementary material.     

Erythrocyte Mean Corpuscular Volume Associated with Severity of Peripheral Arterial Disease: An Angiographic Evaluation

Elevated erythrocyte mean corpuscular volume (MCV) may be a risk factor for peripheral arterial disease (PAD). The aim of the present study was to evaluate whether MCV was associated with the severity of atherosclerotic findings in the lower limbs of PAD patients, as measured by an angiographic scoring system based on vessel lumen reduction. One hundred male patients with symptomatic PAD were studied. MCV was significantly correlated with the angiographic score (rs = 0.247, p = 0.013). PAD patients with an angiographic score in the lower third were compared to those with values in the upper third using a logistic regression model with age, smoking, hypertension, MCV, homocysteine, and total cholesterol and triglycerides as independent variables. This model revealed significant odds ratios (OR) for MCV (OR = 2.02 for an increment of 5 fl, 95% CI = 1.08-3.8) and for age (OR = 2.41 for an increment of 10 years, 95% CI = 1.21-4.81) and facilitated classification of 71% of all subjects correctly. In conclusion, MCV may be associated with angiographically determined disease severity in patients with PAD. This finding supports the hypothesis that MCV is a risk factor for PAD, although the mechanism by which MCV may contribute to the presence and severity of the disease is not yet determined.     

Helicobacter pylori antibody responses and evolution of precancerous gastric lesions in a Chinese population

Helicobacter pylori‐specific proteins are involved in gastric carcinogenesis. To investigate the seroprevalence of six H. pylori‐specific antibodies in patients with different gastric histology, and the impact of seropositivities on the evolution of precancerous gastric lesions, a follow‐up study was conducted in Linqu County, China. The seropositivities for CagA, VacA, GroEL, UreA, HcpC and gGT were assessed by recomLine analysis in 573 H. pylori‐positive subjects and correlated with evolution of precancerous gastric lesions. We found that the score of H. pylori recomLine test was significantly increased in subjects with chronic atrophic gastritis (CAG, p < 0.0001) or intestinal metaplasia (IM, p = 0.0125), and CagA was an independent predictor of advanced gastric lesions, adjusted odds ratios (ORs) were 2.54 (95% CI = 1.42–4.55) for IM and 2.38 (95% CI = 1.05–5.37) for dysplasia (DYS). Moreover, seropositivities for CagA and GroEL were identified as independent predictors for progression of gastric lesions in a longitudinal study, and ORs were 2.89 (95% CI = 1.27–6.59) and 2.20 (95% CI = 1.33–3.64), respectively. Furthermore, the risk of progression was more pronounced in subjects with more than three positive antigens (p_{for trend} = 0.0003). This population‐based study revealed that seropositivities for CagA and GroEL might be potential markers to identify patients infected with high‐risk H. pylori strains, which are related to the development of GC in a Chinese high‐risk population, and recomLine test might serve as a tool for risk stratification.     

First clinical evaluation of a novel capacitive ECG system in patients with acute myocardial infarction

Objective  

The ECG plays a central role in the rapid diagnosis of acute myocardial infarctions (MI). In haemodynamically instable patients, adhesion of electrodes sometimes is difficult and assessing ECGs through layers of clothes has not been done so far. A novel capacitive measurement of ECG signals is possible without skin contact. Whether this technical innovation can be used in patients with MI is unclear.