Efficacy and safety of an intravenous monoclonal anti-HBs in chronic hepatitis B patients

Background Aims: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. Methods: We included ten chronic hepatitis B patients: four received monotherapy, and six combination therapy with interferon alpha 2b. Results: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. Conclusions: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load - and therefore minimizes the risk of adverse events - may result in clinical efficacy should be investigated

Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy

Introduction Some patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information. Methods We performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation. Results Within the estrogen receptor-positive (ER+) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER+/ER-). Conclusion A highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy

Non-standard errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Oral health and obesity indicators

<p>Abstract</p> <p>Background</p> <p>In western Sweden, the aim was to study the associations between oral health variables and total and central adiposity, respectively, and to investigate the influence of socio-economic factors (SES), lifestyle, dental anxiety and co-morbidity.</p> <p>Methods</p> <p>The subjects constituted a randomised sample from the 1992 data collection in the Prospective Population Study of Women in Gothenburg, Sweden (n = 999, 38- > =78 yrs). The study comprised a clinical and radiographic examination, together with a self-administered questionnaire. Obesity was defined as body mass index (BMI) > =30 kg/m², waist-hip ratio (WHR) > =0.80, and waist circumference >0.88 m. Associations were estimated using logistic regression including adjustments for possible confounders.</p> <p>Results</p> <p>The mean BMI value was 25.96 kg/m², the mean WHR 0.83, and the mean waist circumference 0.83 m. The number of teeth, the number of restored teeth, xerostomia, dental visiting habits and self-perceived health were associated with both total and central adiposity, independent of age and SES. For instance, there were statistically significant associations between a small number of teeth (<20) and obesity: BMI (OR 1.95; 95% CI 1.40-2.73), WHR (1.67; 1.28-2.19) and waist circumference (1.94; 1.47-2.55), respectively. The number of carious lesions and masticatory function showed no associations with obesity. The obesity measure was of significance, particularly with regard to behaviour, such as irregular dental visits, with a greater risk associated with BMI (1.83; 1.23-2.71) and waist circumference (1.96; 1.39-2.75), but not with WHR (1.29; 0.90-1.85).</p> <p>Conclusions</p> <p>Associations were found between oral health and obesity. The choice of obesity measure in oral health studies should be carefully considered.</p

Development of an ICU discharge instrument predicting psychological morbidity : a multinational study

PURPOSE: To develop an instrument for use at ICU discharge for prediction of psychological problems in ICU survivors. METHODS: Multinational, prospective cohort study in ten general ICUs in secondary and tertiary care hospitals in Sweden, Denmark and the Netherlands. Adult patients with an ICU stay ≥ 12 h were eligible for inclusion. Patients in need of neurointensive care, with documented cognitive impairment, unable to communicate in the local language, without a home address or with more than one limitation of therapy were excluded. Primary outcome was psychological morbidity 3 months after ICU discharge, defined as Hospital Anxiety and Depression Scale (HADS) subscale score ≥ 11 or Post-traumatic Stress Symptoms Checklist-14 (PTSS-14) part B score &gt; 45. RESULTS: A total of 572 patients were included and 78% of patients alive at follow-up responded to questionnaires. Twenty percent were classified as having psychological problems post-ICU. Of 18 potential risk factors, four were included in the final prediction model after multivariable logistic regression analysis: symptoms of depression [odds ratio (OR) 1.29, 95% confidence interval (CI) 1.10-1.50], traumatic memories (OR 1.44, 95% CI 1.13-1.82), lack of social support (OR 3.28, 95% CI 1.47-7.32) and age (age-dependent OR, peak risk at age 49-65 years). The area under the receiver operating characteristics curve (AUC) for the instrument was 0.76 (95% CI 0.70-0.81). CONCLUSIONS: We developed an instrument to predict individual patients' risk for psychological problems 3 months post-ICU, http://www.imm.ki.se/biostatistics/calculators/psychmorb/ . The instrument can be used for triage of patients for psychological ICU follow-up. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov, NCT02679157