Health‐related quality of life assessment in randomised controlled trials in multiple myeloma: a critical review of methodology and impact on treatment recommendations

Objectives: Patients with multiple myeloma (MM) often have pronounced symptoms and substantially reduced quality of life. The aims of treatment are to control disease, maximise quality of life and prolong survival. Hence, health‐related quality of life (HRQOL) should be an important end‐point in randomised controlled trials (RCTs) in addition to traditional endpoints. We wanted to evaluate whether trials reporting HRQOL outcomes have influenced clinical decision making and whether HRQOL was assessed robustly according to predefined criteria. Methods: A systematic review identified RCTs in MM with HRQOL assessment as a study end‐point. The methodological quality of these studies was assessed according to a checklist developed for evaluating HRQOL outcomes in clinical trials. The impact of the HRQOL results on clinical decision making was assessed, using published clinical guidelines as a reference. Results: Fifteen publications presenting RCTs with HRQOL as a study end‐point were identified. In 13 trials, the author stated that HRQOL results should influence clinical decision making. We found, however, that the HRQOL data only had a limited impact on published treatment guidelines for bisphosphonates, high‐dose treatment, interferon, erythropoiesis‐stimulating agents and novel agents. Conclusion: The present review indicates that the there are still few RCTs in MM including HRQOL as a study end‐point. Systematic incorporation of HRQOL measures into clinical trials allows for a comparison of treatment arms that includes the patients’ perspective. Before the full impact on clinical decisions can be realised, the quality and methodology of collecting HRQOL data must be further improved and the results rendered more comprehensible to clinicians.     

Learning by viewing versus learning by doing: A comparative study of observer and participant experiences during an interprofessional simulation training

Larger student groups and pressure on limited faculty time have raised the question of the learning value of merely observing simulation training in emergency medicine, instead of active team participation. The purpose of this study was to examine observers and hands-on participants’ self-reported learning outcomes during simulation-based interprofessional team training regarding non-technical skills. In addition, we compared the learning outcomes for different professions and investigated team performance relative to the number of simulations in which they participated. A concurrent mixed-method design was chosen to evaluate the study, using questionnaires, observations, and focus group interviews. Participants included a total of 262 postgraduate and bachelor nursing students and medical students, organised into 44 interprofessional teams. The quantitative data showed that observers and participants had similar results in three of six predefined learning outcomes. The qualitative data emphasised the importance of participating in different roles, training several times, and training interprofessionally to enhance realism. Observing simulation training can be a valuable learning experience, but the students’ preferred hands-on participation and learning by doing. For this reason, one can legitimise the observer role, given the large student groups and limited faculty time, as long as the students are also given some opportunity for hands-on participation in order to become more confident in their professional roles.     

Artificial background and induced levels of oxidative base damage in DNA from human cells

The pre-mutagenic oxidative DNA base damage of 8-hydroxy-guanine is present in DNA isolated from cells and the amount present increases with exposure of cells to oxidative stress. The oxidative DNA base damage may be present before isolation of DNA or it may be produced during isolation and processing of DNA. We have found that the amount of oxidative base damage measured in DNA can be reduced to a stable lower level by adding increasing concentrations of the antioxidants desferrioxamine, histidine and reduced glutathione immediately before cell lysis. Inclusion of these antioxidants after cell lysis did not affect the level of DNA damage. Oxidative DNA base damage produced by ultraviolet A irradiation of human cells was also reduced by adding antioxidants after irradiation and before cell lysis. Thus, unidentified oxidants induced by ultraviolet A irradiation may damage DNA significantly during extractions of DNA from cells subsequent to ultraviolet A irradiation.      

Investigation of premolar rotation in a group of 15-year-old Norwegian children

The first aim of this study was to devise a meaningful, objective, and reproducible method of measuring premolar rotation on study casts. A new method of measurement was devised, using standardized arch forms as the reference line superimposed on the study casts. The method error of the difference in two determinations was calculated as +/- 2.95 degrees. Using this method, premolar rotations were measured on study casts at 15 years of 203 children enrolled in the Nittedal Growth Study. Histograms of the frequency distribution for each premolar were drawn and the mean rotations compared. Correlation coefficients were then calculated to determine if any intra-quadrant, intra-arch, or inter-arch relationships existed. Significant correlations were found between contra-lateral teeth in the same arch (P less than 0.001) and to a lesser degree between premolars in the same quadrant. Significant inter-arch correlation was found between left upper and lower second premolars (P less than 0.001). Surprisingly, some cross-arch relationships were found between the upper left second premolar and lower right second premolar (P less than 0.001), and between the upper right second premolar and lower left second premolar (P less than 0.01). It is suggested that aetiological factors in premolar rotation are genetic and, to a lesser extent, local factors. The significant correlation found between the upper and lower left second premolars suggests that occlusal factors may have a role to play.     

31P NMR studies of resting zone cartilage from growth plate.

31P NMR of superfused resting cartilage demonstrated the presence of phosphocreatine in chondrocytes. Changes in pH and in the NTP level were followed during carbon source starvation. From 31P spectra of perchloric acid extracts, phosphoethanolamine, phosphocholine, and the corresponding glycerol diesters were identified as the major phosphomonoester and phosphodiester components.     

Facial skeletal dimensions in patients with nasal septal deviation

The anatomy and the concomitant function of the face seem to be reciprocal issues. Previous studies have shown that stenosis in the posterior part of the nose, hampering nasal air flow, is associated with a retrognathic face and a posterior rotation of the lower jaw, i.e. components of the adenoid syndrome. The present study examines facial cephalometric morphology in adults with a deviated nasal septal cartilage, i.e. an anteriorly positioned nasal stenosis. Compared to a group of unafflicted individuals, also with regard to rhinomanometric resistance, a significantly smaller posterior facial height, smaller height of the anterior nasal aperture, a posterior rotation of the lower jaw and a shorter nasal floor and ceiling were found. This may mean that growth of the nasal septal cartilage and growth of the surrounding skeletal areas are out of step. A relatively undersized skeletal frame, in the sagittal plane, may have led to the buckled non-fitting septal cartilage, with increased air flow resistance as a secondary effect. If this interpretation is correct, an early cautious surgical correction of the septal deviation, also balancing this growth incongruence, might be worth serious consideration.