Use of the European Organisation for Research and Treatment of Cancer multiple myeloma module (EORTC QLQ-MY20): a review of the literature 25 years after development.

The European Organisation for Research and Treatment of Cancer Quality of Life Multiple Myeloma Questionnaire (EORTC QLQ-MY20) was developed in 1996 to assess health-related quality of life (HRQoL) in patients with multiple myeloma. Since its development new therapies have prolonged survival in patients with myeloma and new combination agents are likely to impact HRQoL outcomes and its measurement.The aim of this review was to explore the use of the QLQ-MY20 and reported methodological issues.An electronic database search was conducted (1996-June 2020) to identify clinical studies/research that used the QLQ-MY20 or assessed its psychometric properties. Data were extracted from full-text publications/conference abstracts and checked by a second rater.The search returned 65 clinical and 9 psychometric validation studies. The QLQ-MY20 was used in interventional (n = 21, 32%) and observational (n = 44, 68%) studies and the publication of QLQ-MY20 data in clinical trials increased over time. Clinical studies commonly included relapsed patients with myeloma patients (n = 15, 68%) and assessed a range of combinations therapies.QLQ-MY20 subscales (disease symptoms [DS], side effects of treatment [SE], future perspectives [FP], body image [BI]) were defined as secondary (n = 12, 55%) or exploratory (n = 7, 32%) trial endpoints, particularly DS (n = 16, 72%) and SE (n = 16, 72%). Validation articles demonstrated that all domains performed well regarding internal consistency reliability (>0.7), test-reset reliability (intraclass correlation coefficient > =0.85), internal and external convergent and discriminant validity. Four articles reported a high percentage of ceiling effects in the BI subscale; all other subscales performed well regarding floor and ceiling effects.The EORTC QLQ-MY20 remains a widely used and psychometrically robust instrument. While no specific problems were identified from the published literature, qualitative interviews are ongoing to ensure new concepts and side effects are included that may arise from patients receiving novel treatments or from longer survival with multiple lines of treatment.

Prolonged survival of actively enhanced rat renal allografts despite accelerated cellular infiltration and rapid induction of both class I and class II MHC antigens.

Administration of 1 ml of donor whole blood 7 d before renal transplantation produces long-term (greater than 100 d) graft survival in the DA (RT1a) into PVG (RT1c) rat strain combination. Using this model, the pattern and phenotype of infiltrating leukocytes were examined in rejecting and enhanced renal allografts, at days 1, 3, 5, and 7 after transplantation, by immunohistologic techniques. Paradoxically, enhanced grafts showed a more rapid and substantial leukocyte infiltrate, the phenotype of which was similar to that in rejecting grafts except for a reduced number of MRC OX-8+ cells and MRC OX-39+ cells. Graft infiltrating cells and splenocytes from transfused animals showed similar, although modest, levels of both nonspecific cytotoxicity and alloantigen-specific cytotoxicity. Immunohistologic analysis of MHC antigen distribution within the allograft revealed, unexpectedly, that enhanced grafts underwent an accelerated and extensive induction of both donor class I and class II MHC antigens. These findings were confirmed by allospecific quantitative absorption analysis, which showed severalfold increases in class I and class II MHC antigens by day 3 in enhanced grafts but not until day 5 in rejecting grafts. An additional observation was the more rapid disappearance of donor interstitial cells from enhanced grafts. These findings emphasize the overwhelming suppressive effect induced by an organ allograft after preoperative blood transfusion despite the associated induction of large numbers of potential effector cells and increased target antigen density within the graft.

Feasibility and Acceptability of Computerised Cognitive Training of Everyday Cognition in Parkinson's Disease.

OBJECTIVES: We piloted a computerised cognitive training battery in a group of participants with Parkinson's disease without dementia to investigate the relevance of the training to daily life and the feasibility and the acceptability of the tasks. Previous studies of CT have had limited success in the benefits of training, extending to improvements in everyday function. By taking a pragmatic approach and targeting training to the cognitive skills affected by Parkinson's disease (planning, attention, and recollection), whilst using tasks that emulated real-life scenarios, we sought to understand whether participants perceived the training to be effective and to identify the elements of the training that elicited beneficial effects. METHODS: Four participants completed a cognitive training session comprising three distinct tasks 5 days a week over two weeks. Participants completed baseline questionnaires examining health-related quality of life, everyday cognition, and apathy before the training period, after the last session, and two weeks after the last session. An interview was held after participants had completed the training. RESULTS: The findings indicated that participants felt the training was acceptable, enhanced their awareness, and encouraged them to monitor their thinking abilities. The group interview indicated that the training was feasible; participants felt the tasks had potential to improve everyday performance, but more supporting information should be provided to facilitate this transfer. Responses to the questionnaires reflected these findings, indicating improvement for some participants' cognition and quality of life. Objective measures supported the subjective reports; there were improvements in some but not all domains. Performance on the planning and recollection tasks improved over the training period, and the evidence for improvement on the attention task was mixed. CONCLUSION: This study has found that pragmatic computer-based training with real-life outcomes is both feasible and acceptable and should be evaluated more extensively using controlled methods.

Surgery after initial chemotherapy for localized small-cell carcinoma of the lung.

Despite the high response rates induced by chemotherapy, many patients with limited small-cell lung cancer (SCLC) relapse at the site of primary disease. Failure of radiotherapy to overcome this has led to the use of surgery as part of a combined modality approach. Between December 1981 and December 1985, 189 patients with SCLC were assessed for suitability for surgery after an initial three cycles of chemotherapy (doxorubicin, cyclophosphamide, and etoposide). Fifty-seven were found to have limited disease, and of these, 19 were ineligible or unfit for surgery. Of the 38 eligible patients, 84% had an objective response to three cycles of chemotherapy and 25 were deemed suitable for surgery after restaging. At thoracotomy, four were inoperable, nine had a lobectomy, and 12 had a pneumonectomy. There was no evidence of viable SCLC in four resection specimens (one stage 1, two stage 2, one stage 3 at presentation), no viable SCLC but an entirely separate focus of viable poorly differentiated squamous carcinoma (SqLC) in one, and the remaining specimens contained viable SCLC. Survival of patients selected to undergo tumor resection was excellent (median survival, 33 months; plateau phase, 48% alive at 3 to 5 years), but survival of the entire group with limited SCLC was not dissimilar from that reported in previous series of limited-stage tumor treated with chemotherapy alone. Long-term survival appeared to be largely restricted to those with no evidence of viable SCLC at surgery (no viable SCLC, zero of five relapsed; viable SCLC, 13 of 16 relapsed and/or died). This prospective study confirms the feasibility of the combined modality approach, but suggests that any improvement in overall survival is likely to be small. Until the results from multicenter randomized trials are available, surgery, as part of a combined modality program, should be regarded as experimental.

The use of bronchoscopic sponge biopsy in the diagnosis of pulmonary neoplasms.

A modified method of transbronchoscopic sponge biopsy is presented a series of 212 patients is discussed. A diagnostic accuracy rate of 89 per cent was obtained in the 159 cases of proved carcinoma. False-positive and false-negative results are discussed. This technique was found to be an easy, rapid, accurate, and inexpensive method of obtaining samples for cytologic evaluation in the preoperative work-up of patients with suspected pulmonary malignancies.

Evaluation of three lines of immunodeficient mice for the study of spontaneous metastatic tumors.

Various immunodeficient animals have been used as transplantation recipients for studying the growth of human tumors. We have been assessing the value of immunodeficiencies for the study of naturally arising tumors, using a model system of transgenic mice that spontaneously develop cancer of the pancreas as a result of elastase promoter-driven expression of the large tumor antigen gene of simian virus 40. We previously reported the establishment of transgenic mice that carried the SCID and/or beige mutations, eliminating B- and T-cell function and reducing lytic NK cell activity, respectively. In SCID beige animals, metastasis rates and target organs for metastases were similar to those observed in humans with pancreatic cancer. We describe here analysis of subsequent more highly inbred generations of these mice. The data show that inbreeding has almost negated the value of these immunodeficiencies for enhancing disease progression, and we observe high rates of metastasis even in immunocompetent animals. The data suggest that SCID and beige immunodeficiencies may not always have the same value for the modeling of spontaneous tumors as they do for the study of xenografts.

Comparative bioavailabilities from truncated blood level curves.

The period of time after administration over which blood level measurements are required to obtain a reliable bioavailability comparison of two or more formulations of the same drug was considered by the analysis of bioavailability data taken from the literature. The drugs examined, selected to represent a range of absorption and elimination half-lives, were acetaminophen, aminosalicylic acid, chloramphenicol, chlordiazepoxide, digoxin, isoniazid, phenylbutazone, sulfamethizole, tetracycline, and warfarin. For most drugs, ratios of areas under the curve changed little between the end of the absorption period and the time when blood sampling was terminated. Reliable bioavailability comparisons among different brands of the drugs apparently could have been made by blood sampling over 24 hr or less.

Phenotypic analysis of graft infiltrating cells and major histocompatibility complex expression in actively enhanced rat renal allografts.

In this study donor specific blood transfusion of PVG recipients prevented rejection of DA strain kidneys but, paradoxically, failed to prevent the rapid and progressive accumulation of large numbers of mononuclear cells within enhanced grafts. Morphometric analysis showed that the percentage cellular infiltrate at day 3 was significantly greater in enhanced than in rejecting grafts but a notable feature in the phenotypic analysis of day 5 infiltrates was a markedly reduced number of MRC OX8 positive cells (Tc/s and NK cells) in enhanced grafts. Both rejecting and enhanced allografts showed a marked induction not only of class I but also of class II MHC antigens, and quantitative absorption analysis of donor class I MHC antigens indicated that induction occurred more rapidly in enhanced grafts. Taken together, these findings suggest that blood transfusion sensitizes the recipient, resulting in a more rapid allograft response, but that even in the presence of massive MHC/antigen induction and large numbers of infiltrating cells, immunoregulatory mechanisms are able to suppress the rejection response.

Amyloid disease: association with failure of arterial reconstruction.

Amyloidosis may accompany many chronic diseases and in particular occurs as a complication of myelomatosis in 10% of cases. This paper reports the effects of amyloid in major arteries of the leg, and describes attempts to treat this occlusive disease using vascular grafts. Such disease may be rapidly progressive and its presence may indicate a poor outlook after vascular surgery. Arterial biopsy at the time of operation in patients with diseases associated with amyloidosis may be useful in assessing prognosis.

Ultrasonographic and histopathological findings in equine superficial digital flexor tendon injury.

The ultrasonographic and histopathological findings in 12 normal and 28 injured superficial digital flexor tendons, with lesions ranging in duration from 2 days to 15 months, were compared. A consistent relationship between the ultrasonographic and histological findings was demonstrated. The echogenicity of lesions, the distinctness of their delineation from the surrounding tissue, and the presence and arrangement of the linear echoes were useful features by which to assess the ultrasonograms. Acute lesions were anechoic, a complex mixture of anechoic and hypoechoic areas, or diffusely hypoechoic. These appearances represented haemorrhage, fibrolysis and early granulation tissue. Fibroplasia and granulation tissue produced well to moderately well defined hypoechoic lesions. Chronic fibrosis was characterised by heterogeneously echogenic areas which were poorly defined from the surrounding tissue and had irregularly-arranged linear echoes on longitudinal images. Intratendinous scar formation resulted in multiple hyperechoic foci. Extensive peritendinous lesions were readily apparent on ultrasonograms, but intertendinous adhesions were more difficult to assess, and produced ill-definition of the borders between the superficial and deep digital flexor tendons.

The relationship among current management systems, production, disease and drug usage on Ontario dairy farms.

The study involved 110 randomly selected dairy farms located in the Ontario, Canada counties of Bruce, Grey, Huron, Oxford, Perth, Waterloo and Wellington. Herds were classified as "intensive" and "extensive". On extensive farms, data were collected at the herd level only, while on intensive farms, data were recorded at both the individual animal and herd level. Data collection continued for approximately two and one-half years. At each visit, technicians collected production data from the most recent production recording scheme report and from the "daily log" maintained by each producer. As well as the ongoing data collection procedures, a number of supplementary data collections were made. The average 305 day milk production increased gradually during the three calendar years from 6224.6 kg in 1981 to 6443.7 kg in 1983. The average calving interval was stable at 13.2 months for all three years. The majority of cows removed from the herds were culled for beef (0.243 per animal year). The next highest removal rate was for domestic sale, followed by death, export sale and destroyed. The highest disease rate, for those conditions whose rates were based on calving, was for retained placenta (0.09 per calving), while clinical mastitis was highest for those conditions whose rates were based on animal years (0.37 per animal year). The overall crude antimicrobial dosage rate, that is, including any antimicrobial used for either prophylactic or therapeutic purposes, was 3.85 doses per animal year. The rate for therapeutic purposes only was 3.6 doses per animal year. Penicillin/streptomycin was used most often with a rate of 1.45 doses per animal year.

Sow wastage: reasons for and effect on productivity.

The purpose of this study was to examine the reasons for, the rate and the effect of sow culling on productivity. Sow removal or wastage was investigated by means of producer questionnaires and by detailed production data recorded on 30 swine farms for two years. The sow removal rate was high (mean = 44.2%) with a wide herd-to-herd variation (range = 16% to 100%), and correlated negatively with litter size. Reproductive failure was the most common cause of culling cited by producers. It was concluded that sows on many Ontario farms were being culled prior to reaching their reproductive potential.

Prevalence of respiratory diseases and their association with growth rate and space in randomly selected swine herds.

The prevalence and extent of respiratory tract lesions were measured in 1425 pigs from 27 randomly selected herds in the summer of 1982 and winter of 1983. About 75% of pigs had lesions of enzootic pneumonia, approximately 60% had atrophic rhinitis and approximately 11% had pleuropneumonia and/or pleuritis. Individual pig growth rate was recorded on two of the farms, and it was found that the correlations between growth rate and severity of enzootic pneumonia lesions were positive on one farm and negative on the other. Negative correlations between severity of turbinate atrophy and growth rate existed in one of the two herds. Extent of pneumonia and severity of turbinate atrophy were poorly related in individual pigs but herd averages were moderately and positively correlated. Prevalence of diffuse pleuritis and of pleuropneumonia were positively related, as were the extent of pneumonia and prevalence of localized pleuritis. Prevalence of pleuropneumonia was strongly correlated with increased days-to-market. A method of estimating the average days-to-market using weekly herd data (inventory) was developed.

Selection strategies for limiting the increase in ascites while increasing growth in broilers.

The objective of the current study was to compare the changes in a fitness trait when selection is performed for 5, 10, and 20 generations on a production trait that influenced its expression. Responses to single-trait selection for growth based on phenotype or animal model predictions were compared by computer simulation. Two-trait index selection was performed when a trait, related to the fitness trait, was included in the index with the production trait. The phenotypic expression of the fitness trait among the sibs was also considered as a selection factor for single-trait and two-trait index selection. For a fixed increase in the expression of the fitness trait, mass selection produced a larger increase in the production trait than did use of standard animal model best linear unbiased prediction under single-trait selection. The reduction in the genotypic mean of the fitness trait was accompanied by an increase in its phenotypic expression. The use of sib information and an indicator trait reduced the level of expression reached by the fitness trait.

Genetic variation of broiler feed consumption and efficiency corrected for differences in test body weights.

Feed consumption and feed efficiency data obtained over nine generations from three selected strains of broilers were adjusted for differences in either initial or initial and final test BW (at 28 and 42 d, respectively). Genetic and environmental variables were estimated for each strain using an animal model with restricted maximum likelihood procedures to avoid bias due to reduced genetic variation caused by selection. Variance component and heritability estimates before and after adjustment of these traits for differences in test weights were evaluated. Adjustments of feed consumption data for either initial test BW or both initial and final test BW reduced additive genetic and environmental variation. Reductions were relatively greater for additive genetic than for environmental variance, thereby reducing the heritability of the adjusted trait. Adjustment of feed efficiency for initial test BW altered additive genetic variation little and reduced environmental variation slightly; however, correction for both test BW reduced variation of both components. Heritability of adjusted feed efficiency was 40% larger (.33 to .35 vs .21 to .28) than for uncorrected feed efficiency, but phenotypic variation of the adjusted feed efficiency was reduced 42% (5.82 to 6.13 vs 10.30 to 11.35). Heritabilities of feed consumption and efficiency were essentially the same (.34 and .36) after adjustment for both test weights. Changes in genetic and environmental variation and heritability due to adjustments were similar for the three strains.

Effect of air movement on operant heat demand of chicks.

Chicks, 8 days of age, were housed in a wind tunnel at temperatures from 12 to 28 C in increments of 4 C. The tunnel was equipped with a microswitch, an infrared bulb located above the switch, and a small electric fan controlled by a rheostat. Following learning, chicks were exposed at each temperature to air speeds of 0, .5, 1.0, and 1.5 m/s according to a Latin-square design. Chicks readily responded to air speed and temperature changes. For each increase of .1 m/s the effective environmental temperature dropped .6 C.

Genetic correlations among growth, feed, and carcass traits of broiler sire and dam populations.

Genetic correlations based on sire variance and covariance components were estimated for broiler traits. Data were collected from various selected and control strains of sire and dam populations during five generations of selection. Results of analyses of variance for each of the strains within generations and populations were pooled across strains and generations. Correlations between body and carcass weights were all above .8. Weight gain (WG) had similar correlations with these traits with the exception of body weight at 28 days (.57 in site and .69 in dam populations). Body and carcass weights and WG had high correlations with feed consumption (FC) (greater than .7); however, values for feed efficiency (FE) varied: -.58, -.23 for 28-day body weight; -.17, .16 for 42-day body weight; .25, .43 for WG; and .53 in the dam population for carcass weight. Correlations of body and carcass weights and WG with abdominal fat weight (AFW) and percentage (AFP) were generally small to moderate with values being about half as large for AFP as for AFW. Feed consumption and FE were negatively correlated (-.51, -.22) in both populations. In the dam population, FC was positively correlated with AFW and AFP (.42, .55) but FE was negatively correlated with these traits (-.41, -.70). Abdominal fat weight and AFP were highly correlated (.99, .97). Values tended to be similar not only for these populations but also for this and other studies. Simultaneous genetic improvement of growth rate, FE and carcass leanness is feasible in broilers. Selection for WG, FE, and AFP should be effective.

Performance of large groups of chicks using operant conditioning to control the thermal environment.

In four trials, 408, 320, 160, and 400 chicks were housed on litter in pens 1.8 x 2.4 m. Eight pens were used for each trial. For the first 6 days the environmental temperature was maintained at 28 C; on Day 7 the temperature was reduced to 16 C. Four pens were equipped with microswitches; the remaining four pens were each heated by two infrared lamps in constant operation. When chicks struck the microswitch, infrared lamps were turned on for 1 min during the learning phase when chicks were being conditioned to the experimental setup and 4 min during the experimental phase during which data were collected for analysis. Feed intake, gain, and mortality were recorded. Trials 1 and 2 were concluded at 28 days and Trials 3 and 4 concluded at 21 days. At the conclusion of the trials protein, fat, and water content of the birds were determined. Additional analysis for ash content was performed for Trials 1 and 2 only. No significant differences (P greater than .05) in gain, feed conversion, body composition, and mortality rate were found between treatments. Chicks provided with continuous heat were exposed to three times as much supplemental heat as operant conditioned groups yet feed efficiency was unaffected.

Estimation of genetic parameters for ascites syndrome in broiler chickens.

Genetic parameters for the ascites syndrome (AS) were estimated for meat-type chickens. Data had been collected over 11 generations of selection for body weight and other traits within two distinct breeds (Cornish and White Rock). Linear methods (LM) were used to estimate genetic parameters and also to analyze a binary measure of survival. Survival analyses (SA) were also conducted to estimate the effects of various factors influencing the incidence of AS by evaluating the number of days that the birds survived. The animal model was used exclusively with linear methods. Heritabilities (h2) on the liability scale were 0.12 +/- 0.02 and 0.22 +/- 0.01 in the White Rock and Cornish breeds, respectively; however, the genetic correlation (r(g)) with body weight was not possible to estimate due to the low prevalence of the defect trait studied (1.5% in the Cornish and 1.1% in the White Rock). Because males are more prone to AS, the h2 using the male records only were 0.22 +/- 0.017 and 0.41 +/- 0.009, and the r(g) were 0.35 +/- 0.007 and 0.22 +/- 0.009 in the dam and sire populations, respectively. In conclusion, the heart defect investigated was heritable and had a positive genetic correlation with body weight.

Genetic effects of aging on egg production traits in the first laying cycle of White Leghorn strains and strain crosses.

Three White Leghorn strains, their two-way crosses, and two commercial lines were used to evaluate the effects of aging on mean heterosis, reciprocal, additive, Z-chromosome, and heterotic effects and their variances in two egg production traits during the first laying cycle. Egg number of the survivors (EPF) and egg number including mortality and morbidity (EPM) were evaluated from hens housed one per cage in a randomized block design. For analyses, egg number was divided into 12 periods of 28 d each. Synchronization of the records was achieved by starting recording at age at first egg. The mean heterosis was significant over time and increased with age for both traits (P<0.05). Reciprocal effects were not significant across periods but increased in magnitude with age for EPF. The pattern of age changes in additive, Z-chromosome, and heterotic effects varied among strains, indicating genotypic differences in response to aging. These differences increased, on average, with age. The additive, heterotic, environmental, and phenotypic variances increased with age for both traits. A decline with physiological age was observed in heritabilities, which was due to a faster increase in environmental variance than to an increase in additive variance. Genetic variance of egg production increased with age, indicating that improvement of lifetime performance of layers is possible. This improvement could be achieved by selecting animals at older ages or by favoring individuals with better DNA repair or those who had more genes turned on or off during the course of aging.