Behavioural functioning of retinoblastoma survivors.

OBJECTIVE: To assess behavioural problems in retinoblastoma (RB) survivors. METHODS: This population-based cross-sectional study included 148 RB survivors (8-35 years), registered in the Dutch national RB register. Survivors and parents were asked to fill in behavioural questionnaires. Prevalence rates were computed, based on both self-reports and proxy reports. One-sample T-tests were applied to analyse differences compared with healthy reference samples. Multiple regression analyses were performed to identify predictors for behavioural problems within the RB sample. RESULTS: Between-group differences varied across informants and across age groups. Parents reported significantly elevated total problem behaviour in 30% of their offspring (aged 8-17 years); this against 9% in adolescents (12-17 years) and 12% in adults (18-35 years) based on self-report. Parental reports showed significantly elevated rates of (1) internalising problems in boys and (2) somatic complaints in both girls and boys. Self-reports indicate significantly lowered levels of (1) externalising problems in adolescent and adult women and (2) thought problems in female adolescents and in adult men. Especially survivors who suffered hereditary RB, who had undergone more intensive treatment, and who came from a single-parent family were identified to be at most behavioural risk. CONCLUSION: Perception of severity and the nature of behavioural problems seem to differ between beholder, and to vary between age groups, if not between life stages. Health professionals should be aware that especially those who are confronted with hereditary RB and who subsequently undergo intensive treatment, and who grow up in broken families, run the risk of developing behavioural difficulties.

[Determining factors for deciding whether or not to treat refractive errors and cataract in people with a learning disability]. / Determinanten van het al dan niet behandelen van refractieafwijkingen en cataract bij mensen met een verstandelijke beperking.

OBJECTIVE: A study into the treatment of refractive errors and cataract in a selected population with learning disabilities. Design. Retrospective. METHOD: In the years 1993-2003, 5205 people (mean age: 39 years) were referred to the visual advisory centre of Bartiméus (one of three institutes for the visually impaired in the Netherlands) by learning disability physicians and were assessed ophthalmologically. This assessment consisted of a measurement of visual acuity and refractive error, slitlamp examination and retinoscopy, and was performed at the client's accommodation. Advised treatment for spectacle prescriptions and referral for cataract surgery were registered. RESULTS: Refractive errors were found in 35% (1845/5205) of the patients with learning disabilities; 49% (905/1845) already wore spectacles; another 14% (265/1845) were prescribed spectacles for the first time. Of those with presbyopia, 12% (232/1865) had reading glasses and 10% (181/1865) were given a first prescription for spectacles. The most important determinant for not prescribing spectacles was: presence of severe learning disability (odds ratio (OR): 3.7). Cataract was present in 10% (497/5205) of the population; 399 patients were advised to be referred for surgery, 55% (219/399) were referred ofwhom 26% (57/219) had surgery. Moderately severe bilateral cataract was the only determinant of cataract surgery (OR: 7.8). CONCLUSION: Refractive errors and cataract were not always treated in this group. One of the reasons for non-treatment of refractive errors was a severe learning disability. The reason for treatment or non-treatment in patients with cataract was less clear.

6,220 institutionalised people with intellectual disability referred for visual assessment between 1993 and 2003: overview and trends.

AIMS: To summarise the results of visual performance tests and other data of institutionalised people with intellectual disability referred to a visual advisory centre (VAC) between 1993 and 2003, and to determine trends in these data. METHODS: A retrospective medical record review was undertaken of 6,220 consecutive people examined ophthalmologically according to a standard protocol by one VAC that specialised in visual assessment and treatment of people with intellectual disability, between 1993 and 2003. chi2 test for linear trend was used and linear regression coefficients were calculated. RESULTS: The proportion of people aged > or =50 years increased from 19.3% to 34.2% between 1995 and 2003 (p<0.001); the combined figure of severe or profound intellectual disability decreased from 80.0% to 52.6% (p<0.001); the proportion of mobile people increased from 52.1% to 98.0% (p<0.001); the combined proportion of people with visual impairment or blindness decreased from 70.9% to 22.9% (p<0.001), and that of people with visual disorders decreased from 89.6% to 75.3% (p<0.001). Causes of intellectual disability were identified in 58.4% people; 20.8% had Down's syndrome. CONCLUSION: Many ocular diagnoses were found, indicating the need for ophthalmological monitoring. Specialised centres are helpful, because assessment and treatment of people with intellectual disability is complicated and time consuming. Protocols for efficient referral will have to be developed. A major task lies ahead to improve the treatment rates of refractive errors, cataract and strabismus, and to find specific causes of intellectual disability.

Introduction of sentinel node biopsy and stage migration of breast cancer.

AIM: The purpose of this study was to examine in a large population based group of breast cancer patients treated in a regular care setting whether the introduction of the Sentinel Node Biopsy (SNB) led to detection of a higher percentage of patients with positive regional lymph nodes. METHODS: The study includes 3665 early breast cancer patients, aged 30-85 years, diagnosed in the period 1997-2002 and registered at the Regional Cancer Registry of the Comprehensive Cancer Centre Middle Netherlands. During this period the SNB was introduced. The outcome of staging was compared for groups staged with or without SNB. A logistic regression model was used to adjust for age, calendar period and tumour size. RESULTS: Overall a quarter of all patients over the period 1997-2002 underwent a SNB as method of lymphatic staging. The use of SNB clearly increased over time: from 2% in 1998 to 65% in 2002. The percentage node positive patients also rose significantly; before introduction of the SNB 30% of all patients were diagnosed with positive lymph nodes, and after SNB introduction this percentage was 40%. The increase is largely explained by the increase of patients diagnosed with only micrometastases. Adjustment did not change the results. CONCLUSION: In conclusion, introduction of the SNB in early breast cancer led to significant upstaging of breast cancer patients treated in a regular care setting, due to the detection of more micrometastases. Since the relevance of micrometastases for long term survival is not yet known, this upstaging potentially led to over treatment of patients. On the other side, for some patients axillary lymph node dissection was prevented by the SNB procedure, preventing comorbidity.

Peanut agglutinin, a marker for T-cell acute lymphoblastic leukemia with a good prognosis.

Peanut agglutinin (PNA) binding was studied in cells from 74 children with acute lymphoblastic leukemia (ALL). PNA positivity occurred in 50% of T-ALL (12 of 24) and was rare in other types of ALL. There was no clear relationship between PNA and initial white blood cell count, French-American-British classification, stage of differentiation of leukemic cells, hand mirror cells, and organomegaly at diagnosis. Prognosis, however, was significantly better (continuous complete remission, death) in the PNA-positive T-ALLs. It seems that PNA is a useful marker for a subgroup of T-ALL with a better prognosis.

Predictive value of symptom level measurements for complex regional pain syndrome type I.

The validity with respect to presence or absence of CRPS I according to Veldman's criteria was assessed for measured pain, temperature, volume differences and limitations in range of motion. Evaluated were 155 assessments of 66 outpatients, initially diagnosed with CRPS I, but many of them not so on follow up visits. Pain was measured with VAS and McGill, temperature by infrared thermometry, volume differences by water displacement volumeters and limitations in range of motion by universal goniometers. Sensitivity, specificity, positive and negative predictive value of the measurement instruments at different cut-off points was calculated. Combined symptom scores were evaluated in a similar fashion. High sensitivity was found for the VAS, McGill, and range of motion. The specificity was overall lower, but highest values were obtained for volume differences. The positive predictive value was good for all measurement instruments. Negative predictive value was lower, especially for measurement of temperature and volume asymmetries. If sensitivity and specificity are equally important, VAS>3 cm, McGill>6 words, temperature difference>or=0.4 degrees C, volume difference>6.5% and ROM limitation>15% provide the best results. Using these cut off values, the highest value of sensitivity and of sensitivity and specificity combined, was found for a combination of VAS, McGill and ROM. The highest value of specificity was found for different combinations of 3, 4 and 5 instruments, all containing the VAS. We conclude that the measured pain, temperature, volume and range of motion can be used as diagnostic indicators for establishing presence or absence of CRPS I.

Hepatic trapping of red cells in canine endotoxin shock: a variable phenomenon after splenectomy.

We studied in 20 splenectomised dogs the incidence of early intravascular hepatic pooling after administration of E. coli endotoxin. Autologous red cells were labelled in vitro with 99mTc. Bloodpool imaging and haemodynamic measurements were performed simultaneously. Changes in hepatic red cell volume were estimated from alterations in hepatic activity. In 10 dogs, hepatic red cell activity increased considerably (156 to 359% of the basal value). In the remaining animals the hepatic activity did not change markedly or even decreased. The decline in arterial pressure and cardiac output seemed more pronounced in dogs with clear evidence of hepatic pooling. However no significant differences in absolute haemodynamic values could be demonstrated between dogs with and without pooling. It is concluded that an hepatic outflow block is not a constant feature of canine endotoxin shock. Absolute haemodynamic values do not depend on the presence of an outflow block. Thus the presence of hepatic pooling need not make the canine model inappropriate for studies on human sepsis.

Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women.

To examine the relation of the vitamin D status and the remaining estrogen activity with bone turnover and bone mineral density (BMD) in elderly women, BMD was measured at both hips using dual-energy X-ray absorptiometry and at the distal radius using single photon absorptiometry, in 330 healthy women aged 70 and over. Vitamin D metabolites, sex hormone binding globulin (SHBG), PTH(1-84), osteocalcin, alkaline phosphatase, and hydroxyproline and calcium excretion in 2 h fasting urine were measured. Multiple linear regression was used to adjust for potential confounders. In 65% of the women, serum 25(OH)D was below 30 nmol/l. Only values below a threshold for 25(OH)D were negatively related to serum PTH(1-84) (p = 0.02, threshold at 25 nmol/l) and to osteocalcin levels (p = 0.04, threshold at 30 nmol/l). BMD of the femoral neck and trochanter was positively related to serum 25(OH)D (left neck p = 0.001) with thresholds at 30 nmol/l whereas the distal radius was not (p = 0.32). Serum PTH was negatively related to BMD at all measurement sites (all p < 0.001). Serum SHBG, an inverse measure of estrogen activity, was positively related to osteocalcin levels (p = 0.004) and the urinary hydroxyproline/creatinine ratio (p = 0.002) and negatively related to the BMD of the trochanter (left trochanter p = 0.02) and the distal radius (p = 0.001). We conclude that in elderly women, serum 25(OH)D levels below 30 nmol/l are associated with secondary hyperparathyroidism and increased bone turnover. SHBG is positively related to bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial.

The purpose of the study was to determine the effect of vitamin D supplementation on bone turnover and bone loss in elderly women. Three hundred forty-eight women, ages 70 yr and older, were randomized to receive 400 IU vitamin D3 per day (n = 177) or placebo (n = 171), double-blind, for a period of 2 yr. Main outcome measures were bone mineral density of both hips (femoral neck and trochanter) and the distal radius, as well as biochemical markers of bone turnover. The effect of vitamin D supplementation was expressed as the difference in mean (percentage) change between the placebo group and the vitamin D group. The measurements were repeated in 283 women after 1 yr and in 248 women after 2 yr. Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D (250HD) (+35 nmol/L) and 1,25-dehydroxyvitamin D [1,25-(OH)2D] (+7.0 pmol/L) levels and urinary calcium/creatinine ratios (+0.5%) and significantly decreased PTH(1-84) secretion (-0.74 pmol/L) after 1 yr. No effect was found for the parameters of bone turnover. The effect on the bone mineral density of the left femoral neck was +1.8% in the first yr, +0.2% in the second yr, and +1.9% during the whole period (95% confidence interval 0.4, 3.4%). At the right femoral neck the effects were +1.5%, +1.1%, and +2.6% (confidence interval 1.1, 4.0%), respectively. No effect was found at the femoral trochanter and the distal radius. Supplementation with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion and increases bone mineral density at the femoral neck.

Ultrasound measurements in the calcaneus: precision and its relation with bone mineral density of the heel, hip, and lumbar spine.

Broadband ultrasound attenuation (BUA) and speed of sound (SOS) in the heel are suggested to measure bone density and structure and to predict fracture risk. Short-term precision (five consecutive measurements in 1 h) and long-term precision (six within 3 months) of ultrasound parameters were studied in 20 healthy subjects. The coefficient of variation (CV) did not change over a 3-month period for SOS (1.3%). Short-term precision of BUA was 3.4% (CV) and long-term precision was 4.9% (CV) (not significantly different: p = 0.09). Relationships between ultrasound parameters and BMD at various sites were examined in 42 subjects. BMD at the heel was assessed at the location corresponding to that of the ultrasound measurements (BMDheel). Correlation coefficients, corrected for imprecision in the measurements, for BUA and SOS vs. BMDheel, were 0.81 and 0.76, respectively. The correlation coefficients between heel measurements (BUA, SOS, and BMDheel) and BMD in the hip and lumbar spine ranged from 0.37 to 0.57. The relationships between BUA, SOS, and BMDheel vs. BMD of the hip were modified by physical activity and body weight. Higher physical activity and body weight were associated with higher BMD values at the hip. BUA values < 60 dB/MHz predicted BMD at the femoral neck < 0.70 g/cm2 with a sensitivity and specificity of 80% and 93%, respectively. After the age of 30, 11 participants had sustained vertebral fractures and 12 participants nonvertebral osteoporotic fractures. BUA and SOS values were significantly lower in fracture patients than in participants without fractures. It can be concluded that ultrasound measurements at the heel correlate well to BMD at the same site. BUA can predict BMD at the hip and is lower when the subject has sustained fractures.

Prognostic value of 5'nucleotidase in acute lymphoblastic leukemia with the common-ALL phenotype.

5'-Nucleotidase (5'NT) is an enzyme found on the surface membrane of leukemic cells with the c-ALL phenotype. We studied 79 children with acute lymphoblastic leukemia (ALL). Thirty six of them had the c-ALL phenotype. Within this c-ALL group, ten had 5'-NT positive leukemic cells. Clinical data were available in 33 c-ALL cases. Sex, age and initial white blood cell count were comparable between 5'NT positive and 5'NT negative c-ALL cases. In the 5'NT positive group the probability of complete continuous remission was significantly lower than in the 5'NT negative group (p less than 0.05).

Evaluation of univariate ranges with a multivariate standard.

In medical decision making generally many test results are produced. Several authors have discussed the problems involved and concluded that a multivariate approach often has to be preferred. Because until now such an approach has not often been used in practice and qualitative arguments for a multivariate approach are seldom supported by quantitative results, in this paper the use of univariate reference ranges is evaluated with a multivariate range as the standard, taking into account correlation coefficients. Probabilities of false positive and false negative results and predictive values are computed and displayed for decision rules based on two separate test results with an elliptic region as the gold standard. The conclusion is that the quality of the univariate approach is dependent on the correlation coefficient and on the choice of the decision rule. In the most important cases, however, it falls short compared with a multivariate approach. For example, the probability that a univariate positive result is false is around 50% for all values of the correlation coefficient, which is unacceptably high.

Publications on diagnostic test evaluation in family medicine journals: an optimal search strategy.

Search strategies for articles reporting on diagnostic test evaluations have been subjected to less research than those in the domain of clinical trials. We set out to develop an optimal search strategy for publications on diagnostic test evaluations in general, that could be added to keywords describing the specific diagnostic test at issue. Nine Family Medicine journals were searched from 1992 through 1995 for primary publications on diagnostic test evaluation by hand searching and a Medline search strategy published earlier. Additionally, new search strategies have been developed with stepwise logistic regression, using Mesh terms and free text words related to diagnosis and test evaluation as independent variables. Hand searching identified 75 primary publications on diagnostic test evaluation from a total of 2467 primary publications. The previously published search strategy had a sensitivity of 73%, a specificity of 94%, and a positive predictive value of 29%. The most accurate new search strategy had a sensitivity of 80.0% (60/75; 95% CI: 71.0-89.1), a specificity of 97.3% (2327/2392; 95% CI; 96.6-97.9%), a positive predictive value of 48% (95% CI: 40-56) and diagnostic odds ratio of 149. All four new strategies used the Mesh term "sensitivity and specificity" (exploded with the Mesh terms "predictive value" and "ROC")and cumulatively added the text words "specificity," "false negative," "accuracy," and "screening." The search strategy using the Mesh term "sensitivity and specificity" (exploded) and the text words "specificity," "false negative," and "accuracy" has both higher sensitivity and specificity than the previously published strategy. The increase in specificity in three strategies reduces the absolute number of false-positive articles that have to be screened by 50-75%, compared to the number of false positives in the earlier strategy.

Clinimetric properties of a parent report on their offspring's quality of life.

The objective of this study was to assess the reproducibility, construct validity, and responsiveness of the parent report version of the "How are you" (HAY), a quality of life questionnaire for children with a chronic disease. The reproducibility of the HAY was assessed by comparing the scores of two measurement cycles of children with stable asthma. Construct validity was evaluated by testing the differences between scores of the HAY of parents of children with and without asthma and by investigating the correlations between the HAY and instruments supposed to correlate with the HAY. Responsiveness was investigated in parents of children whose clinical status changed clinically relevant between two measurements. The HAY showed acceptable reproducibility. Also the HAY detected anticipated differences in quality of life between parents of asthmatic and healthy children. It furthermore showed acceptable ability to measure change in health status of children with asthma. The parent report version of the HAY shows acceptable reproducibility, supportive evidence for construct validity, and good responsiveness. The measurement of quality of life of asthmatic children and changes therein can truly rely on parental report.

Reduced complement activation and improved postoperative performance after cardiopulmonary bypass with heparin-coated circuits.

A randomized controlled trial that involved 30 patients undergoing elective coronary artery bypass grafting was done to determine the effect of heparin-coated circuits and full heparinization on complement activation, neutrophil-mediated inflammatory response, and postoperative clinical recovery. Peak concentrations of terminal complement complex were 38% lower (p = 0.004) in 15 patients treated with heparin-coated circuits (median 775 micrograms/L, interquartile range 600 to 996) compared with those in 15 patients treated with uncoated circuits (median 1249 micrograms/L, interquartile range 988 to 1443). Although no significant intergroup differences in concentrations of polymorphonuclear neutrophil elastase were found, a positive correlation (rs = 0.74, p < 0.0007) was calculated between peak concentrations of terminal complement complex and polymorphonuclear neutrophil elastase. Differences in patient recovery were analyzed with use of a score composed of fluid balance, postoperative intubation time, and the difference between rectal temperature and skin temperature. The score was significantly lower in patients treated with heparin-coated circuits (p = 0.03), whereas its components showed no intergroup significance. We conclude that the use of heparin-coated circuits with full systemic heparinization results in improved biocompatibility, as assessed by complement activation, and leads to an improved postoperative recovery of the patient.

Reproducibility of flow cytometric assessment of follicular tumours of the thyroid.

The reproducibility of the DNA index of paraffin wax sections from 44 follicular tumours of the thyroid (18 follicular adenomas and 26 follicular carcinomas), which had been assessed by flow cytometry was analysed in two laboratories, using consecutive sections of the same specimens and two different commercially available flow cytometers. Two slightly different cell preparation and staining techniques were used in the two laboratories. Using strictly defined criteria the histograms were classified blind as diploid, peritetraploid, aneuploid, or inadequate and insufficient by two independent investigators. Both the concordance between the two different flow cytometers and the agreement of duplicate assessments within the same flow cytometers were assessed. The mean coefficient of variation of the G0/G1 peak of the diploid tumours in the PARTEC flow cytometer was 5.5 (range 2.3-9.8) and in the FACS flow cytometer 5.2 (range 3.7-8.3); this difference was not significant. There was concordance of classification between the two laboratories in 35 of 36 cases. In 25 cases (18 diploid, seven aneuploid) the intralaboratory variation showed a 100% concordance in histogram classification. It is concluded that flow cytometer DNA index assessment of follicular tumours of the thyroid is reproducible and can be used to evaluate the discriminating and prognostic value of this feature.

Prognosis of fertility in women with unexplained infertility and sperm agglutinins in the serum.

From 1967 to 1973 serum samples of 1709 infertile women were tested for antispermatozoal antibodies with the gelatin agglutination test. In 110 cases sperm agglutinins were demonstrated in titers ranging from 4 to 1024. The clinical data of 99 couples were evaluable, and in 65 there appeared to be unexplained infertility. Out of these 65 women, 44 became pregnant in the posttesting follow-up period of 6 to 13.5 years (median, 10 years). With increasing titers there was a significant decrease in the probability of becoming pregnant. Of the women who became pregnant, in general, those with higher titers had to wait longer for their pregnancy than those with lower titers. Moreover, with increasing titers there was a tendency toward a longer duration of infertility before the serum was tested. This latter observation supports the contention that the agglutinin titer influences the fecundability rate. The titers of those becoming pregnant and those remaining infertile, however, showed considerable overlap. Favorable results in the postcoital test were associated with a better prognosis, but this was independent of the titers.

Prognosis of fertility of men with sperm agglutinins in the serum.

PIP: A retrospective study of 254 infertile men with serum sperm agglutination titers ranging from 4 to 1024 determined by the Kibrick agglutination test between 1954 and 1968 and reexamined in the 1970s is presented. 36 of the subjects had become fertile in the years following the testing, 30 of whom were normospermic. With titers of 32 or more, the probability of becoming fertile was considerably lower than with lower titers. It was confirmed that the longer infertility existed, the less probable was fertility to occur (p less than .01). The serum of 22 men who regained fertility was tested. 19 of the subjects showed no difference in titers between the first and last test. 2 of the 3 remaining fertile men had fathered 2 children each despite titers of 1024 in 1970. The 3rd subject's titer value decreased from 512 to 4 in 1970. It was concluded that sperm agglutinins are involved in the pathogenesis of male infertility.^ieng

Incidence and survival of retinoblastoma in The Netherlands: a register based study 1862-1995.

AIM: The aim of this study was to determine the (time trends in) incidence and survival of hereditary (familial and sporadic) and non-hereditary retinoblastoma for male and female patients born in the Netherlands between 1862 and 1995. METHOD: The national retinoblastoma register was updated and now consists of 955 patients. The missing dates of death were obtained from the municipal registers and the Central Bureau of Genealogy in The Hague. Mortality was compared with the Dutch vital statistics. RESULTS: From 1862 to 1995 no significant differences in incidence for retinoblastoma were found in the hereditary subgroups. Further, no significant differences between males and females were found, both overall and in the hereditary subgroups. The average incidence of retinoblastoma increased until 1944, probably due to incompleteness of the register, and stabilised after 1945 (1 per 17000 live births). From 1900 to 1995 the standardised mortality ratio increased for hereditary retinoblastoma patients from 2.9 to 9.0 and decreased for non-hereditary retinoblastoma patients from 1.9 to 1.0. CONCLUSION: Although survival for retinoblastoma was significantly better after 1945 than before, in comparison with the Dutch population the mortality between 1900 and 1990 increased for the hereditary and decreased for the non-hereditary retinoblastoma patients.

Chemonucleolysis versus discectomy: a randomized multicenter trial.

A randomized clinical trial was carried out to compare the results of open discectomy with those of chemonucleolysis in 151 patients suffering from a disc herniation at L4-5 or L5-S1. All patients fulfilled strict entry criteria; 78 patients underwent open discectomy and 73 were subjected to chemonucleolysis. An increase in radicular pain immediately after treatment was encountered in 16 patients (22%) in the chemonucleolysis group, as compared to none in the discectomy group. The efficacy of discectomy appeared to be definitely superior to that of chemonucleolysis. Within a follow-up period of 1 year, 18 patients (25%) required open discectomy following failed chemonucleolysis; two patients (3%) in the discectomy group needed a second operation. Open discectomy following previous chemonucleolysis was successful in only 44% of cases. Comparison of the final results of the two modes of treatment 12 months after the last intervention (including second treatment) did not reveal any significant differences. The duration of the preoperative symptoms, the level of disc herniation, and the leakage of contrast medium out of the disc appeared to be of no relevance to the final outcome. The complication rates in both treatment groups were low.