A longitudinal mixed methods study on changes in body weight, body composition, and lifestyle in breast cancer patients during chemotherapy and in a comparison group of women without cancer: study protocol.

BACKGROUND: More than 60% of women diagnosed with early stage breast cancer receive (neo)adjuvant chemotherapy. Breast cancer patients receiving chemotherapy often experience symptoms such as nausea, vomiting and loss of appetite that potentially affect body weight and body composition. Changes in body weight and body composition may detrimentally affect their quality of life, and could potentially increase the risk of disease recurrence, cardiovascular disease and diabetes. To date, from existing single method (quantitative or qualitative) studies is not clear whether changes in body weight and body composition in breast cancer patients are treatment related because previous studies have not included a control group of women without breast cancer. METHODS: We therefore developed the COBRA-study (Change Of Body composition in BReast cancer: All-in Assessment-study) to assess changes in body weight, body composition and related lifestyle factors such as changes in physical activity, dietary intake and other behaviours. Important and unique features of the COBRA-study is that it used I) a "Mixed Methods Design", in order to quantitatively assess changes in body weight, body composition and lifestyle factors and, to qualitatively assess how perceptions of women may have influenced these measured changes pre-, during and post-chemotherapy, and II) a control group of non-cancer women for comparison. Descriptive statistics on individual quantitative data were combined with results from a thematic analysis on the interviews- and focus group data to understand patients' experiences before, during and after chemotherapy. DISCUSSION: The findings of our mixed methods study, on chemotherapy treated cancer patients and a comparison group, can enable healthcare researchers and professionals to develop tailored intervention schemes to help breast cancer patients prevent or handle the physical and mental changes they experience as a result of their chemotherapy. This will ultimately improve their quality of life and could potentially reduce their risk for other co-morbidity health issues such as cardiovascular disease and diabetes.

Perceptions of Dutch health care professionals on weight gain during chemotherapy in women with breast cancer.

PURPOSE: Dutch Health care professionals (HCPs) provide little information concerning health risks associated with weight gain during chemotherapy for breast cancer. Women with breast cancer have specified the need for more information on nutrition and physical activity to deal with weight gain. The aims of this study were to assess the perceptions of Dutch HCPs on weight gain during chemotherapy and in addition evaluate whether and what kind of information on dietary intake and physical activity HCPs provide to prevent/treat weight gain during (neo)adjuvant chemotherapy. METHODS: A qualitative study was conducted using semi-structured interviews with 34 HCPs involved in breast cancer care: general practitioners, oncologists, specialized nurses, and dieticians. RESULTS: To date, little information about nutrition, physical activity, and weight gain is given during chemotherapy because it is not part of most HCPs' training, it is not included in the guidelines and it is not the best time to bring up information in the opinion of HCPs. Weight gain was perceived as just a matter of a few kilos and not an important health issue during treatment. All HCPs felt it is better that women themselves addressed their weight gain after chemotherapy. CONCLUSION: More knowledge about health risks associated with chemotherapy-induced weight gain and how to combat these issues needs to be made readily available to the HCPs and should become part of their training. Existing patient guidelines should include information on how to prevent and/or reduce weight gain through self-management of nutrition intake and physical activity during and post chemotherapy.

Symptom burden and its association with change in glucose metabolism status over a 7-year period: the Hoorn Study.

AIMS: To study symptom burden among older people and its associations with change in glucose metabolism status over a 7-year period. METHODS: We conducted a prospective population-based cohort study among 397 older people. We used the revised Diabetes Symptom Checklist to assess symptom burden. Glucose metabolism status was determined using an oral glucose tolerance test. Analyses were adjusted for multiple confounders, including cardiovascular risk and risk of depression (Center for Epidemiological Studies Depression Scale score ≥ 16). RESULTS: Revised Diabetes Symptom Checklist total scores (range 0-100) increased slightly over time among people with normal glucose metabolism (mean difference ß1.04; P = 0.04) and those with impaired glucose metabolism (ß1.96; P = 0.01), but not among people with Type 2 diabetes (ß0.46; P = 0.55). These associations between symptom burden and glucose status were attenuated after full adjustment for multiple confounders and remained statistically significant for those with impaired glucose status. Linear mixed models showed significant mean differences in revised Diabetes Symptom Checklist total scores over time when comparing people with Type 2 diabetes with those with normal or impaired glucose metabolism, but not when comparing subjects with impaired vs normal glucose metabolism; these results did not alter after full adjustment. CONCLUSIONS: Symptom burden increased gradually over time in the people with impaired glucose metabolism and those with normal glucose metabolism, but not in patients with Type 2 diabetes over a 7-year follow-up period.

Predictors of functional improvement and future work status after the disability benefit claim: a prospective cohort study.

OBJECTIVE: In most industrialized countries, disability benefit rates have increased substantially in the past decade. Few beneficiaries return into employment once disability benefit is awarded. The present study aims to investigate which factors predict functional improvement and future work status among persons claiming disability benefit after having been on long-term sickness leave. METHODS: Prospective cohort study with 1 year follow-up among disability claimants (n = 375; response rate: 24.3 %) conducted in the Netherlands (October 2008-April 2011). Logistic regression was used to analyze associations between predictors [demographics; outcomes of the 12-item General Health Questionnaire (GHQ-12); 10-item Kessler Psychological Distress scale; Alcohol Use Disorders Identification Test; Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness; Utrecht Coping List; Social Support Questionnaire for Transactions and Satisfaction; certified International Classification of Diseases 10th edition (ICD-10) diagnosis; loss of earning capacity (LEC)] and outcomes [functional improvement on the World Health Organization Disability Schedule 2.0 (WHODAS 2.0) exceeding the standard error of measurement; work status at follow-up]. RESULTS: Functional improvement on total WHODAS was reported by 84 (31.9 % of 263 claimants included in analysis). Of those not having work at baseline (n = 338), 34 (9.1 %) respondents had paid work 1 year later. Predictors of functional improvement: GHQ-12 sum score >20 [odds ratios (OR) 2.9; 95 % confidence intervals (CI) 1.54-5.34]; of future work status: work status at baseline (OR 16.8; 95 % CI 6.55-43.14), LEC < 80 % (OR 4.6; 95 % CI 1.87-11.42), contact with a medical specialist (OR 0.4; 95 % CI 0.19-0.87). CONCLUSIONS: Only a limited number of factors were found to significantly predict functional improvement and return to paid work after the disability benefit claim, having paid work at baseline being by far the most important factor.

Predicting improvement of functioning in disability claimants.

PURPOSE: In the Netherlands, disability claimants are assessed after 2 years of sick leave, but their functioning may still improve. An accurate prognosis of functioning is difficult. Self predictions may be more accurate than those of professionals. The aim of this study, is to assess and compare the accuracy of predictions by disability claimants and insurance physicians (IPs) working at the Social Security Institute. It is further studied whether the accuracy differs between subgroups of claimants with mental or somatic health conditions. METHODS: We used data from the prospective cohort study cohort study. Following the assessment of the disability claim (n = 375) and after 1 year follow up (T1, n = 276) data on functioning were obtained from respondents by self-report questionnaire World Health Organization Disability Schedule 2.0. Both claimants and IPs were asked to predict improvement of functioning. Accuracy of their predictions were assessed by sensitivity, specificity, and area under the receiver operating curves (AUC). Mixed logistic regression was conducted to explore differences in accuracy between claimants with mental and somatic conditions. RESULTS: One-third (32 %) of disability claimants improved beyond the standard error of measurement. Disability claimants' and IPs were able to predict this improvement of functioning, but to a limited extent, with an AUC of 0.61 for IPs and 0.62 for disability claimants. We found no statistically significant differences in the accuracy of the predictions in claimants with mental or somatic health conditions. CONCLUSIONS: Improvements of functioning were not uncommon. However, both IPs and disability claimants were unable to predict improvement with high levels of accuracy in both mental and somatic health conditions.

Reproducibility of measurements of mid-upper arm circumference in older persons.

BACKGROUND: Mid-upper arm circumference (MUAC) is used as an alternative measure for body mass index to determine thinness in older persons. However, there are limited data on the reproducibility of this measurement in an older population. The present study examined the reproducibility of MUAC measurements in older persons, as well as the influence of different body positions and clothing. METHODS: A cross-sectional reproducibility study was performed in a nursing home (n = 43; age 65-96 years) and swimming pool facilities (n = 107; age 65-88 years). A different pair of observers independently measured the MUAC of each participant in the upright position on two occasions within 1 week. In the nursing home, measurements were also performed for each participant in the laying position and with clothes covering the upper arm. RESULTS: Mean differences and the 95% limit of agreement for inter-observer reproducibility of MUAC were 0.0 cm (-2.6 to 2.5 cm) for the swimming pool facilities and 0.3 cm (-0.6 to 1.3 cm) for the nursing home. Intra-class correlation coefficients (ICCs) were 0.89 and 0.92, respectively. Mean differences between laying and upright positions were 0.1 cm (-2.0 to 2.2 cm) and 0.0 cm (-1.9 to 2.0 cm) for each observer, respectively (ICC 0.96-0.97). Mean differences between clothes versus bare upper arm were -2.7 cm (-6.2 to 0.7) and -2.4 (-5.6 to 0.9 cm) (ICC 0.75 and 0.78). CONCLUSIONS: The reproducibility of the MUAC measurement in older persons is acceptable for group comparisons and, although borderline for the swimming pool facilities, remains acceptable for clinical purposes. The measurement can also be performed in the laying position but not with clothes covering the upper arm.

2D dosimetry in a proton beam with a scintillating GEM detector.

A two-dimensional position-sensitive dosimetry system based on a scintillating gas detector is being developed for pre-treatment verification of dose distributions in particle therapy. The dosimetry system consists of a chamber filled with an Ar/CF(4) scintillating gas mixture, inside which two gas electron multiplier (GEM) structures are mounted (Seravalli et al 2008b Med. Phys. Biol. 53 4651-65). Photons emitted by the excited Ar/CF(4) gas molecules during the gas multiplication in the GEM holes are detected by a mirror-lens-CCD camera system. The intensity distribution of the measured light spot is proportional to the 2D dose distribution. In this work, we report on the characterization of the scintillating GEM detector in terms of those properties that are of particular importance in relative dose measurements, e.g. response reproducibility, dose dependence, dose rate dependence, spatial and time response, field size dependence, response uniformity. The experiments were performed in a 150 MeV proton beam. We found that the detector response is very stable for measurements performed in succession (sigma = 0.6%) and its response reproducibility over 2 days is about 5%. The detector response was found to be linear with the dose in the range 0.05-19 Gy. No dose rate effects were observed between 1 and 16 Gy min(-1) at the shallow depth of a water phantom and 2 and 38 Gy min(-1) at the Bragg peak depth. No field size effects were observed in the range 120-3850 mm(2). A signal rise and fall time of 2 micros was recorded and a spatial response of

Time-of-day and days-on-shift predict increased fatigue over two-week offshore day-shifts.

OBJECTIVES: The purpose of this study was to investigate the accumulation of fatigue over a two-week offshore period. In particular, the effects of (1) time-of-day and days-on-shift as well as (2) acute and chronic sleep loss on the rate at which fatigue accumulates were investigated. METHODS: 42 day-shift offshore workers were examined. Fatigue was measured using pre- and post-shift scores on the Karolinska Sleepiness Scale (KSS). Total sleep time was measured using actigraphy (Motionwatch8, Camntech). Data was analyzed using a linear mixed model analyses. RESULTS: Average sleep loss per night was 92 min (95%CI: 89.6-94.0; p < .001). Mean cumulative sleep loss across the study was 21:20hrs (SD = 08:10hrs) over the 14 days. Chronic sleep loss was significantly related to a modest increase in sleepiness (KSS) across the shift (95%CI: 0.01-0.17; p = .020) and in post-shift scores (95%CI:.07-0.19; p < .001). Time-of-day (95%CI: 0.63 to -0.01; p = .042) and days-on-shift (95%CI: 0.03-0.08; p < .001) as well as their interaction (95%CI: 0.08 to -0.00; p = .027) influenced the rate at which fatigue accumulated over a two-week offshore period. CONCLUSIONS: Pre- and post-shift fatigue accumulate in different ways over the two-week offshore period. The accumulation of post-shift fatigue scores was positively related to successive days-on-shift and chronic sleep loss. Our results suggest that prolonging offshore periods will likely result in elevated fatigue risk. Accumulating fatigue and sleep loss over two-week offshore periods should be considered in fatigue risk management plans and systems.

Characterization of a scintillating GEM detector with low energy x-rays.

A two-dimensional position-sensitive dosimetry system based on a scintillating gas detector is being developed with the aim of using it for pre-treatment verification of dose distributions in charged particle therapy. The dosimetry system consists of a chamber filled with an Ar/CF(4) scintillating gas mixture, inside which two cascaded gas electron multipliers (GEMs) are mounted. A GEM is a thin kapton foil with copper cladding structured with a regular pattern of sub-mm holes. In such a system, light quanta are emitted by the scintillating gas mixture during the electron avalanches in the GEM holes when radiation traverses the detector. The light intensity distribution is proportional to the energy deposited in the detector's sensitive volume by the beam. In the present work, we investigated the optimization of the scintillating GEM detector light yield. The light quanta are detected by means of a CCD camera or a photomultiplier tube coupled to a monochromator. The GEM charge signal is measured simultaneously. We have found that with 60 microm diameter double conical GEM holes, a brighter light signal and a higher electric signal are obtained than with 80 microm diameter holes. With an Ar + 8% CF(4) volume concentration, the highest voltage across the GEMs and the largest light and electric signals were reached. Moreover, we have found that the emission spectrum of Ar/CF(4) is independent of (1) the voltages applied across the GEMs, (2) the x-ray beam intensity and (3) the GEM hole diameter. On the other hand, the ratio of Ar to CF(4) peaks in the spectrum changes when the concentration of the latter gas is varied.

Examining courses of sleep quality and sleepiness in full 2 weeks on/2 weeks off offshore day shift rotations.

To better understand sleep quality and sleepiness problems offshore, we examined courses of sleep quality and sleepiness in full 2-weeks on/2-weeks off offshore day shift rotations by comparing pre-offshore (1 week), offshore (2 weeks) and post-offshore (1 week) work periods. A longitudinal observational study was conducted among N=42 offshore workers. Sleep quality was measured subjectively with two daily questions and objectively with actigraphy, measuring: time in bed (TIB), total sleep time (TST), sleep latency (SL) and sleep efficiency percentage (SE%). Sleepiness was measured twice a day (morning and evening) with the Karolinska Sleepiness Scale. Changes in sleep and sleepiness parameters during the pre/post and offshore work periods were investigated using (generalized) linear mixed models. In the pre-offshore work period, courses of SE% significantly decreased (p=.038). During offshore work periods, the courses of evening sleepiness scores significantly increased (p<.001) and significantly decreased during post-offshore work periods (p=.004). During offshore work periods, TIB (p<.001) and TST (p<.001) were significantly shorter, SE% was significantly higher (p=.002), perceived sleep quality was significantly lower (p<.001) and level of rest after wake was significantly worse (p<.001) than during the pre- and post-offshore work periods. Morning sleepiness was significantly higher during offshore work periods (p=.015) and evening sleepiness was significantly higher in the post-offshore work period (p=.005) compared to the other periods. No significant changes in SL were observed. Courses of sleep quality and sleepiness parameters significantly changed during full 2-weeks on/2-weeks off offshore day shift rotation periods. These changes should be considered in offshore fatigue risk management programmes.

Rational and design of an individual participant data meta-analysis of spinal manipulative therapy for chronic low back pain-a protocol.

BACKGROUND: Chronic low back pain (LBP) is the leading cause of pain and disability, resulting in a major socioeconomic impact. The Cochrane Review which examined the effect of spinal manipulative therapy (SMT) for chronic LBP concluded that SMT is moderately effective, but was based on conventional meta-analysis of aggregate data. The use of individual participant data (IPD) from trials allows for a more precise estimate of the treatment effect and has the potential to identify moderators and/or mediators. The aim is (1) to assess the overall treatment effect of SMT for primary and secondary outcomes in adults with chronic LBP, (2) to determine possible moderation of baseline characteristics on treatment effect, (3) to identify characteristics of intervention (e.g., manipulation/mobilization) that influence the treatment effect, and (4) to identify mediators of treatment effects. METHODS: All trials included in the Cochrane Review on SMT for chronic LBP will be included which were published after the year 2000, and the search will be updated. No restrictions will be placed on the type of comparison or size of the study. Primary outcomes are pain intensity and physical functioning. A dataset will be compiled consisting of individual trials and variables included according to a predefined coding scheme. Variables to be included are descriptive of characteristics of the study, treatment, comparison, participant characteristics, and outcomes at all follow-up periods. A one-stage approach with a mixed model technique based on the intention-to-treat principle will be used for the analysis. Subsequent analyses will focus on treatment effect moderators and mediators. DISCUSSION: We will analyze IPD for LBP trials in which SMT is one of the interventions. IPD meta-analysis has been shown to be more reliable and valid than aggregate data meta-analysis, although this difference might also be attributed to the number of studies that can be used or the amount of data that can be utilized. Therefore, this project may identify important gaps in our knowledge with respect to prognostic factors of treatment effects. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015025714.

Different methods to analyze stepped wedge trial designs revealed different aspects of intervention effects.

OBJECTIVES: Within epidemiology, a stepped wedge trial design (i.e., a one-way crossover trial in which several arms start the intervention at different time points) is increasingly popular as an alternative to a classical cluster randomized controlled trial. Despite this increasing popularity, there is a huge variation in the methods used to analyze data from a stepped wedge trial design. STUDY DESIGN AND SETTING: Four linear mixed models were used to analyze data from a stepped wedge trial design on two example data sets. The four methods were chosen because they have been (frequently) used in practice. Method 1 compares all the intervention measurements with the control measurements. Method 2 treats the intervention variable as a time-independent categorical variable comparing the different arms with each other. In method 3, the intervention variable is a time-dependent categorical variable comparing groups with different number of intervention measurements, whereas in method 4, the changes in the outcome variable between subsequent measurements are analyzed. RESULTS: Regarding the results in the first example data set, methods 1 and 3 showed a strong positive intervention effect, which disappeared after adjusting for time. Method 2 showed an inverse intervention effect, whereas method 4 did not show a significant effect at all. In the second example data set, the results were the opposite. Both methods 2 and 4 showed significant intervention effects, whereas the other two methods did not. For method 4, the intervention effect attenuated after adjustment for time. CONCLUSION: Different methods to analyze data from a stepped wedge trial design reveal different aspects of a possible intervention effect. The choice of a method partly depends on the type of the intervention and the possible time-dependent effect of the intervention. Furthermore, it is advised to combine the results of the different methods to obtain an interpretable overall result.

High prevalence of early onset mental disorders among long-term disability claimants.

PURPOSE: To provide information on prevalence, comorbidity, age-of-onset and severity of mental disorders among persons claiming disability after long-term sickness absence. METHOD: Cross-sectional analysis of a cohort of Dutch disability claimants (n = 346). Composite International Diagnostic Interview (CIDI) 3.0 was used to generate DSM-IV classifications of mental disorder, age-of-onset and severity; registry data were used on demographics and ICD-10 classifications of somatic disorder. RESULTS: The mean age of respondents was 49.8 (range 22-64). The most prevalent broad categories of mental disorders were mood and anxiety disorder with a 12-month prevalence of 28.6% and 32.9%, respectively. Mood and most anxiety disorders had ages of onset in adolescence and early adulthood. The phobias start at school age. Of all respondents, 33.7% had ≥1 12-month mental disorder. Co-occurrence of substance use disorders, phobias and depression/anxiety disorders is frequent. Urogenital and gastrointestinal diseases, and cancer coincide with 12-month mental disorder in 66.7%, 53.9% and 51.7% of cases, respectively. More than two out of three specific mental disorders are serious in terms of disability and days out of working role. CONCLUSIONS: Disability claimants constitute a vulnerable population with a high prevalence of serious mental disorder, substantial comorbidity and ages-of-onset in early working careers. More research is needed to help prevent long-term sickness absence and disability of claimants with mental health problems. IMPLICATIONS FOR REHABILITATION: This study shows common mental disorders, such as mood and anxiety disorders, to be highly prevalent among persons claiming disability benefit after long-term sickness absence, to have early onsets and to often co-occur with somatic disorders. Professionals in primary and occupational health care should assess need for treatment of workers at risk, while at the same time being careful not to medicalize normal life problems. Insurance physicians assessing disability benefit claims should identify factors that caused claimants to call in sick and start interventions to promote return to work.

Evidence-based guidelines on the referral of visually impaired persons to low vision services.

PURPOSE: One to two percent of the population in the Western world is visually impaired or blind. For most of these people there is no curative therapy. Therefore, the Dutch Ophthalmic Society has taken the initiative to develop an evidence-based guideline for the referral of visually impaired persons to low vision services. METHODS: A systematic literature search was performed in the Embase (1991-2001) and Medline (1966-2003) databases. Literature was searched for definitions of visual impairment, for physician-patient communication, and for outcome of interventions for visually impaired persons. Results of the articles that were selected were summarized and rated according to the level of evidence. Other considerations such as the current organization of rehabilitation for visually impaired persons in the Netherlands were also taken into account. RESULTS: The World Health Organization criteria were slightly adapted in order to include all people who experience problems with reading and other daily life activities due to visual impairment. A large number of recommendations were devised. Among these is that the complete diagnosis should be communicated to the patient and that a second appointment should be offered in which the diagnosis and potential treatment options are discussed again. Another recommendation is that in general visually impaired adults eligible for referral should be referred for the provision of low vision aids and that patients with complex problems or extensive rehabilitative demand should be referred to a rehabilitation center. CONCLUSIONS: This article presents a summary of the first European evidence-based guideline for the referral of visually impaired persons.

[Referral for rehabilitation in case of permanent visual handicap; guideline of the Dutch Society of Ophthalmology]. / Verwijzing naar revalidatie bij blijvende visuele beperkingen; richtlijn van het Nederlands Oogheelkundig Gezelschap.

The Dutch Society of Ophthalmology (NOG) has developed an evidence-based guideline for the referral of visually impaired people for rehabilitation and support. Referral for rehabilitation and support must be preceded by diagnosis and treatment. Consultation of an ophthalmologist is essential. Information about the disease should be given to the patient orally as well as in writing. The ophthalmologist brings up the possibility of rehabilitation in the presence of a visual acuity < 0.5 and/or visual field of < 30 degrees in the better eye and a well-defined request for help. Visually impaired patients with a relatively simple request for help are referred to a specialised optometrist whenever possible. Visually impaired patients with more complex requests for help are referred to a multidisciplinary (regional or national) rehabilitation centre for people with a visual handicap. Visually impaired and blind patients are informed about the existence of patient organisations. Referral for rehabilitation is done by means of a structured letter with all relevant information. A copy of this letter should be sent to the family physician and all other attending physicians.

Development and validation of the Diagnostic Interview Adjustment Disorder (DIAD).

Adjustment disorders (ADs) are under-researched due to the absence of a reliable and valid diagnostic tool. This paper describes the development and content/construct validation of a fully structured interview for the diagnosis of AD, the Diagnostic Interview Adjustment Disorder (DIAD). We developed the DIAD by partly adjusting and operationalizing DSM-IV criteria. Eleven experts were consulted on the content of the DIAD. In addition, the DIAD was administered by trained lay interviewers to a representative sample of disability claimants (n = 323). To assess construct validity of the DIAD, we explored the associations between the AD classification by the DIAD and summary scores of the Kessler Psychological Distress 10-item Scale (K10) and the World Health Organization Disability Assessment Schedule (WHODAS) by linear regression. Expert agreement on content of the DIAD was moderate to good. The prevalence of AD using the DIAD with revised criteria for the diagnosis AD was 7.4%. The associations of AD by the DIAD with average sum scores on the K10 and the WHODAS supported construct validity of the DIAD. The results provide a first indication that the DIAD is a valid instrument to diagnose AD. Further studies on reliability and on other aspects of validity are needed.

Risk of third malignancies and death after a second malignancy in retinoblastoma survivors.

Retinoblastoma patients have a strongly increased risk of second malignancies, and survivors with a third or subsequent malignancy are increasingly observed. However, it has not been examined whether survivors who developed a second malignancy have a greater risk of a subsequent malignancy. On the basis of the Dutch retinoblastoma registry, the risk of a third malignancy was compared with cancer risk in the Dutch population. Cox model analysis with a time-dependent covariate was used to compare the subsequent malignancy risk and survival among patients with and without a second malignancy. Risk of a third malignancy was increased 8-fold compared with the general population. The hazard ratio (HR) of a third malignancy after a second malignancy was more than 7-fold increased compared to the risk of a second malignancy after retinoblastoma. Radiotherapy increased the risk 3-fold. A third malignancy was associated with worse survival compared with survival of patients only diagnosed with a second malignancy (HR=5.0). Survivors of retinoblastoma who already developed a second primary malignancy have an even higher risk of subsequent primary malignancies than retinoblastoma survivors without a second malignancy. Treating physicians and patients should be aware of this higher risk.

Cancer mortality in long-term survivors of retinoblastoma.

This study examined long-term cause-specific mortality among 998 Dutch retinoblastoma survivors, diagnosed from 1862 to 2005, according to follow-up time, treatment and heredity. After a median follow-up of 30.8 years, only cause-specific mortality for second malignancies among hereditary retinoblastoma survivors was statistically significantly increased with 12.8-fold. Risk of death from second malignancies among non-hereditary survivors was not increased. Mortality rates of second malignancy among hereditary patients were non-significantly elevated with 1.6-fold for treated with radiotherapy, compared to those treated otherwise. Standardised mortality ratios (SMRs) for second malignancy among hereditary patients increased during the first three decades after retinoblastoma diagnosis. Whereas these risks decreased after three decades, the absolute excess risk (AER) increased significantly, up to 23.2 excess cases per 1000 patients/year after five decades of follow-up. Fifty years after retinoblastoma diagnosis the cumulative mortality from any second malignancy was 17.3% for hereditary patients. Very long-term follow-up of retinoblastoma patients revealed an emerging excess risk of mortality in hereditary retinoblastoma survivors. This implies that lifelong follow-up is needed, whereas at the same time, patients and their physicians must be alerted to the increased second malignancy risks.

Evaluation of cross-sectional and longitudinal construct validity of two vision-related quality of life questionnaires: the LVQOL and VCM1.

The Low Vision Quality of Life (LVQOL) questionnaire and the Vision-related Quality of Life Core Measure (VCM1) are two of the many vision-related quality of life (QOL) questionnaires that have been developed in recent years. Although psychometric properties of the LVQOL and VCM1 compare well with other vision-related QOL questionnaires, construct and longitudinal validity have not been assessed (adequately). The purpose of this study was to examine the cross-sectional and longitudinal construct validity of these questionnaires by testing specific pre-specified hypotheses about the relations of these questionnaires with other measures. The percentage of hypotheses regarding the cross-sectional construct validity that were refuted for the LVQOL was 22% for the basic aspects of vision subscale, 50% for the mobility subscale, 39% for the adjustment subscale and 17% for the reading and fine work subscale. For the VCM1 this percentage was 57%. For the longitudinal construct validity the percentage of hypotheses that were refuted ranged from 33 to 75% for the LVQOL subscales and was 50% for the VCM1. In conclusion, cross-sectional construct validity was satisfactory for the LVQOL subscales, but seemed poor for the VCM1. In addition, the longitudinal validity of these scales was poor to moderate.