Investigating young children's physical activity through time and place.

BACKGROUND: Previous research indicates the start of primary school (4-5-year-old) as an essential period for the development of children's physical activity (PA) patterns, as from this point, the age-related decline of PA is most often observed. During this period, young children are exposed to a wider variety of environmental- and social contexts and therefore their PA is influenced by more diverse factors. However, in order to understand children's daily PA patterns and identify relevant opportunities for PA promotion, it is important to further unravel in which (social) contexts throughout the day, PA of young children takes place. METHODS: We included a cross-national sample of 21 primary schools from the Startvaardig study. In total, 248 children provided valid accelerometer and global positioning (GPS) data. Geospatial analyses were conducted to quantify PA in (social) environments based on their school and home. Transport-related PA was evaluated using GPS speed-algorithms. PA was analysed at different environments, time-periods and for week- and weekend days separately. RESULTS: Children accumulated an average of 60 min of moderate-to-vigorous PA (MVPA), both during week- and weekend days. Schools contributed to approximately half of daily MVPA during weekdays. During weekends, environments within 100 m from home were important, as well as locations outside the home-school neighbourhood. Pedestrian trips contributed to almost half of the daily MVPA. CONCLUSIONS: We identified several social contexts relevant for children's daily MVPA. Schools have the potential to significantly contribute to young children's PA patterns and are therefore encouraged to systematically evaluate and implement parts of the school-system that stimulate PA and potentially also learning processes. Pedestrian trips also have substantial contribution to daily MVPA of young children, which highlights the importance of daily active transport in school- and parental routines.

In utero antidepressant exposure not associated with ADHD in the offspring: A case control sibling design.

Recent studies have reported an association between antidepressant (AD) use during pregnancy and the risk to develop attention-deficit/hyperactivity disorder (ADHD) in the offspring. However, the association might be confounded by risk factors in the pregnant parent. To control for unmeasured factors between pregnancies carried by the same parent, we set up a case-control sibling study using the University of Groningen prescription database IADB.nl. Children receiving medication for ADHD (cases) before the age of 16 years were matched to siblings not receiving such medication (controls). Exposure was defined as at least two prescriptions for any AD during pregnancy, i.e., the period of 39 weeks before the birth date of the offspring. Secondary analyses were performed to assess the effects of the degree of exposure (the amount of Defined Daily Doses) and the type of AD exposed to. Univariate and multivariate logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals (CI). In total, 2,833 children (1,304 cases and 1,529 controls) were included in the analysis. Exposure rate to ADs among cases and controls was 2.2% and 2.4%, respectively. After adjusting for the birth date of the child (as a proxy for the date of pregnancy), age of the pregnant parent at birth, use of psychostimulants, opioids, and antiepileptic drugs by the pregnant parent in the 15 months before birth of the child, an adjusted OR of 1.11 (95% CI 0.67-1.83) was found for the risk of ADHD in the offspring when exposed in utero to ADs. This indicates no increased risk of ADHD in offspring following in utero exposure to ADs. The secondary analyses revealed no statistically significant associations either. The present study provides further evidence that an association between in utero AD exposure and ADHD in offspring might not exist. This perceived association may be caused (at least partially) by confounding by indication. The extent to which depression in the pregnant parent could cause mental disorders such as ADHD in offspring, and the mechanisms involved, should be investigated in further studies.

Applying an ecosystem approach to explore modifiable factors related to the risk for low motor competence in young children.

OBJECTIVES: Early childhood is a crucial phase for motor development in which differences between children can manifest. These differences might be related to factors in ecosystems in which children are raised, of which little is currently known. The current study's purpose was to explore which modifiable factors in children's ecosystems are associated with the odds for low versus higher motor competence (MC) in 4- to 6-year-old children. DESIGN: A cross-sectional study design was conducted to investigate which modifiable social and physical factors in the home environment and direct living environment were associated with differences in MC. METHODS: Children's MC was measured through the Athletic Skills Track in 612 4- to 6-year-olds, from 10 primary schools in Eindhoven, the Netherlands. Parenting practices, characteristics of the home environment, and perceptions of the direct living environment were assessed through parental questionnaires. Hierarchical logistic regression analyses were conducted to evaluate factors associated with low MC in children. RESULTS: The presence of a garden at home and higher perceived sports facilities in the direct living environment decreased the likelihood of children being classified as low MC. Moreover, stronger parental active transportation routines and more discouraging physical activity parenting practices resulted in lower odds of low MC. In addition, girls were more at risk for low MC. CONCLUSIONS: Characteristics of the social and physical home environment and direct living environment were associated with MC disparities during early childhood. Both parenting practices and parental physical activity-involved behaviours are relevant modifiable factors related to differences in children's MC.

Ventilation and air cleaning to limit aerosol particle concentrations in a gym during the COVID-19 pandemic.

SARS-CoV-2 can spread by close contact through large droplet spray and indirect contact via contaminated objects. There is mounting evidence that it can also be transmitted by inhalation of infected saliva aerosol particles. These particles are generated when breathing, talking, laughing, coughing or sneezing. It can be assumed that aerosol particle concentrations should be kept low in order to minimize the potential risk of airborne virus transmission. This paper presents measurements of aerosol particle concentrations in a gym, where saliva aerosol production is pronounced. 35 test persons performed physical exercise and aerosol particle concentrations, CO2 concentrations, air temperature and relative humidity were obtained in the room of 886 m³. A separate test was used to discriminate between human endogenous and exogenous aerosol particles. Aerosol particle removal by mechanical ventilation and mobile air cleaning units was measured. The gym test showed that ventilation with air-change rate ACH = 2.2 h-1, i.e. 4.5 times the minimum of the Dutch Building Code, was insufficient to stop the significant aerosol concentration rise over 30 min. Air cleaning alone with ACH = 1.39 h-1 had a similar effect as ventilation alone. Simplified mathematical models were engaged to provide further insight into ventilation, air cleaning and deposition. It was shown that combining the above-mentioned ventilation and air cleaning can reduce aerosol particle concentrations with 80 to 90% , depending on aerosol size. This combination of existing ventilation supplemented with air cleaning is energy efficient and can also be applied for other indoor environments.

FLAIR-only joint volumetric analysis of brain lesions and atrophy in clinically isolated syndrome (CIS) suggestive of multiple sclerosis.

BACKGROUND: MRI assessment in multiple sclerosis (MS) focuses on the presence of typical white matter (WM) lesions. Neurodegeneration characterised by brain atrophy is recognised in the research field as an important prognostic factor. It is not routinely reported clinically, in part due to difficulty in achieving reproducible measurements. Automated MRI quantification of WM lesions and brain volume could provide important clinical monitoring data. In general, lesion quantification relies on both T1 and FLAIR input images, while tissue volumetry relies on T1. However, T1-weighted scans are not routinely included in the clinical MS protocol, limiting the utility of automated quantification. OBJECTIVES: We address an aspect of this important translational challenge by assessing the performance of FLAIR-only lesion and brain segmentation, against a conventional approach requiring multi-contrast acquisition. We explore whether FLAIR-only grey matter (GM) segmentation yields more variability in performance compared with two-channel segmentation; whether this is related to field strength; and whether the results meet a level of clinical acceptability demonstrated by the ability to reproduce established biological associations. METHODS: We used a multicentre dataset of subjects with a CIS suggestive of MS scanned at 1.5T and 3T in the same week. WM lesions were manually segmented by two raters, 'manual 1' guided by consensus reading of CIS-specific lesions and 'manual 2' by any WM hyperintensity. An existing brain segmentation method was adapted for FLAIR-only input. Automated segmentation of WM hyperintensity and brain volumes were performed with conventional (T1/T1 + FLAIR) and FLAIR-only methods. RESULTS: WM lesion volumes were comparable at 1.5T between 'manual 2' and FLAIR-only methods and at 3T between 'manual 2', T1 + FLAIR and FLAIR-only methods. For cortical GM volume, linear regression measures between conventional and FLAIR-only segmentation were high (1.5T: α = 1.029, R2 = 0.997, standard error (SE) = 0.007; 3T: α = 1.019, R2 = 0.998, SE = 0.006). Age-associated change in cortical GM volume was a significant covariate in both T1 (p = 0.001) and FLAIR-only (p = 0.005) methods, confirming the expected relationship between age and GM volume for FLAIR-only segmentations. CONCLUSIONS: FLAIR-only automated segmentation of WM lesions and brain volumes were consistent with results obtained through conventional methods and had the ability to demonstrate biological effects in our study population. Imaging protocol harmonisation and validation with other MS phenotypes could facilitate the integration of automated WM lesion volume and brain atrophy analysis as clinical tools in radiological MS reporting.

A Pilot Study on the Contamination of Assistance Dogs' Paws and Their Users' Shoe Soles in Relation to Admittance to Hospitals and (In)Visible Disability.

(1) Background: People with disabilities may benefit from an assistance dog (AD). Despite regulations that prohibit the denial of ADs to public places, this still occurs on a regular basis. The main argument for denial of access is that dogs compromise hygiene with their presence, which could cause a health hazard. Meanwhile, people are allowed to walk into and out of public places freely. (2) Objective: As a pilot study, to investigate the number of Enterobacteriaceae and the presence of Clostridium difficile bacteria on the paws of ADs and pet dogs (PDs) as well as the shoe soles of their users and owners. With the results, an assessment can be made as to whether measures are required to reduce environmental contamination (e.g., in hospitals). (3) Methods: In total, 25 ADs, 25 PDs, and their 50 users/owners participated in the study. Each participant walked their dog for 15-30 min prior to the sampling of the front paws. Each PD owner or AD user filled out a general questionnaire about the care of their dogs, and AD users were asked to fill out an additional questionnaire on their experiences regarding the admittance of their ADs to public places (in particular, hospitals). Dutch hospitals were questioned on their protocols regarding the admittance of ADs and their visitor numbers, including the percentage of AD users, to put these numbers into perspective. (4) Results: Dog paws were more often negative for Enterobacteriaceae compared to shoe soles (72% and 42%, respectively) and also had significantly lower bacterial counts (mean of 3.54log10 and 5.03log10 colony-forming units (CFUs), respectively; p < 0.05). This was most distinct in the comparison between PDs and their owners (3.75log10 and 5.25log10 CFUs; p < 0.05); the numbers were similar between ADs and their users (3.09log10 and 4.58log10 CFUs; p = 0.2). C. difficile was found on one (4%) AD user's shoe soles. Moreover, 81% of AD users had been denied access with their current AD once or several times, the main reason being hygiene. The results of the visibly and invisibly disabled were significantly different. The number of AD users as opposed to the total number of hospital visitors was 0.03% in one hospital and is estimated to be 0.02% in the Netherlands. (5) Conclusions: The general hygiene of dogs' paws is far better than that of shoe soles, mostly demonstrated by the better general hygiene of PD paws compared with their owners' shoe soles; ADs and their users had comparable levels of general hygiene. In addition, the number of AD users amongst the total number of hospital visitors in the Netherlands is very limited. Thus, hygiene measures to reduce any contamination due to dog paws do not seem necessary.

Does Social Capital Benefit Older Adults' Health and Well-Being? The Mediating Role of Physical Activity.

Objectives: To assess whether social capital benefits older adults' self-rated health and well-being and whether physical activity mediates this relation. Methods: A survey study was conducted among members of a sociocultural organization (age ≥55 years), both cross-sectionally (baseline Time 1; N = 959) and longitudinally (3-year follow-up Time 2; N = 409). Results: Specific indicators of social capital were positively, though modestly, related to health and well-being at Time 1 and Time 2. Experienced connectedness with age peers emerged as the strongest predictor. Physical activity only mediated the relation with experienced safety in society. Discussion: The relative importance of older adults' experienced connectedness with their age peers underlines the importance of internalized group membership as a determinant of their health and well-being. Physical activity seems to play only a minor mediating role.

Subtyping psychological distress in the population: a semi-parametric network approach.

AIMS: The mechanisms underlying both depressive and anxiety disorders remain poorly understood. One of the reasons for this is the lack of a valid, evidence-based system to classify persons into specific subtypes based on their depressive and/or anxiety symptomatology. In order to do this without a priori assumptions, non-parametric statistical methods seem the optimal choice. Moreover, to define subtypes according to their symptom profiles and inter-relations between symptoms, network models may be very useful. This study aimed to evaluate the potential usefulness of this approach. METHODS: A large community sample from the Canadian general population (N = 254 443) was divided into data-driven clusters using non-parametric k-means clustering. Participants were clustered according to their (co)variation around the grand mean on each item of the Kessler Psychological Distress Scale (K10). Next, to evaluate cluster differences, semi-parametric network models were fitted in each cluster and node centrality indices and network density measures were compared. RESULTS: A five-cluster model was obtained from the cluster analyses. Network density varied across clusters, and was highest for the cluster of people with the lowest K10 severity ratings. In three cluster networks, depressive symptoms (e.g. feeling depressed, restless, hopeless) had the highest centrality. In the remaining two clusters, symptom networks were characterised by a higher prominence of somatic symptoms (e.g. restlessness, nervousness). CONCLUSION: Finding data-driven subtypes based on psychological distress using non-parametric methods can be a fruitful approach, yielding clusters of persons that differ in illness severity as well as in the structure and strengths of inter-symptom relationships.

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study.

Background: Venetoclax is a selective, potent inhibitor of the anti-apoptotic B-cell leukemia/lymphoma-2 protein approved for treatment of chronic lymphocytic leukemia. We conducted a dose-finding study of venetoclax in combination with bendamustine-rituximab (BR) in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL). Patients and methods: BR was given for six cycles at standard doses. Intermittent and continuous oral venetoclax administration was explored at 50-1200 mg daily doses. Co-primary objectives included safety, pharmacokinetics (PKs), maximum-tolerated dose (MTD), and recommended phase II dose (RP2D); secondary objective was preliminary efficacy. Results: Sixty patients were enrolled: 32 with follicular lymphoma, 22 with diffuse large B-cell lymphoma, and 6 with marginal zone lymphoma. Nausea (70%), neutropenia (68%), diarrhea (55%), and thrombocytopenia (52%) were the most frequent adverse events (AEs). Most common grade 3/4 AEs were neutropenia (60%) and lymphopenia (38%). Serious AEs were reported in 24 patients; the most frequent were febrile neutropenia and disease progression (8% each). Five patients died from either disease progression (n = 4) or respiratory failure (n = 1). MTD was not reached; RP2D for venetoclax-BR combination was established as 800 mg daily continuously. Venetoclax PK exposure with and without BR was comparable. For all patients, overall response rate was 65%. Median duration of overall response, overall survival, and progression-free survival was 38.3 months [95% confidence interval (CI) 10.4-NR], not yet reached, and 10.7 months (95% CI 4.3-21.0), respectively. Conclusions: This study established the safety profile of venetoclax in combination with BR, and results demonstrated tolerability and preliminary efficacy of the combination. Additional follow-up is needed to better determine the future role of BR plus venetoclax in the treatment of relapsed/refractory B-cell NHL. Trial registered: Clinicaltrials.gov, NCT01594229.

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.

Direct anterior approach versus posterolateral approach in total hip arthroplasty : one surgeon, two approaches.

Early research shows several advantages of the Direct Anterior Approach (DAA) in total hip arthroplasty (THA), although no studies evaluated the DAA on a regular operating table without using fluoroscopy. We performed a retrospective cohort study on the outcome of this variation of the DAA compared with the posterolateral approach (PLA) with one year follow-up. All procedures were uncemented THA performed in 2012 by a single surgeon. Patients in the DAA group (N = 45) had a lower Body Mass Index (p > .001) than the PLA group (N = 38). Functional outcome, pain scores and complications were comparable between the two approaches. Compared with PLA, the DAA was associated with longer operation time (p > 0.001), more blood loss (p > 0.001), shorter length of stay (p = .009), and more adequate acetabular cup inclination (p = .004). This study shows that the DAA on a regular operating table without using fluoroscopy has several advantages compared to the PLA.

Variety in diagnosis and treatment of periprosthetic joint infections in Belgium and the Netherlands.

Recently, guidelines regarding diagnosis and treatment of periprosthetic joint infection (PJI) have been published, but it is unknown how well these are -followed in the Netherlands and Belgium. Therefore, a survey study was performed in the Netherlands and Belgium. 81 orthopedic departments responded (54% in the Netherlands, 52% in Belgium). The majority used protocols for antibiotic and surgical treatment. To discriminate between early and late infection, differences in periods used were seen between respondents, and between countries. Empirical antibiotic treatment varied greatly. Debridement, antibiotics, irrigation and retention of the prosthesis (DAIR) is the -almost unanimous treatment of choice for early PJI. Guidelines are available, but seem not (yet) to be -followed accurately, and do not have answers to all possible treatment options. Perhaps, national guidelines might produce more standardized care, and -consequentially, easier comparison for research, more transparency for patients, and less health care costs.

In situ observations of a possible skate nursery off the western Antarctic Peninsula.

A dense aggregation of skate egg cases was imaged during a photographic survey of the sea floor along the western Antarctic Peninsula in November 2013. Egg cases were noted in a narrow band between 394 and 443 m depth. Although some skate species in other oceans are known to utilize restricted areas to deposit eggs in great numbers, such nurseries have not been described in the Southern Ocean.

T2 mapping outperforms normalised FLAIR in identifying hippocampal sclerosis.

RATIONALE: Qualitatively, FLAIR MR imaging is sensitive to the detection of hippocampal sclerosis (HS). Quantitative analysis of T2 maps provides a useful objective measure and increased sensitivity over visual inspection of T2-weighted scans. We aimed to determine whether quantification of normalised FLAIR is as sensitive as T2 mapping in detection of HS. METHOD: Dual echo T2 and FLAIR MR images were retrospectively analysed in 27 patients with histologically confirmed HS and increased T2 signal in ipsilateral hippocampus and 14 healthy controls. Regions of interest were manually segmented in all hippocampi aiming to avoid inclusion of CSF. Hippocampal T2 values and measures of normalised FLAIR Signal Intensity (nFSI) were compared in healthy and sclerotic hippocampi. RESULTS: HS was identified on T2 values with 100% sensitivity and 100% specificity. HS was identified on nFSI measures with 60% sensitivity and 93% specificity. CONCLUSION: T2 mapping is superior to nFSI for identification of HS.

A randomized clinical trial of cognitive behavioral therapy and interpersonal psychotherapy for panic disorder with agoraphobia.

BACKGROUND: Interpersonal psychotherapy (IPT) seems to be as effective as cognitive behavioral therapy (CBT) in the treatment of major depression. Because the onset of panic attacks is often related to increased interpersonal life stress, IPT has the potential to also treat panic disorder. To date, a preliminary open trial yielded promising results but there have been no randomized controlled trials directly comparing CBT and IPT for panic disorder. METHOD: This study aimed to directly compare the effects of CBT versus IPT for the treatment of panic disorder with agoraphobia. Ninety-one adult patients with a primary diagnosis of DSM-III or DSM-IV panic disorder with agoraphobia were randomized. Primary outcomes were panic attack frequency and an idiosyncratic behavioral test. Secondary outcomes were panic and agoraphobia severity, panic-related cognitions, interpersonal functioning and general psychopathology. Measures were taken at 0, 3 and 4 months (baseline, end of treatment and follow-up). RESULTS: Intention-to-treat (ITT) analyses on the primary outcomes indicated superior effects for CBT in treating panic disorder with agoraphobia. Per-protocol analyses emphasized the differences between treatments and yielded larger effect sizes. Reductions in the secondary outcomes were equal for both treatments, except for agoraphobic complaints and behavior and the credibility ratings of negative interpretations of bodily sensations, all of which decreased more in CBT. CONCLUSIONS: CBT is the preferred treatment for panic disorder with agoraphobia compared to IPT. Mechanisms of change should be investigated further, along with long-term outcomes.

[The role of CSF markers in the early diagnosis of Alzheimer's disease]. / De rol van liquormarkers bij de vroege diagnostiek van de ziekte van Alzheimer.

BACKGROUND: Biomarkers in cerebrospinal fluid (CSF) are being used increasingly to diagnose early Alzheimer's disease (AD). A CSF profile that is suggestive of ad is an abnormal ratio of the proteins Ab1-42 to total tau. AIM: To describe the prevalence and prognosis of a CSF profile in patients without dementia but with subjective memory problems and mild cognitive impairments (MCI) at a memory clinic. METHOD: A multi-centre study. RESULTS: A European multi-centre study showed that a CSF AD profile was often present in patients with subjective complaints and patients with MCI . The CSF AD profile predicted a decline in cognition and daily functioning over a period of 3 years in patients with MCI. Patients with amnestic MCI and a CSF AD profile developed AD more often within this period than patients without this profile. CONCLUSION: CSF markers suggestive of ad are common in persons without dementia. It may be possible to use these markers for the prognosis of patients who have MCI .

Distinct gene signature revealed in white blood cells, CD4(+) and CD8(+) T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide.

Tolerizing mice polygenically predisposed to lupus-like disease (NZB/NZW F1 females) with a peptide mimicking anti-DNA IgG sequences containing MHC class I and class II T cell determinants (pConsensus, pCons) results in protection from full-blown disease attributable in part to the induction of CD4(+)CD25(+)Foxp3+ and CD8(+)Foxp3+ regulatory T cells. We compared 45 000 murine genes in total white blood cells (WBC), CD4(+) T cells, and CD8(+) T cells from splenocytes of (NZBxNZW) F1 lupus-prone mice tolerized with pCons vs untreated naïve mice and found two-fold or greater differential expression for 448 WBC, 174 CD4, and 60 CD8 genes. We identified differentially expressed genes that played roles in the immune response and apoptosis. Using real-time PCR, we validated differential expression of selected genes (IFI202B, Bcl2, Foxp3, Trp-53, CCR7 and IFNar1) in the CD8(+)T cell microarray and determined expression of selected highly upregulated genes in different immune cell subsets. We also determined Smads expression in different immune cell subsets, including CD4(+) T cells and CD8(+) T cells, to detect the effects of TGF-beta, known to be the major cytokine that accounts for the suppressive capacity of CD8(+) Treg in this system. Silencing of anti-apoptotic gene Bcl2 or interferon genes (IFI202b and IFNar1 in combination) in CD8(+) T cells from tolerized mice did not affect the expression of the other selected genes. However, silencing of Foxp3 reduced expression of Foxp3, Ifi202b and PD1-all of which are involved in the suppressive capacity of CD8(+) Treg in this model.

Psychological causes of non-compliance with electronically monitored occlusion therapy for amblyopia.

AIM: To analyse psychological causes for low compliance with occlusion therapy for amblyopia. METHOD: In a randomised trial, the effect of an educational programme on electronically measured compliance had been assessed. 149 families who participated in this trial completed a questionnaire based on the Protection Motivation Theory after 8 months of treatment. Families with compliance less than 20% of prescribed occlusion hours were interviewed to better understand their cause for non-compliance. RESULTS: Poor compliance was most strongly associated with a high degree of distress (p<0.001), followed by low perception of vulnerability (p = 0.014), increased stigma (p = 0.017) and logistical problems with treatment (p = 0.044). Of 44 families with electronically measured compliance less than 20%, 28 could be interviewed. The interviews confirmed that lack of knowledge, distress and logistical problems resulted in non-compliance. CONCLUSION: Poor parental knowledge, distress and difficulties implementing treatment seemed to be associated with non-compliance. For the same domains, the scores were more favourable for families who had received the educational programme than for those who had not.

Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study.

BACKGROUND: We previously reported results of the phase 2, multicenter PINNACLE study, which confirmed the substantial single-agent activity of bortezomib in patients with relapsed or refractory mantle cell lymphoma (MCL). MATERIALS AND METHODS: We report updated time-to-event data, in all patients and by response to treatment, after extended follow-up (median 26.4 months). RESULTS: Median time to progression (TTP) was 6.7 months. Median time to next therapy (TTNT) was 7.4 months. Median overall survival (OS) was 23.5 months. In responding patients, median TTP was 12.4 months, median duration of response (DOR) was 9.2 months, median TTNT was 14.3 months, and median OS was 35.4 months. Patients achieving complete response had heterogeneous disease characteristics; among these patients, median TTP and DOR were not reached, and median OS was 36.0 months. One-year survival rate was 69% overall and 91% in responding patients. Median OS from diagnosis was 61.1 months, after median follow-up of 63.7 months. Activity was seen in patients with refractory disease and patients relapsing following high-intensity treatment. Toxicity was generally manageable. CONCLUSIONS: Single-agent bortezomib is associated with lengthy responses and notable survival in patients with relapsed or refractory MCL, with considerable TTP and TTNT in responding patients, suggesting substantial clinical benefit.