Irregular screening participation increases advanced stage breast cancer at diagnosis: A population-based study.

OBJECTIVE: To evaluate the effect of irregular screening behaviour on the risk of advanced stage breast cancer at diagnosis in Flanders. METHODS: All women aged 50-69 who were invited to the organized breast cancer screening and diagnosed with breast cancer before age 72 from 2001 to 2018 were included. All prevalent screen and interval cancers within 2 years of a prevalent screen were excluded. Screening behaviour was categorized based on the number of invitations and performed screenings. Four groups were defined: regular, irregular, only-once, and never attenders. Advanced stage cancer was defined as a stage III + breast cancer. The association between screening regularity and breast cancer stage at diagnosis was evaluated in multivariable logistic regression models, taking age of diagnosis and socio-economic status into account. RESULTS: In total 13.5% of the 38,005 breast cancer cases were diagnosed at the advanced stage. Compared to the regular attenders, the risk of advanced stage breast cancer for the irregular attenders, women who participated only-once, and never attenders was significantly higher with ORadjusted:1.17 (95%CI:1.06-1.29) and ORadjusted:2.18 (95%CI:1.94-2.45), and ORadjusted:5.95 (95%CI:5.33-6.65), respectively. CONCLUSIONS: In our study, never attenders were nearly six times more likely to be diagnosed with advanced stage breast cancer than regular attenders, which was much higher than the estimates published thus far. An explanation for this is that the ever screened women is a heterogeneous group regarding the participation profiles which also includes irregular and only-once attenders. The benefit of regular screening should be informed to all women invited for screening.

Determinants of Non-Participation in Population-Based Breast Cancer Screening: A Systematic Review and Meta-Analysis.

Background: Breast cancer (BC) screening can be performed in a screening program (BCSP) or in opportunistic screening. The existing reviews on the determinants of non-participation depend on self-reported data which may be biased. Furthermore, no distinction was made between the probably different determinants of both screening strategies. Objective: To find the determinants of non-participation in BCSP by means of a meta-analysis. Methods: PubMed, Embase, and Web of Science were searched for observational studies which quantified factors associated with non-participation in BCSP in a general population. Studies on opportunistic screening and studies using self-reported data were excluded. A random-effect model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Potential sources of heterogeneity were explored by stratification of the results. Results: Twenty-nine studies with in a total of 20,361,756 women were included. Low income (OR: 1.20, 95% CI: 1.10-1.30), low education (OR: 1.18, 95% CI: 1.05-1.32), living far from an assigned screening unit (OR: 1.15, 95% CI: 1.07-1.24), being immigrant (OR: 2.64, 95% CI: 2.48-2.82), and having a male family doctor (OR: 1.43, 95% CI: 1.20-1.61) was associated with higher non-participation in screening. Reminders sent to non-attenders and estimations of ORs (adjusted or not) partly explained substantial heterogeneity. Conclusion: In this meta-analysis excluding studies on the non-participation in opportunistic screening, or with self-reported data on non-participation, the well-known determinants for non-participation are still significant, but less strong. This analysis only supports the relevance of meta-analysis of studies with registered non-participation in a BCSP. Systematic Review Registration: PROSPERO, CRD42020154016.

Physiotherapists' knowledge, attitude and practice behavior to prevent chronification in patients with non-specific, non-traumatic, acute- and subacute neck pain: A qualitative study.

BACKGROUND: The purpose of this study was to explore physiotherapists' knowledge, attitude, and practice behavior in assessing and managing patients with non-specific, non-traumatic, acute- and subacute neck pain, with a focus on prognostic factors for chronification. METHOD: A qualitative study using in-depth semi-structured interviews was conducted with 13 physiotherapists working in primary care. A purposive sampling method served to seek the broadest perspectives. The knowledge-attitude and practice framework was used as an analytic lens throughout the process. Textual data were analyzed using qualitative content analysis with an inductive approach and constant comparison. RESULTS: Seven main themes emerged from the data; physiotherapists self-estimated knowledge and attitude, role clarity, therapeutic relationship, internal- and external barriers to practice behavior, physiotherapists' practice behaviors, and self-reflection. These findings are presented in an adjusted knowledge-attitude and practice behavior framework. CONCLUSION: A complex relationship was found between a physiotherapist's knowledge about, attitude, and practice behavior concerning the diagnostic process and interventions for non-specific, non-traumatic, acute, and subacute neck pain. Overall, physiotherapists used a biopsychosocial view of patients with non-specific neck pain. Physiotherapists' practice behaviors was influenced by individual attitudes towards their professional role and therapeutic relationship with the patient, and individual knowledge and skills, personal routines and habits, the feeling of powerlessness to modify patients' external factors, and patients' lack of willingness to a biopsychosocial approach influenced physiotherapists' clinical decisions. In addition, we found self-reflection to have an essential role in developing self-estimated knowledge and change in attitude towards their therapeutic role and therapist-patient relationship.

Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment.

BACKGROUND: Cancer patients are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment remain unclear. PATIENTS AND METHODS: In this interventional prospective multicohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Vaccine safety and efficacy (until 3 months post-booster) were assessed. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) antibody levels were followed over time (until 28 days after the booster) and in vitro SARS-CoV-2 50% neutralization titers (NT50) toward the wild-type Wuhan strain were analyzed 28 days after the booster. RESULTS: Local and systemic adverse events (AEs) were mostly mild to moderate (only 1%-3% of patients experienced severe AEs). Local, but not systemic, AEs occurred more frequently after the booster dose. Twenty-eight days after the booster vaccination of 197 cancer patients, RBD-binding antibody titers and NT50 were lower in the chemotherapy group {234.05 IU/ml [95% confidence interval (CI) 122.10-448.66] and 24.54 (95% CI 14.50-41.52), respectively} compared with healthy individuals [1844.93 IU/ml (95% CI 1383.57-2460.14) and 122.63 (95% CI 76.85-195.67), respectively], irrespective of timing of vaccination during chemotherapy cycles. Extremely low antibody responses were seen in hematology patients receiving rituximab; only two patients had RBD-binding antibody titers necessary for 50% protection against symptomatic SARS-CoV-2 infection (<200 IU/ml) and only one had NT50 above the limit of detection. During the study period, five cancer patients tested positive for SARS-CoV-2 infection, including a case of severe COVID-19 in a patient receiving rituximab, resulting in a 2-week hospital admission. CONCLUSION: The BNT162b2 vaccine is well-tolerated in cancer patients under active treatment. However, the antibody response of immunized cancer patients was delayed and diminished, mainly in patients receiving chemotherapy or rituximab, resulting in breakthrough infections.

Wnt/ß-catenin pathway and cell adhesion deregulation in CSDE1-related intellectual disability and autism spectrum disorders.

Among the genetic factors playing a key role in the etiology of intellectual disabilities (IDs) and autism spectrum disorders (ASDs), several encode RNA-binding proteins (RBPs). In this study, we deciphered the molecular and cellular bases of ID-ASD in a patient followed from birth to the age of 21, in whom we identified a de novo CSDE1 (Cold Shock Domain-containing E1) nonsense variation. CSDE1 encodes an RBP that regulates multiple cellular pathways by monitoring the translation and abundance of target transcripts. Analyses performed on the patient's primary fibroblasts showed that the identified CSDE1 variation leads to haploinsufficiency. We identified through RNA-seq assays the Wnt/ß-catenin signaling and cellular adhesion as two major deregulated pathways. These results were further confirmed by functional studies involving Wnt-specific luciferase and substrate adhesion assays. Additional data support a disease model involving APC Down-Regulated-1 (APCDD1) and cadherin-2 (CDH2), two components of the Wnt/ß-catenin pathway, CDH2 being also pivotal for cellular adhesion. Our study, which relies on both the deep phenotyping and long-term follow-up of a patient with CSDE1 haploinsufficiency and on ex vivo studies, sheds new light on the CSDE1-dependent deregulated pathways in ID-ASD.

Changes in serum PSA after endoscopic enucleation of the prostate are predictive for the future diagnosis of prostate cancer.

PURPOSE: After Endoscopic Enucleation of the Prostate (EEP) for benign prostatic obstruction (BPO), men remain at risk for prostate cancer (PCa). Significant PSA changes occur after enucleation, which interfere with later screening for PCa. It remains unclear which patients need further diagnostic investigations for PCa after EEP. The goal of this study was to identify an independent predictor for PCa diagnosis after Holmium Laser Enucleation of the Prostate (HoLEP) in patients whose HoLEP resection specimen did not show PCa. METHODS: Data of 773 patients who underwent HoLEP for BPO between 2010 and 2018 in a referral center were analyzed. Exclusion criteria were PCa detection in the HoLEP specimen or absence of post-operative PSA values. Patients were divided in a PCa group and Control group depending on whether or not PCa was detected during follow-up after HoLEP. The predictive value for future diagnosis of PCa of different forms of PSA-change after HoLEP was analyzed by multivariate Cox regression and ROC analysis. RESULTS: Overall, 24 (4.2%) patients developed PCa after HoLEP. At 5 year follow-up, the PCa-free survival rate was 85%. First post-operative PSA was an independent predictor of PCa diagnosis after HoLEP (HR 1.106, 95% CI 1.074-1.139, p < 0.001, ROC AUC 0.903) with an optimal cut-off value of 1.73 ng/ml (sensitivity 83.3%, specificity 82.3%). CONCLUSIONS: For patients who underwent HoLEP for BPO, post-operative PSA after HoLEP is an independent predictor for future PCa diagnosis. When PSA is > 1.73 ng/ml within the first year after HoLEP, rigorous follow-up and diagnostic investigations for PCa are indicated.

Coverage determinants of breast cancer screening in Flanders: an evaluation of the past decade.

BACKGROUND: Breast cancer (BC) is the most common cancer in women in the developed world. In order to find developing cancers in an early stage, BC screening is commonly used. In Flanders, screening is performed in and outside an organized breast cancer screening program (BCSP). However, the determinants of BC screening coverage for both screening strategies are yet unknown. OBJECTIVE: To assess the determinants of BC screening coverage in Flanders. METHODS: Reimbursement data were used to attribute a screening status to each woman in the target population for the years 2008-2016. Yearly coverage data were categorized as screening inside or outside BCSP or no screening. Data were clustered by municipality level. A generalized linear equation model was used to assess the determinants of screening type. RESULTS: Over all years and municipalities, the median screening coverage rate inside and outside BCSP was 48.40% (IQR: 41.50-54.40%) and 14.10% (IQR: 9.80-19.80%) respectively. A higher coverage rate outside BSCP was statistically significantly (P < 0.001) associated with more crowded households (OR: 3.797, 95% CI: 3.199-4.508), younger age, higher population densities (OR: 2.528, 95% CI: 2.455-2.606), a lower proportion of unemployed job seekers (OR: 0.641, 95% CI: 0.624-0.658) and lower use of dental care (OR: 0.969, 95% CI: 0.967-0.972). CONCLUSION: Coverage rate of BC screening is not optimal in Flanders. Women with low SES that are characterized by younger age, living in a high population density area, living in crowded households, or having low dental care are less likely to be screened for BC in Flanders. If screened, they are more likely to be screened outside the BCSP.

Pain-related fear in adolescents with chronic musculoskeletal pain: process evaluation of an interdisciplinary graded exposure program.

BACKGROUND: For studying the effectiveness of treatment, it is important to check whether a new treatment is performed as originally described in the study-protocol. OBJECTIVES: To evaluate whether an interdisciplinary graded exposure program, for adolescents with chronic musculoskeletal pain reporting pain-related fear, was performed according to protocol, and whether it is feasible to implement the program in rehabilitation care. METHODS: A process evaluation where quantitative and qualitative data on participant characteristics (adolescents, parents and therapists), attendance and participants' opinion on the program were collected, by means of registration forms, questionnaires and group interviews. To evaluate treatment fidelity, audio and video recordings of program sessions were analyzed. RESULTS: Thirty adolescents were offered the program, of which 23 started the program. Adolescents attended on average 90% of the sessions. At least one parent per adolescent participated in the program. Analysis of 20 randomly selected recordings of treatment sessions revealed that treatment fidelity was high, since 81% of essential treatment elements were offered to the adolescents. The program was considered client-centered by adolescents and family-centered by parents. Treatment teams wished to continue offering the program in their center. CONCLUSION: The interdisciplinary graded exposure program was performed largely according to protocol, and therapists, adolescents and their parents had a favorable opinion on the program. Implementation of the program in rehabilitation care is considered feasible. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT02181725 (7 February 2014).

Flemish breast cancer screening programme: 15 years of key performance indicators (2002-2016).

BACKGROUND: We examined 15 years of key performance indicators (KPIs) of the population-based mammography screening programme (PMSP) in Flanders, Belgium. METHODS: Individual screening data were linked to the national cancer registry to obtain oncological follow-up. We benchmarked crude KPI results against KPI-targets set by the European guidelines and KPI results of other national screening programmes. Temporal trends were examined by plotting age-standardised KPIs against the year of screening and estimating the Average Annual Percentage Change (AAPC). RESULTS: PMSP coverage increased significantly over the period of 15 years (+ 7.5% AAPC), but the increase fell to + 1.6% after invitation coverage was maximised. In 2016, PMSP coverage was at 50.0% and opportunistic coverage was at 14.1%, resulting in a total coverage by screening of 64.2%. The response to the invitations was 49.8% in 2016, without a trend. Recall rate decreased significantly (AAPC -1.5% & -5.0% in initial and subsequent regular screenings respectively) while cancer detection remained stable (AAPC 0.0%). The result was an increased positive predictive value (AAPC + 3.8%). Overall programme sensitivity was stable and was at 65.1% in 2014. In initial screens of 2015, the proportion of DCIS, tumours stage II+, and node negative invasive cancers was 18.2, 31.2, and 61.6% respectively. In subsequent regular screens of 2015, those proportions were 14.0, 24.8, and 65.4% respectively. Trends were not significant. CONCLUSION: Besides a suboptimal attendance rate, most KPIs in the Flemish PMSP meet EU benchmark targets. Nonetheless, there are several priorities for further investigation such as a critical evaluation of strategies to increase screening participation, organising a biennial radiological review of interval cancers, analysing the effect that preceding opportunistic screening has on the KPI for initial screenings, and efforts to estimate the impact on breast cancer mortality.

Does lack of deeper understanding of shared decision making explains the suboptimal performance on crucial parts of it? An example from breast cancer care.

PURPOSE: Although most of the clinicians in breast cancer care seem to approve of shared decision making (SDM), actual implementation is limited. The aim of this study was to explore the experiences, issues and concerns of early-adopter professionals with regards to shared decision making. METHODS: This qualitative descriptive study was part of a pilot study aimed at implementing SDM in breast cancer teams. We interviewed 27 clinicians; 9 breast cancer surgeons, 11 nurse practitioners and 7 nurses. The teams were exposed to a multifaceted implementation programme, among others: a patient decision aid (PtDA), a procedure to disseminate the PtDA and advice on redesigning the clinical pathway. RESULTS: Participants considered SDM, including the delivery of the PtDA, to be a team effort, in which every professional should take responsibility. Most clinicians primarily focused on the first steps of SDM ignoring preference and decision talk. The remaining steps, like the uptake of the PtDA in the clinical pathway, were regarded as challenging, with surgeons, intentionally or unconsciously, delegating this responsibility to nurses. One barrier to successfully implementing SDM seems to lie in the fact that clinicians were unaware of their lack of competency regarding SDM. CONCLUSIONS: A deeper understanding is needed among clinicians of what SDM actually is and how a PtDA contributes to this process. Nurses play an important role in the delivery of the PtDA, but their role is not clearly defined. Teams should consider a clear realignment of tasks between surgeons and nurses, which implies redesign of the pathway.

Maternal quality of life in routine labor epidural analgesia versus labor analgesia on request: results of a randomized trial.

INTRODUCTION: The purpose of this study was to evaluate the changes in maternal quality of life (QOL) from pregnancy to 6 weeks after delivery between routine labor epidural analgesia (EA) and pain relief on maternal request only. METHODS: \Women delivering of a singleton in cephalic presentation beyond 36 + 0 weeks' gestation were randomly allocated to EA as a routine during labor (routine EA group), or to any kind of analgesia on request only (control group). The Short Form health survey (SF-36) was used to assess women's QOL before randomization, and 6 weeks postpartum. Data were analyzed according to the intention to treat principle. RESULTS: A total of 488 women were included, and antepartum as well as postpartum SF-36 questionnaires were filled in by 356 (73.0%) women, 176 (49.4%) in the routine EA group, and 180 (50.6%) in the control group. Changes from the QOL antepartum to the QOL 6 weeks postpartum were comparable between both groups, also in the subgroup of women in the control group who gave birth without any pain medication (n = 41, 22.8%). Maternal age and the incidence of adverse events related to EA, which were both higher in the routine EA group, had no influence on the changes in QOL. Differences in request for pain relief were comparable with other studies. CONCLUSION: Routine administration of EA during labor and pain relief on maternal request only are associated with comparable changes of women's QOL antepartum to 6 weeks postpartum.

Anxiety affects disability and quality of life in patients with painful diabetic neuropathy.

BACKGROUND: Painful diabetic neuropathy (PDN) is known to negatively affect psychosocial functioning as expressed by enhanced levels of anxiety and depression. The aim of this study was to specify diabetes and pain-related fears. METHODS: This questionnaire-based cross-sectional study included 154 patients with PDN (mean age 65.7 ± 6.6 years). Correlation analyses corrected for age, gender, pain intensity, pain duration and insulin treatment were performed to assess the associations of fear of hypoglycaemia (Hypoglycaemia Fear Survey, HFS), kinesiophobia (Tampa Scale of Kinesiophobia, TSK), fear of pain (Pain Anxiety Symptom Scale, PASS-20), fear of falling (Falls Efficacy Scale-I, FES-I), fear of fatigue (Tampa Scale of Fatigue, TSF) and fear of negative evaluation (Brief Fear of Negative Evaluation Scale, BFNE), with quality of life (QoL) (Norfolk Quality of Life Questionnaire, Diabetic Neuropathy Version, QOL-DN) and disability (Pain Disability Index, PDI), respectively. RESULTS: In univariate analyses, all fears were independently associated with QOL-DN and PDI (p < 0.001 for all variables). Linear regression models including all fears and confounders, showed that pain intensity, pain duration and FES-I were significantly associated with QOL-DN (R2  = 0.603). Pain intensity, male gender and FES-I were significantly associated with PDI (R2  = 0.526). CONCLUSIONS: After controlling for confounders, levels of pain intensity, duration of pain and fear of falling were negatively associated with QoL in patients with PDN. Pain intensity, male gender and fear of falling were positively associated with disability. Specifying fears enables us to identify potential targets for behavioural interventions that aim to improve psychosocial well-being in patients with PDN. SIGNIFICANCE: This study shows that patients with PDN suffer from various fears, which should enable us to design a treatment strategy that directly targets these fears, hereby improving physical and psychosocial well-being in these patients.

A cognitive-behavioral program for parents of children with chronic musculoskeletal pain; A feasibility study.

BACKGROUND: The purpose of the study is to evaluate the feasibility of a newly developed parent program for parents of children with non-specific chronic musculoskeletal pain. This program is part of the child's interdisciplinary outpatient pain rehabilitation treatment. The goal of the parent program is to change parent's thoughts/behaviour regarding pain with the ultimate intention to further improve their child's functioning. There were two main objectives in the study: First, to evaluate the feasibility of the parent program. Second, to evaluate changing in parental behavioral factors pre- and posttreatment. METHODS: Participants were parents of adolescents, who underwent a interdisciplinary outpatient pain program for non-specific chronic musculoskeletal pain. Parents participated in a parent program as part of their child's treatment. Adolescents reported their level of disability, pain intensity, fear of pain and pain catastrophizing by filling out questionnaires. Parents reported catastrophic thinking about their child's pain, fear of pain and disabilities of their child. In addition, they evaluated the parent program. RESULTS: Sixty five parents (36 mothers and 29 fathers) of 44 adolescents filled in the baseline questionnaires. Result showed significant and clinically relevant improvements for both parents as well for adolescents. Parents were positive about the content of the parent program, they evaluated the program as supportive and informative. CONCLUSION: Adding a parent program to a interdisciplinary outpatient pain program for adolescent with chronic musculoskeletal pain, seems to be feasible in daily life of the parents and results in positive behavioural changes for both parents and adolescents. SIGNIFICANCE: A parent program, designed to change cognition and behaviour of parents of children with chronic musculoskeletal pain is feasible.

Future goals of adolescents and young adults with chronic musculoskeletal pain.

BACKGROUND: Chronic non-specific musculoskeletal pain is a common problem among adolescents. This study investigates the importance of future goals and goal frustration for adolescents and young adults with chronic musculoskeletal pain compared to healthy adolescents. It also explores the impact that pain intensity, pain catastrophizing and depressive symptoms have on goal frustration for adolescents with chronic pain. METHODS: Using a cross-sectional design, we compared the importance and frustration of future goals for 42 adolescents and young adults with chronic musculoskeletal pain (41 women, 1 man) to those of 42 adolescents without pain (35 women, 7 men). For the adolescents with chronic pain, we also examined levels of pain intensity, pain catastrophizing and depressive symptoms to assess their ability to explain goal frustration levels. Statistics included t-tests, Mann-Whitney test and multivariate regression analysis. RESULTS: We found no differences in the importance of future goals, except for goals related to health, which were more important for adolescents with chronic pain (p = 0.03). Furthermore, adolescents with chronic pain perceived higher levels of goal frustration in all domains, except that related to school (p = 0.16). Depression explained goal frustration related to personal values (p = 0.02), social acceptance (p < 0.01), self-acceptance (p < 0.01) and health (p < 0.01). CONCLUSIONS: Dealing with chronic pain in adolescence and early adulthood does not seem to change future goals, but is associated with perceiving barriers to achieving them. The level of depressive symptoms seems to influence this relationship. Some caution is required in generalizing the results due to the relatively low number of male participants.

The psychometric characteristics of an assessment instrument for perceived harmfulness in adolescents with musculoskeletal pain (PHODA-youth).

BACKGROUND: Cognitive-behavioural models of chronic pain predict that dysfunctional assumptions about harmfulness of activities may maintain pain-related fear and disability. To assess perceived harmfulness in adolescents, the Photograph Series of Daily Activities for youth (PHODA-youth) was developed. Information concerning its methodological quality is currently lacking. OBJECTIVE: To investigate psychometric characteristics (factor structure, test-retest reliability, construct validity) and feasibility of the PHODA-youth in adolescents with chronic musculoskeletal pain. STUDY DESIGN: Test-retest design. STUDY POPULATION: Adolescents aged 13-21 years with chronic nonspecific musculoskeletal pain. METHODS: Participants filled in an electronic version of the PHODA-youth including 89 items twice with a 4-week interval. The instrument's factor structure was determined by a factor analysis. Construct validity was studied with criterion variables: catastrophizing (Pain Catastrophizing Scale for Children), pain intensity (visual analogue scale), depression (Children's Depression Inventory) and pain-related disability (Functional Disability Inventory) using regression analysis. Test-retest reliability was evaluated based on the Pearson correlation coefficient. Feasibility was studied with self-constructed questions. RESULTS: Seventy-one adolescents participated. Results show a three-factor structure for the PHODA-youth including 51 items with subscales labelled as: 'activities of daily life', 'intensive physical activities' and 'social activities'. Total and subscale scores showed a high internal consistency. Its test-retest reliability was good (r = 0.94) and its construct validity is supported by the finding that both catastrophizing (ß = 0.25; p = 0.02) and disability (ß = 0.71; p < 0.001) were uniquely related to the PHODA-youth. In addition, feasibility appeared adequate. CONCLUSION: The findings support the PHODA-youth as a valid and reliable measure of the perceived harmfulness of activities in adolescents with musculoskeletal pain.

Improvements in phenotype studies of hemoglobin disorders brought by advances in reversed-phase chromatography of globin chains.

INTRODUCTION: Phenotype studies still occupy a key position in the diagnosis of hemoglobin (Hb) disorders. MATERIAL AND METHODS: In addition to the conventional methods for diagnosis of Hb disorders which are mostly based on differences in charge of the Hb molecules, some progresses have been brought by studying other properties of the globin chains. Among those, difference in hydrophobicity that may be investigated by reversed-phase HPLC (RP-HPLC) discriminates between variants displaying identical charges. RESULTS: In this study, we show how an update of this method allows to recognize an α-chain variant from a γ-chain variant, a problem frequently during neonatal screening. We illustrate that RP-HPLC may also unravel unclear phenotypes which are modified by the presence of an additional variant not detected by the conventional methods, and help to characterize rare mutants. Also we show that it allows a clear distinction between variants with identical electrophoretical charges as exemplified by Hb Lepore Boston-Washington and Lepore Baltimore. CONCLUSIONS: In view of our results, RP-HPLC is a technique that needs to be used as a second step in the general strategy for a correct characterization of Hb variants.

Quantifying independent risk factors for failing to rescreen in a breast cancer screening program in Flanders, Belgium.

BACKGROUND: Mammographic screening may reduce breast cancer mortality by about 20%, provided participation is high and women screen regularly. We quantified independent risk factors for failing to rescreen and built a model to predict how rescreening rates change if these risk factors would be modified. METHODS: Multivariate analysis was used to analyze data from a prospective study which included a self-administered questionnaire and rescreening status 30months after a t0 mammogram, using a random sample of women 50-67years (Belgium 2010-2013). RESULTS: A false positive result at the most recent past mammogram (Odds Ratio=5.0, 95% Confidence Interval 3.6-6.8), an interval until new invitation greater than 25months (Odds Ratio=4.8 for >29months, 95% Confidence Interval 2.9-8.1), waiting times in the mammography unit >1h (Odds Ratio=2.1, 95% Confidence Interval 1.2-3.7) and difficulties in reaching the unit (Odds Ratio=2.5, 95% Confidence Interval 1.4-4.4) were the strongest independent predictors for failing to rescreen. The area under the curve of the receiver operating characteristic analysis was 0.705 for the model development stage and 0.717 for the validation stage and goodness-of-fit was good. CONCLUSIONS: Maintaining an invitation cycle of maximum 25months, limiting waiting time in the mammography unit and lowering the number of false positives could increase breast cancer screening compliance.

SALL4 and NFATC2: two major actors of interstitial 20q13.2 duplication.

Interstitial duplication within the long arm of chromosome 20 is an uncommon chromosome structural abnormality. We report here the clinical and molecular characterization associated with pure 20q13.2 duplication in three unrelated patients. The most frequent clinical features were developmental delay, facial dysmorphism, cardiac malformation and skeletal anomalies. All DNA gains occurred de novo, ranging from 1.1 Mb to 11.5 Mb. Compared with previously reported conventional cytogenetic analyses, oligonucleotides array CGH allowed us to refine breakpoints and determine the genes of interest in the region. Involvement of SALL4 in cardiac malformations and NFATC2 gene disruption in both cardiac and skeletal anomalies are discussed.

Practitioner review: evidence-based practice guidelines on alcohol and drug misuse among adolescents: a systematic review.

BACKGROUND: Context-specific evidence-based guidelines on how to prevent and treat substance misuse among adolescents are currently lacking in many countries. Due to the time consuming nature of de novo guideline development, the ADAPTE collaboration introduced a methodology to adapt existing guidelines to a local context. An important step in this method is a systematic review to identify relevant high-quality evidence-based guidelines. This study describes the results of this step for the development of guidelines on adolescent alcohol and drug misuse in Belgium. METHODS: Rigorous systematic review methodology was used. This included searches of electronic databases (Medline, Embase, Cinahl, PsychInfo, and ERIC in June 2011), websites of relevant organizations, and reference lists of key publications. Experts in the field were also contacted. Included were Dutch, English, French, or German evidence-based practice guidelines from 2006 or later on the prevention, screening, assessment, or treatment of alcohol or illicit drug misuse in persons aged 12-18 years. Two independent reviewers assessed the quality of the guidelines using the AGREE II (Appraisal of Guidelines for Research and Evaluation) instrument. SCOPE: This overview provides a framework of current knowledge in adolescent alcohol and drug misuse prevention and treatment. RESULTS: This systematic review identified 32 relevant evidence-based guidelines on substance misuse among adolescents. Nine guidelines were judged to be of high quality; of which four had recommendations specifically on adolescents: one on school-based prevention, one on substance misuse prevention in vulnerable young people and two on alcohol misuse with specific sections for the adolescent population. There were few commonalities as guidelines focused on different target groups, professional disciplines and type and level of substance misuse. Evidence to support the recommendations was sparse, and many recommendations were based on expert consensus or on studies among adults. Also, the link between evidence and recommendations was often unclear. CONCLUSIONS: There are a substantial number of guidelines addressing substance misuse in adolescents. However, only four high-quality guidelines included recommendations specific for adolescents. The current level of evidence that underpins the recommendations in these high-quality guidelines is low.