Changes in coronal knee-alignment parameters during the osteoarthritis process in the varus knee.

OBJECTIVES: The idea to aim for an "individualized" alignment, whereby the constitutional alignment is restored, has gained much interest among knee surgeons. This requires insight into the prediseased, natural alignment of our patients' knees. The aim of this study is (1) to determine how the hip-knee-ankle (HKA) angle is influenced during the arthritic process and (2) to investigate the correlation between joint line changes and the progression of osteoarthritis (OA). It is our hypothesis that the most pronounced coronal parameter changes appear at the proximal tibia and at the joint line. METHODS: One hundred sequential full-length X-rays with a minimum follow-up of 1 year were retrospectively reviewed from a radiographic joint database. Patients had to be at least 50 years of age needed to have an HKA angle of more than 1.3° varus to be included. Patients with ipsilateral total hip arthroplasty, femoral or tibial fracture, osteotomy, or ligamentous repair were excluded. Fifteen alignment parameters were investigated on the sequential full-length X-rays. Moreover, the relationship between the alignment parameters and the Kellgren-Lawrence grade (KL grade) was determined by using linear mixed models. RESULTS: A progressive KL grade is associated with an increase of the HKA (p < 0.001). Mostly, HKA differs due to decrease of the medial tibial plateau (MPTA) angle (0.93°) and an increase of the joint line angle (JLCA) (0.86°). The mLDFA demonstrated the most pronounced changes in the beginning of OA (KL grade 1-2) (p = 0.049). In particular, the MPTA becomes considerably smaller (p = 0.004) in the later stage of OA (KL grade 3). Also, a progressive increase of the JLCA (p < 0.001) is observed upwards of KL grade 3. CONCLUSION: By comparing consecutive full-length X-rays in the same patients, it is possible to define the coronal alignment changes during the arthritic process. The HKA angle increases according the arthritic progression, whereby the most pronounced changes appear at the proximal tibia (MPTA) and at the joint line (JLCA).The alignment changes in varus OA knees can be divided in three stadia: (1) erosion of the distal medial femoral condyle, (2) erosion of the medial tibial plateau, and (3) a progressive increase of the joint line angle. LEVEL OF EVIDENCE: Therapeutic Study, Level III.

Primary constrained-condylar-knee designs outperform posterior-stabilized and cruciate-retaining designs in high-grade varus osteoarthritic knees during short-term follow-up: a pilot study.

INTRODUCTION: High-grade varus osteoarthrosis (OA) is characterized by a pronounced intra-articular varus deformity and associated insufficiency of the lateral ligamentous complex. When performing a total knee arthroplasty (TKA) in such a knee, traditionally the alignment is restored to neutral, and the medial soft tissue structures are released to compensate for the lateral laxity and balance the joint. However, another option would be to leave the medial soft tissues untouched and accept the lateral laxity but to compensate for it using an ML-stabilized constrained-condylar knee (CCK) design. Our aim was to prove our hypothesis that such knees would demonstrate better clinical stability and better functionality as well as subjective outcome scores. MATERIALS AND METHODS: We searched our bicenter database of 912 primary TKAs (from 2016 to 2019) for primary TKA patients with a preoperative varus alignment of > 8°. After inclusion, 60 patients were divided into three groups by implant design: CCK (n = 21), posterior-stabilized (PS) (n = 20) and cruciate-retaining (CR) (n = 19). Oxford Knee Score (OKS), Forgotten Joint Score (FJS), Knee Society Score (KSS), UCLA-activity score, ML instability scores and both radiographic and clinical data were compared between groups. RESULTS: ML stability was significantly better in CCK designs (86% grade 0) compared to CR (37% grade 0) (p = 0.004) but not PS (70% grade 0) designs. No grade II instability was present in CCK and PS implants compared to 16% of CR implants. KSS and UCLA-activity score were higher in CCK designs compared to PS (p = 0.027, p = 0.041) and CR designs (p < 0.001, p = 0.007). OKS and FJS were higher in CCK designs compared to CR (p = 0.025, p = 0.008) but not to PS. CONCLUSION: The use of a CCK design to compensate for the lateral laxity in high-grade varus OA knees allowed to refrain from a medial release. CCK designs displayed improved clinical stability and better functionality as well as subjective outcome scores compared to less-constrained designs.

The pre-diseased coronal alignment can be predicted from conventional radiographs taken of the varus arthritic knee.

INTRODUCTION: The concept of restoring the constitutional, pre-diseased alignment has gained lots of interest among knee surgeons. Previous attempts to use the contralateral limb to bridge the gap between the arthritic and the constitutional alignment were unsuccessful. We investigated the usability of a mathematical formula to predict the constitutional (pre-diseased) coronal alignment once arthritis has occurred. It is our hypothesis that by using the KL grade, CPAK classification and four radiographic measurements of the arthritic knee, the pre-diseased coronal alignment could be predicted. MATERIAL AND METHODS: Hundred arthritic patients with consecutive X-rays were used to determine a mathematical formula. Five alignment parameters were determined on full-length X-rays: HKA angle, mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA) and the tibial joint line angle (TJLA). A refinement of the algorithm was implemented based on a reference cohort, consisted of 250 young adults aged between 20 and 27 years. Moreover, all knees were subdivided based on their CPAK-phenotype and the Kellgren-Lawrence scale (KL scale). An independent arthritic cohort of 289 patients scheduled for primary total knee arthroplasty was included to verify the accuracy of the predicted HKAs (HKAPRED). RESULTS: In CPAK type 1, the HKAPRED was 3.86° varus (STD 1.39) and the HKAYHA was 4.0° varus. In CPAK type 2, the HKAPRED was 1.68° varus (STD 1.95) compared to a HKAYHA of 1.34° (STD 0.81). The average constitutional HKA is not different in both CPAK 1 (p = 0.61) and CPAK 2 (p = 0.25), and the difference in the mean is estimated to be equal to - 0.14 (95CI - 0.68 to 0.40) in CPAK 1 and 0.35 (95CI - 0.06 to 0.75) in CPAK 2. CONCLUSION: Using the KL grade, CPAK classification and four radiographic measurements of the arthritic knee, the pre-diseased coronal alignment can be predicted in 80% of the varus knees with an accuracy of ≤ 0.5°. The predicted HKA (HKAPRED) can be very useful in the current and future clinical practice.

PFAS levels and determinants of variability in exposure in European teenagers - Results from the HBM4EU aligned studies (2014-2021).

BACKGROUND: Perfluoroalkyl substances (PFAS) are man-made fluorinated chemicals, widely used in various types of consumer products, resulting in their omnipresence in human populations. The aim of this study was to describe current PFAS levels in European teenagers and to investigate the determinants of serum/plasma concentrations in this specific age group. METHODS: PFAS concentrations were determined in serum or plasma samples from 1957 teenagers (12-18 years) from 9 European countries as part of the HBM4EU aligned studies (2014-2021). Questionnaire data were post-harmonized by each study and quality checked centrally. Only PFAS with an overall quantification frequency of at least 60% (PFOS, PFOA, PFHxS and PFNA) were included in the analyses. Sociodemographic and lifestyle factors were analysed together with food consumption frequencies to identify determinants of PFAS exposure. The variables study, sex and the highest educational level of household were included as fixed factors in the multivariable linear regression models for all PFAS and each dietary variable was added to the fixed model one by one and for each PFAS separately. RESULTS: The European exposure values for PFAS were reported as geometric means with 95% confidence intervals (CI): PFOS [2.13 µg/L (1.63-2.78)], PFOA ([0.97 µg/L (0.75-1.26)]), PFNA [0.30 µg/L (0.19-0.45)] and PFHxS [0.41 µg/L (0.33-0.52)]. The estimated geometric mean exposure levels were significantly higher in the North and West versus the South and East of Europe. Boys had significantly higher concentrations of the four PFAS compared to girls and significantly higher PFASs concentrations were found in teenagers from households with a higher education level. Consumption of seafood and fish at least 2 times per week was significantly associated with 21% (95% CI: 12-31%) increase in PFOS concentrations and 20% (95% CI: 10-31%) increase in PFNA concentrations as compared to less frequent consumption of seafood and fish. The same trend was observed for PFOA and PFHxS but not statistically significant. Consumption of eggs at least 2 times per week was associated with 11% (95% CI: 2-22%) and 14% (95% CI: 2-27%) increase in PFOS and PFNA concentrations, respectively, as compared to less frequent consumption of eggs. Significantly higher PFOS concentrations were observed for participants consuming offal (14% (95% CI: 3-26%)), the same trend was observed for the other PFAS but not statistically significant. Local food consumption at least 2 times per week was associated with 40% (95% CI: 19-64%) increase in PFOS levels as compared to those consuming local food less frequently. CONCLUSION: This work provides information about current levels of PFAS in European teenagers and potential dietary sources of exposure to PFAS in European teenagers. These results can be of use for targeted monitoring of PFAS in food.

Factors influencing pregnancy outcome with special attention to modified slow-release insemination and a patient-centred approach in a donor insemination programme: a prospective cohort study.

Introduction: A higher pregnancy rate after slow-release insemination instead of bolus injection was described in previous studies. Besides an effective medical treatment most patients wish to receive a patient-centred approach with sufficient emotional support. Study question: Does a patient-friendly approach with slow-release insemination (SRI) increase the clinical pregnancy rate (CPR) after intrauterine insemination (IUI) with donor semen? Study design, size, duration: The data of an ongoing prospective cohort study were analysed investigating the results of 1995 donor inseminations in 606 women from July 2011 until December 2018. As from January 2016 the insemination procedure was performed by midwives instead of medical doctors. Instead of bolus injection of sperm a slow-release IUI was done together with a more patient-centred approach. Materials and Methods: The data of 1995 donor inseminations were analysed to study the importance of different covariates influencing IUI success. Generalized estimating equations (GEEs) were used for statistical analysis. Results of two periods (2011-2015 and 2016-2018) were examined and compared. Results: Clinical pregnancy rates (with foetal heartbeat) following donor inseminations increased from 16.6 % to 20.8 % per cycle, a non-significant increase (p=0.061). Conclusion: A more patient-friendly approach with slow-release of processed semen resulted in a non-significant higher clinical pregnancy rate of 4.2 % per cycle after donor insemination.

The lateral joint line opening: a radiographic indicative parameter for high grade varus knees.

PURPOSE: It is usually assumed that the severity of varus osteoarthritis (OA) of the knee is correlated with the axis deviation of the limb. Despite this, there is currently no clear radiographic definition to define a so-called 'high degree' varus knee, which is characterized by a pronounced lateral ligamentous laxity. The purpose of this study was to radiographically determine if the lateral joint line opening (LJLO) is an indicative parameter when defining so-called high grade varus knees. METHODS: Two hundred forty Full length radiographs of patients with end-stage varus osteoarthritis who were scheduled for Total knee arthroplasty (TKA) were evaluated. The Hip-knee-ankle-angle (HKA-angle), Joint-line-convergence-angle (JLCA) and the lateral joint line opening were measured. The lateral joint line opening is the shortest distance between the lateral tibial plateau and the deepest point of the lateral femoral condyle. Linear regression models were used to investigate the relationships between the radiographic measurements. RESULTS: Hip-knee-angle-angle, joint-line-conversion-angle, and lateral joint line opening were all positively correlated (p < 0.001). An increase of 1 mm lateral joint line opening causes an increase of 0.6° joint-line-conversion-angle (p = 0.029) below a cut-off point of 4.7 mm. For lateral opening values beyond 4.7 mm, the gradient increased to 1.2 (p < 0.001). A lateral joint line opening of 4.7 mm corresponds to a hip-knee-ankle-angle of 6.0° (95% CI [5.5; 6.5]). CONCLUSION: A lateral joint line opening of more than 5 mm in end-stage OA knees is indicative of increased lateral joint laxity. Those knees can be radiographically classified as so-called 'high-grade' varus knees. LEVEL OF EVIDENCE: Therapeutic study, Level III.

Internal exposure of Flemish teenagers to environmental pollutants: Results of the Flemish Environment and Health Study 2016-2020 (FLEHS IV).

The Flemish Environment and Health Study (FLEHS) collects information on internal exposure to a broad range of environmental chemicals in the general population in Flanders, the Northern region of Belgium. The aim is to establish biomonitoring exposure distributions for the general population in support of public health and environmental policy, environmental risk assessment and risk management decisions. In 2017-2018, urine and blood samples were collected from 428 teenagers by a stratified clustered two stage randomized design. Samples were analyzed for a broad range of biomarkers related to exposure to chlorinated and newer pesticides, brominated and organophosphate flame retardants (BFR/OPFR), polychlorinated biphenyls (PCBs), bisphenols, phthalates and alternative plasticizers, per-and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAHs), benzene, metals and trace elements. The geometric mean levels and percentiles of the distribution were estimated for each biomarker, for the whole study population and following stratification for sex, the household educational attainment and the residence area's urbanicity. Geometric means of biomarkers of lead, dichlorodiphenyltrichloroethane (DDT), PCBs, PAHs, regulated phthalates and bisphenol A (BPA) were lower than in the previous FLEHS cycles. Most biomarker levels were below health-based guidance values (HB-GVs). However, HB-GVs of urinary arsenic, blood lead, blood cadmium, sum of serum perfluorooctane sulfonate (PFOS) and perfluoro-1-hexanesulfonate (PFHxS) and the urinary pyrethroid metabolite (3-PBA) were exceeded in respectively 25%, 12%, 39.5%, 10% and 22% of the teenagers. These results suggest that the levels of exposure in the Flemish population to some environmental chemicals might be of concern. At the same time, we noticed that biomarkers for BPA substitutes, metabolites of OPFRs, an expanded list of PFAS, glyphosate and its metabolite could be measured in substantial proportions of participants. Interpretation of these levels in a health-risk context remains uncertain as HB-GVs are lacking. Household educational attainment and residential urbanicity were significant exposure determinants for many biomarkers and could influence specific biomarker levels up to 70% as shown by multiple regression analysis. The research consortium also took care of the broader external communication of results with participants, policy makers, professional groups and civil society organizations. Our study demonstrated that teenagers are exposed to a wide range of chemicals, it demonstrates the success of public policies to reduce exposure but also points to concern and further priorities and needs for follow up.

Uptake of hepatitis C virus screening and treatment in persons under opioid substitution therapy between 2008 and 2013 in Belgium.

BACKGROUND: Hepatitis C is a viral infection caused by the hepatitis C virus (HCV) with people who inject drugs as the main group at risk worldwide. AIM: This study investigated the differences in uptake for HCV screening and treatment between persons in opioid substitution therapy (OST) and the other members of the Christian Health Insurance Fund in Belgium. METHODS: Invoice data were retrospectively collected from the Christian Health Insurance Fund, representing 42% of the healthcare users. Information on demographics, screening, diagnostic tests, treatment and disease progression was obtained from 2008 till 2013. All people in this study were aged 20-65 year. Persons in the OST group were identified as having at least one prescription reimbursed for methadone. This group was compared to the other members of the Insurance Fund not on OST (NOST). RESULTS: The Insurance Fund registered 8,409 unique OST and 3,525,190 members in the general group. HCV RNA screening rate was higher in the OST group after correction for age and gender (4.3% vs. 0.2%). Ribavirin reimbursement, did not differ between the OST and NOST group screened for HCV RNA (16.9% vs. 14.4%), though the probability of having ribavirin reimbursed was smaller for females than for males. Procedures concerning disease progression were reimbursed less frequently in the HCV RNA screened OST group compared to the NOST group (0.3% vs. 1.2%). CONCLUSION: People on OST were screened more often for HCV RNA. However, the general uptake for HCV screening and treatment in both populations remained suboptimal.

Improving IUI success by performing modified slow-release insemination and a patient-centred approach in an insemination programme with partner semen: a prospective cohort study.

BACKGROUND: Pregnancy rates after in vitro fertilisation (IVF) treatment continue to improve, while intrauterine insemination (IUI) programmes show no such trend. There is a need to improve success rates with IUI to retain it as a viable option for couples who prefer avoiding IVF as a first line treatment. OBJECTIVE: To investigate if a modified slow-release insemination (SRI) increases the clinical pregnancy rate (CPR) after intrauterine insemination (IUI) with partner semen. MATERIALS AND METHODS: This was a prospective cohort study in a Belgian tertiary fertility centre. Between July 2011 and December 2018, we studied data from an ongoing prospective cohort study including 989 women undergoing 2565 IUI procedures for unexplained or mild/moderate male infertility. These data were analysed in order to study the importance of different covariates influencing IUI success. Generalised estimating equations (GEEs) were used for statistical analysis. Results of two periods (2011-2015, period 1 and 2016-2018, period 2) were examined and compared. From January 2016 (period 2) onwards, a standardised SRI procedure instead of bolus injection of sperm was applied. The primary outcome parameter was the difference in clinical pregnancy rate (CPR) per cycle between period 1 (bolus IUI) and period 2 (modified SRI). Secondary outcome results included all other parameters significantly influencing CPR after IUI. RESULTS: Following the application of modified SRI the CPR increased significantly, from 9.03% (period 1) to 13.52% (period 2) (p = 0.0016). Other covariates significantly influencing CPR were partner's age, smoking/non-smoking partner, BMI patient, ovarian stimulation protocol and Inseminating Motile Count (after semen processing). CONCLUSIONS: Conclusions: The intentional application of modified slow-release of processed semen appears to significantly increase CPRs after IUI with homologous semen. Future studies should investigate whether SRI, patient-centred measures, or a combination of both, are responsible for this improvement.

Pooled analysis of genotoxicity markers in relation to exposure in the Flemish Environment and Health Studies (FLEHS) between 1999 and 2018.

BACKGROUND: The Flemish Environment and Health Studies (FLEHS) are human biomonitoring surveys running in Flanders since 1999. Additionally to biomarkers of exposure, markers of genotoxicity and oxidative stress have been measured, including the alkaline comet and micronucleus assay in peripheral whole blood cells, and urinary concentrations of 8-oxo-2'-deoxyguanosine (8-oxodG). AIM: Exposure-effect associations were explored in a pooled dataset of nine different cross-sectional FLEHS surveys. Data of adolescents collected in a time frame of about 20 years (1999-2018) were compiled. The aim of the study was to examine whether increased variation in exposure, lifestyle and environmental factors would lead to more powerful and robust exposure-effect associations. MATERIALS & METHODS: The biomarkers were measured in 2283 adolescents in the age range of 14-18 years. Exposure to polycyclic aromatic hydrocarbons [1-hydroxypyrene (1-OHP)], benzene (tt'-muconic acid), metals (arsenic, cadmium, copper, nickel, thallium, lead, chromium), persistent organochlorines and phthalates were assessed in blood or urine. Furthermore, outdoor air levels of particulate matter (PM10 and PM2.5) at the residences of the youngsters were calculated. Pooled statistical analysis was done using mixed models. Study-specific differences in the genotoxicity markers and in the strength/direction of the association were accounted for. This was done by incorporating the random factor 'study' and a random study slope (if possible). The exposure markers were centered around the study-specific mean in order to correct for protocol changes over time. RESULTS: A significant association was observed for the urinary oxidative stress marker 8-oxodG, which was positively associated with 1-OHP (5% increase for doubling of 1-OHP levels, p = 0.001), and with urinary copper (26% increase for doubling of copper levels, p = 0.001), a metal involved in the Fenton reaction in biological systems. 8-oxodG was also associated with the sum of the metabolites of the phthalate di(2-ethylhexyl) phthalate (DEHP) (3% increase for doubling of the DEHP levels, p = 0.02). For those associations, data pooling increased the statistical power. However, some of the associations in the individual surveys, were not confirmed in the pooled analysis (such as comet assay and 8-oxodG vs. atmospheric PM; and 8-oxodG vs. urinary nickel). This may be due to inconsistencies in exposure-effect relations and/or variations in the pollutant mix over time and regions. CONCLUSION: Pooled analysis including a large population of 2283 Flemish adolescents showed that 8-oxodG, a marker of oxidative DNA damage is a valuable marker to assess impact of daily life pollutants, such as PAHs, Cu and the phthalate DEHP.

Risk analysis of tunnel collision in combined anterior cruciate ligament and anterolateral ligament reconstructions.

BACKGROUND: To assess the risk of tunnel collision in combined anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstructions. METHODS: Three-dimensional (3D) CT reconstructions of 32 knees after transtibial (TT) (N = 16) or anteromedial portal (AMP) (N = 16) ACL reconstruction were used to simulate potential tunnel collision of the femoral ACL tunnel if combined with a virtual ALL reconstruction. The minimal distance between tunnels, the ALL tunnel length, and the lateral femoral condyle (LFC) width were measured. Moreover, the relationship between the ALL tunnel and the intercondylar notch, trochlear groove and posterior femoral cortex was determined. RESULTS: The highest rate of tunnel collision (81%) was observed when the ALL tunnel was aimed at 20° in the coronal plane and 0° in the axial plane. However, by aiming the ALL tunnel at 0° coronal and 40° axial angulation, collision was avoided in all patients and no violation of the trochlea was observed. Tunnel collision rate was significantly higher (P = 0.002) when the ACL tunnel was drilled by the AMP technique. CONCLUSIONS: Risk of tunnel collision was significantly increased when the tunnel was drilled at 0° in the axial plane. Tunnel collision was avoided by aiming the ALL tunnel 40° anteriorly and perpendicular to the anatomical axis of the femur. A more horizontal orientation of the ACL with the AMP technique is a risk factor for tunnel conflicts. CLINICAL RELEVANCE: ALL tunnel orientation needs to be adjusted to avoid tunnel conflicts in combined ACL-ALL reconstructions.

High risk of tunnel convergence during combined anterior cruciate ligament and anterolateral ligament reconstruction.

PURPOSE: To assess the risk of femoral tunnel convergence in combined anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstructions. The hypothesis was that a more proximal and anterior orientation of the ALL femoral tunnel should reduce the risk of convergence with the ACL femoral tunnel. METHODS: 15 fresh-frozen cadaver knees were examined. An anatomic ACL femoral tunnel was drilled arthroscopically in each specimen and ALL tunnels were made in two directions: (1) 0° coronal angulation and 20° axial angulation, (2) 30° coronal angulation and 30° axial angulation. Computed tomography scans were performed to investigate tunnel convergence and to measure the minimal distance between tunnels, tunnel length and the LFC width. RESULTS: Tunnel convergence occurred in 20 of 30 cases (67%). Convergence was significantly reduced when tunnels were drilled at 30° coronal and 30° axial angulation (p < 0.05). The mean length of the ALL tunnel was 15.9 mm [95% CI (13.6; 18.1)] and was independent of ALL tunnel angulation. The mean minimal distance between the ALL and ACL tunnel was 3.1 mm [95% CI (2.1; 4.1)]. The odds ratio for tunnel convergence was 3.5 for small LFC, relative to large LFC (n.s.) CONCLUSION: A high risk of tunnel convergence was observed when performing combined ACL and ALL reconstructions. The clinical relevance of this work is that the occurrence of tunnel conflicts can be reduced by aiming the ALL tunnel in a more proximal and anterior direction. Surgeons should be aware of this, since tunnel convergence could jeopardize the ACL reconstruction and fixation.

Reusable endoscopic water bottles: is daily renewal really necessary?

Most guidelines recommend replacing endoscopic water bottles at least daily with newly sterilized or high-level disinfected water bottles. All these recommendations, however, are mainly based on expert opinions and outbreak reports. We tested the water quality from water bottles used in a gastrointestinal endoscopy unit where water bottles were used up to five days. The results show that the reuse of water bottles for more than one day is inadequate. The expert opinion in favour of changing water bottles daily rather than after five days is a sensible and safer option.

Belgian experience with triple therapy with boceprevir and telaprevir in genotype 1 infected patients who inject drugs.

No data have been reported yet on treatment outcome in persons who inject drugs (PWID) infected with hepatitis C virus treated with boceprevir or telaprevir in combination with peginterferon (Peg IFN) and ribavirin (RBV). Additionally, there are concerns about the safety of boceprevir and telaprevir in some subgroups of patients with hepatitis C (HCV). In a cohort of HCV patients infected with genotype 1 in Belgium, treatment outcome of patients infected due to IV drug use was analyzed and compared with patients who have no history of substance use. The study population consisted of 179 patients: 78 PWID and 101 controls treated with boceprevir (n = 79) or telaprevir (n = 100) additional to Peg IFN and RBV; 53 (30%) had advanced disease (F3, F4) and 79 (44%) had an antiviral therapy previously. There were no significant differences in the baseline characteristics between both groups, except that PWID patients were more frequently infected with genotype 1a (67% vs 21%), were younger and were predominantly male. Psychiatric complaints during follow-up occurred more frequently in the PWID patients: 24% versus 11% (P = .02). Treatment failure for other reasons than absence of viral response was 70% and 64% in PWID and non-PWID respectively. The sustained viral response (SVR) rates were similar in both groups (71% in PWID vs 72% in non-PWID); with a non-inferiority test with -5% margin there is a difference of -1% (95% CI [-15%, 13%]) and P = 0.30. There are no reasons to exclude PWID from treatment with boceprevir, telaprevir and novel antiviral therapies.

Pregnant after assisted reproduction: a risk pregnancy is born! 18-years perinatal outcome results from a population-based registry in Flanders, Belgium.

BACKGROUND: Although the increased risk for perinatal morbidity and mortality of babies born after ART is largely attributed to a higher rate of multiple gestations, a significantly worse perinatal outcome for singleton pregnancies following ART compared to pregnancies after natural conception has been reported as well. Most studies only include IVF/ICSI pregnancies; studies describing the perinatal outcome of pregnancies after non-IVF assisted reproduction are scarce. METHODS AND MATERIALS: Population-based cohort study with three exposure groups: a study group of pregnancies (1) after ovarian stimulation (OS), with or without artificial insemination (AI), (2) after IFV or ICSI and (3) a naturally conceived (NC) comparison group. Data from the regional registry of all hospital deliveries in the Dutch-speaking part of Belgium during an 18-years period from January 1993 until December 2010 were used. The perinatal outcome parameters were prematurity, low birth weight, perinatal mortality and morbidity including neonatal intracranial bleeding and need for intubation. Logistic regression analysis was used including mode of conception, female age, foetal sex, parity and year of delivery. RESULTS: Data on 1 079 814 births were studied: 1 039 415 singletons (19 896 IVF/ICSI, 20 469 OS and 999 050 NC) and 39 041 twins (9 353 IVF/ICSI, 4812 OS and 24 876 NC) were available for analysis. IVF/ICSI singletons had a significantly worse outcome when compared to OS and NC for almost all investigated perinatal parameters. Non-IVF/OS singletons were also significantly disadvantaged for prematurity and low birth weight when compared to NC. The outcome of twin pregnancies was similar for the three groups unless only unlike-sex twins were studied separately. Among this subgroup, IVF/ICSI carried a higher risk for low birth weight when compared to NC. OS unlike-sex twins were at increased risk for low birth weight, intra uterine death and perinatal mortality when compared to NC. CONCLUSION: According to our results all ART pregnancies, whether due to IVF/ICSI or non-IVF treatment, have to be considered as risk pregnancies, irrespective of the number of foetuses. LIMITATIONS OF THE STUDY: Although our logistic regression analysis included co-variables with a potential impact on perinatal outcome such as mode of conception, female age, foetal sex, parity and year of delivery, we couldn't correct for other prominent confounders such as the use of fresh or frozen embryos, use of homologous or donor gametes, smoking, obesity, socio-economic status, occupation exposures and pre-existing disease.

Endocrine actions of pesticides measured in the Flemish environment and health studies (FLEHS I and II).

Within the Flemish Environment and Health studies (FLEHS I, 2002-2006, and FLEHS II, 2007-2012), pesticide exposure, hormone levels and degree of sexual maturation were measured in 14-15-year-old adolescents residing in Flanders (Belgium). In FLEHS II, geometric mean concentrations (with 95 % confidence interval (CI)) of 307 (277-341) and 36.5 ng L(-1) (34.0-39.2) were found for p,p'-dichlorophenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB). These values were respectively 26 and 60 % lower than levels in FLEHS I, 5 years earlier. Metabolites of organophosphorus pesticides (OPPs) and of para-dichlorobenzene were measured for the first time in FLEHS II, yielding concentrations of 11.4, 3.27 and 1.57 µg L(-1) for the sum of dimethyl- and diethyl phosphate metabolites and 2,5-dichlorophenol (2,5-DCP), respectively. Data on internal exposure of HCB showed a positive correlation with sexual maturation, testosterone and the aromatase index for boys and with free thyroxine (fT4) and thyroid stimulating hormone (TSH) (both boys and girls). For both p,p'-DDE and HCB, a negative association with sexual development in girls was found. The OPP metabolites were negatively associated with sex hormone levels in the blood of boys and with sexual maturation (both boys and girls). The pesticide metabolite 2,5-DCP was negatively correlated with free T4, while a positive association with TSH was reported (boys and girls). These results show that even exposure to relatively low concentrations of pesticides can have significant influences on hormone levels and the degree of sexual maturation in 14-15-year-old adolescents.

Registration of aggressive incidents in an adolescent forensic psychiatric unit and implications for further practice.

Although aggression is part of daily life in psychiatric units for adolescents, empirical data on its prevalence are sparse. Only few studies have described prevalence of aggressive incidents in adolescent psychiatric wards, and data in forensic psychiatric care are even more limited. Available studies reported high prevalence rates of aggression, ranging from 0.4 to 2.4 incidents of aggression per day across (forensic) child and adolescent psychiatric units. Between 27 and 78 % of all admitted youth committed an aggressive act. In this study, we collected systematically registered data of all aggressive incidents from the first 2 years (2010-2012) on a newly established forensic adolescent psychiatric unit, which used a formal aggression management program embedded in the social competence model, which is based on early intervention in the 'chain of behavior' to prevent any further escalation. The inclusion of also minor aggressive incidents is unique in the literature and the clinical relevance is highlighted. A mean of one incident a day took place, with each adolescent involved in at least one incident. Notably, 1.7 aggressive incidents per month made seclusion of restraint use necessary. Based on the social competence theory, the aggression management model suggests intervening early in the cascade of aggression, in order to prevent further escalation and reduce the need for intrusive interventions. Evidence supported that aggression is a contextual event, as external factors clearly influence the incidence of aggression. Aggression management should be built on both relational and structural security.

Determination of PCDD/Fs, PBDD/Fs and dioxin-like PCBs in human milk from mothers residing in the rural areas in Flanders, using the CALUX bioassay and GC-HRMS.

Since the CALUX (Chemically Activated LUciferase gene eXpression) bioassay is a fast and inexpensive tool for the determination of dioxin-like compounds in a large number of samples and requires only small sample volumes, the use of this technique in human biomonitoring programs provides a good alternative to GC-HRMS. In this study, a new CALUX method for the separate analysis of PCDD/Fs and dioxin-like PCBs (dl-PCBs) in small amounts of human milk samples with the new sensitive H1L7.5c1 cell line was used to analyze 84 human milk samples, collected from mothers residing in the Flemish rural communities. The geometric mean CALUX-Bioanalytical Equivalent (CALUX-BEQ) values, reported for the 84 mothers from the study area were 10.4 (95% CI: 9.4-11.4) pg CALUX-BEQ per gram lipid or 0.41 (95% CI: 0.37-0.45) pg CALUX-BEQ per gram milk for the PCDD/Fs and 1.73 (1.57-1.91) pg CALUX-BEQ per gram lipid or 0.07 (95% CI: 0.06-0.08) pg CALUX-BEQ per gram milk for the dioxin-like PCBs. Multiple regression analysis showed significant associations between PCDD/Fs and weight change after pregnancy, smoking and consumption of local eggs. One pooled human milk sample was analyzed with both CALUX and GC-HRMS. The ratio of CALUX and GC-HRMS results for this sample were respectively 1.60, 0.58 and 1.23 for the PCDD/Fs, the dl-PCBs and the sum of both fractions, when using the 2005-TEF values. Additionally, also low levels of certain brominated dioxins and furans were detected in the pooled sample with GC-HRMS.

Persistent organic pollutants (POPs) in human milk: a biomonitoring study in rural areas of Flanders (Belgium).

To collect information on the concentrations of persistent organic pollutants (POPs) in the rural areas in Flanders (Belgium), 84 breastfeeding mothers were recruited in rural communities in East and West Flanders and Flemish Brabant in 2009-2010. Polychlorinated biphenyl (PCB) congeners, organochlorine pesticides, brominated flame retardants, perfluorinated compounds, polychlorinated dibenzodioxines and dibenzofurans, and dioxin-like PCBs were measured in individual milk samples and in a pooled milk sample, while some additional pollutants were only measured in the pooled sample. For most pollutants, the concentrations in this study were lower or comparable to the concentrations measured in the pooled Belgian sample of the WHO human milk study of 2006, except for the pesticides dichlorodiphenyltrichloroethane DDT (+25% for ΣDDT and metabolites) and trans-nonachlor (+94%), and for the brominated flame retardant hexachlorocyclododecane HBCD (+153%). Perfluorinated compounds were for the first time determined in human milk samples from Belgium and the concentrations were comparable to those from other European countries. Also, interesting associations were found between the concentrations of POPs measured in human milk and personal characteristics as well as dietary habits of the study population. PFOS en PFOA concentrations were significantly higher in milk of primiparous participants compared to mothers who gave birth to their second child. Lower brominated PBDE congeners increased with increasing BMI of the mothers (p=0.01 for BDE 47, p=0.02 for BDE 99 and p=0.02 for BDE 100). Participants consuming milk or dairy products daily had significant higher concentrations of ΣDDTs (p=0.03) and oxychlordane (p=0.047) in their human milk samples.

Quantification of PCDD/Fs and dioxin-like PCBs in small amounts of human serum using the sensitive H1L7.5c1 mouse hepatoma cell line: optimization and analysis of human serum samples from adolescents of the Flemish human biomonitoring program FLEHS II.

Since the CALUX (Chemically Activated LUciferase gene eXpression) bioassay is a fast and inexpensive tool for the throughput analysis of dioxin-like compounds in a large number of samples and requires only small sample volumes, the use of this technique in human biomonitoring programs provides a good alternative to GC-HRMS. In this study, a method for the separate analysis of PCDD/Fs and dioxin-like PCBs (dl-PCBs) in human serum with the new sensitive H1L7.5c1 mouse hepatoma cell line was optimized. Sample dilution factors of 5 and 2.4 were selected for routine analysis of respectively the PCDD/Fs and dl-PCBs. The validation studies showed that repeatability and within-lab reproducibility for the quality control (QC) standard were within the in-house criteria. A long-term within-lab reproducibility of 25% for the PCDD/F fraction and 41% for the dl-PCB fraction for the analysis of pooled serum samples, expressed as pg BEQ/g fat, was determined. CALUX recoveries of the spiked procedural blanks were within the acceptable in-house limits of 80-120% for both fractions and the LOQ was 30.3 pg BEQ/g fat for the PCDD/Fs and 14.5 pg BEQ/g fat for the dl-PCBs. The GC-HRMS recovery of a C13-spiked pooled serum sample was between 60 and 90% for all PCDD/F congeners and between 67 and 82% for the non-ortho PCBs. An adequate separation between both fractions was found. The CALUX/GC-HRMS ratio for a pooled serum sample was respectively 2.0 and 1.4 for the PCDD/Fs and the dl-PCBs, indicating the presence of additional AhR active compounds. As expected, a correlation was found between human serum samples analyzed with both the new H1L7.5c1 cell line and the more established H1L6.1c3 cell line. The geometric mean CALUX-BEQ values, reported for the adolescents of the second Flemish Environment and Health Study (FLEHS II) recruited in 2009-2010, were 108 (95% CI: 101-114) pg CALUX-BEQ/g fat for the PCDD/Fs and 32.1 (30.1-34.2) pg CALUX-BEQ/g fat for the dioxin-like PCBs.