Diagnostics and treatment delay in primary central nervous system lymphoma: What the neurosurgeon should know.

PURPOSE: The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL. METHODS: We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery. RESULTS: Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics. CONCLUSION: Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs.

Magnesium hydroxide versus macrogol/electrolytes in the prevention of opioid-induced constipation in incurable cancer patients: study protocol for an open-label, randomized controlled trial (the OMAMA study).

BACKGROUND: Opioid-induced constipation (OIC) is a common symptom in cancer patients treated with opioids with a prevalence of up to 59%. International guidelines recommend standard laxatives such as macrogol/electrolytes and magnesium hydroxide to prevent OIC, although evidence from randomized controlled trials is largely lacking. The aim of our study is to compare magnesium hydroxide with macrogol /electrolytes in the prevention of OIC in patients with incurable cancer and to compare side-effects, tolerability and cost-effectiveness. METHODS: Our study is an open-label, randomized, multicenter study to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. In total, 330 patients with incurable cancer, starting with opioids for pain management, will be randomized to treatment with either macrogol/electrolytes or magnesium hydroxide. The primary outcome measure is the proportion of patients with a score of < 30 on the Bowel Function Index (BFI), measured on day 14. The Rome IV criteria for constipation, side effects of and satisfaction with laxatives, pain scores, quality of life (using the EQ-5D-5L), daily use of laxatives and escape medication, and cost-effectiveness will also be assessed. DISCUSSION: In this study we aim to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. The outcome of our study will contribute to prevention of OIC and scientific evidence of guidelines on (opioid-induced) constipation. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov: NCT05216328 and in the Dutch trial register: NTR80508. EudraCT number 2022-000408-36.

11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy.

PURPOSE: To assess the potential for 11C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MRCR) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance. PATIENTS AND METHODS: Thirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MRCR between 2016 and 2020. All patients had persistent hyperprolactinemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances. RESULTS: In all 13 patients Met-PET/MRCR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment. CONCLUSIONS: In patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MRCR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

Testing sampling bias in estimates of adolescent social competence and behavioral control.

In 5 of the 6 large Dutch developmental cohorts investigated here, lower SES adolescents are underrepresented and higher SES adolescents overrepresented. With former studies clearly revealing differences between SES strata in adolescent social competence and behavioral control, this misrepresentation may contribute to an overestimation of normative adolescent competence. Using a raking procedure, we used national census statistics to weigh the cohorts to be more representative of the Dutch population. Contrary to our expectations, in all cohorts, little to no differences between SES strata were found in the two outcomes. Accordingly, no differences between weighted and unweighted mean scores were observed across all cohorts. Furthermore, no clear change in correlations between social competence and behavioral control was found. These findings are most probably explained by the fact that measures of SES in the samples were quite limited, and the low SES participants in the cohorts could not be considered as representative of the low SES groups in the general population. Developmental outcomes associated with SES may be affected by a raking procedure in other cohorts that have a sufficient number and sufficient variation of low SES adolescents.

Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients: results from a randomised phase III study.

BACKGROUND: The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to standard high-dose methotrexate-based treatment on HRQoL in patients in a large randomised trial. PATIENTS AND METHODS: Patients from a large phase III trial (HOVON 105/ALLG NHL 24), randomly assigned to receive standard chemotherapy with or without rituximab and followed by 30 Gy whole brain radiotherapy (WBRT) in patients ≤60 years, completed the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 24 months of follow-up or progression. Differences between treatment arms over time in global health status, role functioning, social functioning, fatigue, and motor dysfunction were assessed. Differences ≥10 points were deemed clinically relevant. The effect of WBRT on HRQoL was analysed in irradiated patients. RESULTS: A total of 160/175 patients eligible for the HRQoL study completed at least one questionnaire and were included. Over time, scores improved statistically significantly and were clinically relevant in both arms. Between arms, there were no differences on any scale (range: -3.8 to +4.0). Scores on all scales were improved to a clinically relevant extent at 12 and 24 months compared with baseline in both arms, except for fatigue and motor dysfunction at 12 months (-7.4 and -8.8, respectively). In irradiated patients (n = 59), scores in all preselected scales, except motor dysfunction, remained stable up to 24 months compared with shortly after WBRT, overall mean difference ranging between 0.02 and 4.570. CONCLUSION: Compared with baseline, treatment resulted in improved HRQoL scores. The addition of rituximab to standard chemotherapy did not impact HRQoL over time. WBRT did not result in deterioration of HRQoL in the first 2 years.

Differences in neurology residency training programmes across Europe - a survey among the Residents and Research Fellow Section of the European Academy of Neurology national representatives.

BACKGROUND AND PURPOSE: Neurology is rapidly evolving as a result of continuous diagnostic and therapeutic progress, which influences the daily work of neurologists. Therefore, updating residency training programmes is crucial for the future of neurology. Several countries are currently discussing and/or modifying the structure of their neurology residency training programme. A detailed and up-to-date overview of the available European residency training programmes will aid this process. METHODS: A questionnaire addressing numerous aspects of residency training programmes in neurology was distributed among 38 national representatives of the Resident and Research Fellow Section of the European Academy of Neurology. RESULTS: We obtained data from 32 European countries (response rate 84%). The median (range) duration of the residency training programmes was 60 (12-72) months. In the majority of countries, rotations to other medical disciplines were mandatory, mostly psychiatry (69%), internal medicine (66%) and neurosurgery (59%). However, the choice of medical fields and the duration of rotations varied substantially between countries. In 50% of countries, there were formal regulations regarding training in evidence-based medicine, teaching skills and/or leadership qualities. In many countries (75%), residents had to take an examination. CONCLUSIONS: We found substantial variation among European countries in the duration of residency training programmes, and especially in the choice of obligatory rotations to external medical disciplines. Despite a presumably similar spectrum of patients, neurology residency training programmes across Europe are not harmonized. The structure of the programme should be determined by its relevance for neurologists today and in the future.

Osteocalcin affects bone mineral and mechanical properties in female mice.

Osteocalcin is one of the most abundant noncollagenous proteins in bone. Phenotypes of osteocalcin knock-out mice (OC-/-) may vary on different backgrounds and with sex. Previous studies using adult female (OC-/-) mice on a mixed genetic background (129/B6) showed osteocalcin inhibited bone formation leading to weaker bone in wild-type (OC+/+). Yet on a pure (B6) genetic background male mice revealed osteocalcin improved fracture resistance and OC-/- bones were more prone to fracture. Osteocalcin is decreased with age and in some diseases (diabetes) where bone weakness is observed. The effect of osteocalcin in adult female bone from mice on a pure B6 background is unknown. We investigated differences in bone mineral properties and bone strength in female adult (6 months) (OC+/+) and (OC-/-) mice on a pure C57BL/6J background using Fourier Transform Infrared Imaging (FTIRI), micro-computed tomography (uCT), biomechanical measurements, histomorphometry and serum turnover markers (P1NP, CTX). Similar to female age matched mice on the (129/C57) background we found B6 OC-/- mice had a higher bone formation rate, no change in bone resorption, more immature mineral, decreased crystallinity and increased trabecular bone as compared to OC+/+. In contrast, the OC-/- mice on a pure B6 background had a lower bone mineral density, lower mineral to matrix ratio resulting in reduced stiffness and weaker bone strength. Our results demonstrate some properties of the OC-/- phenotype are dependent on genetic background. This may suggest that reduced osteocalcin may contribute to fracture and weaker bone in some groups of elderly and adults with diseases where osteocalcin is low.

Low-level cyclic tibial compression attenuates early osteoarthritis progression after joint injury in mice.

OBJECTIVE: Mechanical loading and joint health have a unique relationship in osteoarthritis (OA) onset and progression. Although high load levels adversely affect cartilage health, exercise that involves low to moderate load levels can alleviate OA symptoms. We sought to isolate the beneficial effects of mechanical loading using controlled in vivo cyclic tibial compression. We hypothesized that low-level cyclic compression would attenuate post-traumatic OA symptoms induced by destabilization of the medial meniscus (DMM). METHODS: 10-week-old C57Bl/6J male mice underwent DMM surgery (n = 51). After a 5-day post-operative recovery period, we applied daily cyclic tibial compression to the operated limbs at low (1.0N or 2.0N) or moderate (4.5N) magnitudes for 2 or 6 weeks. At the completion of loading, we compared cartilage and peri-articular bone features of mice that underwent DMM and loading to mice that only underwent DMM. RESULTS: Compared to DMM alone, low-level cyclic compression for 6 weeks attenuated DMM-induced cartilage degradation (OARSI score, P = 0.008, 95% confidence interval (CI): 0.093 to 0.949). Low-level loading attenuated DMM-induced osteophyte formation after 2 weeks (osteophyte size, P = 0.033, 95% CI: 3.27-114.45 µm), and moderate loading attenuated subchondral bone sclerosis after 6 weeks (tissue mineral density (TMD), P = 0.011, 95% CI: 6.32-70.60 mg HA/ccm) compared to limbs that only underwent DMM. Finally, loading had subtle beneficial effects on cartilage cellularity and aggrecanase activity after DMM. CONCLUSION: Low-level cyclic compression is beneficial to joint health after an injury. Therefore, the progression of early OA may be attenuated by applying well controlled, low-level loading shortly following joint trauma.

The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis.

OBJECTIVE: Metabolic syndrome is characterized by obesity, hyperglycemia, hypertension, insulin resistance, and dyslipidemia. Metabolic syndrome is associated with osteoarthritis (OA), but it is unclear if the association is attributable to increased mechanical loading on joints caused by obesity or other aspects of metabolic syndrome. Here we examined the effects of altered metabolism, obesity, and the gut microbiome on load-induced OA. DESIGN: Cartilage damage was induced through cyclic compressive loading in four groups of adult male mice: Toll-like receptor-5 deficient (TLR5KO) mice that develop metabolic syndrome due to alterations in the gut microbiome, TLR5KO mice submitted to chronic antibiotics to prevent metabolic syndrome (TLR5KOΔMicrobiota), C57BL/6J mice fed a high fat diet to cause obesity (HFD), and untreated C57BL/6J mice (WT). Loading was applied for 2 weeks (n = 10-11/group) or 6 weeks (n = 10-11/group). RESULTS: After 2 weeks of loading, cartilage damage (OARSI score) was not different among groups. After 6 weeks of loading, HFD mice had increased load-induced cartilage damage, while TLR5KO mice had cartilage damage comparable to WT mice. TLR5KOΔMicrobiota mice had less cartilage damage than other groups. HFD mice had elevated serum inflammatory markers. Each group had a distinct gut microbiome composition. CONCLUSIONS: Severe obesity increased load-induced cartilage damage, while milder changes in adiposity/metabolic syndrome seen in TLR5KO mice did not. Furthermore, the effects of systemic inflammation/obesity on cartilage damage depend on the duration of mechanical loading. Lastly, reduced cartilage damage in the TLR5KOΔMicrobiota mice suggests that the gut microbiome may influence cartilage pathology.

Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice.

OBJECTIVE: Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). DESIGN: Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26 µg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. RESULTS: FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. By contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. CONCLUSIONS: Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression.

Evaluation of the colorectal cancer screening Programme in the Basque Country (Spain) and its effectiveness based on the Miscan-colon model.

The population-based Basque Colorectal Cancer (CRC) Screening Programme started in 2009 with a biennial immunochemical quantitative test (FIT) biennial and colonoscopy under sedation in positive cases. The population target of 586,700 residents was from 50 to 69 years old and the total coverage was reached at the beginning of 2014. The aim of our study was to determine possible scenarios in terms of incidence, mortality and reduction of Life-years-Lost (L-y-L) in the medium and long term of CRC. METHODS: Invitations were sent out by the Programme from 2009 to 2014, with combined organizational strategies. Simulation was done by MISCAN-colon (Microsimulation Screening Analysis) over 30 years comparing the results of screening vs no-screening, taking the population-based Cancer Registry into account. Lifetime population and real data from the Programme were used from 2008 to 2012. The model was run differentially for men and women. RESULTS: 924,416 invitations were sent out from 2009 to 2014. The average participation rate was 68.4%, CRC detection rate was 3.4% and the Advanced Adenoma detection rate was 24.0‰, with differences observed in sex and age. Future scenarios showed a higher decrease of incidence (17.2% vs 14.7%), mortality (28.1% vs 22.4%) and L-y-L (22.6% vs 18.4%) in men than women in 2030. CONCLUSIONS: The Basque Country CRC Programme results are aligned to its strategy and comparable to other programmes. MISCAN model was found to be a useful tool to predict the benefits of the programme in the future. The effectiveness of the Programme has not been formally established as case control studies are required to determine long term benefits from the screening strategy.

Painful decisions: How classifying sensations can change the experience of pain.

BACKGROUND: Categorizing perceptual stimuli is a mechanism for facilitating the processing of sensory input from our environment. This facilitation of perception is achieved through generalization (assimilation) of stimulus characteristics within categories and accentuation between categories. These categorization processes have been demonstrated in visual, auditory, tactile and social perception, but never in pain perception. METHOD: We presented participants with six thermal noxious stimuli, increasing in steps of 0.5 °C. In an experimental group, stimuli were assigned to two categories labelled A and B containing the three lower (A1, A2, A3) and three higher (B1, B2, B3) stimuli. A control group did not receive such category information (stimuli were labelled S1-S6). In a first part of the experiment, participants simply rated pain intensity and unpleasantness for all stimuli. In a second part, we presented stimuli without labels and participants had to identify the label of each stimulus. RESULTS: We found evidence for categorization effects in both pain ratings and stimulus identification data. In particular, unpleasantness ratings within categories were more similar to each other, and ratings between categories less similar, in the experimental compared to control group. Participants in the experimental group also confused stimuli more often within than between categories, and were more confident about category membership of stimuli at the category border, compared to participants in the control group. CONCLUSIONS: Mere category information, using abstract category labels, significantly changes pain perception. Implications for our understanding of cognitive pain modulation mechanisms, as well as clinical implications of categorization effects are discussed. SIGNIFICANCE: Categorization effects in pain perception are demonstrated. Classifying and labelling painful events can modulate early perceptual processes, lead to under- or overestimation of pain symptoms and affect decision-making behaviour related to pain.

Non-invasive mouse models of post-traumatic osteoarthritis.

Animal models of osteoarthritis (OA) are essential tools for investigating the development of the disease on a more rapid timeline than human OA. Mice are particularly useful due to the plethora of genetically modified or inbred mouse strains available. The majority of available mouse models of OA use a joint injury or other acute insult to initiate joint degeneration, representing post-traumatic osteoarthritis (PTOA). However, no consensus exists on which injury methods are most translatable to human OA. Currently, surgical injury methods are most commonly used for studies of OA in mice; however, these methods may have confounding effects due to the surgical/invasive injury procedure itself, rather than the targeted joint injury. Non-invasive injury methods avoid this complication by mechanically inducing a joint injury externally, without breaking the skin or disrupting the joint. In this regard, non-invasive injury models may be crucial for investigating early adaptive processes initiated at the time of injury, and may be more representative of human OA in which injury is induced mechanically. A small number of non-invasive mouse models of PTOA have been described within the last few years, including intra-articular fracture of tibial subchondral bone, cyclic tibial compression loading of articular cartilage, and anterior cruciate ligament (ACL) rupture via tibial compression overload. This review describes the methods used to induce joint injury in each of these non-invasive models, and presents the findings of studies utilizing these models. Altogether, these non-invasive mouse models represent a unique and important spectrum of animal models for studying different aspects of PTOA.

Mechanical load increases in bone formation via a sclerostin-independent pathway.

Sclerostin, encoded by the Sost gene, is an important negative regulator of bone formation that has been proposed to have a key role in regulating the response to mechanical loading. To investigate the effect of long-term Sclerostin deficiency on mechanotransduction in bone, we performed experiments on unloaded or loaded tibiae of 10 week old female Sost-/- and wild type mice. Unloading was induced via 0.5U botulinum toxin (BTX) injections into the right quadriceps and calf muscles, causing muscle paralysis and limb disuse. On a separate group of mice, increased loading was performed on the left tibiae through unilateral cyclic axial compression of equivalent strains (+1200 µe) at 1200 cycles/day, 5 days/week. Another cohort of mice receiving equivalent loads (-9.0 N) also were assessed. Contralateral tibiae served as normal load controls. Loaded/unloaded and normal load tibiae were assessed at day 14 for bone volume (BV) and formation changes. Loss of BV was seen in the unloaded tibiae of wild type mice, but BV was not different between normal load and unloaded Sost-/- tibiae. An increase in BV was seen in the loaded tibiae of wild type and Sost-/- mice over their normal load controls. The increased BV was associated with significantly increased mid-shaft periosteal mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR), and bone formation rate/bone surface (BFR/BS), and endosteal MAR and BFR/BS. Notably, loading induced a greater increase in periosteal MAR and BFR/BS in Sost-/- mice than in wild type controls. Thus, long-term Sclerostin deficiency inhibits the bone loss normally induced with decreased mechanical load, but it can augment the increase in bone formation with increased load.

Validity of the Oral Behaviours Checklist: correlations between OBC scores and intensity of facial pain.

The first purpose of this study was to translate the Oral Behaviours Checklist (OBC) into Dutch and to examine its psychometric properties. The second purpose was to examine the correlations between scores on the OBC and facial pain, while controlling for the possible confounding effects of psychosocial factors, such as stress, depression, somatisation and anxiety. The OBC was translated, following the international RDC/TMD consortium guidelines. Its psychometric properties were examined by assessing the test-retest reliability and concurrent validity [correlations between the OBC and the previously developed Oral Parafunctions Questionnaire (OPQ)]. Participants were 155 patients with TMD (77% female; mean age and s.d. = 43.6 and 14.4 years). The translation of the OBC into Dutch proceeded satisfactorily. The psychometric properties of the Dutch OBC were good; test-retest reliability was excellent (ICC = 0.86, P < 0.001). Concurrent validity was good: the correlation between the OBC and OPQ was high (r = 0.757, P < 0.001), while the correlations between individual items ranged from 0.389 to 0.892 (P < 0.001). Similar to previous Dutch studies using the OPQ, no significant correlation was found between oral parafunctions and facial pain (r = 0.069, P = 0.892). No significant correlations could be found between oral parafunctional behaviours and facial pain.

Oral health-related quality of life in patients with tooth wear.

The aim of this study was to investigate the impact of tooth wear (TW) on patients' oral health-related quality of life. A total of 198 participants were included in the study. They belonged to the following four different diagnostic categories: 51 patients with TW, 46 patients with painful temporomandibular disorders (TMD), 43 complete denture wearers and 58 healthy controls. The Dutch version of the Oral Health Impact Profile (OHIP-NL) was used to assess the patients' oral health-related quality of life. The results of the study show that patients with TW have an impaired oral health-related quality of life compared with healthy controls (P < 0·001). Furthermore, the impact of TW and of edentulousness do not differ significantly, while both of these oral conditions seem to have a lower impact on quality of life compared with painful TMD (P < 0·05). It was concluded that TW has a negative impact on patients' quality of life. This impact is comparable with that of edentulousness.

A rare case of a bisphosphonate-induced peri-prosthetic femoral fracture.

An 81-year-old woman presented with a fracture in the left femur. She had well-fixed bilateral hip replacements and had received long-term bisphosphonate treatment. Prolonged bisphosphonate use has been recently linked with atypical subtrochanteric and diaphyseal femoral fractures. While the current definition of an atypical fracture of the femur excludes peri-prosthetic fractures, this case suggests that they do occur and should be considered in patients with severe osteopenia. Union of the fracture followed cessation of bisphosphonates and treatment with teriparatide. Thus, this case calls into question whether prophylactic intramedullary nailing is sufficient alone to treat early or completed atypical femoral fractures.

Developing abbreviated OHIP versions for use with TMD patients.

The aim of this study was to evaluate the psychometric characteristics of three versions of the Dutch Oral Health Impact Profile (OHIP-NL), for clinical use with temporomandibular disorder (TMD) patients. To that end, two abbreviated OHIP versions (OHIP-NL14 and OHIP-NL5) were developed by respectively selecting 14 and five items from the officially translated and culturally adapted original 49-item OHIP-NL questionnaire. A total of 245 consecutive patients, referred by their dentist to the TMD clinic of the Academic Centre for Dentistry Amsterdam (77% women; mean age ± s.d. = 41·0 ± 14·9 years), completed the Research Diagnostic Criteria for TMD (RDC/TMD) axis II questionnaire and the OHIP-NL. Reliability and validity of all three OHIP versions were compared, and their associations with four psychological axis II variables, indicating the level of impairment of patients with TMD, were examined. According to guidelines for clinical application, internal consistency scores were sufficient for OHIP-NL and OHIP-NL14, but insufficient for OHIP-NL5. Test-retest reliability (n = 64) was excellent for OHIP-NL and OHIP-NL14 and fair to good for OHIP-NL5. For all three versions, there was evidence for score validity: associations between OHIP summary scores on the one hand and validation variables and other RDC/TMD axis II variables on the other hand met the expectations and were statistically significant (P < 0·001). In conclusion, the OHIP-NL and OHIP-NL14 both performed comparatively well and better than the OHIP-NL5. When the length of the questionnaire (i.e. the time needed for its completion) is an issue, the OHIP-14 would therefore be the preferred version.

MicroCT morphometry analysis of mouse cancellous bone: intra- and inter-system reproducibility.

The agreement between measurements and the relative performance reproducibility among different microcomputed tomography (microCT) systems, especially at voxel sizes close to the limit of the instruments, is not known. To compare this reproducibility 3D morphometric analyses of mouse cancellous bone from distal femoral epiphyses were performed using three different ex vivo microCT systems: GE eXplore Locus SP, Scanco µCT35 and Skyscan 1172. Scans were completed in triplicate at 12 µm and 8 µm voxel sizes and morphometry measurements, from which relative values and dependence on voxel size were examined. Global and individual visually assessed thresholds were compared. Variability from repeated scans at 12 µm voxel size was also examined. Bone volume fraction and trabecular separation values were similar, while values for relative bone surface, trabecular thickness and number varied significantly across the three systems. The greatest differences were measured in trabecular thickness (up to 236%) and number (up to 218%). The relative dependence of measurements on voxel size was highly variable for the trabecular number (from 0% to 20% relative difference between measurements from 12 µm and 8 µm voxel size scans, depending on the system). The intra-system reproducibility of all trabecular measurements was also highly variable across the systems and improved for BV/TV in all the systems when a smaller voxel size was used. It improved using a smaller voxel size in all the other parameters examined for the Scanco system, but not consistently so for the GE or the Skyscan system. Our results indicate trabecular morphometry measurements should not be directly compared across microCT systems. In addition, the conditions, including voxel size, for trabecular morphometry studies in mouse bone should be chosen based on the specific microCT system and the measurements of main interest.