Acupuncture for fatigue in breast cancer survivors: a study protocol for a pragmatic, mixed method, randomised controlled trial.

INTRODUCTION: Fatigue is a common symptom observed in post-cancer treatment, yet its underlying mechanisms remain poorly understood. Acupuncture has been employed to alleviate cancer-related fatigue (CRF); however, its effectiveness in addressing associated comorbidities that may influence fatigue is also poorly understood. This study represents the first investigation to use acupuncture as an intervention for fatigue in breast cancer survivors within a Norwegian cohort. The study will employ questionnaires to evaluate various facets of fatigue. As a pragmatic trial, it statistically assesses its clinical relevance, documents adverse events and evaluates the cost-effectiveness of the acupuncture treatment. METHODS AND ANALYSIS: This assessor-blinded, pragmatic, randomised, mixed method, controlled trial with two parallel arms aims to evaluate the effectiveness, safety and cost-effectiveness of acupuncture. It will recruit 250 participants presented with CRF for 6 months or longer. Patients will be randomly allocated either to acupuncture and usual care (n=125) or to usual care alone (n=125). Acupuncture treatments (12 in total) are to be given within 12 weeks. The statistician who will analyse the data will be blinded to group allocation. The primary outcome will be changes in CRF measured by the Chalder fatigue scale. Measurements will be taken 12 weeks and 6 months after randomisation. The secondary outcomes include patient-reported outcomes of pain, anxiety, depression, hot flashes, insomnia and sleepiness. Health-related quality of life and economic evaluation will also be conducted 12 weeks and 6 months after randomisation. Nested within this randomised controlled trial are two qualitative studies and one sub-study measuring biomarkers (C-reactive protein, interleukin (IL)-1, IL-6, tumour necrosis factor alpha (TNF-α) and aPL in addition to the current genotype genes TNF-308 and IL-6-174) from blood samples (n=80). Such biomarkers can potentially address changes in CRF. ETHICS AND DISSEMINATION: Ethical approval of this study has been granted by the Regional Committees for Medical and Health Research Ethics (REC southeast ID number: 112285). Written informed consent will be obtained from all participants. The outcomes of the trial will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04418115.

Detection of metallic objects on digital radiographs with convolutional neural networks: A MRI screening tool.

INTRODUCTION: Screening for metallic implants and foreign bodies before magnetic resonance imaging (MRI) examinations, are crucial for patient safety. History of health are supplied by the patient, a family member, screening of electronic health records or the picture and archive systems (PACS). PACS securely store and transmits digital radiographs (DR) and related reports with patient information. Convolutional neural networks (CNN) can be used to detect metallic objects in DRs stored in PACS. This study evaluates the accuracy of CNNs in the detection of metallic objects on DRs as an MRI screening tool. METHODS: The musculoskeletal radiographs (MURA) dataset consisting of 14.863 upper extremity studies were stratified into datasets with and without metal. For each anatomical region: Elbow, finger, hand, humerus, forearm, shoulder and wrist we trained and validated CNN algorithms to classify radiographs with and without metal. Algorithm performance was evaluated with area under the receiver-operating curve (AUC), sensitivity, specificity, predictive values and accuracies compared with a reference standard of manually labelling. RESULTS: Sensitivities, specificities and area under the ROC-curves (AUC) for the six anatomic regions ranged from 85.33% (95% CI: 78.64%-90.57%) to 100.00% (95% CI: 98.16%-100.00%), 75.44% (95% CI: 62.24%-85.87%) to 93.57% (95% CI: 88.78%-96.75%) and 0.95 to 0.99, respectively. CONCLUSION: CNN algorithms classify DRs with metallic objects for six different anatomic regions with near-perfect accuracy. The rapid and iterative capability of the algorithms allows for scalable expansion and as a substitute MRI screening tool for metallic objects. IMPLICATIONS FOR PRACTICE: All CNNs would be able to assist in metal detection of digital radiographs prior to MRI, an substantially decrease screening time.

Non-grafted versus grafted sinus lift procedures for implantation in the atrophic maxilla: a systematic review and meta-analysis of randomized controlled trials.

The aim of this systematic review and meta-analysis was to critically evaluate the currently existing clinical evidence on the efficacy of graftless maxillary sinus membrane elevation for implantation in the atrophic posterior maxilla. A search protocol without limitations to November 2020 was followed by two independent researchers. Randomized controlled trials using the lateral window approach for graftless sinus membrane elevation were included. Uncontrolled, retrospective, non-comparative studies, case reports, and experimental studies in animals or cadavers were excluded. The search identified 2777 studies. Critical selection by two independent researchers then led to the inclusion of a total of nine studies. A risk of bias assessment was applied using the revised Cochrane risk-of-bias tool for randomized trials. A meta-analysis was conducted for seven studies. Results showed a high overall implant survival rate in both the graftless and bone-grafted sinus lift groups (97.92% and 98.73%, respectively). The graftless sinus lift group showed a significantly lower vertical bone height gain, with a mean difference of -1.73mm (P=0.01), and a significantly lower bone density, with a mean difference of -94.7 HU (P<0.001). The implant stability quotient values did not differ significantly between the test and control groups (P=0.07).

The reliability and validity of the Romanian rapid estimate of adult literacy in dentistry (RREALD-30).

OBJECTIVES: This study aimed to translate and adapt the Rapid Estimate of Adult Literacy in Dentistry (RREALD-30) instrument for Romanian urban adults and to test its reliability and validity for oral health literacy studies. MATERIAL AND METHODS: The study examined urban adult patients (n = 224) who attended the dental school clinic at the Faculty of Dental Medicine, Bucharest. We collected data through face-to-face interviews utilising the REALD-30 instrument. The interviews enquired about the Oral Health Impact Profile (OHIP-14), background characteristics, oral health-related knowledge, visits to dentists and self-rated oral health status. We applied principal component analysis for factor structure and Item Response Theory models to discriminate ability. A structural equation model (SEM) evaluated whether knowledge, perceived oral health, and visits to the dentist mediate the effect of RREALD on OHIP-14. RESULTS: Of the 224 participants, 113 (50.4%) were males. The internal consistency of the RREALD-30 measured by Cronbach's alpha was 0.88. The test-retest reliability was excellent (Spearman's correlation coefficient 0.98, ICC 0.90). RREALD-30 exhibited good concurrent and predictive validity. SEM demonstrated that RREALD mediated the effect of visits to dentist on OHIP-14. CONCLUSION: The RREALD-30 proved satisfactory psychometric properties and may serve to evaluate dental health literacy among Romanian adults.

Nurses' and physicians' experiences with diabetes consultations and the use of dialogue tools in the DiaPROM pilot trial: A qualitative study.

AIM: To explore nurses' and physicians' experiences with diabetes consultations in general and the use of dialogue tools in the Diabetes Patient-Related Outcome Measures (DiaPROM) pilot trial. METHODS: We used a qualitative explorative design by conducting semi-structured in-depth interviews with five nurses and nine physicians engaged in the DiaPROM pilot trial. The pilot trial aimed to test an intervention utilizing the patient-reported Problem Areas In Diabetes (PAID) scale and person-centred communication skills as dialogue tools in clinical consultations with adults with type 1 diabetes. We used thematic analysis to analyse the data. RESULTS: We generated three themes (each including two subthemes) from the analysis of participants' experiences: (1) 'Conflicting demands and priorities' (subthemes: 'Balancing guideline recommendations with patients' main concerns' and 'Experiencing that patients need more support to disclose their emotional concerns'); (2) 'Insights about using dialogue tools' (subthemes: 'The benefits and challenges of using the PAID as a dialogue tool' and 'Communication techniques are helpful'); and (3) 'Facilitating new interventions is challenging' (subthemes: 'Unclear roles and responsibilities in the multidisciplinary teamwork' and 'The capacity sets the limit, not the willingness'). CONCLUSIONS: Our findings indicate that the physicians and nurses experienced substantial challenges related to time and resources in the use of dialogue tools to support people's emotional concerns in clinical diabetes consultations. Thus, there is a need for healthcare organizations to adjust priorities to focus on the emotional burden of diabetes if the multidisciplinary diabetes teams are to successfully integrate psychosocial support into routine diabetes care.

Prevalence of temporomandibular disorder in children and adolescents with juvenile idiopathic arthritis - a Norwegian cross- sectional multicentre study.

BACKGROUND: Children and adolescents with juvenile idiopathic arthritis (JIA) may suffer pain from temporomandibular disorder (TMD). Still, routines for the assessment of temporomandibular joint (TMJ) pain in health and dental care are lacking. The aims of this study were to examine the prevalence of TMD in children and adolescents with JIA compared to their healthy peers and to investigate potential associations between JIA and TMD. METHODS: This comparative cross-sectional study is part of a longitudinal multicentre study performed during 2015-2020, including 228 children and adolescents aged 4-16 years with a diagnosis of JIA according to the ILAR criteria. This particular substudy draws on a subset of data from the first study visit, including assessments of TMD as part of a broader oral health examination. Children and adolescents with JIA were matched with healthy controls according to gender, age, and centre site. Five calibrated examiners performed the clinical oral examinations according to a standardised protocol, including shortened versions of the diagnostic criteria for TMD (DC/TMD) and the TMJaw Recommendations for Clinical TMJ Assessment in Patients Diagnosed with JIA. Symptoms were recorded and followed by a clinical examination assessing the masticatory muscles and TMJs. RESULTS: In our cohort of 221 participants with JIA and 221 healthy controls, 88 (39.8%) participants with JIA and 25 (11.3%) healthy controls presented with TMD based on symptoms and clinical signs. Painful TMD during the last 30 days was reported in 59 (26.7%) participants with JIA vs. 10 (5.0%) of the healthy controls (p <  0.001). Vertical unassisted jaw movement was lower in participants with JIA than in controls, with means of 46.2 mm vs. 49.0 mm, respectively (p <  0.001). Among participants with JIA, a higher proportion of those using synthetic disease-modifying antirheumatic-drugs and biologic disease-modifying antirheumatic-drugs presented with painful masticatory muscles and TMJs at palpation. CONCLUSION: Symptoms and clinical signs of TMD were seen in approximately half of the JIA patients compared to about one fourth of their healthy peers. Painful palpation to masticatory muscles and decreased vertical unassisted jaw movement were more frequent in participants with JIA than among healthy controls and should be part of both medical and dental routine examinations in patients with JIA.

The effects of a probiotic milk drink on bacterial composition in the supra- and subgingival biofilm: a pilot study.

Probiotics can convert a dysbiotic bacterial environment into a healthy one. The aim of the present study was to assess the effect of daily intake of a probiotic milk drink on the composition of bacterial species in dental supra- and subgingival biofilms. Sixteen dental students were enrolled into this study with a crossover, within subject, design. The participants were asked to allow plaque accumulation by refraining from cleaning their molars during two separate periods, each lasting three weeks. Each period consisted of an initial professional dental cleaning procedure done at the university clinic, then a 3 week plaque accumulation period, followed by a return to the clinic for supra- and subgingival plaque sampling. The first period served as a control, and during the second plaque accumulation period the participants drank 200 ml probiotic milk beverage each day. The accumulated plaque removed at the end of the accumulation period was later tested against a panel of 20 oral bacterial species using the checkerboard method. Three weeks consumption of a probiotic beverage led to a significant reduction in 15 of 20 bacterial species present in supragingival plaque and a reduction in 4 of 20 bacterial species in subgingival plaque (all P<0.05). This study showed a favorable effect of probiotics on periodontopathic bacteria in dental biofilms. The potential influence of this kind of probiotic in prevention or treatment of periodontal inflammation deserves further study.

Human dental pulp stromal cell conditioned medium alters endothelial cell behavior.

BACKGROUND: Angiogenesis is of utmost importance for tissue regeneration and repair. Human dental pulp stromal cells (hDPSCs) possess angiogenic potential, as they secrete paracrine factors that may alter the host microenvironment. However, more insight into how hDPSCs guide endothelial cells (ECs) in a paracrine fashion is yet to be obtained. Therefore, the current study aimed to investigate the effect(s) of conditioned medium derived from hDPSCs (hDPSC-CM) on EC behavior in vitro. METHODS: hDPSCs were harvested from third molars scheduled for surgical removal under informed consent. The angiogenic profile of hDPSC-CM was identified using human angiogenesis antibody array and enzyme-linked immunosorbent assay (ELISA). Using real-time reverse transcription-polymerase chain reaction (RT-PCR) and ELISA, the mRNA and protein expression level of specific angiogenic biomarkers was determined in human umbilical vein endothelial cells (HUVECs) exposed to hDPSC-CM. The effect of hDPSC-CM on HUVEC attachment, proliferation and migration was evaluated by crystal violet staining, MTT, transwell migration along with real-time cell monitoring assays (xCELLigence; ACEA Biosciences, Inc.). A Matrigel assay was included to examine the influence of hDPSC-CM on HUVEC network formation. Endothelial growth medium (EGM-2) and EGM-2 supplemented with hDPSC-CM served as experimental groups, whereas endothelial basal medium (EBM-2) was set as negative control. RESULTS: A wide range of proangiogenic and antiangiogenic factors, including vascular endothelial growth factor, tissue inhibitor of metalloproteinase protein 1, plasminogen activator inhibitor (serpin E1), urokinase plasminogen activator and stromal cell-derived factor 1, was abundantly detected in hDPSC-CM by protein profiling array and ELISA. hDPSC-CM significantly accelerated the adhesion phases, from sedimentation to attachment and spreading, the proliferation rate and migration of HUVECs as shown in both endpoint assays and real-time cell analysis recordings. Furthermore, Matrigel assay demonstrated that hDPSC-CM stimulated tubulogenesis, affecting angiogenic parameters such as the number of nodes, meshes and total tube length. CONCLUSIONS: The sustained proangiogenic and promaturation effects of hDPSC-CM shown in this in vitro study strongly suggest that the trophic factors released by hDPSCs are able to trigger pronounced angiogenic responses, even beyond EGM-2 considered as an optimal culture condition for ECs.

Increased infiltration and tolerised antigen-specific CD8+ TEM cells in tumor but not peripheral blood have no impact on survival of HCMV+ glioblastoma patients.

Human cytomegalovirus (HCMV) antigens in glioblastoma (GBM) present opportunities for personalised immunotherapy. However, their presence in GBM tissue is still under debate, and evidence of their impact on functional immune responses and prognosis is sparse. Here, we investigated the presence of pp65 (UL83) and immediate early 1 (IE-1) HCMV antigens in a cohort of Norwegian GBM patients (n = 177), using qPCR, immunohistochemistry, and serology. HCMV status was then used to investigate whether viral antigens influenced immune cell phenotype, infiltration, activation and patient survival. Pp65 and IE-1 were detected by qPCR in 23% and 43% of GBM patients, respectively. Furthermore, there was increased seropositivity in GBM patients relative to donors (79% vs. 48%, respectively; Logistic regression, OR = 4.05, 95%CI [1.807-9.114], P = 0.001, also when adjusted for age (OR = 2.84, 95%CI [1.110-7.275], P = 0.029). Tissue IE-1-positivity correlated with increased CD3+CD8+ T-cell infiltration (P < 0.0001), where CD8+ effector memory T (TEM) cells accounted for the majority of CD8+T cells compared with peripheral blood of HCMV+ patients (P < 0.0001), and HCMV+ (P < 0.001) and HCMV- (P < 0.001) donors. HLA-A2/B8-restricted HCMV-specific CD8+ T cells were more frequent in blood and tumor of HCMV+ GBM patients compared with seronegative patients, and donors irrespective of their serostatus. In biopsies, the HCMV-specific CD8+ TEM cells highly expressed CTLA-4 and PD-1 immune checkpoint protein markers compared with populations in peripheral blood (P < 0.001 and P < 0.0001), which expressed 3-fold greater levels of CD28 (P < 0.001 and P < 0.0001). These peripheral blood T cells correspondingly secreted higher levels of IFNγ in response to pp65 and IE-1 peptide stimulation (P < 0.001). Thus, despite apparent increased immunogenicity of HCMV compared with tumor antigens, the T cells were tolerised, and HCMV status did not impact patient survival (Log Rank3.53 HR = 0.85 95%CI [0.564-1.290], P = 0.45). Enhancing immune functionality in the tumor microenvironment thus may improve patient outcome.

Incorrect dosage of IQSEC2, a known intellectual disability and epilepsy gene, disrupts dendritic spine morphogenesis.

There is considerable genetic and phenotypic heterogeneity associated with intellectual disability (ID), specific learning disabilities, attention-deficit hyperactivity disorder, autism and epilepsy. The intelligence quotient (IQ) motif and SEC7 domain containing protein 2 gene (IQSEC2) is located on the X-chromosome and harbors mutations that contribute to non-syndromic ID with and without early-onset seizure phenotypes in both sexes. Although IQ and Sec7 domain mutations lead to partial loss of IQSEC2 enzymatic activity, the in vivo pathogenesis resulting from these mutations is not known. Here we reveal that IQSEC2 has a key role in dendritic spine morphology. Partial loss-of-function mutations were modeled using a lentiviral short hairpin RNA (shRNA) approach, which achieved a 57% knockdown of Iqsec2 expression in primary hippocampal cell cultures from mice. Investigating gross morphological parameters after 8 days of in vitro culture (8DIV) identified a 32% reduction in primary axon length, in contrast to a 27% and 31% increase in the number and complexity of dendrites protruding from the cell body, respectively. This increase in dendritic complexity and spread was carried through dendritic spine development, with a 34% increase in the number of protrusions per dendritic segment compared with controls at 15DIV. Although the number of dendritic spines had normalized by 21DIV, a reduction was noted in the number of immature spines. In contrast, when modeling increased dosage, overexpression of wild-type IQSEC2 led to neurons with shorter axons that were more compact and displayed simpler dendritic branching. Disturbances to dendritic morphology due to knockdown of Iqsec2 were recapitulated in neurons from Iqsec2 knockout mice generated in our laboratory using CRISPR/Cas9 technology. These observations provide evidence of dosage sensitivity for IQSEC2, which normally escapes X-inactivation in females, and links these disturbances in expression to alterations in the morphology of developing neurons.

Brief intervention, physical exercise and cognitive behavioural group therapy for patients with chronic low back pain (The CINS trial).

BACKGROUND AND OBJECTIVE: Cognitive-behavioural treatments (CBT) and physical group exercise (PE) have both shown promising effects in reducing disability and increasing work participation among chronic low back pain (CLBP) patients. A brief cognitive intervention (BI) has previously been demonstrated to reduce work disability in CLBP. The aim of this study was to test if the effect of BI could be further increased by adding either group CBT or group PE. METHODS: A total of 214 patients, all sick listed 2-10 months due to CLBP, were randomized to BI (n = 99), BI + group CBT (n = 55) or BI + group PE (n = 60). Primary outcome was increased work participation at 12 months, whereas secondary outcomes included pain-related disability, subjective health complaints, anxiety, depression, coping and fear avoidance. RESULTS: There were no significant differences between the groups in work participation at 12 months follow-up (χ2  = 1.15, p = 0.56). No significant differences were found on the secondary outcomes either, except for a statistically significant reduction (time by group) in pseudoneurology one domain of subjective health complaints (sleep problems, tiredness, dizziness, anxiety, depression, palpitation, heat flushes) (F2,136  = 3.109, p = 0.048) and anxiety (F2,143  = 4.899, p = 0.009) for the groups BI + group CBT and BI + group PE, compared to BI alone. However, these differences were not significant in post hoc analyses (Scheffé adjusted). CONCLUSION: There was no support for an effect of the added group CBT or group PE treatments to a brief cognitive intervention in this study of patients on sick leave due to low back pain. SIGNIFICANCE: Our study demonstrates that treatments that previously were found to be effective and are included in most treatment guidelines, such as group cognitive-behavior therapy and exercise, were not effective in this given context compared to a brief, cognitive intervention. This implies that an optimized brief intervention is difficult to outperform in patients on sick leave due to low back pain.

The effect of smoking on inflammatory and bone remodeling markers in gingival crevicular fluid and subgingival microbiota following periodontal therapy.

BACKGROUND AND OBJECTIVE: Periodontal health is mediated by suppressing microorganisms inducing a local inflammatory host response. Smoking may impair this process. This study compares gingival crevicular fluid levels of inflammatory and bone remodeling markers in heavy smokers and non-smokers following active and supportive periodontal therapy in patients with chronic periodontitis. MATERIAL AND METHODS: Gingival crevicular fluid and subgingival plaque were collected from the deepest periodontal pocket in 50 patients, 25 smokers and 25 non-smokers, at baseline (T0), following active (T1) and 12 mo of supportive periodontal therapy (T2). Smoking status was validated measuring serum cotinine levels. Gingival crevicular fluid levels of 27 inflammatory and two bone remodeling markers were analyzed using multiplex and singleplex micro-bed immunoassays, and subgingival plaque samples using checkerboard DNA-DNA hybridization. Amounts of markers in smokers and non-smokers were compared calculating the effect size. RESULTS: Expression of inflammatory and bone-remodeling markers in smokers demonstrated an overall reduced effect size at T0 and T2 (p < 0.001). In particular, proinflammatory markers (p < 0.001), chemokines (p = 0.007) and growth factors (p = 0.003) at T0, osteoprotegerin (p = 0.003) at T1, proinflammatory markers (p = 0.019) and chemokines (p = 0.005) at T2. At T2, interleukin-8 was detected in significantly higher levels in smokers. Ten different markers in non-smokers and none in smokers responded to periodontal therapy (p < 0.05). An overall negative association was revealed between smoking and subgroups of markers at sites presenting ≥ 105 red complex periodontal microbial species. CONCLUSION: Except for an upregulation of interleukin-8, smokers exhibited reduced gingival crevicular fluid levels of several inflammatory markers at baseline and following active and supportive periodontal therapy. Only inflammatory responses in non-smokers adapted to periodontal therapy. Apparently, there seems to be an immunosuppressant effect of smoking regulating the local inflammatory response and bone remodeling markers captured in gingival crevicular fluid following periodontal therapy.

Oral-health-related background factors and dental service utilisation among Sudanese children with and without a congenital heart defects.

BACKGROUND: Sudanese children with congenital heart defects (CHDs) were found to have poorer oral health than those without CHDs. The aims of this study were to: describe the patterns of oral-health-related background factors in children with and without CHD and explore any differences, and to evaluate the effects of background factors on caries and gingivitis prevalence and dental services utilisation. METHODS: In this analytical cross-sectional study, caregivers of children aged 3-12 years with (CHD cases n = 111) and without CHDs (Controls n = 182), underwent face-to-face interviews using a structured questionnaire. The questionnaire items covered several oral health background factors (independent variables) including: child's health status, oral hygiene practices, dental services utilization, mother's level of education, and caregiver's perception and awareness of their child's oral health. The relationship between these factors and occurrence of 'caries' and 'gingivitis' as well as 'child's dental services utilisation' (dependent variables) were explored using multiple adjusted and hierarchal logistic regression analyses. RESULTS: Compared with controls, CHD cases had lower frequencies of brushing and use of fluoridated toothpaste, and their caregivers were less knowledgeable about caries. Among CHD cases, the variables (brushing and fluoridated toothpaste use) had significant impacts on caries prevalence (odd ratio (OR) =5.6, 95% confidence interval (CI): 1.4-22.8 and OR = 0.3, 95% CI: 0.1-0.8 for infrequent compared to frequent ones, respectively) as well as the mother's level of education (OR = 2.6, 95% CI: 1.0-6.4). When differences in background factors were controlled for, the adjusted ORs for caries and gingivitis prevalence in CHD cases compared with controls were 1.8, (95% CI: 1.1-3.2) and 5.3 (95% CI: 2.9-9.4), respectively. Among CHD cases, the child's age (8-12 years: OR = 11.9, 95% CI: 1.9-71.6), and the mother's level of education (lower education: OR = 0.2, 95% CI: 0.03-0.9) were significantly associated with the child's dental services utilisation. CONCLUSIONS: Lower frequencies of brushing and use of fluoride tooth paste were reported among CHD cases, and brushing had the predominant significant impact on caries prevalence. The child's age and the mother's level of education were the main factors affecting the child's (CHD cases) dental services utilisation.

The results of 479 thumb carpometacarpal joint replacements reported in the Norwegian Arthroplasty Register.

In this study we report the results of thumb carpometacarpal (CMC) joint replacements in the Norwegian population over a 17-year period. In total, 479 primary replacements performed from 1994 to 2011 were identified in the Norwegian Arthroplasty Register. Implant survival and risk of revision were analyzed using Cox regression analyses. Four different implant designs were compared and time trends were analyzed. The overall 5 and 10 year survivals were 91% and 90%, respectively. The newer metal total arthroplasties did not outperform the older silicone and mono-block implants. At 5 years, the implant survival ranged from 90% to 94% for the different implant brands. Gender, age, and diagnosis did not influence the risk of revision. The incidence of thumb CMC joint replacement did not change during the study period. Despite relatively satisfactory implant survivorship in our register study, current evidence does not support widespread implementation of thumb CMC replacements.

Authors' reply Cobb correspondence re: J-E. Gjertsen, S. A. Lie, T. Vinje, et al. More re-operations after uncemented than cemented hemiarthroplasty used in the treatment of displaced fractures of the femoral neck: An observational study of 11 116 hemiarthroplasties from a national register. J Bone Joint Surg [Br] 2012;94-B:1113-1119.

We welcome letters to the Editor concerning articles that have recently been published. Such letters will be subject to the usual stages of selection and editing; where appropriate the authors of the original article will be offered the opportunity to reply.

Radiological findings that may indicate a prior silent slipped capital femoral epiphysis in a cohort of 2072 young adults.

The reported prevalence of an asymptomatic slip of the contralateral hip in patients operated on for unilateral slipped capital femoral epiphysis (SCFE) is as high as 40%. Based on a population-based cohort of 2072 healthy adolescents (58% women) we report on radiological and clinical findings suggestive of a possible previous SCFE. Common threshold values for Southwick's lateral head-shaft angle (≥ 13°) and Murray's tilt index (≥ 1.35) were used. New reference intervals for these measurements at skeletal maturity are also presented. At follow-up the mean age of the patients was 18.6 years (17.2 to 20.1). All answered two questionnaires, had a clinical examination and two hip radiographs. There was an association between a high head-shaft angle and clinical findings associated with SCFE, such as reduced internal rotation and increased external rotation. Also, 6.6% of the cohort had Southwick's lateral head-shaft angle ≥ 13°, suggestive of a possible slip. Murray's tilt index ≥ 1.35 was demonstrated in 13.1% of the cohort, predominantly in men, in whom this finding was associated with other radiological findings such as pistol-grip deformity or focal prominence of the femoral neck, but no clinical findings suggestive of SCFE. This study indicates that 6.6% of young adults have radiological findings consistent with a prior SCFE, which seems to be more common than previously reported.

Prevalence of radiographic findings associated with hip dysplasia in a population-based cohort of 2081 19-year-old Norwegians.

In Norway total joint replacement after hip dysplasia is reported more commonly than in neighbouring countries, implying a higher prevalence of the condition. We report on the prevalence of radiological features associated with hip dysplasia in a population of 2081 19-year-old Norwegians. The radiological measurements used to define hip dysplasia were Wiberg's centre-edge (CE) angle at thresholds of < 20° and < 25°, femoral head extrusion index < 75%, Sharp's angle > 45°, an acetabular depth to width ratio < 250 and the sourcil shape assessed subjectively. The whole cohort underwent clinical examination of their range of hip movement, body mass index (BMI), and Beighton hypermobility score, and were asked to complete the EuroQol (EQ-5D) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The prevalence of hip dysplasia in the cohort varied from 1.7% to 20% depending on the radiological marker used. A Wiberg's CE angle < 20° was seen in 3.3% of the cohort: 4.3% in women and 2.4% in men. We found no association between subjects with multiple radiological signs indicative of dysplasia and BMI, Beighton score, EQ-5D or WOMAC. Although there appears to be a high prevalence of hip dysplasia among 19-year-old Norwegians, this is dependent on the radiological parameters applied.

The progression of end-stage osteoarthritis: analysis of data from the Australian and Norwegian joint replacement registries using a multi-state model.

OBJECTIVE: The incidence of joint replacements is considered an indicator of symptomatic end-stage osteoarthritis (OA). We analysed data from two national joint replacement registries in order to investigate whether evidence of a pattern of progression of end-stage hip and knee OA could be found in data from large unselected populations. DESIGN: We obtained data on 78,634 hip and 122,096 knee arthroplasties from the Australian Orthopaedic Association National Joint Replacement Registry and 19,786 hip and 12,082 knee arthroplasties from the Norwegian Arthroplasty Register. A multi-state model was developed where individuals were followed from their first recorded hip or knee arthroplasty for OA to receiving subsequent hip and/or knee arthroplasties. We used this model to estimate relative hazard rates and probabilities for each registry separately. RESULTS: The hazard rates of receiving subsequent arthroplasties in non-cognate joints were higher on the contralateral side than on the ipsilateral side to the index arthroplasty, especially if the index was a hip arthroplasty. After 5 years, the estimated probabilities of having received a knee contralateral to the index hip were more than 1.7 times the probabilities of having received a knee ipsilateral to the index hip. CONCLUSION: The results indicate that there is an association between the side of the first hip arthroplasty and side of subsequent knee arthroplasties. Further studies are needed to investigate whether increased risk of receiving an arthroplasty in the contralateral knee is related to having a hip arthroplasty and/or preoperative factors such as pain and altered gait associated with hip OA.

Emotional development in children with tics: a longitudinal population-based study.

Children with tics often experience accompanying problems that may have more impact on their well being and quality of life than the tics themselves. The present study investigates characteristics and the course of associated problems. In a population-based follow-up study, we investigated the developmental trajectory of children with and without tics when they were 7-9 years old. Parents and teachers completed the strengths and difficulties questionnaire (SDQ) when the children were 7-9 years (wave 1) and 4 years later (wave 2). Using strict criteria, we identified 38 children with tics in the cohort of 4,025 children (0.94% of the total cohort) with a preponderance of boys (78.9%). 22 children (57.9%) in the group with tics had only motor tics, and 16 (42.1%) had both motor and vocal tics. Children with tics had significantly higher parent- and teacher-rated SDQ total difficulty scores and subscale scores in both waves. Children with tics experienced an increase in emotional problems and in peer problems between the first and the second wave. This study in a general population indicates that the presence of tics is associated with a range of internalizing and externalizing difficulties, as well as problems in peer relationships. Moreover, our study indicates that emotional and peer problems tend to increase over time in the group of children with tics.

Maternal undernutrition around the time of conception and embryo number each impact on the abundance of key regulators of cardiac growth and metabolism in the fetal sheep heart.

Poor maternal nutrition before and during pregnancy is associated with an increased risk of cardiovascular disease in later life. To determine the impact of maternal undernutrition during the periconceptional (PCUN: -45 days to 6 days) and preimplantation (PIUN: 0-6 days) periods on cardiac growth and metabolism, we have quantified the mRNA and protein abundance of key regulators of cardiac growth and metabolism in the left ventricle of the sheep fetus in late gestation. The cardiac protein abundance of AMP-activated protein kinase (AMPK), phospho-acetyl CoA carboxykinase (ACC) and pyruvate dehydrogenase kinase-4 (PDK-4) were decreased, whereas ACC was increased in singletons in the PCUN and PIUN groups. In twins, however, cardiac ACC was decreased in the PCUN and PIUN groups, and carnitine palmitoyltransferase-1 (CPT-1) was increased in the PIUN group. In singletons, the cardiac abundance of insulin receptor ß (IRß) was decreased in the PCUN group, and phosphoinositide-dependent protein kinase-1 (PDPK-1) was decreased in the PCUN and PIUN groups. In twins, however, the cardiac abundance of IRß and phospho-Akt substrate 160kDa (pAS160) were increased in the PIUN group. The cardiac abundance of insulin-like growth factor-2 receptor (IGF-2R), protein kinase C alpha (PKCα) and mammalian target of rapamycin (mTOR) were decreased in PCUN and PIUN singletons and extracellular-signal-regulated kinase (ERK) was also decreased in the PIUN singletons. In contrast, in twins, cardiac abundance of IGF-2R and PKCα were increased in the PCUN and PIUN groups, phospho-ribosomal protein S6 (pRPS6) was increased in the PCUN group, and ERK and eukaryotic initiation factor 4E (eIF4E) were also increased in the PIUN fetuses. In conclusion, maternal undernutrition limited to around the time of conception is sufficient to alter the abundance of key factors regulating cardiac growth and metabolism and this may increase the propensity for cardiovascular diseases in later life.