Temporomandibular joint prosthesis as treatment option for mandibular condyle fractures: a systematic review and meta-analysis.

The aim of this study was to perform a systematic review of the literature on the temporomandibular joint (TMJ) prosthesis as a treatment option after mandibular condyle fracture. Three databases were searched (PubMed, Embase, Cochrane Library) and 2670 unique papers were identified. A total of 337 studies were included (121 case reports, 89 case series, and 127 cohort/clinical studies). In total 14,396 patients and 21,560 prostheses were described. Of the 127 cohort or clinical studies, 100 (79%) reported inclusion criteria, 54 (43%) reported exclusion criteria, and 96 (76%) reported the inclusion period. The base population from which patients were recruited was reported in 57 studies (45%). The reason for TMJ prosthesis implantation was reported for 4177 patients (29.0%). A history of condylar fracture was present in 83 patients (2.0%); a history of mandibular trauma was present in 580 patients (13.9%). The meta-analysis showed a pooled prevalence of condylar fracture of 1.6% (95% confidence interval 0.9-2.4%) and a pooled prevalence of trauma or condylar fracture of 11.3% (95% confidence interval 7.1-16.0%). Heterogeneity was highly significant (P < 0.001). The TMJ prosthesis appears to be reserved for patients with persistent pain, bony or fibrous ankylosis, or osteomyelitis after primary closed or open treatment of fractures of the mandibular condyle.

Cost-effectiveness and cost-utility of add-on, low-dose prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic, multicenter, placebo-controlled GLORIA trial.

BACKGROUND: The GLORIA placebo-controlled trial found a favorable balance of benefit and harm for two years of prednisolone (5 mg/day) as add-on treatment for rheumatoid arthritis (RA) patients aged 65+. This study evaluated the cost-effectiveness of low-dose prednisolone in the treatment of RA. METHODS: The economic evaluation had a societal perspective with a time horizon of two years. Cost data were collected with questionnaires and from recorded events, and valued with standard Dutch unit prices of 2017. The primary effectiveness outcome was the disease activity score in 28 joints (DAS28). For cost-utility, quality-adjusted life years (QALYs) were estimated from the EuroQol-5 Dimension (EQ-5D) questionnaire. Bootstrapping assessed the uncertainty around the average differences in costs and health outcomes. RESULTS: In total, 444 of 451 randomized patients were included in the modified intention-to-treat analysis. Patients had median four active comorbidities at baseline. Mean total costs over two years were k€10.8 in the prednisolone group, k€0.5 (95% CI -4.0; 1.8) lower than in the placebo group. Total direct medical costs were k€0.5 (95% CI -4.0; 1.5) lower in the prednisolone group. The mean number of QALYs was similar in both groups (difference 0.02 [-0.03; 0.06] in favor of prednisolone). The DAS28 was 0.38 lower in the prednisolone group than in the placebo group (0.19; 0.56). CONCLUSION: With greater effectiveness (DAS28) at non-significantly lower costs, low-dose, add-on prednisolone is cost-effective for RA compared to placebo over two years. QALYs were equal in both groups, most likely due to the impact of multiple comorbidities.

[18F]Sodium Fluoride PET has the potential to identify active formation of calcinosis cutis in limited cutaneous systemic sclerosis.

OBJECTIVES: Calcinosis cutis affects 20-40% of patients with systemic sclerosis (SSc). When calcinosis cutis becomes clinically apparent, it is irreversible in most cases. Detection of active calcification formation might allow early disease-modifying interventions. We assessed the feasibility of visualizing active calcifications using [18F]Sodium Fluoride ([18F]NaF) PET/low-dose CT (LDCT) in SSc patients with calcinosis cutis. METHODS: In this cross-sectional, observational pilot study patients underwent a whole body [18F]NaF PET/LDCT. All patients met the 2013 ACR/EULAR SSc criteria and had clinically detectable calcinosis cutis. (Sub)cutaneous calcifications were described by three investigators. RESULTS: Nine female patients were included (median age 59.0 years [IQR 51.5-70.5]). [18F]NaF uptake was mostly visible in the fingers (n=7) and knees (n=5). [18F]NaF PET showed calcifications in the fingers of 3 patients where calcifications were undetected on LDCT and in the clinic. Ninety-seven percent of [18F]NaF positive lesions was visible on LDCT. Of all lesions visible on LDCT, 70% was also visible on [18F]NaF PET. CONCLUSION: Imaging of active calcifications in SSc is feasible using [18F]NaF PET/LDCT. Seventy percent of calcifications on LDCT were [18F]NaF PET positive. Although these findings require replication, [18F]NaF PET/LDCT may detect active calcification formation, being potentially suitable for early disease-modifying interventions.

Clinical findings are not helpful in detecting lentigo maligna melanoma in patients with biopsy-proven lentigo maligna.

BACKGROUND: Lentigo maligna (LM) based on biopsy material might be lentigo maligna melanoma (LMM) after excision. OBJECTIVES: Investigate whether clinical and dermoscopic mapping increases the detection rate of LMM when investigating staged excision specimens of biopsy proven LM. METHODS: Patients with biopsy-proven LM planned for staged excision were included. Using clinical inspection and dermoscopy, spots suspicious for LMM were marked. After the excision, needles were placed at the marked spots. Histological examination using vertical sections was done at the needles followed by the standard amount of vertical sections. RESULTS: In 28 of the 58 biopsy-proven LM, there was clinical suspicion of LMM, only 3 of these 28 cases were upgraded into LMM. These three cases showed LMM in other sections, whereas only 1 case showed LMM around the needle. Within the group without clinical suspicion of LMM, 2 cases were LMM. Biopsy-proven LM were in fact LMM in 8.6% of the cases and were found without the clinical guidance of the dermatologist. CONCLUSIONS: 8.6% of the biopsy-proven LM were LMM after complete histological examination. In this study, the dermatologist was not able to increase the detection rate of LMM by using clinical and dermoscopic mapping.

Time motion study to evaluate the impact of flattening filter free beam on overall treatment time for frameless intracranial radiosurgery using Varian TrueBeam® linear accelerator.

BACKGROUND: The aim was to study the impact of the flattening filter free (FFF) beam on overall treatment time for frameless intracranial radiosurgery using TrueBeam® LINAC.The development of frameless stereotactic radiosurgery (SRS) is possible due to the incorporation of image guidance in the delivery of treatment. It is important to analyze the cost and benefits of FFF beams for treating SRS by understanding the impact of FFF beams in reducing the treatment time. MATERIALS AND METHODS: Dynamic conformal arc (DCA ) and volumetric arc therapy (VMAT) plans were generated using 6 MV with a flattening filter (FF) and FFF beams. Overall treatment time was divided into beam on time (BOT) and beam off time (BFT). Percentage beam on time reduction (PBOTR) and Percentage total time reduction (PTTR) factors were defined for the comparison. RESULTS: BOT reduction was observed to be significant for higher dose per fraction but subjected to the treatment technique and modulation differences. PBOTR values are much higher than PTTR values. The 39.9% of PBOTR resulted in only 8% PTTR for DCA and 65.3% resulted in 15.9% PTTR for VMAT. CONCLUSION: Major BFT was utilized for imaging and verification. FFF beam significantly reduced the beam on time and was found to be most effective if the fractional dose was as high as that for SRS. Newly defined PBOTR and PTTR factors are very useful indicators to evaluate the efficacy of FFF beams in terms of time reduction.

A feasibility study on two tailored interventions to improve adherence in adults with haemophilia.

INTRODUCTION: Haemophilia is a congenital bleeding disorder mainly affecting males. To prevent bleeding, patients need to perform regular intravenous injections (prophylaxis) throughout life. Non-adherence often occurs. Problems with acceptance or self-management appear to be the main reasons for non-adherence in haemophilia. The aim of this study was to test the feasibility and effects of two interventions focussed on acceptance (face-to-face) and self-management (online). METHODS: Patients with severe haemophilia and acceptance or self-management problems were eligible. The face-to-face group intervention was based on Acceptance and Commitment Therapy (ACT) (8 sessions/6 months, target N = 8 participants). The online intervention was based on a successful online programme in rheumatoid arthritis (5-8 modules/2 months, target N = 8). Both interventions were designed according to the MRC framework in collaboration with the patient society and experts. We compared adherence (VERITAS-Pro, optimum 0), quality of life (SF-36, optimum 100) and illness perception (BIPQ, optimum 0) before start (T0) and after 2 months (T2). Feasibility criteria were as follows: completion of training by > 50% of participants and ability to collect at least 80% of outcome parameters. RESULTS: The face-to-face intervention was feasible (89% enrolment and recruitment, 100% retention). One hundred percent of the outcome parameters was collected. Results were promising: although adherence (VERITAS-Pro) was stable (from 64 to 62 points), quality of life (SF-36) showed a clinically relevant improvement (> 5 points) in five of eight domains. Illness perception (BIPQ) showed a clinically relevant increase from 47 to 39 points. Patient evaluation was positive. The online intervention, however, was infeasible: enrolment was only 20% (6/30). Only three patients signed informed consent (recruitment 10%), and none completed more than one module (retention 0%). Consequently, the online intervention was terminated. CONCLUSION: The face-to-face acceptance intervention was considered feasible with promising results. Unfortunately, the online intervention was infeasible and therefore terminated. These findings suggest that adapting effective interventions to other settings does not guarantee success, despite the use of established methodology and patient participation. Population differences (only male participants, congenital disease) could be an explanation for failure of the online intervention in haemophilia despite success in rheumatoid arthritis. TRIAL REGISTRATION: NL55883.041.16.

[Is COVID-19 a hype?] / Is covid-19 een hype?

The answer to the question whether COVID-19 is a hype or not depends on how we define a hype. The article loosely builds on philosophical discussions about hypes in knowledge work and information sciences. The central idea is to make clear that hypes always imply a certain overload of information and that the paradoxical outcome of this that it is not just information that is piling up but also disinformation. It is argued that it is in this sense (and only in this sense) that COVID-19 is a hype. How we respond to this hype depends very strongly on subjective sensitivities towards both information and desinformation.

Biodegradable versus titanium osteosynthesis in maxillofacial traumatology: a systematic review with meta-analysis and trial sequential analysis.

Titanium osteosynthesis is currently the fixation system of choice in maxillofacial traumatology. Biodegradable osteosynthesis systems have the ability to degrade in the human body. The aim of this study was to conduct a systematic review, with meta- and trial sequential analyses, to assess the efficacy and morbidity of biodegradable versus titanium osteosynthesis after maxillofacial trauma. MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials and prospective and retrospective controlled studies. Five time periods were studied: perioperative, short-term (0-4 weeks), intermediate (6-12 weeks), long-term (>12 weeks), and overall follow-up. After screening 3542 records, 24 were included. All had a high risk of performance and detection bias due to the nature of the interventions. Meta-analysis showed no differences in efficacy or morbidity between biodegradable and titanium osteosynthesis. The risk of perioperative screw breakage was significantly higher (risk ratio 17.13, 95% confidence interval 2.19-34.18) and the symptomatic plate removal rate lower in the biodegradable group (risk ratio 0.11, 95% confidence interval 0.02-0.57), which was confirmed by the trial sequential analysis. The quality of evidence ranged from very low to moderate. Based on the narrative review and meta-analyses, current evidence shows that biodegradable osteosynthesis is a viable alternative to titanium osteosynthesis when applied in the treatment of maxillofacial trauma, with similar efficacy but significantly lower symptomatic plate removal rates. Perioperative screw breakage occurred significantly more often in the biodegradable group compared to the titanium group.

Out-of-Field Dose Calculation by a Commercial Treatment Planning System and Comparison by Monte Carlo Simulation for Varian TrueBeam®.

PURPOSE: The calculation accuracy of treatment planning systems (TPSs) drops drastically when the points outside the field edges are considered. The real accuracy of a TPS and linear accelerator (linac) combination for regions outside the field edge is a subject which demands more study. In this study, the accuracy of out-of-field dose calculated by a TPS, used with a TrueBeam® (TB) linac, is quantified. MATERIALS AND METHODS: For dose calculation, Eclipse™ version 13.7 commissioned for TB machine was used. For comparison, Monte Carlo (MC) methods, as well as the measurements, were used. The VirtuaLinac, a Geant 4-based MC program which is offered as a cloud solution, is used for the generation of input phase-space (PS) files. This PS file was imported into PRIMO (PENELOPE based MC program) for the simulation of out-of-field dose. RESULTS: In this study, the accuracy of the out-of-field dose calculated by a TPS for a TB linac was estimated. As per the results in comparison with MC simulations, the TPS underestimated the dose by around 45% on an average for the off-axis-distance range considered in this study. As the off-axis distance increased, the underestimation of the dose also increased. CONCLUSION: In this work, it was observed that the TPS underestimates doses beyond the edges of treatment fields for a clinical treatment executed on a TB machine. This indicates that the out-of-field dose from TPSs should only be used with a clear understanding of the inaccuracy of dose calculations beyond the edge of the field.

Fgf8a mutation affects craniofacial development and skeletal gene expression in zebrafish larvae.

Craniofacial development is tightly regulated and therefore highly vulnerable to disturbance by genetic and environmental factors. Fibroblast growth factors (FGFs) direct migration, proliferation and survival of cranial neural crest cells (CNCCs) forming the human face. In this study, we analyzed bone and cartilage formation in the head of five dpf fgf8ati282 zebrafish larvae and assessed gene expression levels for 11 genes involved in these processes. In addition, in situ hybridization was performed on 8 and 24 hours post fertilization (hpf) larvae (fgf8a, dlx2a, runx2a, col2a1a). A significant size reduction of eight out of nine craniofacial cartilage structures was found in homozygous mutant (6-36%, P<0.01) and heterozygous (7-24%, P<0.01) larvae. Also, nine mineralized structures were not observed in all or part of the homozygous (0-71%, P<0.0001) and heterozygous (33-100%, P<0.0001) larvae. In homozygote mutants, runx2a and sp7 expression was upregulated compared to wild type, presumably to compensate for the reduced bone formation. Decreased col9a1b expression may compromise cartilage formation. Upregulated dlx2a in homozygotes indicates impaired CNCC function. Dlx2a expression was reduced in the first and second stream of CNCCs in homozygous mutants at 24 hpf, as shown by in situ hybridization. This indicates an impairment of CNCC migration and survival by fgf8 mutation.

Randomized clinical trial of endovenous laser ablation versus direct and indirect radiofrequency ablation for the treatment of great saphenous varicose veins.

BACKGROUND: The current treatment strategy for many patients with varicose veins is endovenous thermal ablation. The most common forms of this are endovenous laser ablation (EVLA) and radiofrequency ablation (RFA). However, at present there is no clear consensus on which of these treatments is superior. The objective of this study was to compare EVLA with two forms of RFA: direct RFA (dRFA; radiofrequency-induced thermotherapy) and indirect RFA (iRFA; VNUS ClosureFast™). METHODS: Patients with symptomatic great saphenous vein (GSV) incompetence were randomized to receive EVLA, dRFA or iRFA. Patients were followed up at 2 weeks, 6 and 12 months. The primary outcome was GSV occlusion rate. Secondary outcomes included Venous Clinical Severity Score (VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ) score and adverse events. RESULTS: Some 450 patients received the allocated treatment (EVLA, 148; dRFA, 152; iRFA, 150). The intention-to-treat analysis showed occlusion rates of 75·0 (95 per cent c.i. 68·0 to 82·0), 59·9 (52·1 to 67·7) and 81·3 (75·1 to 87·6) per cent respectively after 1 year (P = 0·007 for EVLA versus dRFA, P < 0·001 for dRFA versus iRFA, P = 0·208 for EVLA versus iRFA). VCSS improved significantly for all treatments with no significant differences between them. AVVQ scores also improved significantly for all treatments, but iRFA had significantly better scores than dRFA at 12 months. Significantly more adverse events were reported after treatment with EVLA (103) than after dRFA (61) and iRFA (65), especially more pain. CONCLUSION: Primary GSV occlusion rates were better after iRFA and EVLA than dRFA. All three interventions were effective in improving the clinical severity of varicose veins at 1 year.

Complications of locking and non-locking plate systems in mandibular fractures.

This systematic review and meta-analysis was performed to critically assess the methodological quality of the existing systematic reviews, and to evaluate the postoperative complications of the mandibular fractures treated with locking and non-locking plate systems. An electronic search was conducted in PubMed, Embase, Web of Science, Cochrane library's electronic databases and grey literate using a combination of Medical Subject Heading terms and key words, until September 2018. No restrictions were applied to the search strategy. In total, three relevant systematic reviews were included, and the quality of these studies was low. A total of 33 studies (20 randomized studies and 13 non-randomized studies) were included in this systematic review, and 16 of them were included in meta-analysis. Most of the included randomized studies had an unclear risk of bias (Cochrane Collaboration); the quality of non-randomized studies ranged between 6 and 17 (Methodological Index for Non-Randomized Studies - MINORS). Based on the results of our meta-analysis, we conclude that locking plates are superior only with respect to the need for mandibulomaxillary fixation (MMF) in the early postoperative period.

Substitution of low-risk skin cancer hospital care towards primary care: A qualitative study on views of general practitioners and dermatologists.

BACKGROUND: Rising healthcare expenditures places the potential for substitution of hospital care towards primary care high on the political agenda. As low-risk basal cell carcinoma (BCC) care is one of the potential targets for substitution of hospital care towards primary care the objective of this study is to gain insight in the views of healthcare professionals regarding substitution of skin cancer care, and to identify perceived barriers and potential strategies to facilitate substitution. METHODS: A qualitative study was conducted consisting of 40 interviews with dermatologists and GPs and three focus groups with 18 selected GPs with noted willingness regarding substitution of skin cancer care. The interviews and focus groups focused on general views, perceived barriers and potential strategies to facilitate substitution of skin cancer care, using predefined topic lists. All sessions were audio-taped, transcribed verbatim and analyzed using the program AtlasTi. RESULTS: GPs were generally positive regarding substitution of skin care whereas dermatologists expressed more concerns. Lack of trust in GPs to adequately perform skin cancer care and a preference of patients for dermatologists are reported as barriers by dermatologists. The main barriers reported by GPs were a lack of confidence in own skills to perform skin cancer care, a lack of trust from both patients and dermatologists and limited time and financial compensation. Facilitating strategies suggested by both groups mainly focused on improving GPs' education and improving the collaboration between primary and secondary care. GPs additionally suggested efforts from dermatologists to increase their own and patients' trust in GPs, and time and financial compensation. The selected group of GPs suggested practical solutions to facilitate substitution focusing on changes in organizational structure including horizontal referring, outreach models and practice size reduction. CONCLUSIONS: GPs and, to lesser extent, dermatologists are positive regarding substitution of low-risk BCC care, though report substantial barriers that need to be addressed before substitution can be further implemented. Aside from essential strategies such as improving GPs' skin cancer education and time and financial compensation, rearranging the organizational structure in primary care and between primary and secondary care may facilitate effective and safe substitution of low-risk BCC care.

Recurrence rates of cutaneous squamous cell carcinoma of the head and neck after Mohs micrographic surgery vs. standard excision: a retrospective cohort study.

BACKGROUND: Recurrent cutaneous squamous cell carcinoma (cSCC) has been associated with an increased risk of local functional and aesthetic comorbidity, metastasis and mortality. OBJECTIVES: To compare the risk of recurrence between Mohs micrographic surgery (MMS) and standard excision for cSCC of the head and neck. METHODS: This was a retrospective cohort study of all patients with a cSCC treated with MMS or standard excision at the departments of dermatology of a secondary or tertiary care hospital in the Netherlands between 2003 and 2012. To detect all recurrences, patients were linked to the Dutch pathology registry. To compare the risk of recurrence between MMS and standard excision, hazard ratios (HRs) were used adjusted for clinical tumour size > 2 cm and deep tumour invasion. RESULTS: A total of 579 patients with 672 cSCCs were included: 380 cSCCs were treated with MMS and 292 with standard excision. The risk of recurrence was 8% (22 of 292) after standard excision during a median follow-up of 5·7 years [interquartile range (IQR) 3·5-7·8], which was higher than the 3% (12 of 380) after MMS during a median follow-up of 4·9 years (IQR 2·3-6·0). The cumulative incidence of recurrence was higher for standard excision than for MMS during the entire follow-up period of 8·6 years. Carcinomas treated with MMS were at a three times lower risk of recurrence than those treated with standard excision when adjusted for tumour size and deep tumour invasion (adjusted HR 0·31, 95% confidence interval 0·12-0·66). CONCLUSIONS: MMS might be superior to standard excision for cSCCs of the head and neck because of a lower rate of recurrence.

Recurrence of periocular basal cell carcinoma and squamous cell carcinoma after Mohs micrographic surgery: a retrospective cohort study.

BACKGROUND: Despite the widespread use of Mohs micrographic surgery (MMS) for periocular basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) - together called keratinocyte carcinoma (KC) - follow-up data regarding recurrences are limited. OBJECTIVES: To investigate the recurrence rate for periocular KCs after MMS and to describe our experience with interdisciplinary collaborations. METHODS: Patients with periocular KCs treated with MMS between 2006 and 2016 in a tertiary MMS referral hospital were included in this retrospective cohort study. Descriptive statistics were used to describe the MMS procedure-related characteristics. Using follow-up data from the electronic patient records and linkage with the Dutch nationwide network and registry of histopathology and cytopathology on 30 June 2017, the recurrence rate was evaluated and calculated using a cumulative incidence curve. RESULTS: In total, 683 (93·7%) periocular BCCs and 46 (6·3%) SCCs were treated with MMS. Three-quarters (n = 549) were primary tumours and the majority were located at the medial canthus or lower eyelid (n = 649, 89·0%). In 505 MMS procedures (69·3%) an oculoplastic surgeon participated, and in 63 patients (8·6%) a plastic surgeon performed the reconstruction. After a median follow-up of 46 months the recurrence rate was 3·0%, based on 22 recurrences (20 BCCs and two SCCs). CONCLUSIONS: MMS is an excellent treatment option for periocular KCs, with a low recurrence rate. Due to this specific anatomical location an interdisciplinary approach should pre-eminently be considered.