The intensity of awake bruxism episodes is increased in individuals with high trait anxiety.

OBJECTIVES: Trait anxiety is associated with an increased occurrence of awake bruxism episodes, a behavior characterized by clenching of the teeth contributing to temporomandibular disorders in some individuals. Here we measured the activity of the masseter and the intensity and duration of spontaneous wake-time tooth clenching episodes in healthy individuals with different levels of trait anxiety (TA). MATERIALS AND METHODS: Two hundred fifty-five individuals completed a web survey. Using their TA scores, we allocated them in low (< 20th percentile of the TA score distribution), intermediate (between 20th and 80th ), and high (> 80th) TA groups. We analyzed the electromyographic (EMG) activity of the right masseter during a 15-min silent reading task in forty-three individuals with low (n = 12), intermediate (n = 17), and high TA (n = 14). We tested between-group differences in EMG activity of the masseter, as well as postural activity-the muscular activity that maintains mandibular posture, and amplitude and duration of spontaneous tooth clenching episodes. RESULTS: The activity of the masseter (mean ± SEM %maximum voluntary contraction/MVC) was greater in the high TA (10.23 ± 0.16%MVC) than the intermediate (8.49 ± 0.16%MVC) and low (7.97 ± 0.22%MVC) TA groups (all p < 0.001). Postural activity did not differ between groups (all p > 0.05). The EMG amplitude of tooth clenching episodes was greater in the high TA (19.97 ± 0.21 %MVC) than the intermediate (16.40 ± 0.24%MVC) and low (15.48 ± 0.38 %MVC) TA groups (all p < 0.05). The cumulative duration of clenching episodes was not different between groups (p = 0.390). CONCLUSIONS: Increased TA is associated with both increased masseter muscle activity and intensity of wake-time tooth clenching episodes. CLINICAL RELEVANCE: TA may contribute significantly to masticatory muscle overload.

Increased somatosensory amplification is associated with decreased pressure pain thresholds at both trigeminal and extra-trigeminal locations in healthy individuals.

BACKGROUND: The diagnosis of temporomandibular disorders (TMD) is based on patient history and physical examination, and may require medical imaging. Masticatory muscle palpation is essential to make a diagnosis of TMD. However, the response of masticatory muscles to mechanical pressure stimuli depends on many physical and psychological factors. OBJECTIVE: This study aimed at determining the impact of somatosensory amplification (SSA)-an estimate of somatic awareness and bodily hypervigilance-on pressure pain thresholds (PPTs) measured at both trigeminal and extra-trigeminal locations in healthy individuals. METHODS: PPTs were measured at the right anterior temporalis and superficial masseter, and the thenar eminence of the right hand in one hundred healhty individuals (69F, 31M), divided in three groups based on their SSA scores: low (N = 32), intermediate (N = 34) and high (N = 34). General linear models were used to test between-group differences in PPTs including sex as a covariate. The level of significance was set at P < .05. RESULTS: Individuals with high SSA had lower PPTs at the anterior temporalis than individuals with low (P = .006) and intermediate (P = .001) SSA. No significant between-group differences were found in PPTs measured at the masseter (P = .372). PPTs measured at the thenar eminence were significantly lower in the high than the low SSA group (P = .009). Females had lower PPTs at the masseter than males (P = .021) but not at other muscle locations (all P > .05). CONCLUSION: Increased somatosensory amplification is associated with decreased pressure pain thresholds at both trigeminal and extra-trigeminal locations in healthy individuals. SSA could be a potential confounder while diagnosing TMD and evaluating treatment outcomes.

Effects of trait anxiety, somatosensory amplification, and facial pain on self-reported oral behaviors.

OBJECTIVES: Oral behaviors are activities, like gum chewing, teeth clenching, and biting of objects, that go beyond normal functioning demands and contribute to the onset of temporomandibular disorders (TMD). Somatosensory amplification refers to the tendency to experience somatic sensations as intense, noxious, and disturbing and is related to bodily hypervigilance. Clinical experience suggests that individuals with bodily hypervigilance also present with occlusal hypervigilance and continuously check their occlusion. This study aimed at investigating whether somatosensory amplification and trait anxiety, a characteristic correlated with hypervigilance, are associated with a greater incidence of oral behaviors, and verifying how self-reported facial TMD pain affect this relationship. MATERIALS AND METHODS: The State-Trait Anxiety Inventory, the Somatosensory Amplification Scale, the Oral Behavior Checklist (OBC), and the TMD-Pain Screener Questionnaire were filled out by 255 University students with self-reported facial TMD pain (PAIN group; 47 subjects, 24.8 ± 4.2 years) and without pain (CTR group; 208 subjects, 26.0 ± 4.8 years) using a web survey. RESULTS: Trait anxiety, somatosensory amplification, and OBC scores were greater in the PAIN than CTR group (all p < 0.05). Trait anxiety and somatosensory amplification were positively associated with the frequency of oral behaviors, as measured with the OBC (all p < 0.05). A significant effect of the interaction study group*trait anxiety (p = 0.028) on OBC scores was found. CONCLUSIONS: Individuals with greater trait anxiety and somatosensory amplification report more frequent oral behaviors. The relationship between anxiety and oral behaviors is affected by concurrent facial pain. CLINICAL RELEVANCE: Individuals with increased trait anxiety and concurrent facial pain report more frequent oral behaviors than those without pain. Clinicians should evaluate patients' anxiety and somatosensory amplification before starting dental treatment.

Sample size calculations for randomized clinical trials published in anesthesiology journals: a comparison of 2010 versus 2016.

PURPOSE: Although every randomized clinical trial (RCT) needs participants, determining the ideal number of participants that balances limited resources and the ability to detect a real effect is difficult. Focussing on two-arm, parallel group, superiority RCTs published in six general anesthesiology journals, the objective of this study was to compare the quality of sample size calculations for RCTs published in 2010 vs 2016. METHODS: Each RCT's full text was searched for the presence of a sample size calculation, and the assumptions made by the investigators were compared with the actual values observed in the results. Analyses were only performed for sample size calculations that were amenable to replication, defined as using a clearly identified outcome that was continuous or binary in a standard sample size calculation procedure. RESULTS: The percentage of RCTs reporting all sample size calculation assumptions increased from 51% in 2010 to 84% in 2016. The difference between the values observed in the study and the expected values used for the sample size calculation for most RCTs was usually > 10% of the expected value, with negligible improvement from 2010 to 2016. CONCLUSION: While the reporting of sample size calculations improved from 2010 to 2016, the expected values in these sample size calculations often assumed effect sizes larger than those actually observed in the study. Since overly optimistic assumptions may systematically lead to underpowered RCTs, improvements in how to calculate and report sample sizes in anesthesiology research are needed.

Primary Assessment of the Patient With Orbital Fractures Should Include Pupillary Response and Visual Acuity Changes to Detect Occult Major Ocular Injuries.

PURPOSE: Sight-threatening injuries associated with orbital fractures are of major concern to maxillofacial surgeons whom are often the first asked to assess these patients. Eliciting signs and symptoms that are predictive of these injuries would allow expedited ophthalmic consultation and appropriate management. We hypothesized that abnormal pupillary response is predictive of major ocular injuries. PATIENTS AND METHODS: A retrospective cohort study of patients with facial fractures was instituted with review of all associated ophthalmic injuries. The primary predictor variables were the presence or absence of post-traumatic ocular symptoms and signs (visual acuity change, diplopia, flashes and floaters, pain on globe movement, abnormal pupillary response, restriction of eye movement, and visual field defects). Secondary predictors were pattern of fracture and mechanism of fracture. The primary outcome variable was the presence or absence of major ocular injury assessed during formal ophthalmology consultation. Descriptive statistics were calculated as categorical values. Correlation between the presence or absence of predictors and outcome (major ocular injury) was calculated using χ2 analysis, with the significance value set at P ≤ .01. RESULTS: The study included 75 patients (25% of whom were female patients) with a mean age of 41 ± 22 years. We recorded 165 minor ocular injuries and 43 major ocular injuries. The mechanisms of injury included assault (48%, n = 36), motor vehicle accident (21%, n = 16), fall (17%, n = 13), sport (11%, n = 8), and occupational (3%, n = 2). The fracture pattern included zygomaticomaxillary (36%, n = 27), isolated orbital floor (25%, n = 19), complex (20%, n = 15), and isolated orbital nonfloor (19%, n = 14). Of the primary outcome predictors, only abnormal pupillary response (odds ratio, 36; P < .001) and subjective visual acuity changes (odds ratio, 10; P < .001) were predictive of major ocular injury. The mechanism of injury and pattern of fracture were not predictive of major ocular injury. CONCLUSIONS: During primary assessment of the patient with orbital fractures, abnormal pupillary response and subjective visual acuity changes are key predictors of occult major ocular injury.

The degree of adherence to CONSORT reporting guidelines for the abstracts of randomised clinical trials published in anaesthesia journals: A cross-sectional study of reporting adherence in 2010 and 2016.

BACKGROUND: Abstracts are intended to be concise summaries of the entire randomised clinical trial (RCT). Despite their importance, few studies have examined the reporting quality of abstracts in the anaesthesiology literature. OBJECTIVES: To examine the quality of RCT abstract reporting according to the CONSORT for Abstracts guidelines and determine whether recommended items omitted from the abstract were present in the body of the article. DESIGN: A cross-sectional study of RCTs. SETTING: This study was performed at the University of Western Ontario and University Hospital, London Health Sciences Centre. PARTICIPANTS: All RCTs meeting inclusion criteria that were published in 2010 or 2016 in six general anaesthesiology journals (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia and European Journal of Anaesthesiology). MAIN OUTCOME MEASURES: The 16 checklist items from the CONSORT for Abstracts statement were used to create a convenience score as a proxy for RCT abstract reporting quality, with each criterion measured as being reported in abstract, not reported in abstract but reported in full-text article, or not reported in abstract or full-text article. RESULTS: Of the 395 RCTs identified, 219 were published in 2010 and 176 were published in 2016. Out of the maximum possible score of 16, the median abstract score increased from 4 points [interquartile range (IQR): 3 to 5] in 2010 to 6 points [IQR: 5 to 8] in 2016. Although most checklist items showed improvement from 2010 to 2016, around 75% of RCTs in 2016 met fewer than half of the 16 items with no RCTs reporting all 16 items in the abstract. A majority of the RCTs had the information present in the full-text. In 2016, only 71 out of 176 (40%) of RCTs reported outcomes conforming to the CONSORT guidelines (with an effect size and a confidence interval around the effect size) in the Abstract. CONCLUSION: Abstracts for many anaesthesiology RCTs are incomplete selective summaries of the entire article.

Comparison of Registered and Reported Outcomes in Randomized Clinical Trials Published in Anesthesiology Journals.

BACKGROUND: Randomized clinical trials (RCTs) provide high-quality evidence for clinical decision-making. Trial registration is one of the many tools used to improve the reporting of RCTs by reducing publication bias and selective outcome reporting bias. The purpose of our study is to examine whether RCTs published in the top 6 general anesthesiology journals were adequately registered and whether the reported primary and secondary outcomes corresponded to the originally registered outcomes. METHODS: Following a prespecified protocol, an electronic database was used to systematically screen and extract data from RCTs published in the top 6 general anesthesiology journals by impact factor (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and European Journal of Anaesthesiology) during the years 2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents was performed (in duplicate) to identify eligible RCTs. An adequately registered trial was defined as being registered in a publicly available trials registry before the first patient being enrolled with an unambiguously defined primary outcome. For adequately registered trials, the outcomes registered in the trial registry were compared with the outcomes reported in the article, with outcome discrepancies documented and analyzed by the type of discrepancy. RESULTS: During the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to be adequately registered (12%). The proportion of adequately registered trials increased over time, with 38% of RCTs being adequately registered in 2015. The most common reason in 2015 for inadequate registration was registering the RCT after the first patient had already been enrolled. Among adequately registered trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42% of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at least 1 secondary outcome discrepancy. CONCLUSIONS: Despite trial registration being an accepted best practice, RCTs published in anesthesiology journals have a high rate of inadequate registration. While mandating trial registration has increased the proportion of adequately registered trials over time, there is still an unacceptably high proportion of inadequately registered RCTs. Among adequately registered trials, there are high rates of discrepancies between registered and reported outcomes, suggesting a need to compare a published RCT with its trial registry entry to be able to fully assess the quality of the study. If clinicians base their decisions on evidence distorted by primary outcome switching, patient care could be negatively affected.

Myocardial Hypertrophic Remodeling and Impaired Left Ventricular Function in Mice with a Cardiac-Specific Deletion of Janus Kinase 2.

The Janus kinase (JAK) system is involved in numerous cell signaling processes and is highly expressed in cardiac tissue. The JAK isoform JAK2 is activated by numerous factors known to influence cardiac function and pathologic conditions. However, although abundant, the role of JAK2 in the regulation or maintenance of cardiac homeostasis remains poorly understood. Using the Cre-loxP system, we generated a cardiac-specific deletion of Jak2 in the mouse to assess the effect on cardiac function with animals followed up for a 4-month period after birth. These animals had marked mortality during this period, although at 4 months mortality in male mice (47%) was substantially higher compared with female mice (30%). Both male and female cardiac Jak2-deleted mice had hypertrophy, dilated cardiomyopathy, and severe left ventricular dysfunction, including a marked reduction in ejection fractions as assessed by serial echocardiography, although the responses in females were somewhat less severe. Defective cardiac function was associated with altered protein levels of sarcoplasmic reticulum calcium-regulatory proteins particularly in hearts from male mice that had depressed levels of SERCA2 and phosphorylated phospholamban. In contrast, SERCA2 was unchanged in hearts of female mice, whereas phosphorylated phospholamban was increased. Our findings suggest that cardiac JAK2 is critical for maintaining normal heart function, and its ablation produces a severe pathologic phenotype composed of myocardial remodeling, heart failure, and pronounced mortality.

Applicability of the Greulich and Pyle bone age standards to Taiwanese children: A Taipei experience.

BACKGROUND: The Greulich and Pyle (GP) method is one of the most common radiographic techniques for bone age (BA) assessment. The applicability of this method to ethnic populations outside of the United States has been investigated in several recent studies worldwide. Currently, limited data are available on the accuracy of the GP method for the Taiwanese population. The purpose of this study was to determine whether the GP standards are applicable to contemporary Taipei children. METHODS: Clinical data from October 1, 2010, to March 31, 2020, were retrospectively collected from a general hospital in Taipei. BA was determined by a senior pediatrician and was reviewed by a senior pediatric radiologist according to the GP standards. Comparison of BA and chronological age (CA) was performed in children with body weight and height in the 15th to the 85th percentiles of normal children. Ethnic variations in the maturation process in the ulnar bone were investigated. All data were statistically analyzed. RESULTS: In total, 2465 medical records were collected. After excluding those with diseases and unqualified data, 654 records of boys and 809 of girls were analyzed. In boys, the mean BA was significantly delayed between 6 and 9 years of age compared with the CA. In girls, the mean BA was generally advanced between 7 and 15 years of age. Ulnar bone maturation tended to be delayed in young boys. CONCLUSION: A significant discrepancy between CA and BA was observed in our population. Delayed ulnar bone maturation in young boys was confirmed. Children in Taipei exhibit a different maturation pattern than children on whom the GP standards were based.

Impact of Stress and Trait Anxiety on the Sensory and Jaw Motor Responses to a Tonic Orofacial Nociceptive Stimulus.

AIMS: To investigate how trait anxiety and stress jointly affect the sensory and jaw motor responses to a tonic orofacial nociceptive stimulus. METHODS: Orthodontic separators were placed between the first molars in 45 adults with low (n = 14), intermediate (n = 17), and high (n = 14) trait anxiety. Tooth pain, occlusal discomfort, tooth clenching (as a jaw motor behavior), and situational stress were measured three times a day for 5 days using visual analog scales. Mixed-effects regression models were used to evaluate the sensory and motor outcome measures. RESULTS: Pain, discomfort, and frequency of tooth-clenching trajectories were affected by trait anxiety (P = .007, P < .001, and P = .055, respectively) and stress (P < .001, P < .001, and P = .044, respectively). Individuals with high anxiety reported their highest pain (17.7 ± 2.9 mm) and discomfort (35.2 ± 4.1 mm) 24 hours earlier than those with low anxiety (pain: 15.9 ± 2.6 mm, discomfort: 28.8 ± 3.7 mm). Tooth clenching decreased progressively in response to the stimulus (P < .001). CONCLUSION: A tonic orofacial nociceptive stimulus triggers an avoidance jaw motor behavior. Both trait anxiety and situational stress heighten the sensory response to such a stimulus, but weakly affect the motor response to it.

Rhinovirus-associated dilated cardiomyopathy.

Rhinovirus is the main cause of the common cold. There is little to no published literature of rhinoviral associated myocarditis. We report a rare case of rhinovirus infection in a patient with myocarditis leading to dilated cardiomyopathy. Infection is an established cause of myocarditis. Prodromal "flu-like" symptoms in a young patient with unexplained heart failure should raise concern for viral myocarditis. Diagnosis is often made by clinical presentation and not by endomyocardial biopsy due to invasiveness. Polymerase chain reaction is a rapid test that supports the diagnosis and may elucidate the role of the virus in myocarditis. Defining causes and mechanisms leading to this severe cardiovascular condition may prove critical to targeted therapy. Physician should be aware that rhinovirus as a possible pathogen for severe myocarditis and dilated cardiomyopathy.

Recent pubertal timing trends in Northern Taiwanese children: Comparison with skeletal maturity.

BACKGROUND: International studies have reported an early age of onset of puberty in girls and boys. However, the current situation of puberty onset in Taiwanese children is unknown. In this study, the timing of menarche and pubertal change in testicular volume (TV) in Taiwanese children was examined, and bone age (BA) was used as an internal somatic maturity scale and compared with the chronological age (CA) at pubertal timing. METHODS: Clinical data from October 1, 2010, to March 31, 2018, were retrospectively collected from a general hospital in Taipei. The data of patients who were diagnosed with endocrine/genetic disorders were excluded. Clinical data included CA, timing of menarche, and X-ray images of TV and BA. BA was determined by a senior pediatrician and a senior pediatric radiologist. The reliability and validity of BA readings were tested. Collected data were analyzed statistically. RESULTS: Overall, TV records of 241 boys and the menarche timing data of 98 girls were collected from 1823 children. CA for menarche was 11.35 ± 1.06 years (mean ± SD), and BA for menarche was 12.95 ± 0.80 years. CA and BA at TV = 15 mL in male puberty was 12.32 ± 1.22 and 13.46 ± 0.68 years, respectively. A stronger correlation was observed between TV and BA than between TV and CA during the pubertal period. CONCLUSION: The secular trend of earlier puberty timing continues. The decline rate of menarche timing was approximately 0.43 years per decade in the past 30 years. Among boys, an advance of more than 1 year in pubertal timing age was observed over the past 20 years. BA and TV showed high correlation during puberty.

Effectiveness of High-Intensity Interval Training for Fitness and Mobility Post Stroke: A Systematic Review.

OBJECTIVE: To evaluate the evidence on the effectiveness of high-intensity interval training (HIIT) in improving fitness and mobility post stroke. TYPE: Systematic review. LITERATURE SURVEY: Medline, Embase, CINAHL, PsycINFO, and Scopus were searched for articles published in English up to January 2018. METHODOLOGY: Studies were included if the sample was adult human participants with stroke, the sample size was ≥3, and participants received >1 session of HIIT. Study and participant characteristics, treatment protocols, and results were extracted. SYNTHESIS: Six studies with a total of 140 participants met inclusion criteria: three randomized controlled trials and three pre-post studies. HIIT protocols ranged 20 to 30 minutes per session, 2 to 5 times per week, and 2 to 8 weeks in total. HIIT was delivered on a treadmill in five studies and a stationary bicycle in one study. Regarding fitness measures, HIIT produced significant improvements in peak oxygen consumption compared to baseline, but the effect was not significant compared to moderate intensity continuous exercise (MICE). Regarding mobility measures, HIIT produced significant improvements on the 10-Meter Walk Test (10MWT), 6-Minute Walk Test (6MWT), Berg Balance Scale (BBS), Functional Ambulation Categories (FAC), Timed Up and Go Test, and Rivermead Motor Assessment compared to baseline. The effect of HIIT was significant compared to MICE on the 10MWT and FAC but not on the 6MWT or BBS. CONCLUSIONS: There is preliminary evidence that HIIT may be an effective rehabilitation intervention for improving some aspects of cardiorespiratory fitness and mobility post stroke. LEVEL OF EVIDENCE: I.

Deprescribing benzodiazepines among hospitalised older adults: quality improvement initiative.

Benzodiazepines are recognised as being potentially inappropriate medications for seniors due to their considerable side-effect profile, yet they are commonly prescribed and infrequently discontinued (deprescribed). The study's primary objective was the deprescription or the dose reduction of benzodiazepines among newly hospitalised seniors using a patient education intervention. A 3-month duration quality improvement study based on the plan-do-study-act model was conducted across two units (3C and 4D) in the Glenrose Rehabilitation Hospital to improve benzodiazepine deprescribing among newly admitted seniors (65 years or older) who were using benzodiazepines. The primary outcome measure was the number of eligible patients who had benzodiazepine deprescribing initiated. A patient education intervention comprising a structured medication review, written patient education (the Eliminating Medications Through Patient Ownership of End Results (EMPOWER) brochure) and at least one brief supportive counselling session by the clinical pharmacist or physician was applied to all eligible patients. All 12 eligible patients consented to benzodiazepine deprescribing; however, only 11 of them (92%) initiated benzodiazepine deprescribing. Six of the 11 patients (55%) had their benzodiazepines discontinued, with the 5 remaining patients (45%) achieving greater than 50% dosage reduction. Seven patients (64%) experienced side effects during the deprescribing process, with over half (57%, n=4) of these seven patients experiencing worsening anxiety symptoms. Five of the 11 patients (45%) required benzodiazepine substitute medications. The use of a structured patient education intervention involving the use of a structured medication review, written patient education material and one-on-one patient counselling can promote benzodiazepine deprescribing. Although worsening anxiety was frequently observed, this was easily managed by the substitution of a more appropriate and clinically indicated medication, which was well tolerated and acceptable by all of our participants. Targeted screening for the presence of anxiety would help to guide the deprescribing process and the need for medication substitution.

Botulinum Toxin Conditioning Enhances Motor Axon Regeneration in Mouse and Human Preclinical Models.

BACKGROUND: Peripheral axon regeneration is improved when the nerve lesion under consideration has recently been preceded by another nerve injury. This is known as the conditioning lesion effect (CLE). While the CLE is one of the most robust and well characterized means to enhance motor axon regeneration in experimental models, it is not considered a clinically feasible strategy. A pharmacological means to re-produce the CLE is highly desirable. OBJECTIVE: To test whether chemodenervation with a clinical grade formulation of botulinum toxin A (BoTX) would be sufficient to reproduce the CLE. METHODS: We examined the effects of a 1-week preconditioning administration of BoTX on motor axon regrowth in both a mouse tibial nerve injury and human embryonic stem cell (hESC)-based model. We assessed neuronal reinnervation in vivo (mice) with retrograde tracers and histological analysis of peripheral nerve tissue after injections into the triceps surae muscle group. We assessed motor neuron neurite outgrowth in vitro (hESC) after incubation in BoTX by immunohistochemistry and morphometric analysis. RESULTS: We found that BoTX conditioning treatment significantly enhanced outgrowth of both murine motor axons in vivo and human MN neurites in vitro. CONCLUSIONS: BoTX preconditioning represents a pharmacological candidate approach to enhance motor axon regeneration in specific clinical scenarios such as nerve transfer surgery. Further studies are needed to elucidate the molecular mechanism.

Advancement of global health: key messages from the Disease Control Priorities Project.

The Disease Control Priorities Project (DCPP), a joint project of the Fogarty International Center of the US National Institutes of Health, the WHO, and The World Bank, was launched in 2001 to identify policy changes and intervention strategies for the health problems of low-income and middle-income countries. Nearly 500 experts worldwide compiled and reviewed the scientific research on a broad range of diseases and conditions, the results of which are published this week. A major product of DCPP, Disease Control Priorities in Developing Countries, 2nd edition (DCP2), focuses on the assessment of the cost-effectiveness of health-improving strategies (or interventions) for the conditions responsible for the greatest burden of disease. DCP2 also examines crosscutting issues crucial to the delivery of quality health services, including the organisation, financial support, and capacity of health systems. Here, we summarise the key messages of the project.

When Is Evidence Enough Evidence? A Systematic Review and Meta-Analysis of the Trabectome as a Solo Procedure in Patients with Primary Open-Angle Glaucoma.

The purpose of this systematic review and meta-analysis was to examine the availability of evidence for one of the earliest available minimally invasive glaucoma surgery (MIGS) procedures, the Trabectome. Various databases were searched up to December 20, 2016, for any published studies assessing the use of the Trabectome as a solo procedure in patients with primary open-angle glaucoma (POAG). The standardized mean differences (SMD) were calculated for the change in intraocular pressure (IOP) and number of glaucoma mediations used at 1-month, 6-month, and 12-month follow-up. After screening, three studies and one abstract with analyzable data were included. The meta-analysis showed statistically significant reductions in IOP and number of glaucoma medications used at all time points. Though the Trabectome as a solo procedure appears to lower IOP and reduces the number of glaucoma medications, more high-quality studies are required to make definitive conclusions. The difficulty of obtaining evidence may be one of the many obstacles that limit a full understanding of the potential safety and/or efficacy benefits compared to standard treatments. The time has come for a thoughtful and integrated approach with stakeholders to determine optimal access to care strategies for our patients.

The pathway to RCTs: how many roads are there? Examining the homogeneity of RCT justification.

BACKGROUND: Randomized controlled trials (RCTs) form the foundational background of modern medical practice. They are considered the highest quality of evidence, and their results help inform decisions concerning drug development and use, preventive therapies, and screening programs. However, the inputs that justify an RCT to be conducted have not been studied. METHODS: We reviewed the MEDLINE and EMBASE databases across six specialties (Ophthalmology, Otorhinolaryngology (ENT), General Surgery, Psychiatry, Obstetrics-Gynecology (OB-GYN), and Internal Medicine) and randomly chose 25 RCTs from each specialty except for Otorhinolaryngology (20 studies) and Internal Medicine (28 studies). For each RCT, we recorded information relating to the justification for conducting RCTs such as average study size cited, number of studies cited, and types of studies cited. The justification varied widely both within and between specialties. RESULTS: For Ophthalmology and OB-GYN, the average study sizes cited were around 1100 patients, whereas they were around 500 patients for Psychiatry and General Surgery. Between specialties, the average number of studies cited ranged from around 4.5 for ENT to around 10 for Ophthalmology, but the standard deviations were large, indicating that there was even more discrepancy within each specialty. When standardizing by the sample size of the RCT, some of the discrepancies between and within specialties can be explained, but not all. On average, Ophthalmology papers cited review articles the most (2.96 studies per RCT) compared to less than 1.5 studies per RCT for all other specialties. CONCLUSIONS: The justifications for RCTs vary widely both within and between specialties, and the justification for conducting RCTs is not standardized.

MUC1 mediates transendothelial migration in vitro by ligating endothelial cell ICAM-1.

MUC1 is a transmembrane glycoprotein expressed by normal breast epithelium and virtually all breast cancers. MUC1 is normally restricted to the apical surface of epithelia and loss of this polarized distribution in breast carcinomas is associated with lymph node metastasis. Our previous work found that MUC1 can bind intercellular adhesion molecule-1 (ICAM-1), mediating adhesion of breast cancer cells to a simulated blood vessel wall, and also triggering a calcium-based signal in the MUC1-bearing cells. It is possible that the depolarized membrane distribution of MUC1 in breast carcinomas may facilitate interactions with stromal/endothelial ICAM-1 leading to adhesion and subsequent migration through the vessel wall. In the current study, we provide evidence that ICAM-1 can influence the migration of cells that express endogenous or transfected MUC1. Migration across a gelatin-coated Transwell membrane could be increased in a step-wise manner by the sequential addition of ICAM-1-expressing cells (endothelial cells and fibroblasts), and ICAM-1-inducing inflammatory cytokines (tumour necrosis factor-alpha and interleukin-1 beta). Antibodies against MUC1 or ICAM-1, but not a control antibody, could abrogate migratory increases. Cells that did not express MUC1 were unresponsive to ICAM-1. Our current findings build on our earlier work, by suggesting that the end result of the MUC1/ICAM-1-mediated cell-cell adhesion and calcium-based signal is migration. This has implications for the exit of circulating tumour cells from the vasculature, as well as tumour cell migration through fibroblast-containing stroma underlying the endothelial wall.