Healthcare visits for new neurodevelopmental problems before and during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic disrupted healthcare delivery. We hypothesized that children with neurodevelopmental problems would have reduced healthcare utilization during the pandemic compared to before the pandemic. METHODS: We conducted a population-based study of healthcare visits for new neurodevelopmental problems among children ages 0-6 years in Ontario, Canada. Our outcome measure was rate per 1000 children-months for healthcare visits for new neurodevelopmental problems. We compared changes in monthly rates before and during the pandemic using interrupted time series analysis (ITSA). RESULTS: The rate of new neurodevelopmental problems before the pandemic was 6.31 per 1000 children-months and during the pandemic was 6.58 per 1000 children-months. However, using ITSA, there were no differences in monthly rates of healthcare visits for new neurodevelopmental problems before and during the pandemic. The observed rate during the first 30 days of the pandemic dropped to 3.40 per 1000 children-months. CONCLUSION: We found no significant difference in rates of healthcare visits for new neurodevelopmental problems before and during the pandemic. There was a decrease in the number of visits during the first 30 days of the pandemic compared to all months prior. IMPACT: This study found no significant difference in rates of healthcare visits for new neurodevelopmental problems before and during the pandemic. There was a decrease in the number of visits during the first 30 days of the pandemic compared to all months prior. This study adds information on healthcare access for children during the COVID-19 pandemic. The rapid deployment of virtual healthcare delivery in Ontario, Canada may explain the fast recovery of healthcare utilization for children with neurodevelopmental problems.

Impact of performance and information feedback on medical interns' confidence-accuracy calibration.

Diagnostic errors are a major, largely preventable, patient safety concern. Error interventions cannot feasibly be implemented for every patient that is seen. To identify cases at high risk of error, clinicians should have a good calibration between their perceived and actual accuracy. This experiment studied the impact of feedback on medical interns' calibration and diagnostic process. In a two-phase experiment, 125 medical interns from Dutch University Medical Centers were randomized to receive no feedback (control), feedback on their accuracy (performance feedback), or feedback with additional information on why a certain diagnosis was correct (information feedback) on 20 chest X-rays they diagnosed in a feedback phase. A test phase immediately followed this phase and had all interns diagnose an additional 10 X-rays without feedback. Outcome measures were confidence-accuracy calibration, diagnostic accuracy, confidence, and time to diagnose. Both feedback types improved overall confidence-accuracy calibration (R2No Feedback = 0.05, R2Performance Feedback = 0.12, R2Information Feedback = 0.19), in line with the individual improvements in diagnostic accuracy and confidence. We also report secondary analyses to examine how case difficulty affected calibration. Time to diagnose did not differ between conditions. Feedback improved interns' calibration. However, it is unclear whether this improvement reflects better confidence estimates or an improvement in accuracy. Future research should examine more experienced participants and non-visual specialties. Our results suggest that feedback is an effective intervention that could be beneficial as a tool to improve calibration, especially in cases that are not too difficult for learners.

School-based health care: improving academic outcomes for inner-city children-a prospective cohort quasi-experimental study.

BACKGROUND: We examined whether a school-based health center model improved academic achievement compared to usual care. METHODS: This was a quasi-experimental prospective cohort study. The primary outcome was an academic achievement. In addition, we analyzed sociodemographic characteristics and their relationship to academic achievement, and the wait time for a developmental assessment. RESULTS: The differences in change of grades over time (from 2016/2017 to 2018/2019) were small for reading (-0.83, 95% CI -3.48, 1.82, p = 0.51), writing (-1.11, 95% CI -3.25, 1.03, p = 0.28), and math (0.06, 95% CI -3.08, 2.94, p = 0.98). The experimental arm's average wait time for developmental assessment was 3.4 months. CONCLUSION: In this small, quasi-experimental prospective cohort study, we did not find evidence that our SBHC model improved academic achievement; however, the wait time at the SBHCs was considerably less than the provincial wait time for a developmental assessment. TRIAL REGISTRATION: NCT04540003. IMPACT: This study describes a unique and innovative school-based health center model. Our findings support the benefits of school-based health centers in diagnosing and treating children with developmental and mental health disorders for disadvantaged communities. This study did not find an improvement in academic achievement for school-based health center users. This study found that the wait time to developmental assessment was shorter for school-based health center users compared to the wait time reported in the community. Pandemic-associated school disruptions have highlighted the importance of accessible school-based health services for children requiring mental health and developmental assessments and care.

Operative time, length of stay and reoperation rates for orthognathic surgery.

Orthognathic surgery improves quality of life in terms of oral function and facial aesthetics. Our aim was to establish and compare operative time and length of inpatient stay for orthognathic procedures, and to assess the reoperation rate. Departmental electronic data base was used to identify all patients undergoing orthognathic surgery in a single unit between the 01/01/2016 and the 01/08/2018. 251 patients were identified who underwent 409 orthognathic surgery procedures. The mean operating time for a bimaxillary osteotomy (n=107) was 139.3 min. For single jaw procedures, the mean operating time for a Le Fort I osteotomy (n= 42) was 82.2 min and for a bilateral sagittal split osteotomy (BSSO) (n= 102) was 80.3min. Bimaxillary osteotomy combined with genioplasty (n=17) this increased the operating time on average by 31 min. and of a BSSO combined with a genioplasty (n=14) by 27 mins. The mean postoperative hospital stay was 1.2 ± 0.2 days. 96.4% patients spent only one postoperative night in hospital. 6/251 (2.4%) patients required re-operation. In regression analysis, age was the only significant factor in increasing length of stay (p<0.008), 95% CI 0.03-0.2). Our review shows short operating times and postoperative inpatient stays in a large cohort of patients undergoing orthognathic surgery. This is combined with a low reoperation rate. This may point to a patient benefit from high volume orthognathic centres.

Process mapping and Lean principles applied to orthognathic surgery.

Process mapping in industry is a well-established tool to improve efficiency. It is defined as a quality improvement technique that breaks down a process, or task, into its individual components, or steps, then analyses it. Lean principles are used to reduce waste and produce consistently good outcomes. Improving the operative efficiency of orthognathic surgery has many benefits. There is increasing demand for this complex surgery, and patients have appropriately high expectations with relation to their outcome. There are also increasing pressures for hospitals to reduce costs. In a recent paper by our group (Bowe et al, in press), we have published operating times for orthognathic procedures that are significantly shorter than in previously available series, with an average time for a bimaxillary osteotomy of 2 hours and 19 mins. Through observation of the senior authors' uniform technique, refined from experience of over 2,000 cases, a bimaxillary osteotomy was broken down into individual steps, all arranged in a process-mapped template with which to increase efficiency and results. We show here the multiple small operative efficiencies we have developed, and the Lean surgical principles which we use. This has enabled us to reduce the operative time of these common procedures, without compromising outcomes. This study presents an approach to process map bimaxillary orthognathic operations and shows how the application of Lean principles improves operative efficiency, and produces consistent results.

Sentinel lymph node biopsy for melanoma of the head and neck: a multicentre study to examine safety, efficacy, and prognostic value.

Sentinel lymph node biopsy (SLNB) is an accurate staging procedure for malignant melanoma but its use in patients with melanoma of the head and neck has been questioned in the past because of a perceived record of poor safety and accuracy. Technical improvements have sought to redress this. Vital structures and variable lymphatic pathways can make its use in the head and neck challenging. In our study we have examined the data and the experiences of clinicians from University Hospital Southampton and the Royal Surrey County Hospital. We retrospectively analysed the data and case notes of 143 patients who had SLNB to establish its safety, efficacy, and prognostic value. The detection rate of at least one sentinel lymph node was 100%. Nodes positive for metastatic melanoma were found in 20% of patients. Of them, 76% went on to have completion lymphadenectomy. Multivariate Cox regression analysis suggested that positive SLNB was a strong predictor of reduced overall survival for all Breslow-thickness melanomas (HR=3.9, p=0.019) and intermediate melanomas (HR=6.3, p=0.007). It predicted reduced recurrence-free survival for all melanomas (HR=7.4, p<0.001) and was a strong predictor for those of intermediate thickness (HR=8.3, p<0.001). The false negative rate was 9.4% and false omission rate 2.6%. Temporary and permanent morbidity rates were 2.1% and 0%, respectively. SLNB for melanoma in the head and neck is a safe, accurate staging procedure that offers prognostically useful information. The upstaging of disease allows access to trial-based targeted treatments.

Loss of orofacial tissue secondary to septic shock caused by Streptococcus pneumoniae.

Purpura fulminans is a rare complication of septic shock with a high mortality. It can result in a severe loss of skin, and often amputation of limbs. Managing the loss of tissue is a challenge that requires a multidisciplinary approach.

Familial adenomatous polyposis: not all masses are desmoids.

Familial adenomatous polyposis (FAP) is a multi-system disease characterised by the development of hundreds to thousands of colorectal adenomas which inevitably progress to carcinoma without treatment. It is commonly associated with extra colonic lesions including osteomas, epidermoid cysts and desmoid tumours. Desmoid tumours are troublesome due to their size and bulk and are a significant cause of morbidity and mortality in FAP. This series highlights three cases in which patients with FAP developed masses thought initially to be manifestations of the condition. Further investigation in fact demonstrated neurofibromatosis type 1 in all three patients. All masses in FAP patients cannot be assumed to be disease related (desmoid, osteoma, epidermoid cyst or carcinoma).

Identification of a terminal ileum carcinoid tumour during bowel screening colonoscopy - should terminal ileoscopy be performed as best practice?

The UK National Bowel Cancer Screening Programme invites men and women aged between 60 - 74 years old to be routinely screened every 2 years. A 90% caecal intubation rate or intubation of the terminal ileum is considered to be the best practice means of identifying completeness. This case report describes how terminal ileal intubation carried out during a routine screening colonoscopy led to the identification and treatment of a carcinoid tumour. Despite evidence for improving colonic diagnoses, completion of colonoscopy by passing through the ileocaecal valve is not performed routinely due to the perceived difficulty of the manoeuvre. With practice, ileoscopy has been shown to be achievable in at least 85% of routine colonoscopies and contributes significantly to quality assurance and to the diagnostic yield.

Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2.

Failure of remyelination is largely responsible for sustained neurologic symptoms in multiple sclerosis (MS). MS lesions contain hyaluronan deposits that inhibit oligodendrocyte precursor cell (OPC) maturation. However, the mechanism behind this inhibition is unclear. We report here that Toll-like receptor 2 (TLR2) is expressed by oligodendrocytes and is up-regulated in MS lesions. Pathogen-derived TLR2 agonists, but not agonists for other TLRs, inhibit OPC maturation in vitro. Hyaluronan-mediated inhibition of OPC maturation requires TLR2 and MyD88, a TLR2 adaptor molecule. Ablated expression of TLR2 also enhances remyelination in a lysolecithin animal model. Hyaluronidases expressed by OPCs degrade hyaluronan to hyaluronan oligomers, a requirement for hyaluronan/TLR2 signaling. MS lesions contain both TLR2(+) oligodendrocytes and low-molecular-weight hyaluronan, consistent with their importance to remyelination in MS. We thus have defined a mechanism controlling remyelination failure in MS where hyaluronan is degraded by hyaluronidases into hyaluronan oligomers that block OPC maturation and remyelination through TLR2-MyD88 signaling.

Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.

To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.

Thymidine phosphorylase expression and stromal vascularity in ductal carcinoma in situ of the breast.

AIMS: Periductal angiogenesis in ductal carcinoma in situ is associated with an increased risk of subsequently developing a recurrence. This study aimed to (1) identify the relation between periductal and stromal vascularity and recurrence and (2) determine whether thymidine phosphorylase (TP) is associated with angiogenesis or recurrence in ductal carcinoma in situ (DCIS). METHODS: Twenty cases of DCIS that did not subsequently recur, 20 that developed a subsequent in situ recurrence, and 12 that developed a subsequent invasive recurrence were investigated. Periductal and stromal (hotspot) microvessel density were determined quantitatively using antibodies to CD34 and von Willebrandt factor (vWF). TP expression by DCIS was assessed semiquantitatively using the H score method. RESULTS: Stromal and periductal microvessel density assessed by anti-vWF gave similar mean values, and showed a strong positive correlation. When angiogenesis was assessed with anti-CD34 this association was lost. Not only were the mean values for both types of microvessel density higher than those obtained with anti-vWF, but the periductal microvessel density was significantly greater than the stromal microvessel density. TP expression was associated with stromal microvessel density assessed with anti-vWF, but not with anti-CD34. TP expression was not related to recurrence. No significant difference was identified in TP expression or stromal vascularity in DCIS between cases that recurred as DCIS and those that recurred as invasive carcinoma. CONCLUSIONS: Recurrent in situ or invasive disease after excision of DCIS does not appear to be related to stromal microvessel density or to TP expression by DCIS cells.

Age-dependent myelin degeneration and proteolysis of oligodendrocyte proteins is associated with the activation of calpain-1 in the rhesus monkey.

Myelin provides important insulating properties to axons allowing for propagation of action potentials over large distances at high velocity. Disruption of the myelin sheath could therefore contribute to cognitive impairment, such as that observed during the normal aging process. In the present study, age-related changes in myelin, myelin proteins and oligodendrocyte proteins were assessed in relationship to calpain-1 expression and cognition in the rhesus monkey. Isolation of myelin fractions from brain white matter revealed that as the content of the intact myelin fraction decreased with age, there was a corresponding increase in the floating or degraded myelin fraction, suggesting an increased breakdown of intact myelin with age. Of the myelin proteins examined, only the myelin-associated glycoprotein decreased with age. Levels of the oligodendrocyte-specific proteins 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin/oligodendrocyte-specific protein (MOSP) increased dramatically in white matter homogenates and myelin with age. Age-related increases in degraded CNPase also were demonstrable in white matter in association with increases in activated calpain-1. Degraded CNPase was also detectable in myelin fractions, with only the floating fraction containing activated calpain-1. The increases in the activated enzyme in white matter were much greater than those found in myelin fractions suggesting a source other than the myelin membrane for the marked overexpression of activated calpain-1 with age. In addition, CNPase was demonstrated to be a substrate for calpain in vitro. In summary, changes in myelin and oligodendrocyte proteins occur with age, and they appear to have a significant relationship to cognitive impairment. The overexpression of CNPase and MOSP suggests new formation of myelin by oligodendrocytes, which may occur in response to myelin degradation and injury caused by proteolytic enzymes such as calpain.

Angiogenesis and invasive recurrence in ductal carcinoma in situ of the breast.

The development of an invasive recurrence following treatment for ductal carcinoma in situ (DCIS) converts a non-fatal disease to one associated with mortality. To date, no pathological or molecular features have been found to predict for the type of recurrence. Previous studies have suggested that in DCIS angiogenesis may be an important factor in determining the transformation from in situ to invasive carcinoma. We looked at 355 cases of DCIS and found that 32 had subsequently developed recurrent disease. In these 32 cases and in matched controls, periductal vascular density was determined using morphometry and anti-endothelial antibodies, von Willebrand factor (vWF) and CD34. Vascular density was related to the risk of both invasive and in situ recurrence. Normal lobules at least 2 mm away were used as controls. Differences in the phenotype of individual blood vessels was detected by performing dual staining immunofluorescence on selected cases. The microvessel density (MVD), as detected with the CD34 antibody, was higher around foci of DCIS than around normal breast lobules (P=0.001). Furthermore, it was significantly higher in cases of DCIS that recurred (P<0.0001). The findings with the vWF antibody were less clear cut and suggested a trend in decreasing MVD with increasingly aggressive disease. Dual immunofluorescence staining shows that the increase in MVD seen around DCIS is due to an increase in CD34+/vWF-blood vessels. An increase in CD34+/vWF-of blood vessels may be able to predict cases of DCIS that are at a high risk of developing a recurrence.

Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast.

Up to 50% of recurrences of ductal carcinoma in situ of the breast are associated with invasive carcinoma but no pathological or molecular features have yet been found to predict for the development of invasive disease. For a tumour to invade, it requires the formation of new blood vessels. Previous studies have described a vascular rim around ducts involved by ductal carcinoma in situ, raising the possibility that the characteristics of periductal vascularisation may be important in determining transformation from in situ to invasive disease. Periductal vascular density and phenotype were determined using morphometry and a panel of anti-endothelial antibodies (von Willebrand factor, CD31, CD141 and CD34) and related to the presence of invasive carcinoma and other histological features. Compared to normal lobules, pure ductal carcinoma in situ exhibited a greater density of CD34+ and CD31+ vessels but a decrease in those that were immunopositive for vWF, indicating a difference in phenotype and in density. Ductal carcinoma in situ associated with invasive carcinoma showed a profile of vascular immunostaining similar to that of pure ductal carcinoma in situ but there were significantly greater numbers of CD34+ and CD141+ vessels and fewer staining for vWF. There was a significant negative correlation between vascular density and both the cross-sectional areas of the ducts involved and the extent of the necrosis of the tumour they contained. A correlation between vascular density and nuclear grade was also noted, being highest in the intermediate grade. The greater density of CD34+ and CD141+ vessels around ductal carcinoma in situ associated with invasive carcinoma could reflect a greater predisposition to invade but a direct effect of co-existent invasive carcinoma cannot entirely be ruled out in the present study. The relationship between vascular density, grade, duct size and nuclear grade suggests that periductal angiogenesis increases with tumour growth rate but is unable to keep pace with the most rapidly growing lesions.