Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

BACKGROUND: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals. AIM: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice. METHODS: A micro-costing approach for SARS-CoV-2 WGS was conducted. Data on IPC management resource use and costs were collected from interviews with IPC teams from 14 participating sites and used to assign cost estimates for IPC activities as collected in the trial. Activities included IPC-specific actions following a suspicion of healthcare-associated infection (HAI) or outbreak, as well as changes to practice following the return of data via SRT. FINDINGS: The mean per-sample costs of SARS-CoV-2 sequencing were estimated at £77.10 for rapid and £66.94 for longer turnaround phases. Over the three-month interventional phases, the total management costs of IPC-defined HAIs and outbreak events across the sites were estimated at £225,070 and £416,447, respectively. The main cost drivers were bed-days lost due to ward closures because of outbreaks, followed by outbreak meetings and bed-days lost due to cohorting contacts. Actioning SRTs, the cost of HAIs increased by £5,178 due to unidentified cases and the cost of outbreaks decreased by £11,246 as SRTs excluded hospital outbreaks. CONCLUSION: Although SARS-CoV-2 WGS adds to the total IPC management cost, additional information provided could balance out the additional cost, depending on identified design improvements and effective deployment.

Endodontic implications of a patient with arteriovenous malformation: a case report and literature review.

AIM: To present the endodontic management of a patient diagnosed with a high-flow arteriovenous malformation (AVM) requiring root canal treatment and to discuss the relevant endodontic literature for this rare but significant problem. SUMMARY: AVM is a complex communication of an artery and a vein in which the oxygenated blood is forced away from the intended tissue. The incidence of its occurrence in the face and neck is rare, and when present, the most common sign is gingival bleeding. Arteriovenous malformation is both a diagnostic and therapeutic challenge for dentists. Also, there is ambiguity regarding the precautions to be taken whilst doing endodontic procedures in such cases. Hence, there is a need to understand the disease process and its implications in order to prevent life-threatening complications during treatment. This case report highlights the successful endodontic management of a cariously exposed right maxillary second premolar in a patient diagnosed with high-flow AVM. On an orthopantomogram, the AVM was spreading in the left submandibular space involving the left ramus area. The clinical findings of limited mouth opening with inter-appointment swelling and trismus during treatment made the case unusual and challenging. This paper addresses the current understanding of the classification, diagnosis, clinical features and endodontic management, together with specific guidelines and recommendations whilst performing endodontic procedures in AVM cases. KEY LEARNING POINTS: The classification and oral manifestations of AVM must be known and understood. Practitioners should be aware of the radiographic appearance of AVM. Recommended precautions should be taken when carrying out restorative and endodontic procedures in a patient with AVM. Antibiotic prophylaxis may be considered before endodontic treatment in a patient with AVM. Multidisciplinary treatment planning may be required.

Association between concentration of active MMP-9 in pulpal blood and pulpotomy outcome in permanent mature teeth with irreversible pulpitis - a preliminary study.

AIM: To investigate the correlation between the concentration of active-matrix metalloproteinases-9 (aMMP-9) in pulpal blood and the outcome of pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis (SIP). METHODOLOGY: Forty permanent molar teeth with a clinical diagnosis of SIP and normal apical tissues with periapical index (PAI) score ≤ 2 and ten permanent teeth (8 molars and two premolars) with a diagnosis of normal pulp that required root canal treatment for prosthetic reasons from patients between the ages of 15-35 years were recruited. All clinical procedures were performed under local anaesthesia and rubber dam isolation. After access opening, the coronal pulp tissue was amputated up to the canal orifice. A 100 µL volume of the pulpal blood was collected using a micropipette and transported to the laboratory. Sodium hypochlorite (2.5 %) was used as a haemostatic agent, and mineral trioxide aggregate (MTA) was used as the pulp capping material. The tooth was restored with composite at the same visit. Teeth with normal pulps were treated with single-visit root canal treatment. Patients with pulpotomy were recalled at 6 and 12 months. Outcome assessment of teeth with pulpotomy was carried out at 12 months and was categorized as success (asymptomatic patients with PAI score ≤ 2) or failure (symptomatic patients or PAI score ≥ 3). Quantification of aMMP-9 in pulpal blood was achieved using a fluorometric assay. The following statistical analyses were performed to assess the data: t-test, Fisher's exact test, kappa coefficient, non-parametric test, Wilcoxon rank-sum test, Spearman rank correlation test and receiver operating characteristic curve (ROC). RESULT: The success rate of pulpotomy was 88 % at 12-months. There was a significant difference between the median concentrations of aMMP-9 in pulpal blood of teeth with normal pulps (52 (12-96) ng mL-1 :) and SIP (193.3 (25.8-607.7) ng mL-1 :) (P = 0.0003) and successful (132.3 (25.8-548.3) ng mL-1 :) and failed cases (512.4 (334.8-607.7 ng mL-1 :) (P = 0.0015) of MTA pulpotomy. A significant association was established between aMMP-9 concentration and outcome of pulpotomy. The area under the receiver operating characteristics curve (0.9484, 95%CI) suggested excellent discriminatory power of aMMP-9 concentration in pulpal blood to predict the pulpotomy outcome. CONCLUSION: The pulpal blood concentration of aMMP-9 was significantly associated with the outcome of pulpotomy in teeth with symptomatic irreversible pulpitis, where it may be used as a potential prognostic biomarker.

Safety and efficacy of superior calyceal access versus inferior calyceal access for pelvic and/or lower calyceal renal calculi- a prospective observational comparative study.

OBJECTIVE: To compare efficacy and safety between superior calyceal access and inferior calyceal access for pelvic and/or lower calyceal renal stones. METHODS: Consecutive patients presenting with Pelvic and/or inferior calyceal renal calculi were allocated to the superior calyceal access (group 1) or inferior calyceal access (group 2) treatment arm. Allocation of treatment access was based on the surgeon's preference. Variables studied included stone free rate, operating time, intraoperative and postoperative complications. Statistical analysis was executed using SPSS, Version 16.0. The statistical significance was evaluated at 5% level of significance (p value < 0.05). RESULTS: Between July 2018 and February 2019, 63 patients were included in each group. The percutaneous inserted guidewire entered the ureter in 92% in group1 and 74.6% in group 2 (p = 0.034). Stone fragments migrated to the middle calyx in 3.2% in group1 and 9.5% in group 2 (p = 0.033). A second puncture was required in one patient in group 1 and in 5 patients in group 2 (p = 0.04). The operative duration (minutes) was 13.46 ± 1.09 in the group 1 while 16.58 ± 1.44 in the group 2 (p = 0.002). Thoracic complications (hydropneumothorax) occurred to 2 patients in superior calyceal access group managed with intercostal tube drainage (p = 0.243).Post operatively blood transfusion was required in two patients in group 2 (p = 0.169). Angioembolization was done in one patient among the inferior calyceal access approach (p = 0.683). Complete stone clearance assessed at 3 months was 96.8% in group 1 and 85.7% in group 2 (p = 0.046). CONCLUSIONS: Superior calyceal access is a safe and most efficacious in terms of achieving complete stone clearance rate with reduced operative time, minimal blood loss, less need for a second puncture and auxiliary procedures at minimal complications. STUDY REGISTRATION: Clinical trials registry - INDIA; CTRI/2018/07/014,687.

Exploration of a new model of care in a psychiatry unit.

The model established at Orillia Soldiers Memorial Hospital involves family physicians as the most responsible physician. They act as "admission gatekeeper" for all unattached patients who are admitted to the psychiatry in-patient unit. A PubMed, EBSCO, OVID Medline, Embase, CINAHL, and Web of Science database review of the last 10 years (2006-2016) was undertaken. A satisfaction survey was undertaken. An intensive literature review found this model to be unique. The model has proved to be extremely efficient and cost-effective.

The validity and reproducibility of cross table radiographs compared with CT scans for the measurement of anteversion of the acetabular component after total hip arthroplasty.

AIMS: The aim of this study was to assess the reproducibility and validity of cross table radiographs for measuring the anteversion of the acetabular component after total hip arthroplasty (THA) and to compare it with measurements using CT scans. PATIENTS AND METHODS: A total of 29 patients who underwent THA between June 2010 and January 2016 were included. There were 17 men and 12 women. Their mean age was 43 years (26 to 65). Seven patients underwent a bilateral procedure. Thus, 36 THAs were included in the study. Lateral radiographs and CT scans were obtained post-operatively and radiographs repeated three weeks later. The anteversion of the acetabular component was measured using the method described by Woo and Morrey and the ischiolateral method described by Pulos et al and these were compared with the results obtained from CT scans. RESULTS: The mean anteversion was 18.35° (3° to 38°) using Woo and Morrey's method, 51.45° (30° to 85°) using the ischiolateral method and 21.22° (2° to 48°) using CT scans. The Pearson correlation coefficient was 0.754 for Woo and Morrey's method and 0.925 for the ischiolateral method. There was a linear correlation between the measurements using the ischiolateral method and those using CT scans. We derived a simple linear equation between the value of the CT scan and that of ischiolateral method to deduce the CT scan value from that of ischiolateral method and vice versa. CONCLUSION: The anteversion of the acetabular component measured using both plain radiographic methods was consistently valid with good interobserver reproducibility, but the ischiolateral method which is independent of pelvic tilt was more accurate. As CT is costly, associated with a high dose of radiation and not readily available, the ischiolateral method can be used for assessing the anteversion of the acetabular component. Cite this article: Bone Joint J 2017;99-B:1006-11.

Transforming activity and therapeutic targeting of C-terminal-binding protein 2 in Apc-mutated neoplasia.

Overexpression of the transcriptional coregulators C-terminal binding proteins 1 and 2 (CtBP1 and 2) occurs in many human solid tumors and is associated with poor prognosis. CtBP modulates oncogenic gene expression programs and is an emerging drug target, but its oncogenic role is unclear. Consistent with this oncogenic potential, exogenous CtBP2 transformed primary mouse and human cells to anchorage independence similarly to mutant H-Ras. To investigate CtBP's contribution to in vivo tumorigenesis, Apcmin/+ mice, which succumb to massive intestinal polyposis, were bred to Ctbp2+/- mice. CtBP interacts with adenomatous polyposis coli (APC) protein, and is stabilized in both APC-mutated human colon cancers and Apcmin/+ intestinal polyps. Ctbp2 heterozygosity increased the median survival of Apcmin/+ mice from 21 to 48 weeks, and reduced polyp formation by 90%, with Ctbp2+/- polyps exhibiting reduced levels of ß-catenin and its oncogenic transcriptional target, cyclin D1. CtBP's potential as a therapeutic target was studied by treating Apcmin/+ mice with the CtBP small-molecule inhibitors 4-methylthio-2-oxobutyric acid and 2-hydroxy-imino phenylpyruvic acid, both of which reduced polyposis by more than half compared with vehicle treatment. Phenocopying Ctbp2 deletion, both Ctbp inhibitors caused substantial decreases in the protein level of Ctbp2, as well its oncogenic partner ß-catenin, and the effects of the inhibitors on CtBP and ß-catenin levels could be modeled in an APC-mutated human colon cancer cell line. CtBP2 is thus a druggable transforming oncoprotein critical for the evolution of neoplasia driven by Apc mutation.

Chronic Administration of Anacetrapib Is Associated With Accumulation in Adipose and Slow Elimination.

Anacetrapib is a novel cholesteryl-ester transfer protein (CETP) inhibitor in late-stage clinical development, shown in preceding clinical trials to have residual pharmacological activity after prolonged washout after chronic dosing. Preclinical findings suggest that white adipose tissue is a potential depot and that accumulation into adipose tissue governs the long-term kinetics of anacetrapib in mice. A phase I study performed to test this hypothesis in humans revealed that plasma exposure was correlated with fat content in food administered with the drug. Plasma concentrations of anacetrapib seemed to reach plateau faster than adipose concentrations. Anacetrapib continued to accumulate in adipose during the treatment period despite apparent plateau in plasma with only minimal decline in adipose levels up to 1 year postdose. Because of its high lipophilicity, anacetrapib partitions into adipose tissue, this likely forms a drug reservoir that, in turn, contributes to the long residence time of the drug in plasma.

A review of chitosan and its derivatives in bone tissue engineering.

Critical-sized bone defects treated with biomaterials offer an efficient alternative to traditional methods involving surgical reconstruction, allografts, and metal implants. Chitosan, a natural biopolymer is widely studied for bone regeneration applications owing to its tunable chemical and biological properties. However, the potential of chitosan to repair bone defects is limited due to its water insolubility, faster in vivo depolymerization, hemo-incompatibility, and weak antimicrobial property. Functionalization of chitosan structure through various chemical modifications provides a solution to these limitations. In this review, current trends of using chitosan as a composite with other polymers and ceramics, and its modifications such as quaternization, carboxyalkylation, hydroxylation, phosphorylation, sulfation and copolymerization in bone tissue engineering are elaborated.

Do Congenitally Blind Individuals have Better Haptic Object Perception Compared to Blindfolded Sighted Individuals?

Objective: Haptic perceptual enhancement in congenitally blind people is a subject of intense debate. There is no consensus whether the congenitally blind get the benefit of their haptic experience or the sighted get the benefit of previous visual experience when it comes to recognizing objects by manual exploration using different constraints. The present study compared haptic object perception between congenitally blind and blindfolded sighted participants in a situation where manual exploration of objects was constrained. Methods: Thirty congenitally blind braille readers and 30 age and gender matched controls were studied. All participants were required to identify the objects haptically, without the aid of vision. Manual exploration of the objects was constrained by permitting touching of the object with only the exposed tip of the index finger with the aim to limit cues about material information. Performance was evaluated in terms of speed and accuracy with which objects were identified. Result: The recognition time analysis showed that congenitally blind participants recognize objects much faster than blindfolded sighted participants. The analysis of haptic recognition rates showed that congenitally blind participants identified the objects more accurately compared to blindfolded normal sighted individuals. Conclusion: Congenitally blind individuals appear to possess a definite enhanced haptic perceptual ability allowing for faster and more accurate recognition of objects even when manual exploration is constrained.

MRI of perianal fistulae: a pictorial kaleidoscope.

Perianal fistulae are an abnormal communication between the anorectum and the perianal skin. A seemingly benign condition, it can be a cause of considerable distress to the patient if it is not mapped out adequately before embarking upon surgical correction. The persistence of residual disease complicates and up-stages the grade of the remnant fistula with increased risk of anal incontinence following surgery secondary to damage to the anal sphincter complex. Magnetic resonance imaging (MRI) can play a critical role in mapping the fistulae tract in relation to the anal sphincter complex and hence, act as a reliable guide for the surgeon to chart the optimised management of perianal fistulae. This review illustrates the role of MRI in the imaging evaluation of perianal fistulae, to facilitate a well-planned surgical course.

Tell tale of tablets in bronchus.

Foreign body (FB) aspiration is an emergency of concern at all ages. However, in adults, it can present with atypical symptoms such as shortness of breath, wheezing or rarely cyanosis. Aspiration of oral medications is seen in the elderly population with impairment of protective airway mechanism. Treatment of choice is endoscopic removal of the foreign body. We report such a case of foreign body aspiration (potassium chloride tablet), diagnosed on imaging and subsequently developed bronchostenosis. There are a very few reported cases of oral potassium supplement aspiration and associated complications in the literature.

Intravenous albumin infusion is an effective therapy for hyponatremia in patient with malignant ascites.

There are few reports about the treatment of moderate to severe hyponatremia associated with malignant liver metastasis. Here, we report using intravenous salt poor albumin infusion to treat hypervolemic cirrhosis related hyponatremia. A 58-year-old female with ascites secondary to metastatic breast cancer was referred to our department with symptomatic hyponatremia (serum sodium concentration of 121 mEq/L). The serum sodium level was corrected slowly over 2 days with intravenous albumin infusion and the patient's symptoms - fatigue, nausea, dizziness and headache improved.