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The purpose of this study was to determine and compare the shear force (N) required to fracture or dislodge an all-ceramic zirconia-based crown using different luting cement with those of polycarbonate crown and strip crown for the primary anterior teeth in vitro. Study design: Four groups of esthetic restoration for primary anterior teeth were tested for fracture strength: 1) Fifteen all-ceramic zirconia-based crowns cemented with glass ionomer cement, 2) Fifteen all-ceramic zirconia-based crowns bonded with a self-adhesive resin cement, 3) Fifteen polycarbonate crowns cemented with a polymer reinforced zinc-oxide eugenol and 4) Fifteen resin strip crowns. All restorations were placed and cemented on reproductions of dies in an independent laboratory at Delhi, India. All samples underwent loading until fracture or dislodgement with the Universal Testing Machine. The force in Newton (N) required to produce failure was recorded for each sample and the type of failures was also noted and characterized. One-way analysis of variance (ANOVA) test and the Tukey and Scheffe’s post hoc comparisons were used for statistical analyses. Results: In this invitro study, results were measured in Newtons (N). Group 1 (410.9±79.5 N) and Group 2 (420.5±57.8 N) had higher fracture strength than Group 3 (330.3±85.6 N) and Group 4 (268.4±28.2 N). These differences were statistically significant at P≤.05 among the sample groups. No significant difference was found between groups 1 and 2 (P = 0.984) nor between groups 3 and 4 (P =0.104). Among type of failures, majority of restoration fractures for zirconia-based crowns and resin strip crowns were due to cohesive failures and polycarbonate crowns had predominantly mixed failures. Conclusions: Under the limitations of this in vitro study, it could be concluded that all-ceramic zirconia-based crowns attained the highest fracture strength among all restorative samples tested regardless of the type of luting agent employed (P

Autologous stem cell transplantation (ASCT) remains a key therapeutic strategy for treating patients with relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Clonal hematopoiesis (CH) has been proposed as a major contributor not only to the development of therapy-related myeloid neoplasms but also to inferior overall survival (OS) in patients who had undergone ASCT. Herein, we aimed to investigate the prognostic implications of CH after ASCT in a cohort of 420 lymphoma patients using ultra-deep, highly sensitive error-correction sequencing. CH was identified in the stem cell product samples of 181 patients (43.1%) and was most common in those with T-cell lymphoma (72.2%). The presence of CH was associated with a longer time to neutrophil and platelet recovery. Moreover, patients with evidence of CH had inferior 5-year OS from the time of first relapse (39.4% vs. 45.8%, p = .043) and from the time of ASCT (51.8% vs. 59.3%, p = .018). The adverse prognostic impact of CH was not due to therapy-related myeloid neoplasms, the incidence of which was low in our cohort (10-year cumulative incidence of 3.3% vs. 3.0% in those with and without CH, p = .445). In terms of specific-gene mutations, adverse OS was mostly associated with PPM1D mutations (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.13-2.67, p = .011). In summary, we found that CH is associated with an increased risk of non-lymphoma-related death after ASCT, which suggests that lymphoma survivors with CH may need intensified surveillance strategies to prevent and treat late complications.

BACKGROUND: Access to primary care outside of regular working hours is limited in many countries. This study investigates the relation between the after-hours premium, an incentive for primary care physicians to provide services after hours, and less-urgent visits to the emergency department in Ontario, Canada. METHODS: We analyzed a retrospective cohort of a random sample of Ontario residents from April 2002 to March 2006, and a subcohort of patients followed from April 2005 to March 2016. We linked patient and primary care physician data with emergency department visit data. We used fixed-effects regression models to analyze the association between the introduction of the after-hours premium, as well as subsequent increases in the value of the premium, and the number of monthly emergency department visits. RESULTS: The sample consisted of 586 534 patients between 2002 and 2006, and 201 594 patients from 2005 to 2016. After controlling for patient and physician characteristics, seasonality and time-invariant patient confounding factors, introduction of the after-hours premium was associated with a reduction of 1.26 less-urgent visits to the emergency department per 1000 patients per month (95% confidence interval −1.48 to −1.04). Most of this reduction was observed in after-hours visits. Sensitivity analysis showed that the monthly reduction in less-urgent visits to the emergency department was in the range of −1.24 to −1.16 per 1000 patients. Subsequent increases in the after-hours premium were associated with a small reduction in less-urgent visits to the emergency department. INTERPRETATION: Ontario’s experience suggests that incentivizing physicians to improve access to after-hours primary care reduces some less-urgent visits to the emergency department. Other jurisdictions may consider incentives to limit less-urgent visits to the emergency department.

In this review paper, the most recent research on intracerebral hemorrhage (ICH) is summarized and novel perspectives are offered on the pathomechanisms of ICH. These underlying pathomechanisms of ICH provide clues for development of novel drugs or drug target screening. Specifically, recent research has provided evidence that iron chelators, lipid peroxidation/ferroptosis inhibitors, agonists or antagonists of prostaglandin E2 receptors (EP1/3 or EP2), and nonsteroidal anti-inflammatory drugs protect against ICH-induced brain edema, secondary brain tissue damage as well as inhibition of the toxicity in related tissue damage products. This review will provide a theoretical basis for testing new compounds that may have potential for future clinical trials.

ImportanceInferior vena cava filters are commonly implanted and infrequently retrieved. Nonretrieval contributes to significant morbidity, motivating US Food and Drug Administration and multisociety communications emphasizing the need for improved device surveillance. Current guidelines suggest that implanting physicians and referring physicians should be responsible for device follow-up, but it is not known whether shared responsibility contributes to lower retrieval.ObjectiveTo determine if primary responsibility for follow-up care assumed by the implanting physician team is associated with increased device retrieval.Design, Setting, and ParticipantsThis retrospective cohort study examined a prospectively collected registry of patients with inferior vena cava filters implanted from June 2011 to September 2019. Medical record review and data analysis was completed in 2021. The study included 699 patients who underwent implantation of retrievable inferior vena cava filters at an academic quaternary care center.ExposuresPrior to 2016, implanting physicians had a passive surveillance strategy whereby letters highlighting indications for and the need for timely retrieval were mailed to patients and ordering clinicians. Starting in 2016, implanting physicians assumed active responsibility for surveillance, whereby candidacy for device retrieval was assessed periodically via phone calls and retrieval scheduled when appropriate.Main Outcomes and MeasuresThe main outcome was the odds of inferior vena cava filter nonretrieval. Within regression modeling of the association between the surveillance method and nonretrieval, additional covariates of patient demographics, concomitant malignant neoplasm, and presence of thromboembolic disease were included.ResultsOf the 699 patients who received retrievable filter implants, 386 (55.2%) were followed up with passive surveillance, 313 (44.8%) with active surveillance, 346 (49.5%) were female, 100 (14.3%) were Black individuals, and 502 (71.8%) were White individuals. The mean (SD) age at filter implantation was 57.1 (16.0) years. Mean (SD) yearly filter retrieval increased following the adoption of active surveillance, from 190 of 386 (48.7%) to 192 of 313 (61.3%) (P P Conclusions and RelevanceThe findings of this cohort study suggest that active surveillance by implanting physicians is associated with improved inferior vena cava filter retrieval. These findings support encouraging physicians who implant the filter to take primary responsibility for tracking and retrieval.

Autoimmune bullous diseases (AIBDs) are a group of skin-related disorders that involve damage to structures maintaining cell-cell adhesion, such as desmosomes and hemidesmosomes. Key autoimmune bullous diseases include pemphigus related diseases, pemphigoid related conditions, acquired epidermolysis bullosa (EBA), and dermatitis herpetiformis (DH). Each group of conditions exhibits characteristic clinical lesion patterns and is associated with specific autoantibodies targeting epidermal and dermal structures involved in cell-cell adhesion and skin integrity. Pemphigus diseases primarily target desmoglein (Dsg) 3 and Dsg1 proteins but several non-desmoglein autoantibodies have also been linked to pemphigus. Pemphigoid diseases typically target BP (bullous pemphigoid)180 and BP230; EBA is associated with antibodies directed against anti-type VII collagen; and DH by IgA autoantibodies against tissue transglutaminase and deaminated gliadin. Investigation into the serological biomarkers found in autoimmune bullous diseases have allowed the development of diagnostic assessments (ie. tissue antibody detection and serological testing) based on the unique autoantibody profiles of a particular disease group. The methods for the detection and quantification of disease-associated autoantibodies continue to evolve and improve.

Objective We investigated the diagnostic performance of semi-quantitative hyperintensity on T2-weighted short-tau-inversion-recovery black-blood (T2W-STIR-BB) images in identifying active cardiac sarcoidosis (CS) in patients, and compared it with that of18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Methods This retrospective study included 40 steroid-naive patients (age 63.1±12.9 years, 20 men) diagnosed with CS who underwent both cardiac MRI and FDG-PET imaging. Active CS cases were defined as satisfying at least one of the following criteria for conventional indices: exacerbation of ventricular arrhythmia, newly identified advanced atrioventricular block, greater than 5% decrease in left ventricular ejection fraction on echocardiography, positive finding on gallium-scintigraphy or elevated levels of sarcoidosis-related serum biomarkers. T2W-STIR-BB images were semi-quantitatively analysed using a myocardium-to-spleen ratio (MSR). The diagnostic performance of T2W-STIR-BB and FDG-PET imaging for detecting active CS was investigated. Results Thirty-three patients satisfied at least one criterion and were considered as having active CS. Thirty patients (75%) tested positive with T2W-STIR-BB imaging, and 25 patients (63%) tested positive with FDG-PET. The sensitivity, specificity, accuracy, and positive and negative predictive values for identifying active CS by semi-quantitative MSR on T2W-STIR-BB images were 79%, 43%, 73%, 87% and 30%, respectively. These results were statistically comparable to those of FDG-PET (70%, 71%, 70%, 92% and 33%, respectively). Conclusions When using conventional diagnostic indices for active CS as the gold standard, T2W-STIR-BB imaging demonstrated comparable diagnostic performance to that of FDG-PET. The semi-quantitative analysis of high signal intensity on T2W-STIR-BB images using MSR was useful for detection of active CS.

This article introduces Aizone, an after-school day treatment program for children with emotional/behavioral disturbances, and examines its effectiveness. Aizone targets children whose problems require intensive care, but are not severe enough to warrant hospitalization, and prioritizes those from low-income families. Based on the bio-psycho-social model, this program provides a variety of therapeutic interventions for both children and their parents, including individual and group therapy integrated under the concept of milieu therapy, as well as community linkage services. This study uses a prospective comparative method to examine the effectiveness of Aizone by comparing and validating the treatment outcomes of seven Aizone programs across Seoul. The Korean Child Behavior Checklist was administered by caregivers before and after intervention and the data was used in a repeated measures analysis. The effectiveness of the program in terms of reduction in emotional, behavioral symptoms, as well as the implications of the results are discussed.

Whether aldosterone itself contributes directly to macro- or microcirculatory disease in man or to adverse cardiovascular outcomes is not fully known. We report our long-term single-practice experience in 5 patients with chronic hyperaldosteronism (HA, including 3 with glucocorticoid remediable aldosteronism, GRA) treated with low-dose amiloride (a specific epithelial sodium channel [ENaC] blocker) 5-10 (mean 7) mg daily for 14-28 (mean 20) years. Except for 1 GRA diagnosed in infancy, all had severe resistant hypertension. In each case, BP was normal or near-normal within 1-4 weeks after starting amiloride and office BP's were well controlled for 20 years thereafter. Vascular studies and 24-hour ambulatory BP monitoring with pulse wave analysis (cardiac output, vascular resistance, augmentation index, and reflection magnitude) were assessed after a mean of 18 years as were regional pulse wave velocities, pulse stiffening ratio, ankle-brachial index, serum creatinine, estimated glomerular filtration rate, and spot urinary albumin:creatinine ratio. All indicators were completely normal in all patients after 18 years of amiloride, and none had a cardiovascular event during the 20-year mean follow-up. We conclude that long-term ENaC blockade can normalize BP and protect macro- and microvascular function in patients with HA. This suggests that (a) any vasculopathic effects of aldosterone are mediated via ENaC, not MR activation itself, and are fully preventable or reversible with ENaC blockade or (b) aldosterone may not play a major BP-independent role in human macro- and microcirculatory diseases. These and other widely divergent results in the literature underscore the need for additional studies regarding aldosterone, ENaC, and vascular disease.

Significant transducer, embedded, and wireless advancements on a novel system, AbStats, has led to the first non-hospital commercialization of a new system called, Wireless AbStats. The architecture for the Wireless AbStats system is presented. This thesis will cover the hardware and software design and implementation of the system, which includes the transducer properties of the acoustic sensor, an embedded node for local storage and wireless communication, a powerful, intermediate smartphone node for data collection, and a server enterprise for further integration with internet services. Additionally, we see improvements made to various aspects of the system, like design, manufacture, and deployment since the previous iteration. Overall, the new capabilities offered by the Wireless AbStats system, which include wireless support, smaller form-factor, and improved signal-to-noise ratio, can lead to new insights and solutions in high-impact and far-reaching problems and applications, such as veterinary care, animal husbandry, neonatal intensive care unit monitoring, and optimal athlete nutrition.

BackgroundSurgical site infections (SSIs) are morbid and costly complications after elective colorectal surgery. SSI prevention bundles have been shown to reduce SSI in colorectal surgery, but their impact on organ space infections (OSI) is variable. Adoption of an evidence-based practice without an implementation strategy is often unsuccessful. Our aim was to successfully implement an OSI prevention bundle and to achieve a cost-effective reduction in OSI following elective left-sided colorectal operations.MethodsThe Translating Research into Practice model was used to implement an OSI prevention bundle in all patients undergoing elective left-sided colorectal resections by a single unit from November 2018 to September 2019. The new components included oral antibiotics with mechanical bowel preparation, when required, and use of impermeable surgical gowns. Other standardised components included alcoholic chlorhexidine skin preparation, glove change after bowel handling prior to wound closure with clean instruments. The primary outcome was OSI. Secondary outcomes included bundle compliance, unintended consequences and total patient costs. Outcomes were compared with all patients undergoing elective left-sided colorectal resections at the same institution in 2017.ResultsElective colorectal resections were performed in 173 patients across two cohorts. The compliance rate with bundle items was 63% for all items and 93% for one omitted item. There was a reduction in OSI from 12.9% (11 of 85) to 3.4% (3 of 88, pConclusionSuccessful implementation of an OSI prevention bundle was associated with a reduced rate of OSI after elective colorectal surgery. The OSI bundle and its implementation were cost-effective. Further study is required to investigate the sustainability of the OSI prevention bundle.

Advances in medical imaging have enabled patient-specific biomechanical modelling of arterial lesions such as atherosclerosis and aneurysm. Geometry acquired from in-vivo imaging is already pressurized and a zero-pressure computational start shape needs to be identified. The backward displacement algorithm was proposed to solve this inverse problem, utilizing fixed-point iterations to gradually approach the start shape. However, classical fixed-point implementations were reported with suboptimal convergence properties under large deformations. In this paper, a dynamic learning rate guided by the deformation gradient tensor was introduced to control the geometry update. The effectiveness of this new algorithm was demonstrated for both idealized and patient-specific models. The proposed algorithm led to faster convergence by accelerating the initial steps and helped to avoid the non-convergence in large-deformation problems.

Objective. The objective of this study is to assess the effectiveness of erythropoietin (EPO) on mortality, neurological outcomes, and adverse event in the treatment of traumatic brain injury (TBI). Methods. We searched databases including PubMed, OVID, and the Cochrane Library from inception until October 18, 2019 for randomized controlled trials (RCTs) to compare EPO treatment group and placebo in patients with TBI. Two authors independently processed the data and evaluated the quality of inclusion studies. Statistical analysis was performed with heterogeneity test with I 2 and chi-square tests. We summarized the mortality, prognosis of neurological function, and deep vein thrombosis (DVT) outcomes and presented as risk ratio (RR) or risk difference (RD) with a 95% CI. Results. Seven RCTs accounting for 1180 patients were included after meeting the inclusion criteria. Compared with placebo, the overall mortality of EPO-treated patients was significantly reduced (RR 0.68 [95% CI 0.50-0.93]; p = 0.02 ). EPO therapy did not improve neurological prognosis (RR 1.21 [95% CI 0.93-1.15]; p = 0.16 ) or increase the occurrence of DVT (RR 0.83 [95% CI 0.61–1.13]; p = 0.242 ), which showed no significant difference. Conclusions. The results showed that the administration of EPO may reduce the risk of mortality without enhancing the occurrence of DVT in TBI patients. However, the effect of EPO on neurological outcome remains indistinct. Through subgroup analysis, we demonstrated that the dose of EPO may be a potential factor affecting the heterogeneity in neurological function and that the follow-up duration may influence the stability of the result.

Introduction The origin of contactin-associated protein-like 2 (Caspr2) antibodies in patients with Morvan syndrome is currently unknown. This case report investigated a possible association between the production of Caspr2 antibodies and aberrant proliferation of B lymphocytes. Case report We admitted a critically ill 65-year-old female patient with a suspected infection of the central nervous system (CNS). In addition to acquired neuromyotonia and CNS involvement, Caspr2 antibodies detected in her serum led to the presumptive diagnosis of Morvan syndrome. However, steroid and immunoglobulin treatment did not result in a satisfactory therapeutic outcome. On the basis of findings from immunohistochemistry, flow cytometric analysis, and immunoglobulin/T-cell receptor gene rearrangement detection of cerebrospinal fluid cells, we also made a concurrent diagnosis of diffuse large B-cell lymphoma in the CNS of this patient. The patient then received 4 cycles of rituximab and methylprednisolone therapy with an interval of 2 weeks, which temporarily led to a near-complete remission of her symptoms. Upon follow-up, her symptoms relapsed at 3 months after the last treatment with rituximab and methylprednisolone. Conclusions This is a first reported case of a patient who was concurrently diagnosed with Morvan syndrome and diffuse large B-cell lymphoma in the CNS. Additional studies are needed to determine whether aberrantly proliferating B lymphocytes are responsible for the production of Caspr2 antibodies.

To examine the effect of discontinuing hydroxyethyl starch (HES) solutions on length of hospital stay, transfusion, risk of death, acute kidney injury (AKI), and dialysis. We conducted a historical cohort study of linked administrative and clinical databases in patients undergoing coronary artery bypass surgery (CABG) on cardiopulmonary bypass. We used propensity scores to match patients who did not receive HES (after discontinuation) with patients exposed to HES (before discontinuation) and also controlled for albumin exposure. Hospital length of stay (the primary outcome) was analyzed using Fine-Gray proportional hazard regression, with hospital discharge as the outcome and death as a competing risk. Adverse outcomes were compared between matched patients using conditional logistic regression. We compared 1,085 propensity score-matched pairs (n = 2,170) from a pool of 2,757 patients. Discontinuation of HES was associated with shorter length of hospital stay, as evidenced by an increased probability of discharge (hazard ratio, 1.24; 95% confidence interval [CI], 1.14 to 1.35) and a reduced risk of red blood cell transfusion (odds ratio [OR], 0.68; 95% CI, 0.55 to 0.84), plasma transfusion (OR, 0.48; 95% CI, 0.34 to 0.66), and platelet transfusion (OR, 0.62; 95% CI, 0.44 to 0.87). Discontinuation of HES was not associated with in-hospital mortality (OR, 0.74; 95% CI, 0.36 to 1.54), AKI (OR, 0.84; 95% CI, 0.57 to 1.25), or dialysis (OR, 0.83; 95% CI, 0.25 to 2.73). For patients undergoing CABG on cardiopulmonary bypass, discontinuation of HES was associated with reduced hospital length of stay and reduced blood product transfusion, without measurable change in renal failure, dialysis rate, or in-hospital mortality. Our results should be interpreted with caution, though we found no evidence of harms associated with discontinuing HES. www.clinicaltrials.gov (NCT02329158); registered 31 December, 2014.

Riluzole is a glutamatergic modulator of particular interest in autism spectrum disorder (ASD). In this 12-week randomized, double-blind, placebo-controlled, crossover pilot study we evaluated the safety and tolerability of 5-week of adjunctive riluzole treatment (vs. 5-week of placebo, with 2-week washout period) targeting ASD-associated drug-refractory irritability in eight individuals age 12-25 years. All participants tolerated riluzole 200 mg per day, however there were no statistically significant findings for the overall treatment effect, the treatment effect by week within period of the study, or a cross-over effect across the periods of the study on the Clinical Global Impression Improvement Scale or the Aberrant Behavior Checklist Irritability subscale. The results of this trial indicate that 5-week of riluzole treatment was well tolerated, but had no significant effect on the target symptoms. Trial Registration ClinicalTrials.gov Identifier NCT02081027, Registered 5 August 2013, First participant enrolled 19 September 2013.

Background In this study, the authors examine the cost-effectiveness of light-polymerized resin-based fluoride sealants on primary molars in high caries risk children younger than 6 years. Methods The authors examined the cost-effectiveness of pit-and-fissure sealant (PFS) treatment on primary molars by comparing sealed and unsealed molars treated in the outpatient clinic or operating room. Using 1,884 primary molars followed over a 5-year period, the authors used a mixed-effects regression model to estimate the probability of caries development. They used restricted means to estimate years free of caries for carious molars. They used a decision tree to address uncertainty due to PFS treatment failure, predict the expected value associated with each strategy, and estimate the incremental cost-effectiveness ratio using a 3% discount rate to adjust future cost and outcomes to present value. Results Over 5 years, the cost of care was $90 for unsealed molars and $75 for sealed molars. Unsealed molars remained caries free for 4.32 years compared with 4.85 years in sealed molars. The cost-effectiveness of PFS treatment was dominant, leading to a savings of $25 for each caries-free year gained and overall savings of $742 million for the United States dental health system over a 5-year period. Conclusions PFS treatment is associated with cost savings and a delay in caries development and should be considered in children with high caries risk. Practical Implications Policy makers should consider reimbursement of PFS treatment on primary molars in high caries risk children.

Objective To quantify changes in motor function, sensation, and lower extremity quality of life following anterior lateral thigh free flap (ALT) resection. Methods This mixed methods study contained both a prospective cohort arm (n = 20) and retrospective cross-sectional arm (n = 20). In both arms, patients underwent formal motor and sensation testing of the ipsilateral and contralateral thigh by sphygmomanometry and monofilament testing. In the prospective arm, data was collected preoperatively and at the 6-month and 1-year follow-up visits. In the retrospective arm, consecutive patients with a minimum of 6-month postoperative follow-up were enrolled. Results Postoperatively, 82% of participants endorsed some degree of numbness and tingling at the donor site. On monofilament testing, patients from the prospective arm showed decreased sensibility of the midthigh at both the 6- and 12-month assessment (P < 0.01). Two-point discrimination scores were moderately correlated with the cross-sectional surface area of the flap. Donor thighs demonstrated a similar peak isometric quadriceps contraction (retrospective [retro]: 47 ± 24 mmHg, prospective [pro]: 90 ± 36 mmHg) to the unoperated thighs (retro: 43 mmHg ± 22, pro: 69 ± 35.3 mmHg, P = 0.49). When stratified by perforator anatomy, no significant differences were noted. Subjective donor site morbidity measured with the lower extremity function scale demonstrated no statistically significant difference between the preoperative and 12-month postoperative assessment. Conclusion The ALT flap offers minimal donor site morbidity. Reduced sensibility of the ALT flap is a common complaint among patients. Quadriceps strength is not significantly affected by an ALT free flap harvest. Level of Evidence 4. Laryngoscope, 2017

This study was designed to investigate whether functional and molecular MRI techniques are sensitive biomarkers for assessment of neuroinflammation and drug efficacy after traumatic brain injury (TBI) in rats. We subjected rats to a controlled cortical impact model and used behavioral tests, histology, and immunofluorescence to assess whether flavonoid pinocembrin provides cerebral protection and improves functional recovery. Most importantly, we used multiple noninvasive structural, functional, and molecular MRI techniques to examine whether the pinocembrin-related neuroprotection and attenuation of neuroinflammation can be detected in vivo . Significant increases in cerebral blood flow (CBF) and amide proton transfer-weighted (APTw) MRI signals were observed in the perilesional areas in untreated TBI rats at 3 days and could be attributed to increased glial response. In addition, increased apparent diffusion coefficient and decreased magnetization transfer ratio signals in untreated TBI rats over time were likely due to edema. Post-treatment with pinocembrin decreased microglial/macrophage activation at 3 days, consistent with the recovery of CBF and APTw MRI signals in regions of secondary injury. These findings suggest that pinocembrin provides cerebral protection for TBI and that multiple MRI signals, CBF and APTw in particular, are sensitive biomarkers for identification and assessment of neuroinflammation and drug efficacy in the TBI model.

Despite continuing improvements in the management of classical Hodgkin lymphoma (cHL), relapse remains associated with a risk of lymphoma-related mortality. The biological composition of relapse tumour biopsies shows interpatient variability, which can be leveraged to design prognostic biomarkers. Here, we validated the RHL30 assay, a previously reported gene expression model in an independent cohort of 41 patients with relapsed cHL. Patients classified as high-risk by the RHL30 assay had inferior failure-free survival (FFS) after autologous stem cell transplantation (2-year FFS 41% vs. 92%, P = 0·035). The RHL30 model is a robust biomarker that risk-stratifies patients considered for autologous stem cell transplantation.

Background: Government interest in commercial physical activity apps has increased with little evidence of their cost-effectiveness. This is the first study to our knowledge to examine the cost-effectiveness of a commercial physical activity app (Carrot Rewards). Methods: A cost-effectiveness analysis was performed to calculate the incremental cost-effectiveness ratio (ICER) of Carrot Rewards compared to a no-intervention reference scenario using a five-year time horizon. An age-, sex-, and geography-dependent Markov model was developed assuming a public healthcare payer perspective. A closed cohort (n=38,452) representing the population reached in two Canadian provinces (British Columbia, Newfoundland & Labrador) at the time of a 12-month prospective study was used. Costs and effects were both discounted at 1.5% and expressed in 2015 Canadian dollars. Subgroup analyses were conducted to compare ICERs between provinces, sexes, age groups, and engagement levels. Findings: Carrot Rewards had an ICER of $11,113 CAD per quality adjusted life year (QALY), well below the $50,000 CAD per QALY willingness-to-pay (WTP) threshold. Subgroup analyses revealed that the app was more cost-effective for British Columbians, females, highly engaged users, and adults aged 35-64yrs, and was dominant for older adults (65+yrs). Deterministic sensitivity analyses revealed that the ICER was most influenced by the relative risk of diabetes. Probabilistic sensitivity analyses revealed varying parameter estimates predominantly resulted in ICERs below the WTP threshold. Interpretation: Carrot Rewards is cost-effective, and dominant for older adults. These results provide, for the first time, rigorous health economic evidence for a commercial physical activity app as part of public health programming. Funding Statement: Public Health Agency of Canada (PHAC) Multi-Sectoral Partnership Approach to Healthy Living and Chronic Disease Prevention, as well as the Baycrest’s Soupcoff Family Fellowship, Mitacs Elevate, Sandra Rotman Centre for Health Sector Strategy Fellowship, Social Sciences and Humanities Research Council Partnership Grants. Declaration of Interests: MM received consulting fees from Carrot Insights Inc. from 2015 to 2018 as well as travel reimbursement in January and March 2019. MM had stock options in the company as well but these are now void since Carrot Insights Inc. went out of business in June 2019. RR was employed as a research intern by Carrot Insights Inc. from March 2018 to July 2018. RR was a Mitacs postdoc from February 2019 to June 2019 MH and SS declare that they have no conflicts of interests. Ethics Approval Statement: Ethical approval for this study was provided by Western University’s Human Research Ethics Board (#113322). This study involved the secondary use of de-identified data. There was no consent for this secondary data analysis. However, app users were informed of and had to accept the app’s privacy policy describing how de-identified data may be used for reporting purposes and presented in aggregate.

In this review, we summarize recent research related to intracerebral hemorrhage (ICH) and offer new insight into its pathomechanisms. These underlying pathomechanisms of ICH provide clues for development of novel drugs or drug target screening. Specifically, recent research has provided evidence that iron chelators, lipid peroxidation/ferroptosis inhibitors, antagonists or agonists of prostaglandin E2 receptors (EP1/3 or EP2), and nonsteroidal anti-inflammatory drugs protect against ICH-induced brain edema and secondary brain tissue damage, and inhibit the toxicity of related tissue damage products. This review will provide a theoretical basis for testing new compounds that may have potential for future clinical trials.

Objective The staging of cutaneous squamous cell cancers (cSCC) was revised by the American Joint Committee on Cancer in 2010 to incorporate known prognostic factors and expand the N (node) category. The purpose of this study was to validate this staging system using a North American cohort, and to compare it to the O'Brien P (Parotid) and N staging system. Methods An exhaustive collaborative database search was performed for all patients with cSCC metastasis to the parotid gland treated at three major Canadian tertiary referral centers from December 1999 to March 2015. The data collected for each patient included overall survival; disease-free survival; tumor, node, and metastasis) staging; and postoperative radiation status. Post-hoc analysis was completed to discern the strongest prognostic factors of survival as they relate to the abovementioned staging systems. Results Of 136 patients identified, 80% had a documented history of previously treated head and neck cSCC an average of 27 months prior to presentation. Average size of the parotid lesion at recurrence was 4.5 cm. Ninety-six percent of patients underwent surgical resection of the parotid metastasis. Five-year overall and disease-free survival is 79% and 55%, respectively. Only cSCC staging and cSCC-N category had statistically significant differences between groups. cSCC staging had the largest percentage of variation in overall survival explained. Conclusion Patients with cSCC metastasis to the parotid gland proved to have a moderate survival rate, despite presenting with advanced disease. cSCC staging in the setting of parotid metastasis, despite its limitations, currently offers the most predictive staging system available. Level of Evidence 4. Laryngoscope, 127:2063–2069, 2017

Postpartum hemorrhage (PPH) is a common source of morbidity and mortality for delivering mothers worldwide, resulting in greater than 100,000 deaths per annum. Pathologic postpartum hemorrhage is defined as blood loss greater than 500 mL for vaginal deliveries and 1,000 mL for caesarean births, which occurs in up to 10% of deliveries. Severe postpartum hemorrhage can progress to shock, disseminated intravascular coagulation (DIC) and death. PPH is further characterized by time of onset; primary PPH occurs within 24 hours of parturition, and secondary PPH beyond that. Secondary hemorrhage is discussed in a separate article in this issue, this article will exclusively explore primary postpartum hemorrhage. PPH arises from a number of etiologies, including uterine atony, birth canal/perineal lacerations and intrapelvic arterial injuries. PPH is primarily managed by standard medical obstetric maneuvers including uterotonics, fundal massage, intrauterine (Bakri) balloon tamponade and direct control of hemorrhage where applicable. Definitive control with hysterectomy is preserved for hemorrhage refractory to conservative and minimally-invasive management. First described in 1979, angiography and trans-catheter embolization represent valuable tools in the control of postpartum hemorrhage of most etiologies. Embolization is an acceptable, effective alternative to hysterectomy, particularly in patients who desire future fertility. It has high clinical success rates and a body of literature supporting preserved post-embolization fertility.

Whether aldosterone itself contributes directly to macro- or microcirculatory disease in man or to adverse cardiovascular outcomes is not fully known. We report our long-term single-practice experience in an unusual group of five patients with chronic hyperaldosteronism (HA, including three with glucocorticoid-remediable aldosteronism, GRA) treated with low-dose amiloride (a specific epithelial sodium channel [ENaC] blocker) 5-10 (mean 7) mg daily for 14-28 (mean 20) years. Except for one GRA diagnosed in infancy, all had severe resistant hypertension. In each case, BP was normalized within 1-4 weeks after starting amiloride and office BP's remained well controlled throughout the next two decades. 24-hour ambulatory BP monitoring with pulse wave analysis (cardiac output, vascular resistance, augmentation index, reflection magnitude), regional pulse wave velocities, pulse stiffening ratio, ankle-brachial index, serum creatinine, estimated glomerular filtration rate, and spot urinary albumin:creatinine ratio were measured after a mean of 18 years; all of these indicators were essentially normal. Over two additional years of observation (100 patient-years total), no cardiovascular or renal event occurred. We conclude that long-term ENaC blockade with amiloride can normalize BP and protect macro- and microvascular function in patients with HA. This suggests that either (a) putative vasculopathic effects of aldosterone are mediated via ENaC or (b) aldosterone may not play a direct role in age-dependent vasculopathic changes in humans independent of blood pressure. These findings, coupled with our literature review in both animal and human results, underscore the need for additional studies.

Background The authors examined the association between light-polymerized resin-based fluoride-releasing sealants and the development of pit-and-fissure caries on primary molars. Methods In this 3-year retrospective study, the authors reviewed the dental records of 297 children (1,352 teeth) younger than 6 years who were at high caries risk. Sealant placement or nonplacement on primary molars in the outpatient clinic and operating room setting was recorded, and random-effects logistic regression analysis accounting for the effect of data clustering was performed to measure caries incidence over time. Results The odds of developing pit-and-fissure carious lesions on sealed primary molars were 0.055 times (95% confidence interval [CI], 0.011 to 0.285; P = .001) and 0.013 times (95% CI, 0.001 to 0.159; P = .001) the odds of that on nonsealed primary molars in the outpatient clinic and in the operating room, respectively. In molars that became carious, those sealed were associated with longer time to caries development in both the outpatient clinic (2.69 years, 95% CI, 2.08 to 3.29) and operating room (1.97 years, 95% CI, 1.45 to 2.48). Conclusions Sealed primary molars were less likely to develop pit-and-fissure caries when placed in both the clinic and operating room settings. Practical Implications Dental sealants on primary molars should be considered for children at high caries risk.