Real-world implications of IMACS malignancy screening guidelines for idiopathic inflammatory myopathies: An evaluation of compliance and economic impact at a tertiary referral center.

AIM: An inaugural set of consensus guidelines for malignancy screening in idiopathic inflammatory myopathy (IIM) were recently published by an international working group. These guidelines propose different investigation strategies based on "high", "intermediate" or "standard" malignancy risk groups. This study compares current malignancy screening practices at an Australian tertiary referral center with the recommendations outlined in these guidelines. METHODS: We conducted a retrospective analysis of newly diagnosed IIM patients. Relevant demographic and clinical data regarding malignancy screening were recorded. Existing practice was compared with the guidelines using descriptive statistics; costs were calculated using the Australian Medicare Benefit Schedule. RESULTS: Of the 47 patients identified (66% female, median age: 63 years [IQR: 55.5-70], median disease duration: 4 years [IQR: 3-6]), only one had a screening-detected malignancy. Twenty patients (43%) were at high risk, while 20 (43%) were at intermediate risk; the remaining seven (15%) had IBM, for which the proposed guidelines do not recommend screening. Only three (6%) patients underwent screening fully compatible with International Myositis Assessment and Clinical Studies recommendations. The majority (N = 39, 83%) were under-screened; the remaining five (11%) overscreened patients had IBM. The main reason for guideline non-compliance was the lack of repeated annual screening in the 3 years post-diagnosis for high-risk individuals (0% compliance). The mean cost of screening was substantially lower than those projected by following the guidelines ($481.52 [SD 423.53] vs $1341 [SD 935.67] per patient), with the highest disparity observed in high-risk female patients ($2314.29/patient). CONCLUSION: Implementation of the proposed guidelines will significantly impact clinical practice and result in a potentially substantial additional economic burden.

Diagnosing and characterizing inflammatory myopathies at an Australian tertiary public hospital: Resource utilization and direct healthcare costs.

AIM: To determine the direct health service costs and resource utilization associated with diagnosing and characterizing idiopathic inflammatory myopathies (IIMs), and to assess for limitations and diagnostic delay in current practice. METHODS: A retrospective, single-center cohort analysis of all patients diagnosed with IIMs between January 2012 and December 2021 in a large tertiary public hospital was conducted. Demographics, resource utilization and costs associated with diagnosing IIM and characterizing disease manifestations were identified using the hospital's electronic medical record and Health Intelligence Unit, and the Medicare Benefits Schedule. RESULTS: Thirty-eight IIM patients were identified. IIM subtypes included dermatomyositis (34.2%), inclusion body myositis (18.4%), immune-mediated necrotizing myopathy (18.4%), polymyositis (15.8%), and anti-synthetase syndrome (13.2%). The median time from symptom onset to diagnosis was 212 days (IQR: 118-722), while the median time from hospital presentation to diagnosis was 30 days (8-120). Seventy-six percent of patients required emergent hospitalization during their diagnosis, with a median length of stay of 8 days (4-15). The average total cost of diagnosing IIM was $15 618 AUD (STD: 11331) per patient. Fifty percent of patients underwent both MRI and EMG to identify affected muscles, 10% underwent both pan-CT and PET-CT for malignancy detection, and 5% underwent both open surgical and percutaneous muscle biopsies. Autoimmune serology was unnecessarily repeated in 37% of patients. CONCLUSION: The diagnosis of IIMs requires substantial and costly resource use; however, our study has identified potential limitations in current practice and highlighted the need for streamlined diagnostic algorithms to improve patient outcomes and reduce healthcare-related economic burden.

Normalised repeat serum prostate-specific antigen: associations with age and magnetic resonance imaging results.

OBJECTIVE: To assess the value of a repeat prostate-specific antigen measurement (PSA2) before magnetic resonance imaging (MRI) in men with a raised PSA (PSA1) <10 µg/L. METHOD: Medical records of men aged < 75 years referred in 2021 for PSA1 3.0-9.9 µg/L (< 70 years) or 5.0-9.9 µg/L (70-74 years) were reviewed. PSA2 was sampled before MRI within 60 days from PSA1. Odds ratios (ORs) were calculated with logistic regression. Chi-square and trend-test were used for categorical variables. RESULTS: A total of 341 men were included. Median time between PSA1 and PSA2 was 28 days (interquartile range 20-35 days). PSA normalised in 16% (95% confidence interval [CI]: 13-21). Younger men were more likely to have a normal PSA2 (OR: 0.95 per year older, 95% CI: 0.92-0.99). Among men aged < 70 years, those with PSA1 < 5 µg/L were more likely to have normalised PSA2 than those with PSA1 ≥ 5 µg/L (21% vs. 10%, p = 0.01). A greater proportion of men with normalised PSA2 had a Prostate Imaging Data and Reporting System MRI score of 1-3 than men with non-normalised PSA2 (93% vs. 77%, p = 0.01). CONCLUSIONS: A clinically significant proportion of men with a moderately raised PSA value have a normal PSA2. Younger men and men with lower PSA1 were more likely to have a normal PSA2. Few men with normalised PSA2 had suspicious MRI findings. Routine repeat PSA-testing may be motivated in men with a moderately raised PSA value to save MRI resources, particularly in younger men.

Hearing Loss and Sociodemographic Barriers to Health Care Access Using the All of Us Research Program.

OBJECTIVE: To explore how gender and low-income status independently influence general health care access in patients with hearing loss. STUDY DESIGN: Cross-sectional study. SETTING: National database. METHODS: Patients with a diagnosis of sensorineural hearing loss from the National Institutes of Health All of Us database were included. Data entered from May 2018 to November 2022 was analyzed. Patient demographics such as age, gender, educational level, and insurance status were assessed. Multivariate logistic regressions were performed for statistical evaluation. RESULTS: A subset of 8875 patients (48.3% male, mean age 69) were evaluated. After multivariate analysis, female participants were more likely than male participants to report difficulty affording prescribed medications (odds ratio [OR]: 1.7, p < .0005) and specialists (OR: 1.4, p < 0.005). Female patients were also more likely to delay care due to elder care responsibilities (OR: 2.6, p < .0005), employment obligations (OR: 1.7, p < .0005), and feelings of apprehension in seeing a provider (OR: 1.7, p < .0005). Finally, female participants reported feeling less likely to be involved in their own medical care compared to males (OR: 1.2, p < .005). Low-income (<$25,000) participants reported less likely to feel respected (OR: 3.2, p < .0005) and delivered understandable health information (OR: 2.3, p < .0005) by providers compared to participants of higher income. CONCLUSION: This work suggests that patients with hearing loss, female gender, and lower socioeconomic status independently introduce barriers to health care access and utilization. These factors should be considered in efforts to promote equity in the care of patients with hearing loss.

Kidney disease progression in pediatric and adult posterior urethral valves (PUV) patients.

BACKGROUND: Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. METHODS: We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20 ml/min/1.73 m2 after 1 year of age, no dialysis or kidney transplant history, and ≥ 2 yearly serum creatinine values after age 1 year. eGFRs were calculated using creatinine-based estimating formulas for children (CKID U25) or adults (CKD-EPI). The primary outcome was annualized change in eGFR, assessed with linear mixed effects models. We also examined the association of acute kidney injury (AKI), proteinuria, hypertension (HTN), and recurrent febrile urinary tract infections (UTIs) with eGFR decline. RESULTS: Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m2/year. Children (n = 35) and adults (n = 17) demonstrated progressive decline. Proteinuria and recurrent UTIs were significantly associated with faster progression; AKI and HTN were also associated but did not reach significance. CONCLUSION: PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies.

Endolymphatic Sac Surgery: Understanding the Historical Influence of Circumstance and Statistics.

In 1981, Danish physician Jens Thomsen conducted the first and only documented sham-controlled surgical trial in the history of otolaryngology. This trial is historically significant as it was the first in the field to use a methodologically sound study design to address a frustratingly complex disorder such as Ménière's disease. Despite this, historical interpretations of this work have varied, and questions about the results have been raised. We review the fascinating historical context of this landmark trial and detail how it was influenced by the rise of the randomized controlled trial. We examine how subsequent statistical analyses and interpretations of this historical work have affected surgical treatment paradigms in Ménière's disease, and we look forward to suggest the legacy of this work as a sham-controlled surgical trial in otolaryngology.

A National Analysis of Inpatient Pediatric Adenoidectomy.

OBJECTIVE: Hospital admission following pediatric adenoidectomy without tonsillectomy is not well characterized. The objective of our study is to better characterize risk factors for post-operative complications in younger children undergoing inpatient adenoidectomy. METHODS: A cross-sectional analysis using data derived from the Kid's Inpatient Database (KID) was performed. Study participants included children <3 years of age who underwent an adenoidectomy and were admitted to hospitals participating in the KID for years 1997, 2000, 2003, 2006, 2009, and 2012. Descriptive statistical analysis and a multivariate logistic regression analysis were performed to identify risk factors for post-operative complication. RESULTS: A total of 3406 children (mean age 1.1 ± 0.7 years) were included. The overall post-operative bleeding and respiratory complication rates were 0.6% and 5.4%, respectively. Children less than 18 months of age demonstrated increased rates of post-operative respiratory complications (P = .009), but not bleeding complications (P = .857). Presence of cardiopulmonary congenital malformations (OR 1.54, 95% CI 1.07-2.20), chronic respiratory disease of the newborn (OR 5.03, 95% CI 2.86-8.85), and neuromuscular disorders (OR 1.97, 95% CI 1.09-3.57) were associated with post-operative respiratory distress. CONCLUSIONS: This analysis of a national dataset suggests that otherwise healthy children less than 18 months of age and children 18 months to 3 years of age with certain comorbidities may benefit from overnight observation following adenoidectomy.

Telehealth in the times of SARS-CoV-2 infection for the otolaryngologist.

OBJECTIVE: In response to the American Academy of Otolaryngology - Head and Neck Surgery's recommendations to limit patient care activities in the times of SARS-CoV-2, many elective surgeries have been canceled without patient clinics transitioning to virtual visits. With regulations for telemedicine loosened, new possibilities for the practice of otolaryngology have opened. To address the uncertain duration of this pandemic, a review was conducted of current literature on use of telemedicine services in the current SARS-CoV-2 pandemic and in previous national emergencies to reveal the role telemedicine can play for otolaryngology practices. DATA SOURCES: Pubmed articles with an independent search query were utilized. METHODS: Literature review performed by one author searched for all published English-language literature on telehealth in the SARS-CoV-2 era. Articles were considered for discussion if they provided relevant developments for telemedicine in the context of the SARS-CoV-2 pandemic. RESULTS: Telemedicine can be up-scaled in the current SARS-CoV-2 pandemic where exposure containment is of the utmost priority. With patient interaction possible through virtual communication, telemedicine allows continued patient care while minimizing the risk of viral spread. In the realm of otolaryngology, telemedicine has been used in the past during disasters with other studies demonstrating high diagnostic concordance with inpatient visits. Many institutions have recognized the potential for such care as they begin utilize both virtual visits and in-person care during this pandemic. CONCLUSION: To limit the spread of SARS-CoV-2, we support the AAO-HNS recommendation for the adoption of novel ways to employ telemedicine in this era. Many emergency departments and health care systems have the infrastructure necessary for synchronous video telemedicine visits that can be leveraged to provide quality care with patients. With the continued need to socially distance, telemedicine can protect both physicians and patients from unnecessary exposure to the virus.

Head and neck survivorship care in the times of the SARS-CoV-2 pandemic.

With the arrival of the coronavirus disease (SARS-CoV-2) in the United States, care practice paradigms have drastically changed. Data from China suggest that the new virus poses additional risks as case fatality of patients with cancer was higher at 5.6% compared to 2.3% of the general population. There are three proposed major strategies to address care for patients with cancer in this SARS-CoV-2 pandemic with postponing treatment for those with stable cancer, increasing personal protection provisions for patients with cancer, and increasing monitoring if a patient becomes infected with SARS-CoV-2. In this present commentary, we discuss the unique mental health challenges and burdens of patients with head and neck cancer in the times of the SARS-CoV-2 pandemic and approaches to mitigate these stressors through telemedicine to reduce future burdens to the patient and the health care system.

Comparison of Materials Used for 3D-Printing Temporal Bone Models to Simulate Surgical Dissection.

OBJECTIVE: To identify 3D-printed temporal bone (TB) models that most accurately recreate cortical mastoidectomy for use as a training tool by comparison of different materials and fabrication methods. BACKGROUND: There are several different printers and materials available to create 3D-printed TB models for surgical planning and trainee education. Current reports using Acrylonitrile Butadiene Styrene (ABS) plastic generated via fused deposition modeling (FDM) have validated the capacity for 3D-printed models to serve as accurate surgical simulators. Here, a head-to-head comparison of models produced using different materials and fabrication processes was performed to identify superior models for application in skull base surgical training. METHODS: High-resolution CT scans of normal TBs were used to create stereolithography files with image conversion for application in 3D-printing. The 3D-printed models were constructed using five different materials and four printers, including ABS printed on a MakerBot 2x printer, photopolymerizable polymer (Photo) using the Objet 350 Connex3 Printer, polycarbonate (PC) using the FDM-Fortus 400 mc printer, and two types of photocrosslinkable acrylic resin, white and blue (FLW and FLB, respectively), using the Formlabs Form 2 stereolithography printer. Printed TBs were drilled to assess the haptic experience and recreation of TB anatomy with comparison to the current paradigm of ABS. RESULTS: Surgical drilling demonstrated that FLW models created by FDM as well as PC and Photo models generated using photopolymerization more closely recreated cortical mastoidectomy compared to ABS models. ABS generated odor and did not represent the anatomy accurately. Blue resin performed poorly in simulation, likely due to its dark color and translucent appearance. CONCLUSIONS: PC, Photo, and FLW models best replicated surgical drilling and anatomy as compared to ABS and FLB models. These prototypes are reliable simulators for surgical training.

Improvement in Patient-reported Hearing After Treatment With Bevacizumab in People With Neurofibromatosis Type 2.

OBJECTIVE: Assess patient-reported outcomes (PRO) for hearing and tinnitus relative to clinical hearing assessment in people with neurofibromatosis 2 (NF2) associated hearing loss. STUDY DESIGN: Prospective, open label, phase-II clinical trial with PRO administered pre-, post-, and after treatment. SETTING: Three tertiary referral centers. PATIENTS: Fourteen patients with NF2, median age of 30 years (range, 14-79 yr) and progressive hearing loss (median baseline word recognition score, 60%; range, 13-82%). Half of these patients achieved objective hearing response (word recognition score improved beyond the 95% critical difference versus baseline). INTERVENTION: Bevacizumab 7.5 mg/kg was administered every 3 weeks for 48 weeks, followed by surveillance for 24 weeks off-drug. MAIN OUTCOME MEASURES: Speech, spatial, and qualities of hearing scale (SSQ) and tinnitus reaction questionnaire (TRQ) to assess hearing difficulties in life situations and tinnitus related distress. RESULTS: Patient-reported speech understanding and auditory quality improved with bevacizumab treatment and were significantly correlated with word recognition scores, but not pure tone threshold average. There was no change in spatial perception after treatment. Reduction in tinnitus distress after treatment with bevacizumab did not reach statistical significance. CONCLUSION: Participants had reductions in hearing difficulty during treatment with bevacizumab, suggesting that patients subjectively experience hearing-related benefit mirroring clinical hearing assessments. We suspect the lack of significant reduction in tinnitus distress is related to small sample size and low intensity of distress in our sample. These data highlight the usefulness of PRO measures to assess benefits of treatment in the setting of NF2-associated hearing loss.

Ganoderma microsporum immunomodulatory protein induces apoptosis and potentiates mitomycin C-induced apoptosis in urinary bladder urothelial carcinoma cells.

Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffer from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants are needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) was used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC50 ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent. After GMIP treatment, UC cells showed apoptotic phenomenon including cell cycle arrest in the G1 phase, elevated sub-G1 population, mitochondrial membrane potential loss, up-regulated p21 expression, p21 nuclear translocation, caspase activation, and PARP cleavage in a p53-independent but p21-mediated pathways. Unlike lung cancer cells, GMIP treated UC cells showed no autophagic scheme including Beclin-1, an autophagy to apoptosis switch marker, was not cleaved by caspase 3 and slight LC3B-II accumulation. Also, the classic autophagic inhibitor, chloroquine had no effect in GMIP-mediated cell death made us conclude that GMIP induced apoptosis through caspase activation but not autophagy in UC cells. Additionally, GMIP showed synergistic effects with MMC in killing UC cells and thus decreased the concentration of MMC usage to reach the comparable apoptotic effects. Our results delineate novel strategies for treatment of UC by GMIP alone or in combination with MMC application and provide a promising therapeutic cocktail for better treatment of urinary bladder urothelial carcinoma.

Sociosexual investigation in sexually experienced, hormonally manipulated male leopard geckos: relation with phosphorylated DARPP-32 in dopaminergic pathways.

Dopaminergic activity is both associated with sociosexual exposure and modulated by sexual experience and hormonal state across vertebrate taxa. Mature leopard geckos, a reptile with temperature-dependent sex determination, have dopaminoceptive nuclei that are influenced by their embryonic environment and sensitive to adult hormonal manipulation. In this study, we exposed hormonally manipulated male leopard geckos from different incubation temperatures to conspecifics and measured their sociosexual investigation, as well as phosphorylated DARPP-32 at Threonine 34 (pDARPP-32) immunoreactivity as a marker for D1 dopamine receptor activity in the nucleus accumbens, striatum, and preoptic area. Social investigation time by males of different incubation temperatures was modulated in opposite directions by exogenous androgen treatment. Males exposed to novel stimuli spent a greater proportion of time investigating females of different incubation temperatures. The time spent investigating females was positively correlated to pDARPP-32 immunoreactivity in the preoptic area. This is the first study quantifying pDARPP-32 in a lizard species, and suggests the protein as a potential marker to measure differences in the dopaminergic pathway in a social setting with consideration of embryonic environment and hormonal state.

El consentimiento informado en anestesiología – parte II: la relación médico paciente como fundamento del consentimiento informado / Informed consent in anesthesiology - Part II: the doctor-patient relationship as the foundation of informed consent

En el artículo publicado como primera parte de esta serie, se trató sobre los fundamentos generales del consentimiento informado. En éste reporte se profundiza en la relación médico-paciente y su importancia para la formulación y aplicación delconsentimiento informado. Esta relación interpersonal de tipo profesional es parte integral de la ética médicaen general y sirve de base para la gestión de salud. En la práctica la relación clínica entre el médico y elpaciente se ha dado en diferentes formas, dependiendo de la actitud que toman ambos actores. Para diligenciarun adecuado consentimiento informado en un acto anestésico, el modelo de relación ideal sería el basadoen la confianza recíproca, donde el propósito final es la búsqueda de las mejores alternativas para lograrla salud del paciente.