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Introduction. Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC) is a rare and recently described subtype of renal cell carcinoma (RCC). As its name indicates, the tumor is composed of three morphological structures: tubules consisted of cuboidal cells, spindle cells, and extracellular mucus. Case report. A 59-year-old female patient was admitted to the Emergency Center of the Clinical Center of Vojvodina due to injuries sustained in a traffic accident. After diagnostic procedures, computer tomography (CT) revealed a large asymptomatic cyst of the upper pole of the left kidney as an incidental finding. Four months later, after recovering from traumatic injuries, a control CT confirmed a well-circumscribed tumor, 90 mm in diameter, confined to a kidney, and a radical nephrectomy was performed. Histopathological evaluation showed that the necrotic tumor mass consisted of tubules made of cuboidal cells and cords made of spindle cells separated by pale mucinous material in some areas, while other tumor parts were of dense cellularity without mucin. No atypia was found. Conclusion. MTSCC is a variant of papillary RCC, thus, it is usually mistaken with papillary RCC with sarcomatoid differentiation. Because of the same immunoprofile as papillary RCC, histomorphology is imposed as the gold standard for making the diagnosis. MTSCC is a tumor with a generally favorable prognosis, and complete surgical excision appears to be adequate treatment, but single cases with metastatic disease have been reported. In this case, there were no signs of the dis-ease one year after surgery.

The aim of our study was to examine the scabies incidence in the Croatian population and to analyse potential related factors.

Introduction. Prostate cancer is one of the most common malignancies in men. The most common type is acinar adenocarcinoma. Small cell prostate cancer (SCPC) usually occurs together with coexisting prostate adenocarcinoma. Case report. A 72-years-old patient with voiding simptoms is presented. Initial level of prostate specific antigen (PSA) was 2.87 ng/mL. Twelve prostate biopsies were taken and in six of them neoplastic tissue was detected. The viewed tissue was most convenient to “small cell carcinoma“. Bone scintigraphy did not demonstrate dissemination of the cancer into the skeletal system. Multislice computed tomography (MSCT) of the pelvis did not reveal any special pathological changes. The patient underwent surgery – radical retropubical prostatectomy. Histopathological analysis revealed a poorly differentiated adenocarcinoma of the prostate with small cell carcinoma zones [Gleason score 5+5 (10), grade III, pT3bN1, stage IV]. Conclusion. Poorly differentiated adenocarcinoma of the prostate, especially in combination with SCPC, is an aggressive malignancy with most cases presenting with the extensive disease dissemination on diagnosis and poor prognosis. Small cell carcinomas of the prostate are extremely rare tumors of the neuroendocrine origin. Patients with mixed prostate cancer, compared to pure SCPC, have a better prognosis and greater survival rate. There is a lack of the evidence guiding treatment for SCPC.

OBJECTIVES: To demonstrate the reliability and feasibility of a standardized protocol to assess and score urinary incontinence care in nursing homes. DESIGN: Descriptive. SETTING: Eighteen nursing homes (NHs). PARTICIPANTS: Four hundred twenty-six incontinent residents. MEASUREMENTS: Resident interview data were used to score three quality indicators, and usable data were retrieved from 117 (27%) of 426 incontinent residents in 18 homes who were selected for interview based on evidence that they could accurately describe the care they received. Medical record data were used to score six quality indicators for a subset of 58 participants in five homes. RESULTS: Zero to 98% of the participants were scored as receiving care consistent with the intent of the indicator across the nine indicators. All NHs failed to provide chart documentation of an assessment to determine an incontinent resident's appropriateness for a scheduled toileting program (0% passed). The absence of an assessment to determine a resident's potential responsiveness to toileting assistance may explain why 103 incontinent residents who were documented on the Minimum Data Set as being on a scheduled toileting program reported that they received the same number of toileting assists per day (1.3) as the group of 114 incontinent residents who were not on a scheduled toileting program (1.0). The received toileting assistance frequencies reported by both groups were too low to maintain continence. CONCLUSION: The standardized quality assessment system generated scores for nine incontinence quality indicators with good interrater reliability and provided explicit scoring rules that can facilitate replication. The focus of the indicators on care processes that are under the control of NH staff make the protocol useful for external survey and internal quality improvement purposes. [ABSTRACT FROM AUTHOR]

Introduction. Leiomyosarcoma of the penis (LSP) is an extremely rare form of penile tumor. LSP can be divided into two subtypes: deep and superficial. The goal of this manuscript is to present very rear case of LSP. Case outline. On exam, the patient presented with a slowly “growing penile bump“, for which an initial diagnosis of non-inflamed penile atheroma was given. Further diagnostic workup was omitted. Outpatient excisional biopsy was performed, and the tumor was sent for pathohistological examina-tion (PHE), which revealed LSP. The patient has not received any further treatment. The most recent follow up was 2.5 years after surgery, and the patient continues to do well without any complications. Conclusion. LSP is an extremely rare disease which can be cured if it is diagnosed in its early stage. PHE is necessary for diagnosis of LSP.

Introduction. Urinoma develops after disruption of collecting system of urinary tract and urine leak in surrounding tissue. Most common causes of urinoma are blunt or penetrating trauma. Less common causes are iatrogenic injuries or urinary tract obstruction. In this article we presented a rare case of the urinoma caused by infiltrative bladder cancer. Case report. Acutely ill, a septic patient with ileus and profound azothaemia was admitted to medical intensive care unit. Native computed tomography revealed moderate ileus, right kidney hydronephrosis, extensive retroperitoneal urinoma and vesical thickening with excluded infiltration of ureteral orifices. Computed tomography guided percutaneous drainage was done. Upon stabilization, patient underwent transurethral bladder tumor electroresection (histopathology report was: infiltrative transitional cell tumor of urinary bladder). Radical cystectomy was done. The patient’s recovery was uneventful. Conclusion. Urinoma formed due to spontaneous rupture of collecting system based on ureteral obstruction caused by urinary bladder tumor is very rare clinical case scenario. In case of urinoma of unclear etiology invasive bladder cancer should be excluded.

The paper looks at some aspects of the Thracian Hero cult on the Danube frontier of Upper Moesia inspired by a reinterpretation of a Latin votive inscription from Diana, which, as the paper proposes, was dedicated to Deo Totovitioni. Based on epigraphic analogies, the paper puts forth the view that it was a dedication to the Thracian Hero, since it is in the context of this particular cult that the epithet Totovitio has been attested in various variants (Toto-viti- / Toto-bisi- / Toto-ithi-).

The paper is considering the stability condition of equilibrium position of a beam undergoing large displacements due to a conservative force. Numerical example is presented.

A new votive inscription from the territory of Doclea has recently been published. The reading of the text needs revision, and consequently, reinterpretation. The inscription should be read as follows: Neptuno ׀ sacrum p׀ericuloru׀m Absolu׀tori Petro׀5nius Aspe׀r v(otum) s(olvit) ׀ l(ibens) a(nimo). Neptune’s attribute periculorum Absolutor appears here for the first time. The noun «Absolutor», i.e. «he who absolves, liberator », attested late in the narrative sources e.g. Cassiod. Var . XI, praef. 3, should be close to the Jupiter’s epithets Liberator or Servator. The dedication could be connected with a successful ending of a journey, possibly after being exposed to maritime perils: the dedicator may well be a person engaged in trade and businesses that involve transmarine voyage. His name - Petronius Asper - implies the connection with the large group of Italian settlers in Dalmatia, whose presence is attested in the province all through the Principate. Such relations are illustrated in the light of other Dalmatian examples.

The lamp stamped Cilices, dating from the Severan epoch and found at Singidunum (Moesia Superior) but overlooked by modern scholars, offers interesting additional evidence on the Cilices contirones, attested by the contemporary altar IMS I, 3. Almost certainly, the two inscriptions refer to the same legionaries, the men of IIII Flavia, grouped professionally (serving as the legion's sailors?) as well as ethnically. The circumstances and the date of the recruitment of the contirones have been studied by H. Nesselhauf and, from another perspective, M.P. Speidel; the inscription of the lamp tends to sustain Professor Speidel's points of view. The archaeological context of the lamp implies its provenance from a military building where the Cilices may have had their club, and/or their sacellum. Similar ethnic clubs and their buildings are well known from military and other inscriptions. For an instructive (but neglected) Upper Moesian parallel see IMS VI, 187 ([Ch]airete, Gal‌‌‌│atai); cf. the Galatian Aur. Asclepiades' conveterani from leg. IIII Flavia (Speidel 1984, 50, no° 28).

Modern society changed the way of communication: instead of communicating face-to-face, people more often communicate using text-based instant messaging (IM) applications. These applications use appropriate protocols to facilitate communication between end users. It is crucial to ensure both the security and an adequate level of privacy for end users. Many existing protocols having the same purpose might be considered potentially suspicious. The reason for this is the usage of encryption - encrypted traffic is often targeted by mass surveillance tools. This paper presents a novel protocol named StegaCloak. By combining cryptography with steganography, this protocol enhances security and privacy in modern text-based IM communication. Furthermore, it addresses one important weakness of other similar protocols - detectability, by hiding real communication within regular chat messages. We described our protocol using two approaches: a simple diagram of messages flow and formal protocol flow notation. The proposed protocol is compared to some of the most well-known IM protocols today, OTR and Signal. Its security is verified using the AVISPA tool, a tool designed for the formal verification of security protocols.

Introduction. In males the ectopic ureter usualy drains into the prostate (50%). During ureteric developement a thin membrane (Chawalla’s membrane) separates the lumen of the ureter and the urogenital sinus at the point where the ureter joins the urogenital sinus. This membrane ruptures allowing urin to drain from the ureter to the urogenital sinus. The authors reported a case of renal dysplasia associated with ipsilateral uretral ectopia mimicking prostatic abscess. Case report. A subfebrile (37.3°C), 23-year-old patient, otherwise healthy, presented with persistent ascending perineal pain non-responsive to antibiotics and analgetics. Digitorectal examination (DRE) showed asymmetric prostate with a soft, tender, buldging left lobe suggestive of prostatic abscess. The diagnosis was suspected using transrectal ultrasonography (TRUS), but the picture of the anechoic tubular structure in the left lobe of the prostate with a proximal undefined extraprostatic extension and a caudal intraprostatic blind end was incoclusive for the definitive diagnosis of prostatic abscess. Magnetic resonance imaging (MRI) was ordered and definitive diagnosis of renal dysplasia associated with the ipsilateral ectopic ureter filled with inflamed content mimicking prostatic abscess was made. Transurethral incision/minimal resection of the distal, blindly closed end of left ectopic ureter was done. Endoscopic surgical treatment was sufficient for relief of clinical symptoms. The patient’s recovery was uneventful. Conclusion. To the best of our knowledge, a case of renal dysplasia with the ipsilateral ectopic ureter mimicking prostate abscess has not been reported so far. Cystic pelvic malformations in males may result from too craniall sprouting of the ureteral bud, with delayed absorption and ectopic opening of the distal end of the ureter.

Objective. The objective of this study was to investigate the impact of extreme maternal BMI on pregnancy outcomes and the costs of perinatal care at tertiary level hospital in Serbia. Methods. We performed a retrospective study of the cohort of pregnant women registered during the first trimester screening in the period from March 2016 to February 2017 and had delivery in Gynaecology and Obstetrics Clinic "Narodni front"; in Belgrade, Serbia. We evaluated 3 who were extremely obese (BMI ≥ 3 kg/m2). Multiple pregnancies were excluded. Data collection about their prepregnancy and perinatal morbidity, pregnancy outcomes and costs of the healthcare we gain using their EHR and electronic hospital bills. Comparisons were made with other pregnant women who had delivery in the observing period. Results. Additional prepregnancy comorbidity was present in the 20.6% of extremely obese patients. Their pregnancy was mostly complicated with gestational diabetes (33.3%) and hypertension (27%). 52.4% pregnancy ended by SC and 47.6% vaginaly out of which 7.9% were preterm. In comparison with other patients OR for delivery complications was 1.45 CI 95% (0.85- 2.47) and OR for SC was 2.31 CI 95% (1.41-3.80). Average length of hospital stay during whole period of pregnancy was 9 days for vaginaly ended pregnancy and 13 for SC respectively. The total costs for the perinatal healthcare of extremely obese pregnant patient were 52.8% above the average after SC and 47% after vaginal delivery in tertiary level hospital. Conclusions. Extremely obese pregnancy becomes entity which demands special clinical attention and resources. Maternal obesity could have a longer-term implications for the mother and infant health and therefore prevention and treatment of obesity may reduce meaningful health consequences and future economic costs. [ABSTRACT FROM AUTHOR]

Importance: Medical school graduates across specialties should be prepared for the start of postgraduate year 1 (PGY-1). Assessments by program directors (PDs) may offer insight to differences in preparedness across medical specialties., Objective: To investigate whether PD assessments of their PGY-1 residents' performance during the transition to residency differed by specialty category., Design, Setting, and Participants: This retrospective, cross-sectional study used Resident Readiness Survey (RRS) data collected from PDs from 2020 through 2023. Annually, eligible PDs (ie, PDs training PGY-1 residents who had graduated from US medical schools included in the RRS process) were invited to respond. A deidentified, individual-level database of PGY-1 residents for whom PDs were asked to complete standardized RRSs was created to examine the association between graduate medical education (GME) program specialty category (among other variables) and PD response to the RRS item "During the transition to GME (0-6 months of PGY-1 year), did this resident meet overall performance expectations?" The response options included exceeded, met, and did not meet expectations. Analyses included χ2 tests to measure bivariate associations and multivariable logistic regression analyses to test independent associations with this outcome., Exposures: PGY-1 in a specialty program during the first 6 months of GME., Main Outcomes and Measures: The main outcomes of interest were PD assessment of PGY-1 residents' overall performance (dichotomized as met or exceeded expectations vs did not meet expectations), PGY-1 year, and GME program specialty category., Results: The PD RRS response rate varied by year (1786 of 2847 [62.7%] for 2020-2021, 2107 of 3406 [61.9%] for 2021-2022, and 2835 of 3659 [77.5%] for 2022-2023; P < .001). Responding PDs provided overall performance ratings for 29 461 PGY-1 residents, including 934 (3.2%) who did not meet expectations and 28 527 (96.8%) who met or exceeded expectations. The percentage of PGY-1 residents who did not meet expectations varied by specialty category (range, 11 of 1482 [0.7%] for transitional year to 235 of 3775 [6.2%] for family medicine; P < .001). In multivariable regression, compared with internal medicine, the odds of residents not meeting (vs met or exceeding) expectations were higher for PGY-1 residents in family medicine (adjusted odds ratio [AOR], 2.09 [95% CI, 1.70-2.58]), general surgery (AOR, 2.05 [95% CI, 1.62-2.58]), and obstetrics and gynecology (AOR, 1.64 [95% CI, 1.24-2.15]); in contrast, the odds were lower for PGY-1 residents in other surgical specialties (AOR, 0.60 [95% CI, 0.42-0.84]), other nonsurgical specialties (AOR, 0.61 [95% CI, 0.44-0.85]), and transitional year (AOR, 0.22 [95% CI, 0.12-0.42]) vs internal medicine., Conclusions and Relevance: Findings from this cross-sectional study indicated that most PGY-1 residents met or exceeded PD expectations. Specialty-specific interventions may further optimize the transition for all US medical graduates.

Introduction: Low birth weight, defined as a birth weight below 2,500 g, represents a significant public health concern with a multifactorial risk dimension. Socio-demographic factors and individual characteristics of women and their social environment could influence low birth weight. This study aimed to analyze the association between the socio-demographic and reproductive characteristics of women living in low-income households and low birth weight in Serbia, Kosovo, and Montenegro., Methods: This study was conducted as secondary data analysis during the Multiple Indicator Cluster Survey - Round 6 in Serbia, Kosovo, and Montenegro. The household questionnaire and the individual questionnaire for women aged 15-49 were used as standard research instruments. We analyzed 1,019 women whose households belonged to the first (poorest) or second (poor) wealth index quintiles and who had given birth to a live child within the 2 years preceding the study. A multivariate logistic regression was applied with low birth weight in newborns as the outcome variable., Results: The univariate regression analysis showed that women with low birth weight newborns were significantly more likely to live in settlements mainly inhabited by Roma, reside in urban areas, marry or enter a union before age 18, have lower education levels, experience higher illiteracy rates, and receive antenatal care not provided by a medical doctor compared to women whose newborns weighed 2.5 kg or more. A multivariate logistic regression model with a low birth weight of newborns as an outcome variable showed the association between women's illiteracy (OR: 1.741; 95% CI: 1.060-2.859) and antenatal care not provided by a medical doctor (OR: 2.735; 95% CI: 1.229-6.087)., Discussion: Illiteracy and limited access to medical doctor services during pregnancy were factors that increased the likelihood of low birth weight in newborns born to women living in low-income households in the selected Western Balkans populations. The cross-sectional design of this study does not allow the establishment of causal relationships among variables, but it can provide important evidence for future prevention strategies. Interventions are needed to enhance the education of women and to improve access to antenatal care across Serbia, Kosovo, and Montenegro., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Grbic, Supic, Todorovic, Nesic, Karic, Jurisic, Kocic, Bukumiric, Cirkovic and Jankovic.)

Aim: Exploring the healthcare costs and resource use among privately insured US patients with post-traumatic stress disorder (PTSD). Methods: This study used Merative MarketScan data. The index date was defined as the first PTSD claim. Study period included a 1-year pre-index and 2-year post-index follow-up. Cases with only acute PTSD, cancer, or insurance gap during the study period were excluded. The PTSD with (PwC) and PTSD without comorbidities (PwoC) cohorts were defined by the presence/absence of comorbid mental health conditions (schizophrenia, bipolar and major depressive disorder). Baseline PTSD (BP) cohort included PwoC cases with only index PTSD event and without FDA-approved PTSD medications or psychotherapy. Sub-analysis is conducted among patients with PTSD and substance/alcohol use disorder. Study cohorts were matched in a 1:1:1 ratio. Results: The matched sample included 5076 patients (1681 PwC, 1681 PwoC, 1714 BP). PwC patients had higher 2-year PTSD-related costs than PwoC and BP patients ($3762 vs $1750 and $841; all p < 0.001). The same trend was noted among all-cause and anxiety-related costs. PwC patients had higher 2-year PTSD-related inpatient and emergency department (ED) rates than PwoC (10.2% vs 1.7% and 6.8% vs 2.6%, all p < 0.001) and inpatient and outpatient rates than BP (10.2% vs 2.1% and 98.0% vs 93.1%; all p ≤ 0.004). The sub-analysis had 3776 patients (3154 PwC, 537 PwoC, 85 BP). PwC had higher 2-year PTSD-related costs than PwoC and BP ($7668 vs $2919 and $1,483; all p < 0.001). The same trend was noted in all-cause and anxiety-related costs. PwC also had higher 2-year PTSD-related inpatient and ED rates than PwoC (25.6% vs 10.4% and 12.7% vs 5.2%; all p < 0.001) and inpatient and outpatient rates than BP (25.6% vs 8.2% and 95.5% vs 84.7%; all p < 0.001). Conclusion: PTSD is associated with high healthcare costs and resource use. The highest economic burden was observed in patients with PTSD and mental health comorbidities.

Objective: To explore the cost-effectiveness of midomafetamine-assisted therapy (MDMA-AT) compared to placebo with therapy (PT) in US healthcare settings., Methods: A health state-transition model was used to analyze the cost-effectiveness of MDMA-AT for treating patients with chronic PTSD of moderate or higher severity. Both treatment arms consisted of 3 preparation (90-min), 3 interventional (8-h), and 9 integration (90-min) sessions, lasting ~4 months total. All sessions included psychotherapy, with interventional also including MDMA or placebo. After receiving treatment, patients were distributed across health states of No PTSD (not meeting PTSD diagnostic criteria), Non-Severe PTSD (treatment responders), Severe PTSD (treatment non-responders), and death. Each state had unique healthcare costs and utilities sourced from real-world data analysis and patient data from MDMA-AT clinical trials (including long-term follow-up). The base-case analysis considered the payer's perspective with a 5-year horizon, 3.5% annual cost and effect discounts, and an assumed MDMA medication price of $12,000 per session. Trial-derived utilities and US life tables mortality data were used to calculate quality-adjusted life years (QALY). The main outcome was an incremental cost-effectiveness ratio (ICER) with a $150,000 willingness-to-pay (WTP) threshold., Results: The base-case ICER was $83,845 per QALY. Total direct costs were $64,745 in the MDMA-AT and $33,132 in the PT arms ($31,613 increment). The costs of intervention were $48,376 for MDMA-AT and $12,376 for PT. The highest MDMA medication cost to fit under the WTP threshold was $20,314 per session. Costs related to PTSD healthcare visits and other PTSD treatments were lower with MDMA-AT than PT (-$2,511 and -$1,877 increments, respectively). Utility benefits were higher in MDMA-AT than PT, with 3.691 and 3.314 QALYs generated over 5 years, respectively (0.377 QALY increment)., Conclusion: These data suggest MDMA-AT may be a cost-effective treatment compared to PT for patients with chronic PTSD of moderate or higher severity., Competing Interests: Filip Stanicic, Vladimir Zah, and Dimitrije Grbic are employees of ZRx Outcomes Research Inc., which received funding from Lykos Therapeutics for this work. Debra De Angelo is an employee of and owns stocks/stock options in Lykos Therapeutics., (Copyright: © 2024 Stanicic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This retrospective claims analysis explored the treatment utilization and characteristics among patients with post-traumatic stress disorder (PTSD) of different severity., Methods: The index date was the first PTSD claim. The analysis observed 12 months pre- and 24 months post-index. Adults with insurance gaps, cancer, or acute PTSD during the observation were excluded. Patients were categorized into three severity cohorts based on treatment and healthcare services utilization for PTSD: 1. Baseline PTSD (BP) (no PTSD visits post-index, no FDA-approved medications/ psychotherapy, and no severe mental health comorbidities); 2. PTSD without Comorbidities (PwoC) (≥1 PTSD visits post-index and no severe mental health conditions); 3. PTSD with Comorbidities (PwC) (≥1 PTSD visits post-index and severe mental health comorbidities present). For the primary analysis, cohorts were propensity-score matched. A sub-analysis examined patients with PTSD and Substance or Alcohol Use Disorder (SUD/AUD)., Results: The primary analysis observed 1714 BP, 1681 PwoC, and 1681 PwC patients. Treatment utilization rates were highest among PwC vs. other cohorts (84.5% psychotherapy, 76.1% off-label medications, and 26.1% FDA-approved medications [p<0.001]). PwC cohort also had the highest number of psychotherapy sessions and medication prescriptions per patient (20.1 sessions, 12.6 off-label prescriptions, and 2.0 FDA-approved prescriptions [p<0.001]). The proportion of days covered (PDC) indicated low medication adherence (0.25-0.40) with adherent patient rates (PDC ≥0.80) between 8.0-17.5%. The SUD/AUD sub-analysis identified 85 BP, 537 PwoC, and 3154 PwC patients. Conclusions were similar, with PwC cohort having highest treatment utilization rates (87.1% psychotherapy, 85.0% off-label medications, 28.2% FDA-approved medications [p≤0.013] with 24.4 sessions, 16.1 off-label prescriptions, and 2.0 FDA-approved prescriptions per patient [p≤0.002]). Only 4.7-11.4% of patients were adherent., Conclusions: PwC patients received psychotherapy and pharmacotherapy more frequently than PwoC and BP patients. Medication adherence among treated patients was low. Patients with SUD/AUD had numerically higher treatment utilization and lower medication adherence., Competing Interests: The authors have read the journal’s policy and have the following competing interests: FS, VZ, and DG are employees of ZRx Outcomes Research Inc., which received funding from Lykos for this work. DDA is an employee of Lykos. WB was an employee of Lykos at the time of the study conduction and manuscript submission. Lykos is developing 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy, which has not been approved by any regulatory agency. The safety and efficacy of MDMA-assisted therapy have not been established for the treatment of PTSD. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no additional patents, products in development, or marketed products associated with this research to declare.", (Copyright: © 2024 Stanicic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study describes graduate medical education (GME) placement outcomes for recent U.S. medical school graduates and examines racial and ethnic differences in GME placement among these graduates., Method: This retrospective, observational study used data collected from and about U.S. medical school graduates for academic years 2015-2016 through 2021-2022. An individual-level, deidentified database was constructed to examine GME placement at graduation in association with race and ethnicity, as well as other demographic and academic and professional development variables. Multilevel (nested by school) logistic regression models identified variables independently associated with GME placement at graduation, reporting unadjusted odds ratios (UORs) and adjusted odds ratios (AORs) with 95% CIs., Results: The study sample included 140,072 of 140,073 eligible graduates (> 99.9%; 1 graduate missing gender information was excluded), of whom 136,022 (97.1%) were placed in GME at graduation. Proportions of graduates placed in GME varied by race and ethnicity and by each covariable examined. In addition, proportions of graduates placed in GME varied by school (N = 152; mean [SD], 96.9% [3.4%]; P < .001). In multilevel (nested by school) models, GME placement UORs were lower for (among other groups examined) Asian (UOR, 0.76; 95% CI, 0.70-0.83), Black or African American (UOR, 0.44; 95% CI, 0.39-0.49), and Hispanic (UOR, 0.70; 95% CI, 0.60-0.80) graduates (vs White). The GME placement AORs, adjusted for all covariables, were similar for Asian (AOR, 0.96; 95% CI, 0.87-1.07), Black or African American (AOR, 0.89; 95% CI, 0.77-1.02), and Hispanic (AOR, 1.06; 95% CI, 0.89-1.25) graduates (vs White)., Conclusions: The proportion of graduates placed in GME at graduation during the 7 years of the study was high. However, there were racial and ethnic differences in this outcome during the study period., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of American Medical Colleges.)

Aim: Explore the safety of Belbuca® (buprenorphine buccal film), buprenorphine transdermal patches and oral opioids for chronic low back pain (cLBP) treatment. Methods: The retrospective analysis of the MarketScan Commercial database (2018-2021) included treatment-naive cLBP adults. The first date of buprenorphine (Belbuca and transdermal patch) or opioid prescription was index date. Cohorts were defined based on the index medication. Observation included a 6-month pre-index period, while post-index lasted until the end of continuous insurance coverage. There were 44 relevant treatment-emergent adverse events (TEAEs) identified in the literature. Incidence rate ratio (IRR) and incidence rate difference (IRD) were used to compare serious TEAE rates (in 1000 person-years) between cohorts. Propensity-score matching minimized the selection bias. Results: Buprenorphine had lower rates of 15 serious TEAEs than oral opioids (all p ≤ 0.037), while higher rates only for serious dizziness (IRR 2.44, p = 0.011; driven by Belbuca), opioid abuse/dependence (IRR 3.13, p = 0.004; driven by patches) and cholecystitis (IRD 20.25, p = 0.044; an outlier). Additionally, a comparison between Belbuca and oral opioids showed lower rates of 13 serious TEAEs (all p ≤ 0.024) and a higher serious dizziness rate (IRR 3.17, p = 0.024). Although the rates of serious opioid abuse/dependence were similar (24.60 vs 26.93, p = 0.921), all Belbuca patients and none of the opioid patients had a positive history of these events. Belbuca also had lower rates of five serious TEAEs than transdermal patches (all p ≤ 0.018), including a serious opioid abuse/dependence (IRR 0.04, p < 0.001), but higher rates of serious cholecystitis (IRD 52.17, p = 0.035; an outlier) and suicidal ideation (IRD 156.50, p < 0.001; an outlier). Conclusion: Buprenorphine had a better safety profile than oral opioids in cLBP treatment. Belbuca showed a more favorable TEAE profile than buprenorphine transdermal patches and oral opioids.

Background & Aims: Treatment outcomes for people living with autoimmune hepatitis (AIH) are limited by a lack of specific therapies, as well as limited well-validated prognostic tools and clinical trial endpoints. We sought to identify predictors of outcome for people living with AIH., Methods: We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis., Results: In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12 months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and IgG values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased the risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival., Conclusion: In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose., Impact and Implications: Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, and uses continuous measurements over follow-up. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side effects., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver transplant (LT)-free survival., Methods: We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at 1 year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥1.67x the upper limit of normal or abnormal serum total bilirubin at 1 year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to LT or death. Results were validated in an external cohort (GLOBAL PBC registry)., Results: A total of 823 patients from eight centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at 1 year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95% CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 95% CI 0.001-0.568), and patients who lost response once more (0.010, 95% CI 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 95% CI 0.040-0.566). Analyses in the GLOBAL PBC registry (n = 2,237) validated these results., Conclusion: Loss of biochemical response at any time is associated with heightened risks of LT or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy., Impact and Implications: Early biochemical response to ursodeoxycholic acid is associated with good prognosis in patients with primary biliary cholangitis (PBC). Our work demonstrates that patients with PBC transition between biochemical response states over time, and that these transitions correspond with changes in risk of liver transplantation or death. Clinicians should re-evaluate risk and optimize treatment decisions for patients with PBC throughout follow-up, regardless of early biochemical response to therapy., (© 2024 The Author(s).)

Purpose: The COVID-19 pandemic resulted in unprecedented changes to the medical education learning environment. The graduating class of 2021 was particularly affected. To better understand how students were affected, the authors explored positive and negative experiences described by graduating U.S. medical students., Method: Using the conceptual framework of affordances, the authors examined narrative responses to 2 new open-ended questions on the Association of American Medical Colleges 2021 Graduation Questionnaire in which graduating students described the pandemic's positive and negative effects on their medical school experiences and career preparation. Conventional content analysis was used to identify affordances and themes in responses., Results: Of 16,611 Graduation Questionnaire respondents, 8,926 (54%) provided narrative responses. Of these 8,926 respondents, responses from 2,408 students (27%) were analyzed. Students described positive and negative perceptions of affordances, centering around virtual learning, social connection, and transition to residency. Fewer in-person and increased virtual clinical rotations offered students flexible scheduling, allowing them greater opportunity to explore academic and professional interests. Additionally, students' sense of isolation from their medical school was alleviated when schools exercised intentional open communication and student involvement in decision making. Although many described a diminished sense of preparedness for residency due to limited access to in-person clinical experiences and to assessing residencies largely through virtual away rotations and interviews, the sense of community, adaptability, and resiliency gained through varied activities reinforced students' professional identity and commitment to medicine during a time of much uncertainty., Conclusions: This national exploration of students' pandemic experiences highlights what students value as fundamental elements of medical education and student support and describes how innovation can improve long-standing practices. These findings, guided by students' insights, can help inform the work of educational leaders as they consider which innovations should remain to continue enhancing student learning, engagement, and well-being., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of American Medical Colleges.)