Citations

OBJECTIVE Despite the use of multiple glucose-lowering medications, glycemic targets are not met in a significant fraction of people with type 2 diabetes. In this prospective, observational study we assessed the prevalence of hypercortisolism, a potential contributing factor to inadequate glucose control. RESEARCH DESIGN AND METHODS Individuals with type 2 diabetes and HbA1c 7.5%–11.5% (58–102 mmol/mol) on two or more glucose-lowering medications with or without micro-/macrovascular complications or taking multiple blood pressure–lowering medications were screened with a 1-mg dexamethasone suppression test. Common causes of false-positive DSTs were excluded. The primary end point was the prevalence of hypercortisolism, defined as post-DST cortisol >1.8 μg/dL (50 nmol/L). Characteristics associated with hypercortisolism were assessed with multiple logistic regression. The percentage and characteristics of participants with hypercortisolism and adrenal imaging abnormalities were also assessed. RESULTS Post-DST cortisol was unsuppressed in 252 of 1,057 participants (prevalence 23.8%; 95% CI 21.3, 26.5). Hypercortisolism prevalence was 33.3% among participants with cardiac disorders and 36.6% among those taking three or more blood pressure–lowering medications. Adrenal imaging abnormalities were reported in 34.7% of participants with hypercortisolism. Use of sodium–glucose cotransporter 2 inhibitors (odds ratio 1.558), maximum-dose glucagon-like peptide 1 receptor agonists (1.544), tirzepatide (1.981), or a higher number of blood pressure–lowering medications (1.390); older age (1.316); BMI <30 kg/m2 (1.639); non-Latino/Hispanic ethnicity (3.718); and use of fibrates (2.676) or analgesics (1.457) were associated with higher prevalence (all P < 0.03). CONCLUSIONS Hypercortisolism was associated with hyperglycemia in approximately one-quarter of individuals with inadequately controlled type 2 diabetes despite multiple medications.

Importance Use of modern neoadjuvant chemotherapy (NAC) regimens has markedly increased rates of pathologic complete response (pCR) in breast cancer, raising the question of whether surgical removal of the primary tumor is required for patients with pCR. For surgery to be omitted, one must be able to accurately predict pCR before surgery. Objective To investigate if adding post-NAC core needle biopsy of the tumor bed to trimodality imaging in patients who have clinical complete response (cCR) will predict pCR (resolution of both invasive disease and ductal carcinoma in situ) in 90% or more cases. Design, Setting, and Participants This was a phase 2, prospective, nonrandomized clinical trial. Patients were enrolled from August 2017 to June 2019. This is the final analysis, which was completed in December 2023. The setting included academic and community hospital center members of NRG (ie, the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group) in the US and Canada. Patients with operable (T1-T3, stage I-III) invasive ductal carcinoma who completed NAC and achieved cCR and radiological complete response (rCR) or near rCR by mammography (mass ≤1 cm and no malignant microcalcifications), ultrasound (mass ≤2 cm), and magnetic resonance imaging (no mass with rapid rise or washout kinetics). Interventions Patients underwent marker-directed stereotactic multiple-core needle biopsy of the tumor bed with marker placement before breast-conservation surgery. Main Outcomes and Measures End points were negative predictive value (NPV) and sensitivity of the biopsy. Results A total of 105 patients were enrolled with 101 evaluable (mean [SD] age, 52.8 [10.5] years); 77 patients (76.2%) were younger than 60 years, and all breast cancer subtypes were represented with 32 (31.7%) triple-negative breast cancer, 21 (20.8%) hormone receptor–positive/epidermal growth factor receptor 2 ( ERBB2 ; formerly HER2 )–negative ( ERBB2 −) breast cancer, and 46 (45.5%) ERBB2 -positive ( ERBB2 +) breast cancer. In 101 evaluable patients, 36 had residual disease at surgery (pCR = 64%). With imaging criteria, NPV of the biopsy was 78.3% (95% CI, 67.9%-86.6%), and the sensitivity of the biopsy was 50% (95% CI, 32.9%-67.1%). In an exploratory subset analysis, the NPV in patients with ERBB2 + breast cancer was 90% (95% CI, 76.3%-97.2%). On retrospective central review, 62 of 101 enrolled patients met imaging eligibility criteria. In this exploratory post hoc analysis, NPV in these patients was 86.8% (95% CI, 74.7%-94.5%). Conclusions and Relevance These findings do not support breast conservation treatment without surgery based on the study criteria for cCR and rCR/near rCR by trimodality imaging and negative tumor-bed biopsy. Strict adherence to imaging criteria may be required to achieve acceptable predictive values. TRIAL Registration ClinicalTrials.gov Identifier: NCT03188393

Introduction: Online self-triage/symptom checkers are a relatively new e-Health modality. We aimed to evaluate the degree to which patient’s chosen symptom during the use of an online self-triage tool was congruent with that chosen by a nurse performing phone triage. Methods: Patient encounters from September 1, 2022, to September 30, 2023, were reviewed for patients who completed both online self-triage and a subsequent nursing phone triage within 24 hours. The symptoms chosen by the patient for their self-triage encounter and the symptoms chosen by the nurse during the subsequent nurse triage were reviewed. The symptoms chosen in these two triage encounters were then compared for congruency. A subset of our database was evaluated for congruency between the self-triage and the nurse phone triage endpoint recommendations. Results: There were 5,443 encounters meeting inclusion criteria to study for congruency between self-triage and nurse triage symptom choice. The range of time between self-triage and nurse triage ranged from 0 min to 1,439 min (23.9 hours) with a median of 23 minutes between self and nurse triage encounters. Symptom congruency between the two methods found 74.2% (4,038) to be completely congruent while 989 (18.2%) were somewhat congruent. Only 7.6% (416) had no apparent congruency. Out of 1,705 self and nurse triage dyads eligible for study for agreement between endpoint recommendations, 244 (14.3%) were under-triaged, 1,110 (65.1%) were triaged to the same level of care and 351 (20.6%) were over-triaged. Conclusion: Congruency between symptoms chosen by the patient for triage and nurse triage were highly congruent with only 7.6% of the sample showing no apparent congruency between the self-triage symptom and the nurse triage symptom. When compared to nurse triage, most self-triage endpoint recommendations were either triaged to the same level of care or were over-triaged to a higher level of care.

AbstractINTRODUCTIONIdentifying individuals with dementia is crucial for prevalence estimation and service planning, but reliable, scalable methods are lacking. We developed novel set algorithms using both structured and unstructured electronic health record (EHR) data, applying Diagnostic and Statistical Manual of Mental Disorders criteria for dementia case identification.METHODSOur cohort (n = 1082) included individuals aged ≥ 60 with dementia identified through specialist clinics and a comparison group without dementia. Clinicians from Australia and the United States informed predictor selection. We developed algorithms through a biostatistics stream for structured data and a natural language processing (NLP) stream for text, synthesizing results via logistic regression.RESULTSThe final structured model retained 16 variables (area under the receiver operating characteristic curve [AUC] 0.853, specificity 72.2%, sensitivity 80.6%). NLP classifiers (logistic regression, support vector machine, and random forest models) performed comparably. The final, combined model outperformed all others (AUC = 0.951, P < 0.001 for comparison to structured model).DISCUSSIONEmbedding text‐derived insights within algorithms trained on structured medical data significantly enhances dementia identification capacity.Highlights Algorithmic tools for detection of individuals with dementia are available; however, previous work has used heterogeneous case definitions which are not clinically meaningful, and has relied on proxies such as diagnostic codes or medications for case ascertainment. We used a novel, dual‐stream algorithmic development approach, simultaneously and separately modeling a clinically meaningful outcome (diagnosis of dementia according to specialized clinical impression) using structured and unstructured electronic health record datasets. Our clinically grounded case definition supported the inclusion of key structured variables (such as dementia International Classification of Disease codes and medications) as modeling predictors rather than outcomes. Our algorithms, published in detail to support validation and replication, represent a major step forward in the use of routinely collected data for detection of diagnosed dementia.

Abstract Parkinson’s disease (PD) is the fastest growing neurodegenerative disease in the world 1 . Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD 2,3,4 . We investigated peripheral relationships that may underlie mechanisms along the gut-blood axis that contribute to PD pathogenesis. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be the catalyst that primes circulating immune cells to body-first PD pathogenesis.

PURPOSE The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged progression-free survival (PFS), but without improvement in overall survival (OS), likely because of toxicity. Acalabrutinib was shown to be efficacious and less toxic than ibrutinib in a head-to-head trial in chronic lymphocytic leukemia and therefore might lead to better outcomes in MCL. METHODS Patients 65 years and older with previously untreated MCL received acalabrutinib (100 mg twice daily) or placebo (until disease progression or unacceptable toxicity), plus six cycles of bendamustine (90 mg/m 2 once daily; days 1 and 2) and rituximab (375 mg/m 2 as a single dose; day 1) followed by rituximab maintenance in responding patients for 2 years. Crossover to acalabrutinib at disease progression was permitted. The primary end point was PFS per the independent review committee; overall response rate and OS were secondary end points. RESULTS In total, 598 patients were randomly assigned, with 299 in each arm. At a median follow-up of 49.8 months using the reverse Kaplan-Meier method, the median PFS was 66.4 months in the acalabrutinib arm and 49.6 months in the placebo arm (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.94]; P = .0160). Benefit was seen across all subgroups, including those with high-risk features. Overall response/complete response rates were 91.0%/66.6% and 88.0%/53.5% in the acalabrutinib and placebo arms, respectively. OS was not significantly different (HR, 0.86 [95% CI, 0.65 to 1.13]; P = .27). Grade 3 or greater adverse events were reported in 88.9% and 88.2% in the acalabrutinib and placebo arms, respectively. CONCLUSION The combination of acalabrutinib with bendamustine-rituximab significantly improved PFS. Clinical benefit of acalabrutinib with bendamustine-rituximab was achieved with manageable toxicity.

Abstract An individual participant data (IPD) meta-analysis can assess the predictive value of data on outcomes at the individual level, offering a potential tool for developing personalized pain management. Pretreatment quantitative sensory testing (QST) may stratify patient groups, which are then linked to treatment outcomes. Our objective was to determine if measures of QST at baseline are related to treatment outcomes (at any time point) for pain and disability in lower-limb osteoarthritis. We performed a systematic review with an IPD meta-analysis. Searches were conducted in 9 databases until May 5, 2023 for intervention studies that measured baseline QST and longitudinal measures of participant-reported pain and disability. We performed a 2-stage approach to analyse longitudinal data. Individual models were fitted to each study and combined using random effects multivariate meta-analytic models. Study quality was assessed using the Joanna Briggs Institute checklist, and certainty of the evidence was assessed using GRADE. We identified 3082 records and included 1 hip and 28 knee datasets consisting of 2522 participants from 40 studies. Local warm detection thresholds (P = 0.024) predicted knee osteoarthritis pain outcomes (very-low certainty). Local warm detection thresholds (P = 0.030), remote cold detection thresholds (P = 0.05), and remote pressure tolerance thresholds (P = 0.007) predicted knee osteoarthritis disability outcomes (very-low certainty). Other QST variables were associated with hip and knee osteoarthritis pain and disability levels (eg, pressure pain thresholds), but this relationship did not change over time. This review finds that mechanism-based, QST methodologies do not consistently predict pain or disability on an individual level in hip or knee osteoarthritis.

Engaging employees in providing exemplary patient experience has been challenging for healthcare leaders in recent years given the pressures of the regulatory environment, increases in staff burnout and rising patient expectations. Amid these challenges, addressing patient experience remains a top priority for healthcare organizations. A novel intervention has been applied at Mayo Clinic with the goal of improving both employee engagement and patient experience. Previous efforts to teach service excellence involved customer service trainings, sometimes purchased through outside vendors. This new initiative is based on our organizational culture and values, input from our employees and patients, and considers the changing needs of a contemporary healthcare workforce. It leverages management practices shown to boost an employee's sense of equity, achievement, and camaraderie. It also highlights staff motivation to do their best work by involving them in conversations about the essential ingredients that make up both exceptional employee and patient experiences.

ABSTRACT Achromobacter species can cause opportunistic infections which are difficult to treat due to a variety of antimicrobial resistance (AMR) mechanisms. As such, antimicrobial susceptibility testing (AST) is a cornerstone to successful treatment for these organisms. Currently, there are no specific Clinical and Laboratory Standards Institute (CLSI) AST guidelines for Achromobacter species. The purpose of this study was to (i) establish tentative CLSI M45 MIC and disk diffusion (DD) breakpoints (BPs), (ii) evaluate the modified carbapenem inactivation method (mCIM), and (iii) understand the mechanisms mediating AMR among Achromobacter species. Contemporary MIC data from multiple sources were collated to define the tentative epidemiological cutoff values (tECVs), and the MIC distributions were used to inform the establishment of MIC BPs for various agents. A disk-to-MIC correlate study with 91 isolates from across the United States was completed by testing reference broth microdilution and DD from the same inoculum and applying the dBETS software to establish DD BPs. Lastly, the mCIM and whole-genome sequencing (WGS) were pursued. The tECVs for piperacillin-tazobactam, imipenem, and meropenem were 1, 2, and 0.5 µg/mL, respectively. Disk correlates met CLSI M23 acceptance criteria with a few exceptions related to a small number of isolates, resulting in high minor errors. WGS revealed that 82 (90.1%) isolates harbored a bla OXA variant with bla OXA-114 predominating (90.2%). Nineteen isolates harbored acquired beta-lactamase genes, including 16 bla AXC , 2 bla VIM-4 , and 1 bla AZM-1. The mCIM had a sensitivity of 100% and specificity of 87%. Upon review, the CLSI M45 committee set tentative MIC and DD BPs for piperacillin-tazobactam, imipenem, meropenem, and trimethoprim-sulfamethoxazole. IMPORTANCE Achromobacter species can cause opportunistic infections which may be difficult to treat due to a variety of antimicrobial resistance mechanisms. Antimicrobial susceptibility testing is a critical component of patient treatment for these infections. Currently, the Clinical and Laboratory Standards Institute M100 non-Enterobacterales susceptibility test interpretive criteria and methodology are utilized for Achromobacter by clinical laboratories and likely do not accurately predict susceptibility results for Achromobacter species. This study was designed to establish tentative MIC and disk diffusion breakpoints specific to Achromobacter species.