BACKGROUND AND PURPOSE:

Overuse of CT-based cerebrovascular imaging in the emergency department and inpatient settings, notably CTA of the head and neck for minor and nonfocal neurologic presentations, stresses imaging services and exposes patients to radiation and contrast. Furthermore, such CT-based imaging is often insufficient for definitive diagnosis, necessitating additional MR imaging. Recent advances in fast MRI may allow timely assessment and a reduced need for head and neck CTA in select populations.

MATERIALS AND METHODS:

We identified inpatients or patients in the emergency department who underwent CTAHN (including noncontrast and postcontrast head CT, with or without CTP imaging) followed within 24 hours by a 3T MRI study that included a 2.5-minute unenhanced multicontrast sequence (NeuroMix) and a 5-minute intracranial time of flight MRA) during a 9-month period (April to December 2022). Cases were classified by 4 radiologists in consensus as to whether NeuroMix and NeuroMix + MRA detected equivalent findings, detected unique findings, or missed findings relative to CTAHN.

RESULTS:

One hundred seventy-four cases (mean age, 67 [SD, 16] years; 56% female) met the inclusion criteria. NeuroMix alone and NeuroMix + MRA protocols were determined to be equivalent or better compared with CTAHN in 71% and 95% of patients, respectively. NeuroMix always provided equivalent or better assessment of the brain parenchyma, with unique findings on NeuroMix and NeuroMix + MRA in 35% and 36% of cases, respectively, most commonly acute infarction or multiple microhemorrhages. In 8/174 cases (5%), CTAHN identified vascular abnormalities not seen on the NeuroMix + MRA protocol due to the wider coverage of the cervical arteries by CTAHN.

CONCLUSIONS:

A fast MR imaging protocol consisting of NeuroMix + MRA provided equivalent or better information compared with CTAHN in 95% of cases in our population of patients with an acute neurologic presentation. The findings provide a deeper understanding of the benefits and challenges of a fast unenhanced MR-first approach with NeuroMix + MRA, which could be used to design prospective trials in select patient groups, with the potential to reduce radiation dose, mitigate adverse contrast-related patient and environmental effects, and lessen the burden on radiologists and health care systems.

BACKGROUND AND PURPOSE:

Mechanical thrombectomy is a fundamental intervention for acute ischemic stroke treatment. While conventional techniques are effective, cyclic aspiration (CyA) shows potential for better recanalization rates. We aim to investigate factors affecting CyA and compare them with static aspiration (StA).

MATERIALS AND METHODS:

StA setup consisted of an aspiration pump connected to pressure transducer. CyA was tested with 5 subsequent iterations: single solenoid valve with air plus saline (i1) or saline alone (i2) as aspiration medium; 2 solenoid valves with air plus saline (i3) as aspiration medium; complete air removal and saline feeding (i4); and pressurized saline feeding (i5). To assess the efficacy of clot ingestion, the pressure transducer was replaced with a distal aspiration catheter. Moderately stiff clot analogs (15 mm) were used to investigate the ingestion quantified as clot relative weight loss. Additionally, the aspiration flow rate was assessed for each setup.

RESULTS:

With CyA i1, the amplitude of the achieved negative pressure waves declined with increasing frequencies but progressively increased with each subsequent iteration, achieving a maximum amplitude of 81 kPa for i5 at 1 Hz. Relative clot weight loss was significantly higher with i5 at 5 Hz than with StA (100% versus 37.8%; P = .05). Aspiration flow rate was lower with CyA than with StA (i5 at 5 Hz: 199.8 mL/min versus StA: 311 mL/min; P < .01).

CONCLUSIONS:

CyA with the appropriate setup may represent an encouraging innovation in mechanical thrombectomy, offering a promising pathway for improving efficacy in clot ingestion and recanalization. The observed benefits warrant confirmation in a clinical setting.

BACKGROUND AND PURPOSE:

Prediction of aneurysm instability is crucial to guide treatment decisions and to select appropriate patients with unruptured intracranial aneurysms (IAs) for preventive treatment. High-resolution 4D MR flow imaging and 3D quantification of aneurysm morphology could offer insights and new imaging markers for aneurysm instability. In this cross-sectional study, we aim to identify 4D MR flow imaging markers for aneurysm instability by relating hemodynamics in the aneurysm sac to 3D morphologic proxy parameters for aneurysm instability.

MATERIALS AND METHODS:

In 35 patients with 37 unruptured IAs, a 3T MRA and a 7T 4D MRI flow scan were performed. Five hemodynamic parameters—peak-systolic wall shear stress (WSS_MAX) and time-averaged wall shear stress (WSS_MEAN), oscillatory shear index (OSI), mean velocity, and velocity pulsatility index—were correlated to 6 3D morphology proxy parameters of aneurysm instability—major axis length, volume, surface area (all 3 size parameters), flatness, shape index, and curvedness—by Pearson correlation with 95% CI. Scatterplots of hemodynamic parameters that correlated with IA size (major axis length) were created.

RESULTS:

WSS_MAX and WSS_MEAN correlated negatively with all 3 size parameters (strongest for WSS_MEAN with volume (r = –0.70, 95% CI –0.83 to –0.49) and OSI positively (strongest with major axis length [r = 0.87, 95% CI 0.76–0.93]). WSS_MAX and WSS_MEAN correlated positively with shape index (r = 0.61, 95% CI 0.36–0.78 and r = 0.49, 95% CI 0.20–0.70, respectively) and OSI negatively (r = –0.82, 95% CI –0.9 to –0.68). WSS_MEAN and mean velocity correlated negatively with flatness (r = –0.35, 95% CI –0.61 to –0.029 and r = –0.33, 95% CI –0.59 to 0.007, respectively) and OSI positively (r = 0.54, 95% CI 0.26–0.74). Velocity pulsatility index did not show any statistically relevant correlation.

CONCLUSIONS:

Out of the 5 included hemodynamic parameters, WSS_MAX, WSS_MEAN, and OSI showed the strongest correlation with morphologic 3D proxy parameters of aneurysm instability. Future studies should assess these promising new imaging marker parameters for predicting aneurysm instability in longitudinal cohorts of patients with IA.

BACKGROUND AND PURPOSE:

Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees.

MATERIALS AND METHODS:

This prospective study was conducted between March 2023 and October 2023. Medical students and resident trainees were asked to identify intracranial hemorrhage and large-vessel occlusion in 100 noncontrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating artificial intelligence for intracranial hemorrhage only (n = 26); the other, for large-vessel occlusion only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for intracranial hemorrhage/large-vessel occlusion detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with the t test; differences in continuous variables were assessed with ANOVA.

RESULTS:

Forty-eight participants completed the study, generating 10,779 intracranial hemorrhage or large-vessel occlusion interpretations. With diagnostic aid, medical student accuracy improved 11.0 points (P < .001) and resident trainee accuracy showed no significant change. Intracranial hemorrhage interpretation time increased with diagnostic aid for both groups (P < .001), while large-vessel occlusion interpretation time decreased for medical students (P < .001). Despite worse performance in the detection of the smallest-versus-largest hemorrhages at baseline, medical students were not more likely to accept a true-positive artificial intelligence result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the artificial intelligence or when supplied with an incorrect artificial intelligence result.

CONCLUSIONS:

This study demonstrated greater improvement in diagnostic accuracy with artificial intelligence for medical students compared with resident trainees. However, medical students were less likely than resident trainees to overrule incorrect artificial intelligence interpretations and were less accurate, even with diagnostic aid, than the artificial intelligence was by itself.

SUMMARY:

Vascular inflammation is widely recognized as an important factor in the atherosclerotic process, particularly in terms of plaque development and progression. Conventional tests, such as measuring circulating inflammatory biomarkers, lack the precision to identify specific areas of vascular inflammation. In this context, noninvasive imaging modalities can detect perivascular fat changes, serving as a marker of vascular inflammation. This review aims to provide a comprehensive overview of the key concepts related to perivascular carotid fat and its pathophysiology. Additionally, we examine the existing literature on the association of pericarotid fat with features of plaque vulnerability and cerebrovascular events. Finally, we scrutinize the advantages and limitations of the noninvasive assessment of pericarotid fat.

Dihydropyrimidinase (DHP) deficiency is an autosomal recessive metabolic disorder caused by biallelic pathogenic variants of DPYS. Patients with DHP deficiency exhibit a broad spectrum of phenotypes, ranging from severe neurological and gastrointestinal involvement to cases with no apparent symptoms. The biochemical diagnosis of DHP deficiency is based on the detection of a significant amount of dihydropyrimidines in urine, plasma, and cerebrospinal fluid samples. Molecular genetic testing, specifically the identification of biallelic pathogenic variants in DPYS, has proven instrumental in confirming the diagnosis and facilitating family studies. This case study documents the diagnostic journey of an 18-yr-old patient with DHP deficiency, highlighting features at the severe end of the clinical spectrum. Notably, our patient exhibited previously unreported skeletal features that positively responded to bisphosphonate treatment, contributing valuable insights to the clinical characterization of DHP deficiency. Additionally, a novel DPYS variant was identified and confirmed pathogenicity through metabolic testing, further expanding the variant spectrum of the gene. Our case emphasizes the importance of a comprehensive diagnostic approach using genetic sequencing and metabolic testing for accurate diagnosis.

We present a unique case of a single patient presenting with two mutationally distinct, PD-L1⁺ diffuse large B-cell lymphomas (DLBCLs). One of these DLBCLs demonstrated exceptionally high mutational burden (eight disease-associated variants and 41 variants of undetermined significance) with microsatellite instability (MSI) and an acquired PMS2 mutation with loss of PMS2 protein expression, detected postchemotherapy. This report, while highlighting the extent of possible tumor heterogeneity across separate clonal expansions as well as possible syndromic B-cell neoplasia, supports the notion that, although rare, PD-L1 expression and associated states permissive of high mutational burden (such as mismatch repair gene loss of function/MSI) should be more routinely considered in DLBCLs. Appropriate testing may be predictive of outcome and inform the utility of targeted therapy in these genetically diverse and historically treatment-refractory malignancies.

The potential for more than one distinct hematolymphoid neoplasm to arise from a common mutated stem or precursor cell has been proposed based on findings in primary human malignancies. Particularly, angioimmunoblastic T-cell lymphoma (AITL), which shares a somatic mutation profile in common with other hematopoietic malignancies, has been reported to occur alongside myeloid neoplasms or clonal B-cell proliferations, with identical mutations occurring in more than one cell lineage. Here we report such a case of an elderly woman who was diagnosed over a period of 8 years with diffuse large B-cell lymphoma, polycythemia vera, and AITL, each harboring identical somatic mutations in multiple genes. Overall, at least five identical nucleotide mutations were shared across multiple specimens, with two identical mutations co-occurring at variable variant allele frequencies in all three specimen types. These findings lend credence to the theory that a common mutated stem cell could give rise to multiple neoplasms through parallel hematopoietic differentiation pathways.

Although the progressive histologic steps leading to endometrial cancer (EndoCA), the most common female reproductive tract malignancy, from endometrial hyperplasia are well-established, the molecular changes accompanying this malignant transformation in a single patient have never been described. We had the unique opportunity to investigate the paired histologic and molecular features associated with the 12-yr development of EndoCA in a postmenopausal female who could not undergo hysterectomy and instead underwent progesterone treatment. Using a specially designed 58-gene next-generation sequencing panel, we analyzed a total of 10 sequential biopsy samples collected over this time frame. A total of eight pathogenic/likely pathogenic mutations in seven genes, APC, ARID1A, CTNNB1, CDKN2A, KRAS, PTEN, and TP53, were identified. A PTEN nonsense mutation p.W111* was present in all samples analyzed except histologically normal endometrium. Apart from this PTEN mutation, the only other recurrent mutation was KRAS G12D, which was present in six biopsy samplings, including histologically normal tissue obtained at the patient's first visit but not detectable in the cancer. The PTEN p.W111* mutant allele fractions were lowest in benign, inactive endometrial glands (0.7%), highest in adenocarcinoma (36.9%), and, notably, were always markedly reduced following progesterone treatment. To our knowledge, this report provides the first molecular characterization of EndoCA development in a single patient. A single PTEN mutation was present throughout the 12 years of cancer development. Importantly, and with potential significance toward medical and nonsurgical management of EndoCA, progesterone treatments were consistently noted to markedly decrease PTEN mutant allele fractions to precancerous levels.

Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers.

Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum–bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement—an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome.

Veterans are at an increased risk for prostate cancer, a disease with extraordinary clinical and molecular heterogeneity, compared with the general population. However, little is known about the underlying molecular heterogeneity within the veteran population and its impact on patient management and treatment. Using clinical and targeted tumor sequencing data from the National Veterans Affairs health system, we conducted a retrospective cohort study on 45 patients with advanced prostate cancer in the Veterans Precision Oncology Data Commons (VPODC), most of whom were metastatic castration-resistant. We characterized the mutational burden in this cohort and conducted unsupervised clustering analysis to stratify patients by molecular alterations. Veterans with prostate cancer exhibited a mutational landscape broadly similar to prior studies, including KMT2A and NOTCH1 mutations associated with neuroendocrine prostate cancer phenotype, previously reported to be enriched in veterans. We also identified several potential novel mutations in PTEN, MSH6, VHL, SMO, and ABL1. Hierarchical clustering analysis revealed two subgroups containing therapeutically targetable molecular features with novel mutational signatures distinct from those reported in the Catalogue of Somatic Mutations in Cancer database. The clustering approach presented in this study can potentially be used to clinically stratify patients based on their distinct mutational profiles and identify actionable somatic mutations for precision oncology.

Electron transport chain (ETC) disorders are a group of rare, multisystem diseases caused by impaired oxidative phosphorylation and energy production. Deficiencies in complex III (CIII), also known as ubiquinol–cytochrome c reductase, are particularly rare in humans. Ubiquinol–cytochrome c reductase core protein 2 (UQCRC2) encodes a subunit of CIII that plays a crucial role in dimerization. Several pathogenic UQCRC2 variants have been identified in patients presenting with metabolic abnormalities that include lactic acidosis, hyperammonemia, hypoglycemia, and organic aciduria. Almost all previously reported UQCRC2-deficient patients exhibited neurodevelopmental involvement, including developmental delays and structural brain anomalies. Here, we describe a girl who presented at 3 yr of age with lactic acidosis, hyperammonemia, and hypoglycemia but has not shown any evidence of neurodevelopmental dysfunction by age 15. Whole-exome sequencing revealed compound heterozygosity for two novel variants in UQCRC2: c.1189G>A; p.Gly397Arg and c.437T>C; p.Phe146Ser. Here, we discuss the patient's clinical presentation and the likely pathogenicity of these two missense variants.

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease–associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).

Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions.

TP53 plays a critical role as a tumor suppressor by controlling cell cycle progression, DNA repair, and apoptosis. Post-translational modifications such as acetylation of specific lysine residues in the DNA binding and carboxy-terminus regulatory domains modulate its tumor suppressor activities. In this study, we addressed the functional consequences of the germline TP53 p.K164E (NM_000546.5: c.490A>G) variant identified in a patient with early-onset breast cancer and a significant family history of cancer. K164 is a conserved residue located in the L2 loop of the p53 DNA binding domain that is post-translationally modified by acetylation. In silico, in vitro, and in vivo analyses demonstrated that the glutamate substitution at K164 marginally destabilizes the p53 protein structure but significantly impairs sequence-specific DNA binding, transactivation, and tumor cell growth inhibition. Although p.K164E is currently considered a variant of unknown significance by different clinical genetic testing laboratories, the clinical and laboratory-based findings presented here provide strong evidence to reclassify TP53 p.K164E as a likely pathogenic variant.

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance.

The usual challenges of conducting primary care research, including randomized trials, have been exacerbated, and new ones identified, during the COVID-19 pandemic. HOMER (Home versus Office for Medication Enhanced Recovery; subsequently, Comparing Home, Office, and Telehealth Induction for Medication Enhanced Recovery) is a pragmatic, comparative-effectiveness research trial that aims to answer a key question from patients and clinicians: What is the best setting in which to start treatment with buprenorphine for opioid use disorder for this patient at this time? In this article, we describe the difficult journey to find the answer. The HOMER study began as a randomized trial comparing treatment outcomes in patients starting treatment with buprenorphine via induction at home (unobserved) vs in the office (observed, synchronous). The study aimed to enroll 1,000 participants from 100 diverse primary care practices associated with the State Networks of Colorado Ambulatory Practices and Partners and the American Academy of Family Physicians National Research Network. The research team faced unexpected challenges related to the COVID-19 pandemic and dramatic changes in the opioid epidemic. These challenges required changes to the study design, protocol, recruitment intensity, and funding conversations, as well as patience. As this is a participatory research study, we sought, documented, and responded to practice and patient requests for adaptations. Changes included adding a third study arm using telehealth induction (observed via telephone or video, synchronous) and switching to a comprehensive cohort design to answer meaningful patient-centered research questions. Using a narrative approach based on the Greek myth of Homer, we describe here the challenges and adaptations that have provided the opportunity for HOMER to thrive and find the way home. These clinical trial strategies may apply to other studies faced with similar cultural and extreme circumstances.

PURPOSE

HIV pre-exposure prophylaxis (PrEP) may increase rates of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM) through risk compensation (eg, an increase in condomless sex or number of partners); however, longitudinal studies exploring the time-dependent nature of PrEP uptake and bacterial STIs are limited. We used marginal structural models to estimate the effect of PrEP uptake on STI incidence.

METHODS

We analyzed data from the iCruise study, an online longitudinal study of 535 Ontarian GBM from July 2017 to April 2018, to estimate the effects of PrEP uptake on incidence of self-reported bacterial STIs (chlamydia, gonorrhea, and syphilis) collected with 12 weekly diaries. The incidence rate was calculated as the number of infections per 100 person-months, with evaluation of the STIs overall and individually. We used marginal structural models to account for time-varying confounding and quantitative bias analysis to evaluate the sensitivity of estimates to nondifferential outcome misclassification.

RESULTS

Participating GBM were followed up for a total of 1,623.5 person-months. Overall, 70 participants (13.1%) took PrEP during the study period. Relative to no uptake, PrEP uptake was associated with an increased incidence rate of gonorrhea (incidence rate ratio = 4.00; 95% CI, 1.67-9.58), but not of chlamydia or syphilis, and not of any bacterial STI overall. Accounting for misclassification, the median incidence rate ratio for gonorrhea was 2.36 (95% simulation interval, 1.08-5.06).

CONCLUSIONS

We observed an increased incidence rate of gonorrhea associated with PrEP uptake among Ontarian GBM that was robust to misclassification. Although our findings support current guidelines for integrating gonorrhea screening with PrEP services, additional research should consider the long-term impact of PrEP among this population.

Annals Early Access article

Patient expectations of receiving antibiotics for common symptoms can trigger unnecessary use. We conducted a survey (n = 564) between January 2020 to June 2021 in public and private primary care clinics in Texas to study the prevalence and predictors of patients’ antibiotic expectations for common symptoms/illnesses. We surveyed Black patients (33%) and Hispanic/Latine patients (47%), and over 93% expected to receive an antibiotic for at least 1 of the 5 pre-defined symptoms/illnesses. Public clinic patients were nearly twice as likely to expect antibiotics for sore throat, diarrhea, and cold/flu than private clinic patients. Lack of knowledge of potential risks of antibiotic use was associated with increased antibiotic expectations for diarrhea (odds ratio [OR] = 1.6; 95% CI, 1.1-2.4) and cold/flu symptoms (OR = 2.9; 95% CI, 2.0-4.4). Lower education and inadequate health literacy were predictors of antibiotic expectations for diarrhea. Future antibiotic stewardship interventions should tailor patient education materials to include information on antibiotic risks and guidance on appropriate antibiotic indications.

The aim of this work is to test whether the use of a transparent capsule affects the residual capsule weight after inhalation as a surrogate of the inhaled delivered dose for patients with non-reversible chronic airway disease. Researchers conducted an observational cross-sectional study with patients using a single-dose dry powder inhaler. The weight of the capsule was measured with a precision microbalance before and after inhalation. Ninety-one patients were included, of whom 63 (69.2%) used a transparent capsule. Inhalation with a transparent capsule achieved a weight decrease of 30.1% vs 8.6% for devices with an opaque capsule (P <0.001). These data reinforce the need to provide patients with mechanisms that verify the correct inhalation technique.

PURPOSE

The impact of digital health on medically underserved patients is unclear. This study aimed to determine the early impact of a digital innovation to grow quality care through an interprofessional care team (DIG IT) on the blood pressure (BP) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score of medically underserved patients.

METHODS

This was a 3-month, prospective intervention study that included patients aged 40 years or more with BP of 140/90 mmHg or higher who received care from DIG IT from August through December 2021. Sociodemographic and clinical outcomes of DIG IT were compared with historical controls (controls) whose data were randomly extracted by the University of California Data Warehouse and matched 1:1 based on age, ethnicity, and baseline BP of the DIG IT arm. Multiple linear regression was performed to adjust for potential confounding factors.

RESULTS

A total of 140 patients (70 DIG IT, 70 controls) were included. Both arms were similar with an average age (SD) of 62.8 (9.7) years. The population was dominated by Latinx (79.3%) persons, with baseline mean BP of 163/81 mmHg, and mean ASCVD risk score of 23.9%. The mean (SD) reduction in systolic BP at 3 months in the DIG IT arm was twice that of the controls (30.8 [17.3] mmHg vs 15.2 [21.2] mmHg; P <.001). The mean (SD) ASCVD risk score reduction in the DIG IT arm was also twice that of the controls (6.4% [7.4%] vs 3.1% [5.1%]; P = .003).

CONCLUSIONS

The DIG IT was more effective than controls (receiving usual care). Twofold improvement in the BP readings and ASCVD scores in medically underserved patients were achieved with DIG IT.

PURPOSE

Meeting scholarly activity requirements continues to be a challenge in many family medicine (FM) residency programs. Studies comprehensively describing FM resident scholarship have been limited. We sought to identify institutional factors associated with increased scholarly output and meeting requirements of the Accreditation Council for Graduate Medical Education (ACGME).

OBJECTIVES

Our goals were to: (1) describe scholarly activity experiences among FM residents compared with ACGME requirements; (2) classify experiences by Boyer’s domains of scholarship; and (3) associate experiences with residency program characteristics and scholarly activity infrastructure.

METHODS

This was a cross-sectional survey. The survey questions were part of an omnibus survey to FM residency program directors conducted by the Council of Academic Family Medicine Educational Research Alliance (CERA). All ACGME-accredited US FM residency program directors, identified by the Association of Family Medicine Residency Directors, were sampled.

RESULTS

Of the 691 eligible program directors, 298 (43%) completed the survey. The respondents reported that 25% or more residents exceeded ACGME minimum output, 17% reported that 25% or more residents published their work, and 50% reported that 25% or more residents delivered conference presentations. Programs exceeding ACGME scholarship requirements exhibit robust infrastructure characterized by access to faculty mentorship, scholarly activity curricula, Institutional Review Board, medical librarian, and statistician.

CONCLUSIONS

These findings suggest the need for codified ACGME requirements for scholarly activity infrastructure to ensure access to resources in FM residency programs. By fostering FM resident engagement in scholarly activity, programs help to create a culture of inquiry, and address discrepancies in funding and output among FM residency programs.

PURPOSE

We undertook a trial to test the efficacy of a technology-assisted health coaching intervention for weight management, called Goals for Eating and Moving (GEM), within primary care.

METHODS

This cluster-randomized controlled trial enrolled 19 primary care teams with 63 clinicians; 9 teams were randomized to GEM and 10 to enhanced usual care (EUC). The GEM intervention included 1 in-person and up to 12 telephone-delivered coaching sessions. Coaches supported goal setting and engagement with weight management programs, facilitated by a software tool. Patients in the EUC arm received educational handouts. We enrolled patients who spoke English or Spanish, were aged 18 to 69 years, and either were overweight (body mass index 25-29 kg/m²) with a weight-related comorbidity or had obesity (body mass index ≥30 kg/m²). The primary outcome (weight change at 12 months) and exploratory outcomes (eg, program attendance, diet, physical activity) were analyzed according to intention to treat.

RESULTS

We enrolled 489 patients (220 in the GEM arm, 269 in the EUC arm). Their mean (SD) age was 49.8 (12.1) years; 44% were male, 41% Hispanic, and 44% non-Hispanic Black. At 12 months, the mean adjusted weight change (standard error) was –1.4 (0.8) kg in the GEM arm vs –0.8 (1.6) kg in the EUC arm, a nonsignificant difference (P = .48). There were no statistically significant differences in secondary outcomes. Exploratory analyses showed that the GEM arm had a greater change than the EUC arm in mean number of weekly minutes of moderate to vigorous physical activity other than walking, a finding that may warrant further exploration.

CONCLUSIONS

The GEM intervention did not achieve clinically important weight loss in primary care. Although this was a negative study possibly affected by health system resource limitations and disruptions, its findings can guide the development of similar interventions. Future studies could explore the efficacy of higher-intensity interventions and interventions that include medication and bariatric surgery options, in addition to lifestyle modification.

PURPOSE

Despite being key to better health outcomes for patients from racial and ethnic minority groups, the proportion of underrepresented in medicine (URiM) physicians remains low in the US health care system. This study linked a nationally representative sample of family physicians (FPs) with Medicaid claims data to explore the relative contributions to care of Medicaid populations by FP race and ethnicity.

METHODS

This descriptive cross-sectional study used 2016 Medicaid claims data from the Transformed Medicaid Statistical Information System and from 2016-2017 American Board of Family Medicine certification questionnaire responses to examine the diversity and Medicaid participation of FPs. We explored the diversity of FP Medicaid patient panels and whether they saw ≥150 beneficiaries in 2016. Using logistic regression models, we controlled for FP demographics, practice characteristics, and characteristics of the communities in which they practiced.

RESULTS

Of 13,096 FPs, Latine, Hispanic, or of Spanish Origin (LHS) FPs and non-LHS Black FPs saw more Medicaid beneficiaries compared with non-LHS White and non-LHS Asian FPs. The patient panels of URiM FPs had a much greater proportion of Medicaid beneficiaries from racial and ethnic minority groups. Overall, non-LHS Black and LHS FPs had greater odds of seeing ≥150 Medicaid beneficiaries in 2016.

CONCLUSIONS

These findings clearly show the critical role URiM FPs play in caring for Medicaid beneficiaries, suggesting physician race and ethnicity are correlated with Medicaid participation. Diversity in the health care workforce is essential for addressing racial health inequities. Policies need to address problems in pathways to medical education, including failures to recruit, nurture, and retain URiM students.

PURPOSE

Currently, 40% of counties in the United States do not have an obstetrician or midwife, and in rural areas the likelihood of childbirth being attended to by a family medicine (FM) physician is increasing. We sought to characterize the effect of the FM presence on unit culture and a key perinatal quality metric in Iowa hospital intrapartum units.

METHODS

Using a cross-sectional design, we surveyed Iowa physicians, nurses, and midwives delivering intrapartum care at hospitals participating in a quality improvement initiative to decrease the incidence of cesarean delivery. We linked respondents with their hospital characteristics and outcomes data. The primary outcome was the association between FM physician, obstetrician (OB), or both disciplines’ presence on labor and delivery and hospital low-risk, primary cesarean delivery rate. Unit culture was compared by hospital type (FM-only, OB-only, or Both).

RESULTS

A total of 849 clinicians from 39 hospitals completed the survey; 13 FM-only, 11 OB-only, and 15 hospitals with both. FM-only hospitals were all rural, with <1,000 annual births. Among hospitals with <1,000 annual births, births at FM-only hospitals had an adjusted 34.3% lower risk of cesarean delivery (adjusted incident rate ratio = 0.66; 95% CI, 0.52-.0.98) compared with hospitals with both. Nurses endorsed unit norms more supportive of vaginal birth and stronger safety culture at FM-only hospitals (P <.05).

CONCLUSIONS

Birthing hospitals staffed exclusively by FM physicians were more likely to have lower cesarean rates and stronger nursing-rated safety culture. Both access and quality of care provide strong arguments for reinforcing the pipeline of FM physicians training in intrapartum care.

BACKGROUND

For many patients with post–COVID-19 condition (long COVID), primary care is the first point of interaction with the health care system. In principle, primary care is well situated to manage long COVID. Beyond expressions of disempowerment, however, the patient’s perspective regarding the quality of long COVID care is lacking. Therefore, this study aimed to analyze the expectations and experiences of primary care patients seeking treatment for long COVID.

METHODS

A phenomenological approach guided this analysis. Using purposive sampling, we conducted semistructured interviews with English-speaking, adult primary care patients describing symptoms of long COVID. We deidentified and transcribed the recorded interviews. Transcripts were analyzed using inductive qualitative content analysis.

RESULTS

This article reports results from 19 interviews (53% female, mean age = 54 years). Patients expected their primary care practitioners (PCPs) to be knowledgeable about long COVID, attentive to their individual condition, and to engage in collaborative processes for treatment. Patients described 2 areas of experiences. First, interactions with clinicians were perceived as positive when clinicians were honest and validating, and negative when patients felt dismissed or discouraged. Second, patients described challenges navigating the fragmented US health care system when coordinating care, treatment and testing, and payment.

CONCLUSION

Primary care patients’ experiences seeking care for long COVID are incongruent with their expectations. Patients must overcome barriers at each level of the health care system and are frustrated by the constant challenges. PCPs and other health care professionals might increase congruence with expectations and experiences through listening, validating, and advocating for patients with long COVID.

Annals Early Access article

New research to better understand the biological factors of suicidal behaviour Researchers at the University of Glasgow are embarking on two new PhD projects to better understand the impact that biological factors may have on suicidal behaviour.

Today, Boston Dynamics and the Toyota Research Institute (TRI) announced a new partnership “to accelerate the development of general-purpose humanoid robots utilizing TRI’s Large Behavior Models and Boston Dynamics’ Atlas robot.” Committing to working towards a general purpose robot may make this partnership sound like a every other commercial humanoid company right now, but that’s not at all that’s going on here: BD and TRI are talking about fundamental robotics research, focusing on hard problems, and (most importantly) sharing the results.

The broader context here is that Boston Dynamics has an exceptionally capable humanoid platform capable of advanced and occasionally painful-looking whole-body motion behaviors along with some relatively basic and brute force-y manipulation. Meanwhile, TRI has been working for quite a while on developing AI-based learning techniques to tackle a variety of complicated manipulation challenges. TRI is working toward what they’re calling large behavior models (LBMs), which you can think of as analogous to large language models (LLMs), except for robots doing useful stuff in the physical world. The appeal of this partnership is pretty clear: Boston Dynamics gets new useful capabilities for Atlas, while TRI gets Atlas to explore new useful capabilities on.

Here’s a bit more from the press release:

The project is designed to leverage the strengths and expertise of each partner equally. The physical capabilities of the new electric Atlas robot, coupled with the ability to programmatically command and teleoperate a broad range of whole-body bimanual manipulation behaviors, will allow research teams to deploy the robot across a range of tasks and collect data on its performance. This data will, in turn, be used to support the training of advanced LBMs, utilizing rigorous hardware and simulation evaluation to demonstrate that large, pre-trained models can enable the rapid acquisition of new robust, dexterous, whole-body skills.

The joint team will also conduct research to answer fundamental training questions for humanoid robots, the ability of research models to leverage whole-body sensing, and understanding human-robot interaction and safety/assurance cases to support these new capabilities.

For more details, we spoke with Scott Kuindersma (Senior Director of Robotics Research at Boston Dynamics) and Russ Tedrake (VP of Robotics Research at TRI).

How did this partnership happen?

Russ Tedrake: We have a ton of respect for the Boston Dynamics team and what they’ve done, not only in terms of the hardware, but also the controller on Atlas. They’ve been growing their machine learning effort as we’ve been working more and more on the machine learning side. On TRI’s side, we’re seeing the limits of what you can do in tabletop manipulation, and we want to explore beyond that.

Scott Kuindersma: The combination skills and tools that TRI brings the table with the existing platform capabilities we have at Boston Dynamics, in addition to the machine learning teams we’ve been building up for the last couple years, put us in a really great position to hit the ground running together and do some pretty amazing stuff with Atlas.

What will your approach be to communicating your work, especially in the context of all the craziness around humanoids right now?

Tedrake: There’s a ton of pressure right now to do something new and incredible every six months or so. In some ways, it’s healthy for the field to have that much energy and enthusiasm and ambition. But I also think that there are people in the field that are coming around to appreciate the slightly longer and deeper view of understanding what works and what doesn’t, so we do have to balance that.

The other thing that I’d say is that there’s so much hype out there. I am incredibly excited about the promise of all this new capability; I just want to make sure that as we’re pushing the science forward, we’re being also honest and transparent about how well it’s working.

Kuindersma: It’s not lost on either of our organizations that this is maybe one of the most exciting points in the history of robotics, but there’s still a tremendous amount of work to do.

What are some of the challenges that your partnership will be uniquely capable of solving?

Kuindersma: One of the things that we’re both really excited about is the scope of behaviors that are possible with humanoids—a humanoid robot is much more than a pair of grippers on a mobile base. I think the opportunity to explore the full behavioral capability space of humanoids is probably something that we’re uniquely positioned to do right now because of the historical work that we’ve done at Boston Dynamics. Atlas is a very physically capable robot—the most capable humanoid we’ve ever built. And the platform software that we have allows for things like data collection for whole body manipulation to be about as easy as it is anywhere in the world.

Tedrake: In my mind, we really have opened up a brand new science—there’s a new set of basic questions that need answering. Robotics has come into this era of big science where it takes a big team and a big budget and strong collaborators to basically build the massive data sets and train the models to be in a position to ask these fundamental questions.

Fundamental questions like what?

Tedrake: Nobody has the beginnings of an idea of what the right training mixture is for humanoids. Like, we want to do pre-training with language, that’s way better, but how early do we introduce vision? How early do we introduce actions? Nobody knows. What’s the right curriculum of tasks? Do we want some easy tasks where we get greater than zero performance right out of the box? Probably. Do we also want some really complicated tasks? Probably. We want to be just in the home? Just in the factory? What’s the right mixture? Do we want backflips? I don’t know. We have to figure it out.

There are more questions too, like whether we have enough data on the Internet to train robots, and how we could mix and transfer capabilities from Internet data sets into robotics. Is robot data fundamentally different than other data? Should we expect the same scaling laws? Should we expect the same long-term capabilities?

The other big one that you’ll hear the experts talk about is evaluation, which is a major bottleneck. If you look at some of these papers that show incredible results, the statistical strength of their results section is very weak and consequently we’re making a lot of claims about things that we don’t really have a lot of basis for. It will take a lot of engineering work to carefully build up empirical strength in our results. I think evaluation doesn’t get enough attention.

What has changed in robotics research in the last year or so that you think has enabled the kind of progress that you’re hoping to achieve?

Kuindersma: From my perspective, there are two high-level things that have changed how I’ve thought about work in this space. One is the convergence of the field around repeatable processes for training manipulation skills through demonstrations. The pioneering work of diffusion policy (which TRI was a big part of) is a really powerful thing—it takes the process of generating manipulation skills that previously were basically unfathomable, and turned it into something where you just collect a bunch of data, you train it on an architecture that’s more or less stable at this point, and you get a result.

The second thing is everything that’s happened in robotics-adjacent areas of AI showing that data scale and diversity are really the keys to generalizable behavior. We expect that to also be true for robotics. And so taking these two things together, it makes the path really clear, but I still think there are a ton of open research challenges and questions that we need to answer.

Do you think that simulation is an effective way of scaling data for robotics?

Tedrake: I think generally people underestimate simulation. The work we’ve been doing has made me very optimistic about the capabilities of simulation as long as you use it wisely. Focusing on a specific robot doing a specific task is asking the wrong question; you need to get the distribution of tasks and performance in simulation to be predictive of the distribution of tasks and performance in the real world. There are some things that are still hard to simulate well, but even when it comes to frictional contact and stuff like that, I think we’re getting pretty good at this point.

Is there a commercial future for this partnership that you’re able to talk about?

Kuindersma: For Boston Dynamics, clearly we think there’s long-term commercial value in this work, and that’s one of the main reasons why we want to invest in it. But the purpose of this collaboration is really about fundamental research—making sure that we do the work, advance the science, and do it in a rigorous enough way so that we actually understand and trust the results and we can communicate that out to the world. So yes, we see tremendous value in this commercially. Yes, we are commercializing Atlas, but this project is really about fundamental research.

What happens next?

Tedrake: There are questions at the intersection of things that BD has done and things that TRI has done that we need to do together to start, and that’ll get things going. And then we have big ambitions—getting a generalist capability that we’re calling LBM (large behavior models) running on Atlas is the goal. In the first year we’re trying to focus on these fundamental questions, push boundaries, and write and publish papers.

I want people to be excited about watching for our results, and I want people to trust our results when they see them. For me, that’s the most important message for the robotics community: Through this partnership we’re trying to take a longer view that balances our extreme optimism with being critical in our approach.

The Tablelands in Gros Morne National Park, a UNESCO World Heritage Site, is one of the most unique landscapes in the world — and its orange peridotite rocks could hold the secret to finding life on Mars.

OpenAI recently introduced a new memory feature for ChatGPT that enables it to remember information about people, including age, gender and beliefs.

A team of scientists from the Lunar and Planetary Laboratory at the University of Arizona, TU Delft, and Caltech has developed a new method to compute how tides affect the interiors of planets and moons in the Solar System.

The post Planetary Researchers Examine Tidal Effects on Interiors of Planets and Their Moons appeared first on Sci.News: Breaking Science News.

The standard model predicted that the NASA/ESA/CSA James Webb Space Telescope would see dim signals from small, primitive galaxies.

The post New Research Questions Standard Theory of How Galaxies Formed in Early Universe appeared first on Sci.News: Breaking Science News.

The British Heart Foundation’s Reflections of Research competition showcases beautiful images captured by researchers studying heart and circulatory disease

They pose no risk to human health, and they're living their best lives.

Researchers in Montreal are pointing to the benefits of bilingualism for the brain's health and efficiency — suggesting it could even help prevent diseases associated with aging, including Alzheimer's.

A dome-shaped device floating in Halifax’s Northwest Arm could easily be confused with a buoy, but it is actually a contraption meant to turn ocean water into fresh water. Two Dalhousie University researchers hope it can help with water scarcity in the real world.

The Indian Council of Medical Research (ICMR) has issued a call for proposals for its Centre for Advanced Research (CAR) initiative under the Extramural Research Programme, inviting experienced research teams to

When chemist Dora Richardson’s employer decided to terminate the breast cancer research on the drug Tamoxifen in the early 1970s, she and her colleagues continued the work in secret.

At this moment in time the pre-pandemic cardiology research agenda needs to be completely reprioritized. There are two broad areas that now take precedence over all existing research concerns. On the one hand, researchers need to achieve a better understanding of the staggering incidence of deferred or delayed treatment of cardiovascular events and conditions as...

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Starting COVID-19 patients on prophylactic anticoagulation within 24 hours of being admitted to hospital has been linked to a reduced risk of mortality.

The type 2 diabetes mellitus drug semaglutide is effective for weight loss in non-diabetic overweight or obese adults, when taken alongside a reduced-calorie diet and exercise, researchers have found.

By Mike Cloonan, Chief Executive Officer of Sionna Therapeutics, as part of the From The Trenches feature of LifeSciVC The drug development process in rare diseases is rife with challenges especially when companies target significant differentiation or first-in-class targets. Identifying

The post Looking for Opportunities to Accelerate Clinical Research in Rare Diseases appeared first on LifeSciVC.

The UK body that oversees health research is writing a new strategy on clinical trial transparency and it wants to hear opinions on it. The Health Research Authority (HRA) says its strategy aims to “make transparency easy, make compliance clear and make information public.” It has opened a public consultation on the strategy and some […]

On this date 349 years ago, Samuel Pepys relates in his famous diary a remarkable story about an upcoming medical experiment. As far as I can tell, this is the first written description of a paid research subject.

According to his account, the man (who he describes as “a little frantic”) was to be paid to undergo a blood transfusion from a sheep. It was hypothesized that the blood of this calm and docile animal would help to calm the man.

Some interesting things to note about this experiment:

• Equipoise. There is explicit disagreement about what effect the experimental treatment will have: according to Pepys, "some think it may have a good effect upon him as a frantic man by cooling his blood, others that it will not have any effect at all".
• Results published. An account of the experiment was published just two weeks later in the journal Philosophical Transactions. 
• Medical Privacy. In this subsequent write-up, the research subject is identified as Arthur Coga, a former Cambridge divinity student. According to at least one account, being publicly identified had a bad effect on Coga, as people who had heard of him allegedly succeeded in getting him to spend his stipend on drink (though no sources are provided to confirm this story).
• Patient Reported Outcome. Coga was apparently chosen because, although mentally ill, he was still considered educated enough to give an accurate description of the treatment effect. 

Depending on your perspective, this may also be a very early account of the placebo effect, or a classic case of ignoring the patient’s experience. Because even though his report was positive, the clinicians remained skeptical. From the journal article:

The Man after this operation, as well as in it, found himself very well, and hath given in his own Narrative under his own hand, enlarging more upon the benefit, he thinks, he hath received by it, than we think fit to own as yet.

…and in fact, a subsequent diary entry from Pepys mentions meeting Coga, with similarly mixed impressions: “he finds himself much better since, and as a new man, but he is cracked a little in his head”.

The amount Coga was paid for his participation? Twenty shillings – at the time, that was exactly one Guinea.

[Image credit: Wellcome Images]

As winter arrives and daylight hours decrease, it gets easier to hit the snooze button and stay in bed. It turns out that there’s a scientific reason behind this phenomenon that helps to explain why people struggle to adjust their internal clocks—also known as circadian rhythm or sleep-wake cycle—when the weather turns colder.

Dr. Cassandra Quave’s path to her work as a leader in antibiotic drug discovery research initiatives at Emory University in Atlanta started when she was a child and she and her family dealt with her own serious health issues that have had life-long repercussions.

Jul 17, 2023

Apekshya Prasai, a political science doctoral candidate at the Massachusetts Institute of Technology, was recently named a 2023 Harry Frank Guggenheim Foundation Emerging Scholar.   The Emerging Scholars (nine in all) are doctoral candidates who are in the final year of writing dissertations on the nature of and responses to violence around the world.