The effect of mailed outreach on FIT completion among patients aged 45-50 in a safety net healthcare system.

PURPOSE: Colorectal cancer screening is recommended starting at age 45, but there has been little research on strategies to promote screening in patients younger than 50. METHODS: An outreach program quasi-randomly assigned patients aged 45-50 without recent fecal immunochemical test (FIT), colonoscopy or contraindications to screening to two intervention arms: electronic outreach with email and text (electronic outreach only) versus electronic outreach plus mailed outreach with FIT, an instructional letter and a prepaid return envelope (mailed + electronic outreach). In response to known disparities in screening uptake, all Black patients were assigned to receive mailed + electronic outreach. RESULTS: Among patients quasi-randomly assigned to an intervention (non-Black patients), the 180-day FIT completion rate was 18.8% in the electronic outreach only group (n = 1,318) and 25.0% in the mailed + electronic outreach group (n = 1,364) (difference 6.2% [95% CI 3.0, 9.4]). FIT completion was 16.6% among Black patients (n = 469), 8.4% (95% CI 4.1, 12.6) lower than among non-Black patients also assigned to mailed + electronic outreach. CONCLUSION: Among patients aged 45-50, mailed + electronic outreach had a greater effect on FIT completion than electronic outreach alone. Crossover between intervention groups likely lead to an underestimation of the effect of mailed outreach.

Sunscreen Use for Photoprotection in Skin of Color: A Literature Review.

BACKGROUND: To understand the prevalence and types of publications addressing darker skin types within the existing evidence base for sunscreen use.  Evidence Review: PubMed was searched from 1988, the time point at which the first skin of color (SOC) article was identified, through December 2022 using PubMed's Medical Subject Headings terms and keyword searches in title and abstract, with and without terms for SOC and ethnicity. Identified articles were reviewed for relevance, de-duplicated, and categorized; results are summarized. FINDINGS: Of the 5927 articles on sunscreen overall, only 314 (5.3%) articles addressed SOC, with the majority published since 2007 and representing only 4% to 7% of total publications annually except in 2022 when the proportion of SOC articles was 23.5%. Of the articles on SOC, many reported sunscreen knowledge and patient behaviors (29%), but very few reported clinical trials (5%). The 3 conditions most often discussed were melasma, post-inflammatory hyperpigmentation, and dyschromia. South Asian ethnicities (India, Pakistan, Bangladesh) had the highest representation within the literature, followed by Hispanics. CONCLUSIONS AND RELEVANCE: Although it was assumed there would be fewer papers discussing the use of sunscreen in darker skin types, the scale of the disparity revealed by this study is stark. The increase in a number of articles in 2022 suggests an increasing focus on SOC, but further discussion of the issues presented here will help the SOC community address gaps in the evidence base and better inform discussions on sunscreen and photoprotection between clinicians and patients.J Drugs Dermatol. 2024;23(7):575-577.  doi:10.36849/JDD.8250.

Small-molecule targeted recruitment of a nuclease to cleave an oncogenic RNA in a mouse model of metastatic cancer.

As the area of small molecules interacting with RNA advances, general routes to provide bioactive compounds are needed as ligands can bind RNA avidly to sites that will not affect function. Small-molecule targeted RNA degradation will thus provide a general route to affect RNA biology. A non-oligonucleotide-containing compound was designed from sequence to target the precursor to oncogenic microRNA-21 (pre-miR-21) for enzymatic destruction with selectivity that can exceed that for protein-targeted medicines. The compound specifically binds the target and contains a heterocycle that recruits and activates a ribonuclease to pre-miR-21 to substoichiometrically effect its cleavage and subsequently impede metastasis of breast cancer to lung in a mouse model. Transcriptomic and proteomic analyses demonstrate that the compound is potent and selective, specifically modulating oncogenic pathways. Thus, small molecules can be designed from sequence to have all of the functional repertoire of oligonucleotides, including inducing enzymatic degradation, and to selectively and potently modulate RNA function in vivo.

The current and potential uses of Electronic Medical Record (EMR) data for primary health care performance measurement in the Canadian context: a qualitative analysis.

BACKGROUND: Electronic Medical Records (EMRs) are a rich data source to measure and improve quality of care. As Canadian primary health care (PHC) EMRs mature, there is increasing potential use of EMR data for performance measurement. This study identifies and describes current uses of EMR data for performance measurement and considerations to further its potential in the Canadian context. METHODS: We applied a qualitative case study design and descriptive assessment in three phases, consulting multiple data sources including scientific and grey literature, system leaders (n = 41), and clinician/researchers (n = 20). Phases included a multimethod approach to identify initiatives using EMR data for performance measurement across Canadian jurisdictions; in-depth review of current initiatives identified from a healthcare performance intelligence lens; and triangulation and thematic analysis across data sources to explore considerations for advancing performance measurement uses of EMR data in the Canadian context. RESULTS: Six initiatives of EMR data use for performance measurement were identified: one multi-jurisdictional; five jurisdiction-specific in the provinces of British Columbia, Manitoba and Ontario. EMR data uses were predominately for micro-level PHC physician and team performance improvement, with some use for meso-level organization/network-wide improvement. Indicator sets varied in number, though shared emphasis on chronic disease management and prevention/screening and to a lesser extent medication management. Key considerations for governing, resourcing and implementing EMR data for performance measurement were identified. CONCLUSIONS: The extent of EMR data use for performance measurement varies across Canada. To further its potential, pan-Canadian data and privacy standards, performance intelligence competencies and renewed core PHC indicators should be prioritized. Experiences across countries, coupled with increasing momentum for performance measurement using real-world data, should be leveraged to avoid unnecessarily slow progress in Canada and abroad.

Measuring the frequency and variation of unnecessary care across Canada.

BACKGROUND: Through the Choosing Wisely Canada (CWC) campaign, national medical specialty societies have released hundreds of recommendations against health care services that are unnecessary, i.e. present little to no benefit or cause avoidable harm. Despite growing interest in unnecessary care both within Canada and internationally, prior research has typically avoided taking a national or even multi-jurisdictional approach in measuring the extent of the issue. This study estimates use of three unnecessary services identified by CWC recommendations across multiple Canadian jurisdictions. METHODS: Two retrospective cohort studies were conducted using administrative health care data collected between fiscal years 2011/12 and 2012/13 to respectively quantify use of 1) diagnostic imaging (spinal X-ray, CT or MRI) among Albertan patients following a visit for lower back pain and 2) cardiac tests (electrocardiogram, chest X-ray, stress test, or transthoracic echocardiogram) prior to low-risk surgical procedures in Alberta, Saskatchewan, and Ontario. A cross-sectional study of the 2012 Canadian Community Health Survey was also conducted to estimate 3) the proportion of females aged 40-49 that reported having a routine mammogram in the past two years. RESULTS: Use of unnecessary care was relatively frequent across all three services and jurisdiction measured: 30.7% of Albertan patients had diagnostic imaging within six months of their initial visit for lower back pain; a cardiac test preceded 17.9 to 35.5% of low-risk surgical procedures across Alberta, Saskatchewan, and Ontario; and 22.2% of Canadian women aged 40-49 at average-risk for breast cancer reported having a routine screening mammogram in the past two years. CONCLUSIONS: The use of potentially unnecessary care appears to be common in Canada. This investigation provides methodology to facilitate future measurement efforts that may incorporate additional jurisdictions and/or unnecessary services.

A Randomized Controlled Trial of Opt-in Versus Opt-Out Colorectal Cancer Screening Outreach.

OBJECTIVES: METHODS:: RESULTS:: Patients randomized to opt-in agreed to participate 23.1% of the time, and only 2.5% of those in opt-out chose not to participate. FIT kits were mailed to 22.4% and 93% of patients in opt-in and opt-out arms, respectively. In intention-to-screen analysis, patients in the opt-out arm had a higher FIT completion rate (29.1%) than in the opt-in arm (9.6%) (absolute difference 19.5%; 95% confidence interval, 10.9-27.9%; P < .001). Results were similar in subgroup analysis of those sent initial messaging through the EHR portal (9.5% opt-in versus 37.5% in opt-out). CONCLUSIONS: .

An Anatomical Analysis of the Supratrochlear Artery: Considerations in Facial Filler Injections and Preventing Vision Loss.

BACKGROUND: Embolia cutis medicamentosa (ECM) is a rare phenomenon attributed to intra-arterial drug injection. Glabellar filler injections can result in potentially devastating visual loss from inadvertent retrograde arteriolar embolization due to the extensive vasculature within the upper face. The minimum amount of filler necessary to potentiate this complication has not yet been reported. OBJECTIVES: We aim to determine the volume of filler necessary to occupy the supratrochlear artery from the glabella to the bifurcation of the ophthalmic and central retinal arteries. We specifically examine the volume of the supratrochlear artery from the glabella to orbital apex. METHODS: The study was approved by Duke University Institutional Review Board and involved surgical dissection of six fresh tissue cadaver heads (12 hemifaces). The arterial system in each cadaver head was injected with latex for visualization. The supratrochlear arteries were isolated anteriorly from the glabella to the orbital apex posteriorly. Intra-orbital vessel radius and length were measured. The vessel volume was calculated by water displacement of the intra-arterial latex. RESULTS: The vessel volumes ranged from 0.04 to 0.12 mL. The average vessel volume was calculated as 0.085 mL, the average length as 51.75 mm, and the average radius as 0.72 mm. CONCLUSIONS: Vascular occlusion from filler injections can lead to devastating visual consequences due to inadvertent retrograde intra-arterial embolization. Our findings indicate that the average entire volume of the supratrochlear artery from the glabella to the orbital apex is 0.085 mL. Injectors should be aware that a bolus of this critical volume may lead to a significant adverse outcome.

Conjunctival Pigmentation Following Minocycline Therapy.

Minocycline is a tetracycline antibiotic commonly used to treat acne and rosacea. Although pigmentation of the skin, nails, teeth, oral mucosa, and sclera is a well-recognized adverse outcome associated with minocycline, ocular pigmentation may be missed on routine examination. The authors present a case of a 43-year-old white woman who demonstrated bilateral pigmented palpebral conjunctival cysts after 12 months of minocycline therapy for cystic acne. To date, only 5 cases of minocycline-induced conjunctival pigmentation have been reported. After drug discontinuation, the patient's examination remained stable and no new ocular lesions were noted.

Antiproliferation activity of a small molecule repressor of liver receptor homolog 1.

The orphan nuclear receptor liver receptor homolog 1 (LRH-1; NR5A2) is a potent regulator of cholesterol metabolism and bile acid homeostasis. Recently, LRH-1 has been shown to play an important role in intestinal inflammation and in the progression of estrogen receptor positive and negative breast cancers and pancreatic cancer. Structural studies have revealed that LRH-1 can bind phospholipids and the dietary phospholipid dilauroylphosphatidylcholine activates LRH-1 activity in rodents. Here we characterize the activity of a novel synthetic nonphospholipid small molecule repressor of LRH-1, SR1848 (6-[4-(3-chlorophenyl)piperazin-1-yl]-3-cyclohexyl-1H-pyrimidine-2,4-dione). In cotransfection studies, SR1848 reduced LRH-1-dependent expression of a reporter gene and in cells that endogenously express LRH-1 dose dependently reduced the expression of cyclin-D1 and -E1, resulting in inhibition of cell proliferation. The cellular effects of SR1848 treatment are recapitulated after transfection of cells with small-interfering RNA targeting LRH-1. Immunocytochemistry analysis shows that SR1848 induces rapid translocation of nuclear LRH-1 to the cytoplasm. Combined, these results suggest that SR1848 is a functional repressor of LRH-1 that impacts expression of genes involved in proliferation in LRH-1-expressing cancers. Thus, SR1848 represents a novel chemical scaffold for the development of therapies targeting malignancies driven by LRH-1.

Antiobesity Effect of a Small Molecule Repressor of RORγ.

The orphan nuclear receptor RORγ is a key regulator for T helper 17 (TH17) cell differentiation, which regulates metabolic and circadian rhythm genes in peripheral tissues. Previously, it was shown that the small molecule inverse agonist of RORγ SR1555 [1-(4-((4'-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-[1,1'-biphenyl]-4-yl)methyl)piperazin-1-yl) ethanone] suppressed TH17 differentiation and stimulated induced T regulatory (iTreg) cells. Here, we show that treatment of cultured pre-adipocyctes with SR1555 represses the expression of RORγ while leading to increased expression of FGF21 and adipoQ. Chronic administration of SR1555 to obese diabetic mice resulted in a modest reduction in food intake accompanied with significant reduction in fat mass, resulting in reduced body weight and improved insulin sensitivity. Analysis ex vivo of treated mice demonstrates that SR1555 induced expression of the thermogenic gene program in fat depots. Further studies in cultured cells showed that SR1555 inhibited activation of hormone-sensitive lipase and increased fatty acid oxidation. Combined, these results suggest that pharmacological repression of RORγ may represent a strategy for treatment of obesity by increasing thermogenesis and fatty acid oxidation, while inhibition of hormone-sensitive lipase activity results in a reduction of serum free fatty acids, leading to improved peripheral insulin sensitivity.

Facial dystonias and rosacea: is there an association?

PURPOSE: Benign essential blepharospasm (BEB) and hemifacial spasm (HFS) belong to a spectrum of focal movement disorders that cause involuntary, spasmodic contractions of the eyelid and facial muscles. In our clinical experience, we have observed an increased prevalence of rosacea in patients who present with BEB and HFS. We investigate our clinical findings with a review of disease pathophysiology and treatment. METHODS: Retrospective study approved by the Ochsner Institutional Review Board and literature review. A total of 140 charts dated from 1990 to 2013 were reviewed, including 87 patients with BEB and 53 patients with HFS. Rosacea, BEB, and HFS were defined by standard diagnostic criteria. RESULTS: Within our BEB and HFS patient cohort, approximately 15% of patients presented with rosacea, compared to the general American population prevalence rate of 1.34% (p < 0.001). Of the 140 patients reviewed, a total of 21 patients (13 with BEB and 8 with HFS) exhibited rosacea (p = 0.995). CONCLUSIONS: Dry eye and tear instability often co-exist in patients with facial dystonias and rosacea, which may provide the initial drive towards tonic eyelid contractions and simultaneously exacerbate rosacea. Studies suggest that neurogenic inflammation and altered vasoregulation jointly contribute to the pathogenesis of rosacea. From our preliminary observations, we suggest the possibility of shared immune-inflammatory pathways involved in both facial dystonias and rosacea. Identification of common inflammatory mediators involved in both disease processes may facilitate a more targeted approach in drug treatment. Further biochemical analysis will likely be necessary to elucidate this potential association.

Do Women with Skin of Color Think They Are Well Represented in Skin Aging Prevention Information?

Objective: There are clinical differences in healthy skin requirements and skin-aging features by race and ethnicity. However, individuals of color are underrepresented in dermatology-related medical information. We sought to gather information from women of color regarding their attitudes about the importance of the prevention of skin aging, available information, and perception of representation in skin-aging prevention information. Methods: This study involved an observational, cross-sectional, online survey of women aged 18 to 70 years residing in the United States. Participants were placed into one of seven cohorts based on self-reported race/ethnicity. Relative frequencies of responses were compared across cohorts; adjusted logistic regression was used to assess perception of representation in skin-aging prevention information. Results: The mean age of the 1,646 participants was 44.4 years. The mean (standard deviation) rating (from 0, "not at all important" to 10, "extremely important") of the importance of the prevention of skin aging ranged from 7.3 to 8.2 across the seven cohorts. All cohorts reported the most trusted source of information for skin-aging prevention products and treatments was a skin-care professional, but not all cohorts believed they are well represented in available sources of information. Older age, lower median household income, and a race/ethnicity of Black, Asian, "Other," and "More Than One Race" were less likely to report being well represented. Limitations: People without internet access could not participate, potentially excluding some older and lower-income groups. Conclusion: Women of color are less likely to feel represented in available information on the prevention of skin aging.

Biologic and clinical analysis of childhood gamma delta T-ALL identifies LMO2/STAG2 rearrangements as extremely high-risk.

Acute lymphoblastic leukemia expressing the gamma delta T cell receptor (yo T-ALL) is a poorly understood disease. We studied 200 children with yo T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. yo T-ALL diagnosed in children under three years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by Poly(ADP-ribose) polymerase (PARP) inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric yo T-ALL.

Facial blanching due to neurotoxins: proposed mechanisms.

BACKGROUND: The effect of perceived facial blanching with neurotoxin therapy has been described in the literature and has been used to treat the undesirable facial flushing of Frey's syndrome. Patients rarely report it as a complication after cosmetic injection, but it can be distressing. OBJECTIVES: To elucidate the proposed mechanism(s) of this unusual vasculocutaneous phenomenon, we reviewed normal physiologic responses to heat stress and the role of cholinergic neurotransmission in modulating cutaneous vascular tone in the context of the literature. MATERIALS/METHODS: We report a case of a 32-year-old woman who complained of white patches on her forehead at sites of abobotulinumtoxinA injections administered 2 weeks before presentation. RESULTS: Acetylcholine is a primary mediator of cutaneous vasodilatation; certain co-transmitters modulate its effect. Chemical denervation by botulinum toxin (BoNT) appears to interfere with these normal signaling pathways and can provide symptomatic relief to patients with undesirable facial flushing. Conversely, it may create an unwanted cosmetic effect in patients who desire isolated muscle paresis. CONCLUSIONS: Skin sites injected with BoNT type A may not experience the expected decrease in cutaneous vessel tone associated with higher body temperature. The exact mechanism remains unclear.

Orbital varix thrombosis following surgical prone positioning for spinal decompression.

Orbital varix is a rare venous malformation within the orbit that is especially susceptible to thrombosis and hemorrhage. We report a unique case of vision-threatening orbital varix thrombosis resulting from prolonged prone positioning during an orthopedic spine procedure.

Order sets in health care: a systematic review of their effects.

OBJECTIVES: Order sets are widely used in hospitals to enter diagnosis and treatment orders. To determine the effectiveness of order sets in improving guideline adherence, treatment outcomes, processes of care, efficiency, and cost, we conducted a systematic review of the literature. METHODS: A comprehensive literature search was performed in various databases for studies published between January 1, 1990, and April 18, 2009. A total of eighteen studies met inclusion criteria. No randomized controlled trials were found. RESULTS: Outcomes of the included studies were summarized qualitatively due to variations in study population, intervention type, and outcome measures. There were no important inconsistencies between the results reported by studies involving different types of order sets. While the studies generally suggested positive outcomes, they were typically of low quality, with simple before-after designs and other methodological limitations. CONCLUSIONS: The benefits of order sets remain eminently plausible, but given the paucity of high quality evidence, further investigations to formally evaluate the effectiveness of order sets would be highly valuable.

Secondary hemophagocytic lymphohistiocytosis associated with Rocky Mountain spotted fever in a toddler: A case report.

A three-year-old boy presented with fever, maculopapular rash involving palms and soles, and hyponatremia two weeks following a tick bite. Empiric doxycycline that he was on was discontinued following negative initial rickettsial serology based on the non-endemicity of Rocky Mountain spotted fever (RMSF) in Northeast Ohio. He demonstrated high inflammatory markers and met the criteria for hemophagocytic lymphohistiocytosis (HLH). With a working diagnosis of macrophage activation syndrome secondary to presumed systemic-onset juvenile idiopathic arthritis (soJIA), he received HLH-directed therapy. Rising antibody titers in convalescent sera established the diagnosis of RMSF. The patient recovered completely with HLH directed therapy and re-institution of doxycycline. This is the first pediatric case report of Rickettsia rickettsii induced HLH demonstrating a favorable outcome despite modified therapy.

The effects of polymer phase ratio and feeding strategy on solid-liquid TPPBs for the production of L-phenylacetylcarbinol from benzaldehyde using Candida utilis.

PURPOSE OF WORK: To increase the bioproduction of L-phenylacetylcarbinol (PAC), a precursor molecule in the synthesis of the decongestants ephedrine and pseudoephedrine and which suffers from substrate, product, and by-product inhibition, by ensuring that the delivery of the substrate, benzaldehyde, is maintained within a strict concentration window. Beads of the commercial polymer, Hytrel G3548L, can act as a sequestering phase to reduce inhibitory effects to cells of Candida utilis while creating a reservoir for high concentrations of products. In this work we varied the polymer phase volume ratio (from 3 to 15%), and modified the benzaldehyde feeding strategy to further improve on system performance, resulting in greater than 100% increase in the PAC productivity relative to a single phase control, as well as robust operation of the two-phase bioreactor with minimal operator intervention.

A Novel approach to catheterizing the Left Gastric Artery for bariatric embolization.

We present the case of a 45 Y/o morbidly obese male who - unable to lose weight despite extensive lifestyle interventions, presented to us for an experimental procedure known as bariatric embolization. This arterial embolization procedure was performed targeting the left gastric artery with aims to restrict blood flow to the gastric fundus, and lowering serum ghrelin levels. In this case the left gastric artery arose cephalad from the celiac, earlier than where it normally branches; a variation known as a "false tripod", causing some initial difficulty with selection. We describe how introducing a tertiary curve on the guidewire proved successful. Adapting the guidewire for difficult anatomy is an often a very underutilized skillset for many interventionalists - but led to success in this rather nascent procedure.

Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(G4C2) repeat expansion in vitro and in vivo ALS models.

The most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD) is an expanded G4C2 RNA repeat [r(G4C2)exp] in chromosome 9 open reading frame 72 (C9orf72), which elicits pathology through several mechanisms. Here, we developed and characterized a small molecule for targeted degradation of r(G4C2)exp. The compound was able to selectively bind r(G4C2)exp's structure and to assemble an endogenous nuclease onto the target, provoking removal of the transcript by native RNA quality control mechanisms. In c9ALS patient­derived spinal neurons, the compound selectively degraded the mutant C9orf72 allele with limited off-targets and reduced quantities of toxic dipeptide repeat proteins (DPRs) translated from r(G4C2)exp. In vivo work in a rodent model showed that abundance of both the mutant allele harboring the repeat expansion and DPRs were selectively reduced by this compound. These results demonstrate that targeted small-molecule degradation of r(G4C2)exp is a strategy for mitigating c9ALS/FTD-associated pathologies and studying disease-associated pathways in preclinical models.