Comparison of No-Test Telehealth and In-Person Medication Abortion.

Importance: In the US, access to medication abortion using history-based (no-test) eligibility assessment, including through telehealth and mailing of mifepristone, has grown rapidly. Additional evidence on the effectiveness and safety of these models is needed. Objective: To evaluate whether medication abortion with no-test eligibility assessment and mailing of medications is as effective as in-person care with ultrasonography and safe overall. Design, Setting, and Participants: Prospective, observational study with noninferiority analysis. Sites included 4 abortion-providing organizations in Colorado, Illinois, Maryland, Minnesota, Virginia, and Washington from May 2021 to March 2023. Eligible patients were seeking medication abortion up to and including 70 days' gestation, spoke English or Spanish, and were aged 15 years or older. Exposure: Study groups reflected the model of care selected by the patient and clinicians and included: (1) no-test (telehealth) eligibility assessment and mailing of medications (no-test + mail) (n = 228); (2) no-test eligibility assessment and pickup of medications (no-test + pickup) (n = 119); or (3) in-person with ultrasonography (n = 238). Main Outcomes and Measures: Effectiveness, defined as a complete abortion without the need for repeating the mifepristone and misoprostol regimen or a follow-up procedure, and safety, defined as an abortion-related serious adverse event, including overnight hospital admission, surgery, or blood transfusion. Outcomes were derived from patient surveys and medical records. Primary analysis focused on the comparison of the no-test + mail group with the in-person with ultrasonography group. Results: The mean age of the participants (N = 585) was 27.3 years; most identified as non-Hispanic White (48.6%) or non-Hispanic Black (28.1%). Median (IQR) gestational duration was 45 days (39-53) and comparable between study groups (P = .30). Outcome data were available for 91.8% of participants. Overall effectiveness was 94.4% (95% CI, 90.7%-99.2%) in the no-test + mail group and 93.3% (95% CI, 88.3%-98.2%) in the in-person with ultrasonography group in adjusted models (adjusted risk difference, 1.2 [95% CI, -4.1 to 6.4]), meeting the prespecified 5% noninferiority margin. Serious adverse events included overnight hospitalization (n = 4), blood transfusion (n = 2), and emergency surgery (n = 1) and were reported by 1.1% (95% CI, 0.4%-2.4%) of participants, with 3 in the no-test + mail group, 3 in the in-person with ultrasonography group, and none in the no-test + pickup group. Conclusions and Relevance: This prospective, observational study found that medication abortion obtained following no-test telehealth screening and mailing of medications was associated with similar rates of complete abortion compared with in-person care with ultrasonography and met prespecified criteria for noninferiority, with a low prevalence of adverse events.

Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities.

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4'-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N3-OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature. Besides being highly cost-effective and significantly reducing synthesis, the reaction yielded 91-98 % of the target products without the need of any additional steps or chromatographic techniques. Two analogues exhibit promising anti-cancer biological activities. Analogue 4l shows highly specific cytostatic activity against lung cancer cells, while analogue 4k exhibits pan-cancer anti-growth activity. A kinase screen suggests compound 4k has single-digit micromolar activity against kinase STK33. High STK33 RNA expression correlates strongly with poorer patient outcomes in both adult and pediatric glioma. Compound 4k potently inhibits cell proliferation, invasion, and 3D neurosphere formation in primary patient-derived glioma cell lines. The observed anti-cancer activity is enhanced in combination with specific clinically relevant small molecule inhibitors. Herein we establish a novel biochemical kinase inhibitory function for click-chemistry-derived OTBN-1,2,3-triazole analogues and further report their anti-cancer activity in vitro for the first time.

Identifying the needs of people with long COVID: a qualitative study in the UK.

OBJECTIVES: To identify the needs of people with long COVID (LC) in the UK. DESIGN: Qualitative study using the Framework Analysis to analyse focus group discussions. PARTICIPANTS: 25 adults with LC aged 19-76 years including 17 men and 8 women. Average disease duration was 80.1 weeks. SETTING: Eight focus groups were conducted in April 2023 online and in-person at the University of Leeds (UoL), UK. Recruitment routes included advertisement via Leeds Community Healthcare services, the English National Opera Breathe Programme and within the UoL. RESULTS: Three key themes/needs were identified. (Theme 1) Support systems including community groups, disability benefits, clinical services and employment support should be accessible and tailored to the needs of people with LC. (Theme 2) Research should investigate the physiology of symptoms, new clinical tests and treatment interventions to improve clinical understanding of the condition and symptom management. (Theme 3) Societal awareness should be promoted via local and national initiatives to educate the public about the condition and reduce stigma. CONCLUSIONS: Participants experienced varied and individual challenges to daily life due to LC. There is a need for government acknowledgement of LC as a disability to ensure people with LC have access to disability support and legal protection. Policy development should be patient-driven and acknowledge the individual needs of people with LC in order to improve their quality of life.

The Disease Triangle of Chestnut: A review of host, pathogen, and environmental interactions of chestnuts cultivated in the eastern United States.

Chestnuts, the edible seeds of the genus Castanea, are a perennial food crop closely tied to the global migration of humans throughout history and have recently been gaining popularity in agriculture and forest restoration in eastern North America. Cultivation of chestnuts yields nutritionally balanced food while fostering economic development, food security, and environmental health. However, diseases and insect pests threaten successful ecological restoration and food production. In this review we explore conditions affecting chestnuts in the eastern United States through the lens of the disease triangle. A "host" in the disease triangle is not merely a single tree, but a tree including its constituent population of fungal endophytes. Chestnut trees are rich with microbial life, and the sustainability of chestnuts in forest and cultivated settings may lie in understanding and manipulating microbial communities to improve plant health and control destructive diseases. To benefit from the ecological and economic potential of chestnuts on the landscape, it may be necessary to select locally adapted chestnut trees, regardless of pedigree, that are resilient against cosmopolitan pathogens. With transport of plants and pathogens throughout the globe, and with landscape level environmental changes over the last century, chestnut trees in the eastern United States (U.S.) are in a unique disease landscape compared to their ancestors. Diseases of economic concern from fungi and fungal-like organisms include chestnut blight (Cryphonectria parasitica) and ink disease (Phytophthora cinnamomi) on American and European chestnuts, oak wilt (Bretziella fagacearum) on all chestnut species, and the emerging diseases of brown rot (Gnomoniopsis smithogilvyi) and chestnut anthracnose (Colletotrichum henanense). The eastern U.S. has experienced profound environmental changes over the 20th century and into the early 21st century. These changes happen to coincide with the demise of the American chestnut in the eastern forest, efforts to re-establish chestnut as a forest species, and the rise in cultivation of multiple chestnut species and hybrids as a culinary crop. Chestnut trees growing in the early 21st century face different environmental circumstances than the American chestnuts of pre-colonial times, including changes in forest composition, rainfall changes and acidification, industrialized agriculture's increased chemical inputs, rising global temperatures, and increased levels of carbon dioxide in the atmosphere. We conclude that chestnut tree species for both forestry and agriculture should be considered based on current fitness, adaptability, and economic and ecological value considering continued dynamics in host and pathogens distributions and anthropogenically driven climatic and edaphic conditions.

A green bio-organic catalyst (taurine) promoted one-pot synthesis of (R/S)-2-thioxo-3,4-dihydropyrimidine(TDHPM)-5-carboxanilides: chiral investigations using circular dichroism and validation by computational approaches.

Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of (R/S)-2-thioxo-DHPM-5-carboxanilides via the Biginelli-type cyclo-condensation reaction of aryl aldehydes, thiourea and various acetoacetanilide derivatives in ethanol at 100 °C. In this protocol, taurine was used as a green and reusable bio-organic catalyst. Twenty-three novel derivatives of (R/S)-TDHPM-5-carboxanilides and their structures were confirmed by various spectroscopy techniques. The aforementioned compounds were synthesized via the formation of one asymmetric centre, one new C-C bond, and two new C-N bonds in the final product. All the newly synthesized compounds were obtained in their racemic form with up to 99% yield. In addition, the separation of the racemic mixture of all the newly synthesized compounds was carried out by chiral HPLC (Prep LC), which provided up to 99.99% purity. The absolute configuration of all the enantiomerically pure isomers was determined using a circular dichroism study and validated by a computational approach. With up to 99% yield of 4d, this one-pot synthetic approach can also be useful for large-scale industrial production. One of the separated isomers (4R)-(+)-4S developed as a single crystal, and it was found that this crystal structure was orthorhombic.

Nebulized medications in the emergency department: A narrative review of nontraditional agents.

PURPOSE: This article summarizes emerging nontraditional therapies administered via the nebulization route for use in the emergency department (ED). SUMMARY: Although traditional routes of medication administration (eg, intravenous) have been the mainstay of administration modalities for decades, these routes may not be appropriate for all patients. Nowhere is this more readily apparent than in the ED setting, where patients with a variety of presentations receive care. One unique route for medication administration that has increasingly gained popularity in the ED is that of aerosolized drug delivery. This route holds promise as direct delivery of medications to the site of action could yield a more rapid and effective therapeutic response while also minimizing systemic adverse effects by utilizing a fraction of the systemic dose. Medication administration via nebulization also provides an alternative that is conducive to rapid, less invasive access, which is advantageous in the emergent setting of the ED. This review is intended to analyze the existing literature regarding this route of administration, including the nuances that can impact drug efficacy, as well as the available literature regarding novel, noncommercial nebulized medication therapy given in the ED. CONCLUSION: Multiple medications have been investigated for administration via this route, and when implementing any of these therapies several practical considerations must be taken into account, from medication preparation to administration, to ensure optimal efficacy while minimizing adverse effects. The pharmacist is an essential bedside team member in these scenarios to assist with navigating unique and complex nuances of this therapy as they develop.

Does repetitive transcranial magnetic stimulation improve cognitive function in age-related neurodegenerative diseases? A systematic review and meta-analysis.

OBJECTIVE: High-frequency, repetitive transcranial magnetic stimulation (rTMS) targeted over the dorsolateral prefrontal cortex (DLPFC) is widely used in research to promote neuroplasticity and cognitive enhancement. RTMS is a promising intervention to tackle cognitive decline in people with age-related neurodegenerative diseases. However, there is currently no systematic evidence examining the effects of DLPFC-targeted, high-frequency rTMS on cognitive function in this population. The aim of this systematic review was to evaluate the efficacy and moderators of this treatment intervention. METHODS: A comprehensive literature search of five electronic databases was performed to identify articles published before October, 2022. Following PRISMA guidelines, the identified articles were screened, data was extracted, and the methodological quality was assessed using the Cochrane tool, Risk of Bias 2. Meta-analyses were performed using R Studio (v.4.1.2). RESULTS: Sixteen studies involving 474 participants met the inclusion criteria, of which 8 studies measured global cognitive function. The results from the random-effects meta-analysis showed rTMS significantly improved global cognitive function relative to control groups shown by a large, significant effect size (g = 1.39, 95% CI, 0.34-2.43; p = 0.017). No significant effects were found between subgroups or for individual cognitive domains. CONCLUSIONS: High-frequency rTMS, targeted over the DLPFC, appears to improve global cognitive function in people with age-related neurodegenerative diseases. However, these results should be interpreted with caution due to the small number of studies included, and high between-study heterogeneity.

Presenters at chiropractic research conferences 2010-2019: is there a gender equity problem?

BACKGROUND: Presenting at professional and scientific conferences can be an important part of an individual's career advancement, especially for researchers communicating scientific findings, and can signal expertise and leadership. Generally, women presenting at conferences are underrepresented in various science disciplines. We aimed to evaluate the gender of presenters at research-oriented chiropractic conferences from 2010 to 2019. METHODS: We investigated the gender of presenters at conferences hosted by chiropractic organisations from 2010 to 2019 that utilised an abstract submission process. Gender classification was performed by two independent reviewers. The gender distribution of presenters over the ten-year period was analysed with linear regression. The association of conference factors with the gender distribution of presenters was also assessed with linear regression, including the gender of organising committees and abstract peer reviewers, and the geographic region where the conference was hosted. RESULTS: From 39 conferences, we identified 4,340 unique presentations. Women gave 1,528 (35%) of the presentations. No presenters were classified as gender diverse. Overall, the proportion of women presenters was 30% in 2010 and 42% in 2019, with linear regression demonstrating a 1% increase in women presenting per year (95% CI = 0.4-1.6%). Invited/keynote speakers had the lowest proportion of women (21%) and the most stagnant trajectory over time. The gender of conference organisers and abstract peer reviewers were not significantly associated with the gender of presenters. Oceanic conferences had a lower proportion of women presenting compared to North America (27% vs. 36%). CONCLUSIONS: Overall, women gave approximately one-third of presentations at the included conferences, which gradually increased from 2010 to 2019. However, the disparity widens for the most prestigious class of keynote/invited presenters. We make several recommendations to support the goal of gender equity, including monitoring and reporting on gender diversity at future conferences.

Regional variation in routes to diagnosis of cholangiocarcinoma in England from 2006 to 2017.

BACKGROUND: Incidence of cholangiocarcinoma (CCA) is rising, with overall prognosis re-maining very poor. Reasons for the high mortality of CCA include its late presentation in most patients, when curative options are no longer feasible, and poor response to systemic therapies for advanced disease. Late presentation presents a large barrier to improving outcomes and is often associated with diagnosis via mergency presentation (EP). Earlier diagnoses may be made by Two Week Wait (TWW) referrals through General practitioner (GP). We hypothesise that TWW referrals and EP routes to diagnosis differ across regions in England. AIM: To investigate routes to diagnosis of CCA over time, regional variation and influencing factors. METHODS: We linked patient records from the National Cancer Registration Dataset to Hospital Episode Statistics, Cancer Waiting Times and Cancer Screening Programme datasets to define routes to diagnosis and certain patient characteristics for patients diagnosed 2006-2017 in England. We used linear probability models to investigate geographic variation by assessing the proportions of patients diagnosed via TWW referral or EP across Cancer Alliances in England, adjusting for potential confounders. Correlation between the proportion of people diagnosed by TWW referral and EP was investigated with Spearman's correlation coefficient. RESULTS: Of 23632 patients diagnosed between 2006-2017 in England, the most common route to diagnosis was EP (49.6%). Non-TWW GP referrals accounted for 20.5% of diagnosis routes, 13.8% were diagnosed by TWW referral, and the remainder 16.2% were diagnosed via an 'other' or Unknown route. The proportion diagnosed via a TWW referral doubled between 2006-2017 rising from 9.9% to 19.8%, conversely EP diagnosis route declined, falling from 51.3% to 46.0%. Statistically significant variation in both the TWW referral and EP proportions was found across Cancer Alliances. Age, presence of comorbidity and underlying liver disease were independently associated with both a lower proportion of patients diagnosed via TWW referral, and a higher proportion diagnosed by EP after adjusting for other potential confounders. CONCLUSION: There is significant geographic and socio-demographic variation in routes to diagnosis of CCA in England. Knowledge sharing of best practice may improve diagnostic pathways and reduce unwarranted variation.

Durable contraception in the female domestic cat using viral-vectored delivery of a feline anti-Müllerian hormone transgene.

Eighty percent of the estimated 600 million domestic cats in the world are free-roaming. These cats typically experience suboptimal welfare and inflict high levels of predation on wildlife. Additionally, euthanasia of healthy animals in overpopulated shelters raises ethical considerations. While surgical sterilization is the mainstay of pet population control, there is a need for efficient, safe, and cost-effective permanent contraception alternatives. Herein, we report evidence that a single intramuscular treatment with an adeno-associated viral vector delivering an anti-Müllerian hormone transgene produces long-term contraception in the domestic cat. Treated females are followed for over two years, during which transgene expression, anti-transgene antibodies, and reproductive hormones are monitored. Mating behavior and reproductive success are measured during two mating studies. Here we show that ectopic expression of anti-Müllerian hormone does not impair sex steroids nor estrous cycling, but prevents breeding-induced ovulation, resulting in safe and durable contraception in the female domestic cat.

Development of a Multiplex Polymerase Chain Reaction (PCR) Assay for the Potential Detection of Insect Contaminants in Food.

Molecular methods can potentially be used to detect insect contaminants of food products. In this study, we used three sets of group-specific primers, two of them targeting the amplification of two regions of the insect's mitochondrial cytochrome c oxidase subunit I (COI-Fa and COI-Fb) and the other targeting a region of the nuclear protein-coding wingless (wg) gene. Using singleplex and multiplex polymerase chain reaction (PCR), we evaluated the three sets of primers using genomic DNA (gDNA) from 48 insect species including food storage insect pests and known vectors of foodborne pathogens. Seven plant-based food matrices were also evaluated for exclusivity testing. Additionally, we spiked fragments from five insect species in a selected food matrix (whole wheat flour). Singleplex and multiplex PCR amplified single specific bands (401-449 bp), corresponding to the wg gene, from insect species belonging to families Blattidae and Formicidae, and in Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae). The COI-Fa primers amplified specific bands (171-188 bp) in all Dipteran species and the COI-Fb primers amplified a specific band (∼140 bp) in DNA from Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) and P. interpunctella. However, the presence of specific bands in most Coleopterans was not consistent. No amplicon bands were observed in any of the food matrixes tested and the expected pattern of amplicon bands was seen in multiplex reactions using gDNA from spiked food samples. Our multiplex PCR assay targeted specific groups of insects that commonly contaminate foods without amplifying bands from the food matrixes tested; thus, molecular methods may be suitable for detecting insects or their fragments in foods.

Role of Serial Phlebotomy in the Management of Blunt Solid Organ Injury in Adults.

BACKGROUND: The management of blunt spleen and liver trauma has become increasingly nonoperative. There is no consensus on timing or duration of serial hemoglobin and hematocrit monitoring in this patient population. OBJECTIVE: This study examined the clinical utility of serial hemoglobin and hematocrit monitoring. We hypothesized that most interventions occur early in the hospital course, based on hemodynamic instability or physical examination findings rather than serial monitoring. METHODS: We conducted a retrospective cohort study of adult trauma patients with blunt spleen or liver injury from November 2014 through June 2019 at our Level II trauma center. Interventions were classified as no intervention, surgical intervention, angioembolization, or packed red blood cell transfusion. Demographics, length of stay, total blood draws, laboratory values, and clinical triggers preceding intervention were reviewed. RESULTS: A total of 143 patients were studied, of whom 73 (51%) received no intervention, 47 (33%) received an intervention within 4 hr of presentation, and 23 (16%) had interventions beyond 4 hr. Of these 23 patients, 13 received an intervention based on phlebotomy results alone. Most of these patients (n = 12, 92%) received blood transfusion without further intervention. Only one patient underwent operative intervention based on serial hemoglobin results on hospital day 2. CONCLUSION: The majority of patients with these injury patterns either require no intervention or declare themselves promptly after arrival. Serial phlebotomy after initial triage and intervention may add little value in the management of blunt solid organ injury.

The Effectiveness of Physical Therapy Interventions for Athletes Post-Concussion: A Systematic Review.

Background: Sports-related concussions are the most common cause of head injury in adolescents and young adults. Typical treatment methods for this injury include cognitive and physical rest. Evidence suggests that physical activity and physical therapy interventions can be beneficial to decrease post-concussion symptoms. Purpose: The aim of this systematic review was to investigate the effectiveness of physical therapy interventions for adolescent and young adult athletes post-concussion. Study Design: Systematic Review. Methods: The following databases were utilized for the search: PubMed, CINAHL, Proquest, MEDLINE, SPORTDiscus, and SCOPUS. The search strategy focused on athletes, concussions, and physical therapy interventions. Data extraction from each article included: Authors, subjects, gender, mean age, age range, specific sport, acute or chronic concussion, first or recurrent concussion, treatments for intervention and control group, and outcomes measured. Results: Eight studies met the inclusion criteria. Six of the eight articles scored seven or higher on the PEDro Scale. Physical therapy intervention(s), such as an aerobic intervention or a multimodal approach, show improvements in time to recovery and reduction of post-concussion symptoms in patients who have had a concussion. Physical activity and physical therapy as early as a couple days following injury, is beneficial at decreasing post-concussion symptoms, allows for earlier return to play, and/or shorter days to recovery, and is considered safe for treating post-concussion symptoms. Conclusion: This systematic review demonstrates that physical therapy interventions including aerobic exercise and multimodal approaches have been found to be beneficial in treating adolescent and young adult athletes post-concussion. Utilizing aerobic or multimodal interventions for this population allows for a quicker symptom recovery and return to sport than traditional treatment of physical and cognitive rest. Future research should investigate the superior intervention for adolescents and young adults with post-concussion syndrome and determine if a single treatment or a multimodal approach is more beneficial.

Determining the preferred liquid reward in adult C57BL/6 mice.

Using food rewards to motivate mice is commonplace in behavioural research. Using a reward which is highly desirable is of benefit, as it can reduce the need to food restrict animals and can encourage higher levels of consumption, allowing for changes in levels of consumption following an intervention to be easily determined. Here, we aimed to determine the preferred milk reward for adult male C57Bl/6 mice. Thirty male C57Bl/6 mice were provided with soya milk, chocolate milk, almond milk or water for a four-hour period in a cross-over design. When planning studies that involve the use of a palatable liquid reward, soya milk is the preferred option for adult male C57BL/6 mice. Providing a liquid reward of high value will give increased levels of consumption, with little or no food restriction required.

Pain Recognition in Rabbits.

Rabbits typically undergo at least one painful procedure during their lifetime and appropriate methods of assessment are essential to reduce or alleviate pain. Various methods of assessing pain in rabbits have been investigated, with the validity of spontaneous behavior and grimace scale scoring being the most studied to date. Assessment of pain is challenging, compounded by rabbits being a prey species that display freezing behavior in the presence of unfamiliar caregivers. Here we discuss some key changes in rabbits that can be used in the assessment of pain and provide some practical suggestions to ensure that the assessment can be carried out effectively.

Cohort study to assess geographical variation in cholangiocarcinoma treatment in England.

BACKGROUND: Outcomes for cholangiocarcinoma (CCA) are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous sub-types. Beyond curative surgery, which is only an option for a minority of patients diagnosed at an early stage, few systemic therapy options are currently recommended to relieve symptoms and prolong life. Stent insertion to manage disease complications requires highly specialised expertise. Evidence is lacking as to how CCA patients are managed in a real-world setting and whether there is any variation in treatments received by CCA patients. AIM: To assess geographic variation in treatments received amongst CCA patients in England. METHODS: Data used in this cohort study were drawn from the National Cancer Registration Dataset (NCRD), Hospital Episode Statistics and the Systemic Anti-Cancer Therapy Dataset. A cohort of 8853 CCA patients diagnosed between 2014-2017 in the National Health Service in England was identified from the NCRD. Potentially curative surgery for all patients and systemic therapy and stent insertion for 7751 individuals who did not receive surgery were identified as three end-points of interest. Linear probability models assessed variation in each of the three treatment modalities according to Cancer Alliance of residence at diagnosis, and for socio-demographic and clinical characteristics at diagnosis. RESULTS: Of 8853 CCA patients, 1102 (12.4%) received potentially curative surgery. The mean [95% confidence interval (CI)] percentage-point difference from the population average ranged from -3.96 (-6.34 to -1.59)% to 3.77 (0.54 to 6.99)% across Cancer Alliances in England after adjustment for patient sociodemographic and clinical characteristics, showing statistically significant variation. Amongst 7751 who did not receive surgery, 1542 (19.9%) received systemic therapy, with mean [95%CI] percentage-point difference from the population average between -3.84 (-8.04 to 0.35)% to 9.28 (1.76 to 16.80)% across Cancer Alliances after adjustment, again showing the presence of statistically significant variation for some regions. Stent insertion was received by 2156 (27.8%), with mean [95%CI] percentage-point difference from the population average between -10.54 (-12.88 to -8.20)% to 13.64 (9.22 to 18.06)% across Cancer Alliances after adjustment, showing wide and statistically significant variation from the population average. Half of 8853 patients (n = 4468) received no treatment with either surgery, systemic therapy or stent insertion. CONCLUSION: Substantial regional variation in treatments received by CCA patients was observed in England. Such variation could be due to differences in case-mix, clinical practice or access to specialist expertise.

Real-Time User Feedback to Support Clinical Decision Support System Improvement.

OBJECTIVES: To improve clinical decision support (CDS) by allowing users to provide real-time feedback when they interact with CDS tools and by creating processes for responding to and acting on this feedback. METHODS: Two organizations implemented similar real-time feedback tools and processes in their electronic health record and gathered data over a 30-month period. At both sites, users could provide feedback by using Likert feedback links embedded in all end-user facing alerts, with results stored outside the electronic health record, and provide feedback as a comment when they overrode an alert. Both systems are monitored daily by clinical informatics teams. RESULTS: The two sites received 2,639 Likert feedback comments and 623,270 override comments over a 30-month period. Through four case studies, we describe our use of end-user feedback to rapidly respond to build errors, as well as identifying inaccurate knowledge management, user-interface issues, and unique workflows. CONCLUSION: Feedback on CDS tools can be solicited in multiple ways, and it contains valuable and actionable suggestions to improve CDS alerts. Additionally, end users appreciate knowing their feedback is being received and may also make other suggestions to improve the electronic health record. Incorporation of end-user feedback into CDS monitoring, evaluation, and remediation is a way to improve CDS.