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BACKGROUND AND OBJECTIVES: The number of family medicine positions unfilled in the Main Match has increased from 2019 to 2023. In the 2023-2024 family medicine application season, the specialty adopted the changes in the Electronic Residency Application Service (ERAS or MyERAS), which included geographic preferences and offered applicants five program signals. We compared the number of unfilled positions from prior years to results of the 2024 family medicine Match after the adoption of these changes. METHODS: We analyzed publicly available data from the National Resident Matching Program to compare the number of positions filled in the Main Match from 2019 to 2024. We estimated the number of expected positions filled using multiple linear regression and application data from ERAS and the number of available positions in the Match. RESULTS: A total of 636 positions were unfilled in the 2024 family medicine Main Match. Our statistical analysis, based only on the number of applicants and the number of available positions, predicted 630.65 unfilled slots with a 95% confidence interval from 605.53 to 655.77. The 2024 family medicine position fill rate decreased slightly at 87.8% compared to 88.7% in the 2023 Match. The number of family medicine programs that did not fill in the Main Match increased in 2024 to 241 (30.3% of programs) compared to 217 (28.1%) in 2023. CONCLUSIONS: MyERAS changes in the 2023-2024 family medicine application season, including geographic preferences and program signaling, were not associated with a change in the number of programs or positions filled in the family medicine Main Match.
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Sleep/wake cycles intricately shape physiological activities including cognitive brain functions, yet the precise molecular orchestrators of sleep remain elusive. Notably, the clinical impact of benzodiazepine drugs underscores the pivotal role of GABAergic neurotransmission in sleep regulation. However, the specific contributions of distinct GABAA receptor subtypes and their principal scaffolding protein, gephyrin, in sleep dynamics remain unclear. The evolving role of synaptic phospho-proteome alterations at excitatory and inhibitory synapses suggests a potential avenue for modulating gephyrin and, consequently, GABAARs for sleep through on-demand kinase recruitment. Our study unveils the distinctive roles of two prevalent GABAA receptor subtypes, α1- and α2-GABAARs, in influencing sleep duration and electrical sleep activity. Notably, the absence of α1-GABAARs emerges as central in sleep regulation, manifesting significant alterations in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during dark or active phases, accompanied by altered electroencephalogram (EEG) patterns across various frequencies. Gephyrin proteomics analysis reveals sleep/wake-dependent interactions with a repertoire of known and novel kinases. Crucially, we identify the regulation of gephyrin interaction with ERK1/2, and phosphorylations at serines 268 and 270 are dictated by sleep/wake cycles. Employing AAV-eGFP-gephyrin or its phospho-null variant (S268A/S270A), we disrupt sleep either globally or locally to demonstrate gephyrin phosphorylation as a sleep regulator. In summary, our findings support the local cortical sleep hypothesis and we unveil a molecular mechanism operating at GABAergic synapses, providing critical insights into the intricate regulation of sleep.
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Sleep debt accumulates during wakefulness, leading to increased slow wave activity (SWA) during sleep, an encephalographic marker for sleep need. The use-dependent demands of prior wakefulness increase sleep SWA locally. However, the circuitry and molecular identity of this "local sleep" remain unclear. Using pharmacology and optogenetic perturbations together with transcriptomics, we find that cortical brain-derived neurotrophic factor (BDNF) regulates SWA via the activation of tyrosine kinase B (TrkB) receptor and cAMP-response element-binding protein (CREB). We map BDNF/TrkB-induced sleep SWA to layer 5 (L5) pyramidal neurons of the cortex, independent of neuronal firing per se. Using mathematical modeling, we here propose a model of how BDNF's effects on synaptic strength can increase SWA in ways not achieved through increased firing alone. Proteomic analysis further reveals that TrkB activation enriches ubiquitin and proteasome subunits. Together, our study reveals that local SWA control is mediated by BDNF-TrkB-CREB signaling in L5 excitatory cortical neurons.
Subject(s)
Brain-Derived Neurotrophic Factor , Cyclic AMP Response Element-Binding Protein , Receptor, trkB , Signal Transduction , Brain-Derived Neurotrophic Factor/metabolism , Animals , Receptor, trkB/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Mice , Sleep/physiology , Male , Mice, Inbred C57BL , Pyramidal Cells/metabolism , Sleep, Slow-Wave/physiologyABSTRACT
Background: There is no consensus on optimal management of pilonidal disease. Surgical practice is varied, and existing literature is mainly single-centre cohort studies of varied disease severity, interventions and outcome assessments. Objectives: A prospective cohort study to determine: ⢠disease severity and intervention relationship ⢠most valued outcomes and treatment preference by patients ⢠recommendations for policy and future research. Design: Observational cohort study with nested mixed-methods case study. Discrete choice experiment. Clinician survey. Three-stage Delphi survey for patients and clinicians. Inter-rater reliability of classification system. Setting: Thirty-one National Health Service trusts. Participants: Patients aged > 16 years referred for elective surgical treatment of pilonidal disease. Interventions: Surgery. Main outcome measures: Pain postoperative days 1 and 7, time to healing and return to normal activities, complications, recurrence. Outcomes compared between major and minor procedures using regression modelling, propensity score-based approaches and augmented inverse probability weighting to account for measured potential confounding features. Results: Clinician survey: There was significant heterogeneity in surgeon practice preference. Limited training opportunities may impede efforts to improve practice. Cohort study: Over half of patients (60%; Nâ =â 667) had a major procedure. For these procedures, pain was greater on day 1 and day 7 (mean difference day 1 pain 1.58 points, 95% confidence interval 1.14 to 2.01 points, nâ =â 536; mean difference day 7 pain 1.53 points, 95% confidence interval 1.12 to 1.95 points, nâ =â 512). There were higher complication rates (adjusted risk difference 17.5%, 95% confidence interval 9.1 to 25.9%, nâ =â 579), lower recurrence (adjusted risk difference -10.1%, 95% confidence interval -18.1 to -2.1%, nâ =â 575), and longer time to healing (>34 days estimated difference) and time to return to normal activities (difference 25.9 days, 95% confidence interval 18.4 to 33.4 days). Mixed-methods analysis: Patient decision-making was influenced by prior experience of disease and anticipated recovery time. The burden involved in wound care and the gap between expected and actual time for recovery were the principal reasons given for decision regret. Discrete choice experiment: The strongest predictors of patient treatment choice were risk of infection/persistence (attribute importance 70%), and shorter recovery time (attribute importance 30%). Patients were willing to trade off these attributes. Those aged over 30 years had a higher risk tolerance (22.35-34.67%) for treatment failure if they could experience rapid recovery. There was no strong evidence that younger patients were willing to accept higher risk of treatment failure in exchange for a faster recovery. Patients were uniform in rejecting excision-and-leave-open because of the protracted nursing care it entailed. Wysocki classification analysis: There was acceptable inter-rater agreement (κâ =â 0.52, 95% confidence interval 0.42 to 0.61). Consensus exercise: Five research and practice priorities were identified. The top research priority was that a comparative trial should broadly group interventions. The top practice priority was that any interventions should be less disruptive than the disease itself. Limitations: Incomplete recruitment and follow-up data were an issue, particularly given the multiple interventions. Assumptions were made regarding risk adjustment. Conclusions and future work: Results suggest the burden of pilonidal surgery is greater than reported previously. This can be mitigated with better selection of intervention according to disease type and patient desired goals. Results indicate a framework for future higher-quality trials that stratify disease and utilise broad groupings of common interventions with development of a patient-centred core outcome set. Trial registration: This trial is registered as ISRCTN95551898. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/17/02) and is published in full in Health Technology Assessment; Vol. 28, No. 33. See the NIHR Funding and Awards website for further award information.
Pilonidal disease is caused by ingrowing hairs between the buttocks. It can cause pain and infection and may need surgery. We do not know which operation gives the best results, or who operations help. PITSTOP aimed to find out which operation is the best and what is important to patients when deciding on surgery, and to suggest ideas for better treatment and future research. We looked at what operations were done and their outcomes. We interviewed patients about their experiences. Some completed a survey to help us understand what operations they might prefer based on risks and outcomes. Surgeons completed a survey about their experiences, and we explored whether a new tool could help us tell the difference between 'mild' and 'bad' disease. We used findings from these studies to help patients and surgeons give priorities for future practice and research. Six hundred and sixty-seven patients joined PITSTOP. People who had a major operation had more pain and took longer to return to normal activities. Some were still affected 6 months after surgery. However, disease recurrence was lower than after a minor procedure. Patients based decisions about treatment on the likelihood of success and the time to recover. The study and the surgeons' survey both showed marked differences in practice. Surgeons tended to offer one or two operations learned during training. A classification tool put cases in similar groups, but this did not influence treatment choices. The consensus exercise identified five research priorities, the top one being to put types of surgery into two groups. Of the five practice priorities, the top one was that surgery should not make the patient worse than the disease. There is variation in the treatment of pilonidal disease. Wound issues and impact on daily living should be avoided. The highlighted research questions should be addressed to improve care.
Subject(s)
Pilonidal Sinus , Humans , Pilonidal Sinus/surgery , Pilonidal Sinus/therapy , Female , Male , Adult , Prospective Studies , Delphi Technique , Recurrence , Middle Aged , Young Adult , Wound Healing , Pain, Postoperative , Patient Preference , Severity of Illness Index , Adolescent , United KingdomABSTRACT
Within cognitive psychology, there are separate experimental fields devoted to the study of creativity, on the one hand, and aesthetics, on the other, with virtually no cross-talk between them. In this article, I propose a means of uniting creativity and aesthetics via a consideration of the mechanisms of cultural evolution. I call this the creativity/aesthetics cycle. The basic tenet of the model is that creativity and aesthetics mediate, respectively, the processes of variation (production) and selection (perception or consumption) in evolutionary models of culture. By means of this cycle, creators produce works that they hope will be evaluated positively by consumers, where such appraisals ultimately feed back to influence the subsequent decision-making processes of creators. I discuss the implications of this model for the fields of creativity and aesthetics.
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We present a case report of diagnosis of cervical spine multiple sclerosis by a chiropractic physician. This unique case contributes an account of a challenging differential diagnosis to the literature. A 30-year-old male presented with a three-year history of diffuse left upper extremity motor strength deficits and paresthesia (numbness and tingling). The patient had seen multiple physicians for these symptoms with no diagnosis of multiple sclerosis and no advanced imaging. The differential diagnosis included lower cervical spine nerve root compression or neurological disorders such as amyotrophic lateral sclerosis, cerebral lesion, motor neuropathy, multiple sclerosis, or spinal cord lesion. MRI of the cervical spine with and without IV contrast revealed evidence of spinal cord multiple sclerosis. The patient was referred to a neurologist where the diagnosis of multiple sclerosis was confirmed. A 10-year follow-up showed the patient was controlling his condition with medications and had no disability. This case underscores the importance for physicians to consider neurological conditions and advanced imaging in the presence of diffuse motor strength deficits and paresthesia in the absence of injury, pain, or any other symptoms.
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Recent media coverage of high-profile cases of cervical artery dissection (CAD) has ignited the discussion about the role of cervical spine manipulation (CSM) in causing cervical artery dissection. However, research does not support a causal association between cervical spine manipulation and cervical artery dissection in a healthy cervical spine. The objective of this study was to review the 10 most recent case reports of cervical spine manipulation and cervical artery dissection for convincing evidence of the causation of cervical artery dissection by cervical spine manipulation. Nine of 10 case reports showed no convincing evidence of a causal relationship between cervical spine manipulation and cervical artery dissection. The 10th case report was exceptional as the CSM was contraindicated by pre-existing cervical spine pathology. We conclude that these 10 case reports provide no convincing evidence of the causation of cervical artery dissection by cervical spine manipulation in a healthy cervical spine. One case report demonstrated that cervical spine manipulation can cause cervical artery dissection when performed in the presence of pre-existing cervical spine pathology. Therefore, we conclude that practitioners should exclude cervical spine pathology before performing cervical spine manipulation.
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BACKGROUND: Research demonstrates gaps in medications for opioid use disorder uptake (MOUDs; methadone, buprenorphine, and naltrexone) especially among adolescents. These gaps may be partly attributable to attitudes about and training in MOUDs among youth-serving professionals. We extended prior research by conducting descriptive analyses of attitudes regarding effectiveness and acceptability of MOUDs, as well as training in MOUDs, among youth legal system (YLS) employees and community mental health center (CMHC) personnel who interface professionally with youth. METHODS: Using survey data from participants (n = 181) recruited from eight Midwest counties, we examined: (1) differences in MOUD attitudes/training by MOUD type and (2) by respondent demographics, and (3) prediction of MOUD attitudes/training by participant-reported initiatives to implement evidence-based practices (EBPs), workplace culture around EBPs, and workplace stress. Attitudes and training were measured in reference to five MOUD types (methadone, oral buprenorphine, injectable buprenorphine, oral naltrexone, injectable naltrexone) on three subscales (effectiveness, acceptability, training). RESULTS: Wilcoxon signed-rank tests demonstrated that most outcomes differed significantly by MOUD type (differences observed among 22 of 30 tests). Kruskal-Wallis tests suggested MOUD differences based on demographics. For methadone, CMHC providers endorsed greater perceived effectiveness than YLS providers and age explained significant differences in perceived effectiveness. For buprenorphine, CHMC providers viewed oral or injectable buprenorphine as more effective than YLS employees, respondents from more rural counties viewed oral buprenorphine as more effective than those from less rural counties, and age explained differences in perceived effectiveness. For naltrexone, perceived gender differed by gender. Hierarchical ordinal logistic regression analysis did not find an association between personal initiatives to implement EBPs, workplace culture supporting EBPs, or workplace stress and effectiveness or acceptability of MOUDs. However, personal initiatives to implement EBPs was associated with training in each MOUD. CONCLUSIONS: These results highlight a few key findings: effectiveness/acceptability of and training in MOUDs largely differ by MOUD type; setting, rurality, age, gender, and education explain group differences in perceived effectiveness of and training in MOUDs; and implementing EBPs is associated with training in MOUDs. Future research would benefit from examining what predicts change in MOUD attitudes longitudinally.
Subject(s)
Attitude of Health Personnel , Buprenorphine , Naltrexone , Opiate Substitution Treatment , Opioid-Related Disorders , Humans , Male , Female , Adult , Opioid-Related Disorders/drug therapy , Naltrexone/therapeutic use , Buprenorphine/therapeutic use , Methadone/therapeutic use , Community Mental Health Centers , Adolescent , Middle Aged , Young Adult , Narcotic Antagonists/therapeutic useABSTRACT
Microbes able to convert gaseous one-carbon (C1) waste feedstocks are increasingly important to transition to the sustainable production of renewable chemicals and fuels. Acetogens are interesting biocatalysts since gas fermentation using Clostridium autoethanogenum has been commercialised. However, most acetogen strains need complex nutrients, display slow growth, and are not robust for bioreactor fermentations. In this work, we used three different and independent adaptive laboratory evolution (ALE) strategies to evolve the wild-type C. autoethanogenum to grow faster, without yeast extract and to be robust in operating continuous bioreactor cultures. Multiple evolved strains with improved phenotypes were isolated on minimal media with one strain, named "LAbrini", exhibiting superior performance regarding the maximum specific growth rate, product profile, and robustness in continuous cultures. Whole-genome sequencing of the evolved strains identified 25 mutations. Of particular interest are two genes that acquired seven different mutations across the three ALE strategies, potentially as a result of convergent evolution. Reverse genetic engineering of mutations in potentially sporulation-related genes CLAU_3129 (spo0A) and CLAU_1957 recovered all three superior features of our ALE strains through triggering significant proteomic rearrangements. This work provides a robust C. autoethanogenum strain "LAbrini" to accelerate phenotyping and genetic engineering and to better understand acetogen metabolism.
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This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO guidelines.
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BACKGROUND: The HIV care cascade is a framework to examine effectiveness of HIV programs and progress toward global targets to end the epidemic but has been conceptualized as a unidirectional process that ignores cyclical care patterns. We present a dynamic cascade that accounts for patient "churn" and apply novel analytic techniques to readily available clinical data to robustly estimate program outcomes and efficiently assess progress toward global targets. METHODS: Data were assessed for 35,649 people living with HIV and receiving care at 78 clinics in East Africa between 2014 and 2020. Patients were aged ≥15 years and had ≥1 viral load measurements. We used multi-state models to estimate the probability of being in 1 of 5 states of a dynamic HIV cascade: (1) in HIV care but not on antiretroviral therapy (ART), (2) on ART, (3) virally suppressed, (4) in a gap-in-care, and (5) deceased and compared these among subgroups. To assess progress toward global targets, we summed those probabilities across patients and generated population-level proportions of patients on ART and virally suppressed in mid-2020. RESULTS: One year after enrollment, 2.8% of patients had not initiated ART, 86.7% were receiving ART, 57.4% were virally suppressed, 10.2% were disengaged from care, and 0.3% had died. At 5 years, the proportion on ART remained steady but viral suppression increased to 77.2%. Of those aged 15-25, >20% had disengaged from care and <60% were virally suppressed. In mid-2020, 90.1% of the cohort was on ART, 90.7% of whom had suppressed virus. CONCLUSIONS: Novel analytic approaches can characterize patient movement through a dynamic HIV cascade and, importantly, by capitalizing on readily available data from clinical cohorts, offer an efficient approach to estimate population-level proportions of patients on ART and virally suppressed. Significant progress toward global targets was observed in our cohort but challenges remain among younger patients.
Subject(s)
HIV Infections , Viral Load , Humans , HIV Infections/drug therapy , Adult , Female , Male , Young Adult , Middle Aged , Adolescent , Anti-HIV Agents/therapeutic use , Africa, Eastern/epidemiology , Health PolicyABSTRACT
The genus Clostridium is a large and diverse group within the Bacillota (formerly Firmicutes), whose members can encode useful complex traits such as solvent production, gas-fermentation, and lignocellulose breakdown. We describe 270 genome sequences of solventogenic clostridia from a comprehensive industrial strain collection assembled by Professor David Jones that includes 194 C. beijerinckii, 57 C. saccharobutylicum, 4 C. saccharoperbutylacetonicum, 5 C. butyricum, 7 C. acetobutylicum, and 3 C. tetanomorphum genomes. We report methods, analyses and characterization for phylogeny, key attributes, core biosynthetic genes, secondary metabolites, plasmids, prophage/CRISPR diversity, cellulosomes and quorum sensing for the 6 species. The expanded genomic data described here will facilitate engineering of solvent-producing clostridia as well as non-model microorganisms with innately desirable traits. Sequences could be applied in conventional platform biocatalysts such as yeast or Escherichia coli for enhanced chemical production. Recently, gene sequences from this collection were used to engineer Clostridium autoethanogenum, a gas-fermenting autotrophic acetogen, for continuous acetone or isopropanol production, as well as butanol, butanoic acid, hexanol and hexanoic acid production.
Subject(s)
Clostridium , Genome, Bacterial , Phylogeny , Clostridium/genetics , Solvents , FermentationABSTRACT
INTRODUCTION: Rates of substance use are high among youth involved in the legal system (YILS); however, YILS are less likely to initiate and complete substance use treatment compared to their non legally-involved peers. There are multiple steps involved in connecting youth to needed services, from screening and referral within the juvenile legal system to treatment initiation and completion within the behavioral health system. Understanding potential gaps in the care continuum requires data and decision-making from these two systems. The current study reports on the development of data dashboards that integrate these systems' data to help guide decisions to improve substance use screening and treatment for YILS, focusing on end-user feedback regarding dashboard utility. METHODS: Three focus groups were conducted with n = 21 end-users from juvenile legal systems and community mental health centers in front-line positions and in decision-making roles across 8 counties to gather feedback on an early version of the data dashboards; dashboards were then modified based on feedback. RESULTS: Qualitative analysis revealed topics related to (1) important aesthetic features of the dashboard, (2) user features such as filtering options and benchmarking to compare local data with other counties, and (3) the centrality of consistent terminology for data dashboard elements. Results also revealed the use of dashboards to facilitate collaboration between legal and behavioral health systems. CONCLUSIONS: Feedback from end-users highlight important design elements and dashboard utility as well as the challenges of working with cross-system and cross-jurisdiction data.
Subject(s)
Focus Groups , Qualitative Research , Substance-Related Disorders , Humans , Adolescent , Substance-Related Disorders/therapy , Male , Female , Juvenile Delinquency/legislation & jurisprudence , Continuity of Patient CareABSTRACT
The suprachiasmatic nucleus (SCN) encodes time of day through changes in daily firing; however, the molecular mechanisms by which the SCN times behavior are not fully understood. To identify factors that could encode day/night differences in activity, we combine patch-clamp recordings and single-cell sequencing of individual SCN neurons in mice. We identify PiT2, a phosphate transporter, as being upregulated in a population of Vip+Nms+ SCN neurons at night. Although nocturnal and typically showing a peak of activity at lights off, mice lacking PiT2 (PiT2-/-) do not reach the activity level seen in wild-type mice during the light/dark transition. PiT2 loss leads to increased SCN neuronal firing and broad changes in SCN protein phosphorylation. PiT2-/- mice display a deficit in seasonal entrainment when moving from a simulated short summer to longer winter nights. This suggests that PiT2 is responsible for timing activity and is a driver of SCN plasticity allowing seasonal entrainment.
Subject(s)
Suprachiasmatic Nucleus , Animals , Suprachiasmatic Nucleus/metabolism , Mice , Neurons/metabolism , Locomotion , Mice, Inbred C57BL , Vasoactive Intestinal Peptide/metabolism , Male , Circadian Rhythm/physiology , Photoperiod , Mice, Knockout , Sodium-Phosphate Cotransporter Proteins, Type III/metabolism , Sodium-Phosphate Cotransporter Proteins, Type III/genetics , Phosphate Transport Proteins/metabolism , Phosphate Transport Proteins/geneticsABSTRACT
AIM: Research in pilonidal disease faces several challenges, one of which is consistent and useful disease classification. The International Pilonidal Society (IPS) proposed a four-part classification in 2017. The aim of this work was to assess the validity and reliability of this tool using data from the PITSTOP cohort study. METHOD: Face validity was assessed by mapping the items/domains in the IPS tool against tools identified through a systematic review. Key concepts were defined as those appearing in more than two-thirds of published tools. Concurrent and predictive validity were assessed by comparing key patient-reported outcome measures between groups at baseline and at clinic visit. The outcomes of interest were health utility, Cardiff Wound Impact Questionnaire (CWIQ) and pain score between groups. Significance was set at p = 0.05 a priori. Interrater reliability was assessed using images captured during the PITSTOP cohort. Ninety images were assessed by six raters (two experts, two general surgeons and two trainees), and classified into IPS type. Interrater reliability was assessed using the unweighted kappa and unweighted Gwet's AC1 statistics. RESULTS: For face validity items represented in the IPS were common to other classification systems. Concurrent and predictive validity assessment showed differences in health utility and pain between groups at baseline, and for some treatment groups at follow-up. Assessors agreed the same classification in 38% of participants [chance-corrected kappa 0.52 (95% CI 0.42-0.61), Gwet's AC1 0.63 (95% CI 0.56-0.69)]. CONCLUSION: The IPS classification demonstrates key aspects of reliability and validity that would support its implementation.
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BACKGROUND: There have been over 772 million confirmed cases of COVID-19 worldwide. A significant portion of these infections will lead to long COVID (post-COVID-19 condition) and its attendant morbidities and costs. Numerous life-altering complications have already been associated with the development of long COVID, including chronic fatigue, brain fog, and dangerous heart rhythms. OBJECTIVE: We aim to derive an actionable long COVID case definition consisting of significantly increased signs, symptoms, and diagnoses to support pandemic-related clinical, public health, research, and policy initiatives. METHODS: This research employs a case-crossover population-based study using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) data generated at Veterans Affairs medical centers nationwide between January 1, 2020, and August 18, 2022. In total, 367,148 individuals with ICD-10-CM data both before and after a positive COVID-19 test were selected for analysis. We compared ICD-10-CM codes assigned 1 to 7 months following each patient's positive test with those assigned up to 6 months prior. Further, 350,315 patients had novel codes assigned during this window of time. We defined signs, symptoms, and diagnoses as being associated with long COVID if they had a novel case frequency of ≥1:1000, and they significantly increased in our entire cohort after a positive test. We present odds ratios with CIs for long COVID signs, symptoms, and diagnoses, organized by ICD-10-CM functional groups and medical specialty. We used our definition to assess long COVID risk based on a patient's demographics, Elixhauser score, vaccination status, and COVID-19 disease severity. RESULTS: We developed a long COVID definition consisting of 323 ICD-10-CM diagnosis codes grouped into 143 ICD-10-CM functional groups that were significantly increased in our 367,148 patient post-COVID-19 population. We defined 17 medical-specialty long COVID subtypes such as cardiology long COVID. Patients who were COVID-19-positive developed signs, symptoms, or diagnoses included in our long COVID definition at a proportion of at least 59.7% (268,320/449,450, based on a denominator of all patients who were COVID-19-positive). The long COVID cohort was 8 years older with more comorbidities (2-year Elixhauser score 7.97 in the patients with long COVID vs 4.21 in the patients with non-long COVID). Patients who had a more severe bout of COVID-19, as judged by their minimum oxygen saturation level, were also more likely to develop long COVID. CONCLUSIONS: An actionable, data-driven definition of long COVID can help clinicians screen for and diagnose long COVID, allowing identified patients to be admitted into appropriate monitoring and treatment programs. This long COVID definition can also support public health, research, and policy initiatives. Patients with COVID-19 who are older or have low oxygen saturation levels during their bout of COVID-19, or those who have multiple comorbidities should be preferentially watched for the development of long COVID.
Subject(s)
COVID-19 , Cross-Over Studies , Post-Acute COVID-19 Syndrome , Humans , COVID-19/epidemiology , COVID-19/complications , Risk Factors , Male , Female , Middle Aged , United States/epidemiology , Aged , International Classification of Diseases , AdultABSTRACT
Despite much progress, image processing remains a significant bottleneck for high-throughput analysis of microscopy data. One popular platform for single-cell time-lapse imaging is the mother machine, which enables long-term tracking of microbial cells under precisely controlled growth conditions. While several mother machine image analysis pipelines have been developed in the past several years, adoption by a non-expert audience remains a challenge. To fill this gap, we implemented our own software, MM3, as a plugin for the multidimensional image viewer napari. napari-MM3 is a complete and modular image analysis pipeline for mother machine data, which takes advantage of the high-level interactivity of napari. Here, we give an overview of napari-MM3 and test it against several well-designed and widely used image analysis pipelines, including BACMMAN and DeLTA. Researchers often analyze mother machine data with custom scripts using varied image analysis methods, but a quantitative comparison of the output of different pipelines has been lacking. To this end, we show that key single-cell physiological parameter correlations and distributions are robust to the choice of analysis method. However, we also find that small changes in thresholding parameters can systematically alter parameters extracted from single-cell imaging experiments. Moreover, we explicitly show that in deep learning-based segmentation, 'what you put is what you get' (WYPIWYG) - that is, pixel-level variation in training data for cell segmentation can propagate to the model output and bias spatial and temporal measurements. Finally, while the primary purpose of this work is to introduce the image analysis software that we have developed over the last decade in our lab, we also provide information for those who want to implement mother machine-based high-throughput imaging and analysis methods in their research.
Subject(s)
Image Processing, Computer-Assisted , Mothers , Female , Humans , Microscopy , Culture , Research PersonnelABSTRACT
AIM: Pilonidal sinus disease is a common condition treated by colorectal surgeons. There is a lack of literature in the field to guide optimal management of this condition. As part of the PITSTOP study, we aimed to identify policy and research priorities to provide direction to the field. METHOD: Patients and surgeons were invited to participate. A 'So what, now what' exercise was conducted, informed by data from PITSTOP. This generated statements for research and practice priorities. A three-round online Delphi study was conducted, ranking statements based on policy and research separately. Statements were rated 1 (not important) to 9 (important). Statements that were rated 7-9 by more than 70% of participants were entered into the consensus meeting. Personalized voting feedback was shown between rounds. A face-to-face meeting was held to discuss statements, and participants were asked to rank statements using a weighted choice vote. RESULTS: Twenty-two people participated in the focus group, generating 14 research and 19 policy statements. Statements were voted on by 56 participants in round 1, 53 in round 2 and 51 in round 3. A total of 15 policy statements and 19 research statements were discussed in the consensus round. Key policy statements addressed treatment strategies and intensity, surgeon training opportunities, need for classification and the impact of treatment on return to work. Research recommendations included design of future trials, methodology considerations and research questions. CONCLUSION: This study has identified research and policy priorities in pilonidal sinus disease which are relevant to patients and clinicians. These should inform practice and future research.