Generation and characterisation of an Arabidopsis thaliana f3h/fls1/ans triple mutant that accumulates eriodictyol derivatives.

BACKGROUND: Flavonoids are plant specialised metabolites, which derive from phenylalanine and acetate metabolism. They possess a variety of beneficial characteristics for plants and humans. Several modification steps in the synthesis of tricyclic flavonoids cause for the amazing diversity of flavonoids in plants. The 2-oxoglutarate-dependent dioxygenases (2-ODDs) flavanone 3-hydroxylase (F3H, synonym FHT), flavonol synthase (FLS) and anthocyanidin synthase (ANS, synonym leucoanthocyanidin dioxygenase (LDOX)), catalyse oxidative modifications to the central C ring. They are highly similar and have been shown to catalyse, at least in part, each other's reactions. FLS and ANS have been identified as bifunctional enzymes in many species, including Arabidopsis thaliana, stressing the capability of plants to bypass missing or mutated reaction steps on the way to flavonoid production. However, little is known about such bypass reactions and the flavonoid composition of plants lacking all three central flavonoid 2-ODDs. RESULTS: To address this issue, we generated a f3h/fls1/ans mutant, as well as the corresponding double mutants and investigated the flavonoid composition of this mutant collection. The f3h/fls1/ans mutant was further characterised at the genomic level by analysis of a nanopore DNA sequencing generated genome sequence assembly and at the transcriptomic level by RNA-Seq analysis. The mutant collection established, including the novel double mutants f3h/fls1 and f3h/ans, was used to validate and analyse the multifunctionalities of F3H, FLS1, and ANS in planta. Metabolite analyses revealed the accumulation of eriodictyol and additional glycosylated derivatives in mutants carrying the f3h mutant allele, resulting from the conversion of naringenin to eriodictyol by flavonoid 3'-hydroxylase (F3'H) activity. CONCLUSIONS: We describe the in planta multifunctionality of the three central flavonoid 2-ODDs from A. thaliana and identify a bypass in the f3h/fls1/ans triple mutant that leads to the formation of eriodictyol derivatives. As (homo-)eriodictyols are known as bitter taste maskers, the annotated eriodictyol (derivatives) and in particular the observations made on their in planta production, could provide valuable insights for the creation of novel food supplements.

A retrospective analysis of perioperative medications for opioid-use disorder and tapering additional postsurgical opioids via a transitional pain service.

AIMS: To investigate perioperative opioid requirements in patients on methadone or buprenorphine as medication for opioid-use disorder (MOUD) who attended a transitional pain clinic (Personalized Pain Program, PPP). METHODS: This retrospective cohort study assessed adults on MOUD with surgery and attendance at the Johns Hopkins PPP between 2017 and 2022. Daily non-MOUD opioid use over 6 time-points was evaluated with regression models controlling for days since surgery. The time to complete non-MOUD opioid taper was analysed by accelerated failure time and Kaplan-Meier models. RESULTS: Fifty patients (28 on methadone, 22 on buprenorphine) were included with a median age of 44.3 years, 54% male, 62% Caucasian and 54% unemployed. MOUD inpatient administration occurred in 92.8% of patients on preoperative methadone but only in 36.3% of patients on preoperative buprenorphine. Non-MOUD opioid use decreased over time postoperatively (ß = -0.54, P < .001) with a median decrease of 90 mg morphine equivalents (MME) between the first and last PPP visit, resulting in 46% tapered off by PPP completion. Older age and duration in PPP were associated with lower MME, while mental health conditions, longer hospital stays and higher discharge opioid prescriptions were associated with higher MME. The average time to non-MOUD opioid taper was 1.79× longer in patients on buprenorphine (P = .026), 2.75× in males (P = .023), 4.66× with mental health conditions (P < .001), 2.37× with chronic pain (P = .031) and 3.51× if on preoperative non-MOUD opioids; however, higher initial MOUD level decreased time to taper (P = .001). CONCLUSIONS: Postoperative opioid tapering utilizing a transitional pain service is possible in patients on MOUD.

Homoeologous non-reciprocal translocation explains a major QTL for seed lignin content in oilseed rape (Brassica napus L.).

KEY MESSAGE: A homoeologous non-reciprocal translocation was identified in the major QTL for seed lignin content in the low lignin line SGDH14. The lignin biosynthetic gene PAL4 was deleted. Oilseed rape is a major oil crop and a valuable protein source for animal and human nutrition. Lignin is a non-digestible, major component of the seed coat with negative effect on sensory quality, bioavailability and usage of oilseed rape's protein. Hence, seed lignin reduction is of economic and nutritional importance. In this study, the major QTL for reduced lignin content found on chromosome C05 in the DH population SGDH14 x Express 617 was further examined. SGDH14 had lower seed lignin content than Express 617. Harvested seeds from a F2 population of the same cross were additionally field tested and used for seed quality analysis. The F2 population showed a bimodal distribution for seed lignin content. F2 plants with low lignin content had thinner seed coats compared to high lignin lines. Both groups showed a dark seed colour with a slightly lighter colour in the low lignin group indicating that a low lignin content is not necessarily associated with yellow seed colour. Mapping of genomic long-reads from SGDH14 against the Express 617 genome assembly revealed a homoeologous non-reciprocal translocation (HNRT) in the confidence interval of the major QTL for lignin content. A homologous A05 region is duplicated and replaced the C05 region in SGDH14. As consequence several genes located in the C05 region were lost in SGDH14. Thus, a HNRT was identified in the major QTL region for reduced lignin content in the low lignin line SGDH14. The most promising candidate gene related to lignin biosynthesis on C05, PAL4, was deleted.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

Quality Improvement Initiative to Improve Postoperative Pain with a Clinical Pathway and Nursing Education Program.

BACKGROUND AND AIMS: We created a multicomponent intervention to improve pain management in the immediate postoperative period with the goal of improving the quality of patient recovery. DESIGN: A multicomponent intervention to improve pain management in the immediate postoperative period with the goal of improving the quality of patient recovery. SETTINGS: Pain management education of postanesthesia recovery room nurses through a practical intervention has the potential to improve patient pain experience, especially in those with a history of opioid tolerance. PARTICIPANTS/SUBJECTS: Postanesthesia recovery nurses/postanesthesia patients. METHODS: The intervention included two components: a clinical pain pathway on multimodal analgesia for both opioid-naïve and opioid-tolerant patients undergoing surgery and an educational program on pain management for frontline clinical nurses in the postanesthesia care unit (PACU). We measured the intervention's impact on time to pain relief, PACU length of stay, and patient satisfaction with pain management, as measured by self-report. RESULTS: Patient PACU surveys indicated a decrease in the percent of patients with opioid tolerance who required more than 60 minutes to achieve adequate pain relief (from 32.7% preintervention to 21.3% postintervention). Additionally, after the intervention, the average time from a patient's PACU arrival to his or her discharge criteria being met decreased by 53 minutes and PACU stay prolongation as a result of uncontrolled pain for opioid-tolerant patients decreased from 45.2% to 25.7%. The sample size was underpowered to perform statistical analysis of this improvement. CONCLUSIONS: After the combined intervention of a clinical pain pathway and interactive teaching workshop, we noted shortened PACU length of stay, reduced time to reach pain control, and improved overall patient satisfaction. Although we could not determine statistical significance, our findings suggest improved management of acute postoperative pain, especially for patients who are opioid tolerant. Because of the paucity of data, we were not able to conduct the analysis needed to evaluate quality improvement projects, as per SQUIRE 2.0. could be adopted by any institution.

High-frequency epidural stimulation across the respiratory cycle evokes phrenic short-term potentiation after incomplete cervical spinal cord injury.

C2 spinal hemilesion (C2Hx) paralyzes the ipsilateral diaphragm, but recovery is possible through activation of "crossed spinal" synaptic inputs to ipsilateral phrenic motoneurons. We tested the hypothesis that high-frequency epidural stimulation (HF-ES) would potentiate ipsilateral phrenic output after subacute and chronic C2Hx. HF-ES (300 Hz) was applied to the ventrolateral C4 or T2 spinal cord ipsilateral to C2Hx in anesthetized and mechanically ventilated adult rats. Stimulus duration was 60 s, and currents ranged from 100 to 1,000 µA. Bilateral phrenic nerve activity and ipsilateral hypoglossal (XII) nerve activity were recorded before and after HF-ES. Higher T2 stimulus currents potentiated ipsilateral phasic inspiratory activity at both 2 and 12 wk post-C2Hx, whereas higher stimulus currents delivered at C4 potentiated ipsilateral phasic phrenic activity only at 12 wk (P = 0.028). Meanwhile, tonic output in the ipsilateral phrenic nerve reached 500% of baseline values at the high currents with no difference between 2 and 12 wk. HF-ES did not trigger inspiratory burst-frequency changes. Similar responses occurred following T2 HF-ES. Increases in contralateral phrenic and XII nerve output were induced by C4 and T2 HF-ES at higher currents, but the relative magnitude of these changes was small compared with the ipsilateral phrenic response. We conclude that following incomplete cervical spinal cord injury, HF-ES of the ventrolateral midcervical or thoracic spinal cord can potentiate efferent phrenic motor output with little impact on inspiratory burst frequency. However, the substantial increases in tonic output indicate that the uninterrupted 60-s stimulation paradigm used is unlikely to be useful for respiratory muscle activation after spinal injury.NEW & NOTEWORTHY Previous studies reported that high-frequency epidural stimulation (HF-ES) activates the diaphragm following acute spinal transection. This study examined HF-ES and phrenic motor output following subacute and chronic incomplete cervical spinal cord injury. Short-term potentiation of phrenic bursting following HF-ES illustrates the potential for spinal stimulation to induce respiratory neuroplasticity. Increased tonic phrenic output indicates that alternatives to the continuous stimulation paradigm used in this study will be required for respiratory muscle activation after spinal cord injury.

Optimization of visual training for full recovery from severe amblyopia in adults.

The severe amblyopia induced by chronic monocular deprivation is highly resistant to reversal in adulthood. Here we use a rodent model to show that recovery from deprivation amblyopia can be achieved in adults by a two-step sequence, involving enhancement of synaptic plasticity in the visual cortex by dark exposure followed immediately by visual training. The perceptual learning induced by visual training contributes to the recovery of vision and can be optimized to drive full recovery of visual acuity in severely amblyopic adults.

The efficacy and safety of epidural-based analgesia in a case series of patients undergoing lung transplantation.

OBJECTIVE: Successful pain management after lung transplantation is critical to ensure adequate respiratory effort and graft expansion. The authors investigated whether thoracic epidural analgesia (TEA) provided adequate pain control after lung transplantation without added morbidity. DESIGN: Retrospective review. SETTING: University teaching hospital. PARTICIPANTS: One hundred twenty-three patients who presented to this institution for lung transplantation from January 2008 to June 2013. INTERVENTIONS: Patient demographics, postoperative pain scores, and epidural-related complications were abstracted from the institutional electronic database. The authors used the previously validated Quality of Recovery (QoR) score and Visual Analog Scale (VAS) as measures of recovery. MEASUREMENTS AND MAIN RESULTS: Of the 123 patients who underwent lung transplantation in this time frame, 119 patients had thoracic epidurals placed for postoperative analgesia. The mean age was 49.4 years (range, 18-73), and 60 (50.4%) were male. The most common indications for transplant were pulmonary fibrosis (33.6%), cystic fibrosis (26.1%), and chronic obstructive pulmonary disease (20.2%). The median length of stay in the intensive care unit and duration of mechanical ventilation were 21 and 1.2 days, respectively. Eight (6.7%) patients experienced postoperative pulmonary compromise (eg, pneumonia, prolonged intubation). No serious complications were associated with TEA placement. On days 1, 3, and 7 after TEA placement, the mean QoR was 7.6, 9.4, and 9.7, and the mean VAS was 2.5, 2.1, and 2.0, respectively. CONCLUSIONS: In this case series, the authors observed excellent analgesia and no serious complications associated with TEA. Therefore, an epidural-centric approach to pain control after lung transplantation should be considered in appropriate patients.

Curriculum development for an advanced regional anesthesia education program: one institution's experience from apprenticeship to comprehensive teaching.

Results of recent attitude survey studies suggest that most practicing physicians are inadequately treating postoperative pain. Residents in anesthesia are confident in performing lumbar epidural and spinal anesthesia, but many are not confident in performing the blocks with which they have the least exposure. Changes need to be made in the training processes to a comprehensive model that prepares residents to perform a wider array of blocks in postgraduate practice. Here, we describe one institution's approach to creating a standardized, advanced regional anesthesia curriculum for residents that follows the six core competencies of the ACGME. Residents received training in anatomy dissection, ultrasound-guided regional anesthesia, traditional nerve stimulation techniques, problem-based learning and simulation sessions, oral board presentation sessions, and journal club sessions. Residents kept a detailed log for their use of peripheral nerve block procedures. We have now redesigned and implemented an advanced regional anesthesia program within our institution to provide residents with experience in regional anesthesia at a competent level. Resident's knowledge in regional anesthesia did improve after the first year of implementation as reflected in improvements between the pre- and post-tests. As the advanced regional anesthesia education program continues to improve, we hope to demonstrate levels of validity, reliability, and usability by other programs.

Improved residents' knowledge after an advanced regional anesthesia education program.

BACKGROUND: Although residents in anesthesia are confident in performing neuraxial anesthesia, many are not confident in performing peripheral nerve blocks. The purpose of this study was to evaluate the effectiveness of a structured regional anesthesia teaching program in a large academic medical center. METHODS: Residents participated in regional anesthesia didactics that took place in a unique resident education program scheduled during two fully protected teaching days a month. The curriculum included hands-on cadaver workshops in the anatomy lab, hands-on ultrasound workshops, hands-on nerve stimulator and surface anatomy workshops, and simulator sessions related to complications of regional anesthesia. Before beginning the formal regional anesthesia teaching program, residents completed a pretest composed of 25 multiple choice questions (MCQ) and a three-section observed standardized clinical examination (OSCE). Seven months later, approximately 1 month after completion of the regional anesthesia curriculum, the residents were evaluated again with the exact same tests. Pretest and post-test results for both the MCQ and the OSCE were compared by using a paired t-test for statistical means. RESULTS: Post-test results were significantly improved (P < 0.05) across all clinical anesthesia (CA) years and for both the MCQ and OSCE examinations. Post-test results were also significantly improved (P < 0.05) across all CA years for each of the three sections of the OSCE. CONCLUSION: The formal regional anesthesia teaching program developed by the departmental faculty was effective in improving resident knowledge.

[Vaccinations for emerging and re-emerging viral diseases]. / Impfungen für neu- und wiederauftretende Viruserkrankungen.

BACKGROUND: Emerging or re-emerging viral diseases have a pandemic potential and threaten global health. Vaccination is of crucial importance in the prevention of emerging and re-emerging viral diseases. OBJECTIVE: Description of the current status of vaccine development against Filoviridae, highly pathogenic coronaviruses, smallpox viruses, influenza viruses and arboviruses. MATERIAL AND METHODS: Focused literature search. RESULTS: The World Health Organization (WHO) regularly publishes a list of infectious diseases that are expected to pose a major threat to humanity as they are could potentially trigger new pandemics; however, in addition to these human-to-human transmissible diseases, some arboviruses also have pandemic potential. In recent years numerous new vaccines, some of which are highly effective, have been licensed against new and re-emerging viral diseases and other promising vaccine candidates are currently in development. CONCLUSION: There are still gaps in the development of vaccines in the area of Filoviridae and highly pathogenic coronaviruses. Vaccinations against smallpox viruses have been available for a long time. Developing influenza vaccines against novel strains in a timely manner is a challenge and universal influenza vaccines could be a possible solution. Modern vaccines are available against the arboviruses dengue and Chikungunya fever.

Abdominal Fibromyxoid Sarcoma in Pregnancy: An Unusual Cause of Preterm Labor and Sepsis.

Cancer in pregnancy is rare, with incidence less than 1%, and the most common cancers being melanoma, breast, and cervical cancers. Fibromyxoid sarcoma is a soft tissue tumor involving deep soft tissues of the extremities and trunk, rarely located in the abdomen. A low-grade fibromyxoid sarcoma (LGFMS) falls in the family of fibrosarcoma. Only two cases of LGFMS in pregnancy have been reported. We report a case of abdominal LGFMS in pregnancy leading to preterm labor, sepsis, and an acute abdomen requiring surgery in the third trimester. A 19-year-old woman, gravida 1 at 32 weeks and 5 days presented to an outside hospital with preterm contractions and cervical effacement. She had a known abdominal mass, suspected to be accessory liver lobe, measuring 9.0 × 6.4 × 7.7 cm in the right upper quadrant. At 33 weeks of gestation, she developed fever and hypotension. Magnetic resonance imaging confirmed the presence of the mass, which was now on the left side of the abdomen and associated with a suspected abscess. She underwent cesarean delivery, and complete surgical resection of the mass along with a small bowel resection. Final pathology of the mass revealed a LGFMS. This case also highlights the need for a multidisciplinary approach to manage a rare presentation of sepsis and preterm labor in pregnancy.

Uncomplicated epidural removal in a patient on a therapeutic heparin infusion: a case report.

BACKGROUND: Unanticipated postoperative thrombotic complications can occur in complex patients who receive preoperative epidurals. Therefore, it is imperative that we consider the risks and benefits of epidural management in the setting of therapeutic anticoagulation. We present a case of epidural catheter removal on a heparin infusion, due to the extreme risk of holding anticoagulation for any duration. CASE REPORT: A woman with hilar cholangiocarcinoma presented after uncomplicated hepatectomy, bile duct resection and hepaticojejunostomy, with a thoracic epidural for analgesia. On postoperative day 1, she developed a total portal vein thrombosis, requiring emergent open thrombectomy, transhepatic stenting and high-dose heparin infusion while the epidural was indwelling. The patient was deemed to have a profound risk of re-thrombosis if heparin were paused. Therefore, a multidisciplinary discussion between hepatobiliary surgery, critical care, neurosurgery, haematology, acute pain service and the patient's family ensued regarding epidural management. Options included catheter-directed thrombolytics to her stent while holding systemic anticoagulation, sterilely leaving the epidural catheter in place indefinitely, injecting prothrombotic agent into the epidural prior to removal, or removing the catheter without holding anticoagulation. Due to the risk of re-thrombosis in the portal vein and liver infarction, the heparin infusion was decreased to achieve the lowest therapeutic anti-Xa level, and the epidural was removed. The patient was continuously monitored in the intensive care unit without any adverse events. CONCLUSION: A multidisciplinary discussion is paramount to weigh the risk of epidural haematoma if a catheter is removed on therapeutic anticoagulation against catastrophic thrombosis if anticoagulation is paused.

Differential gene expression in leaves and roots of Hydrangea serrata treated with aluminium chloride.

Hydrangea serrata, also knowen as the Japanese tea hortensia, is known for its sweet taste and health properties of bevarages produced from this plant. The H. serrata 3,4-dihydroisocoumarins, hydrangenol and phyllodulcin harbour a variety of biological activities and pharmacological properties. Therefore, a detailed understanding of dihydroisocoumarin biosynthesis in H. serrata is of major interest. Their biosynthesis is assumed to be enhanced by elicitors and mediated by polyketide synthases like in cases of phenylpropanoid derived phytoalexins. A de-novo transcriptome assembly of leaves and roots from the aluminium chloride treatment group versus the control group alongside with annotation was generated. Secondary plant metabolites were analysed by LC-MS. It revealed that a terpene synthase and a triterpenoid synthase gene as well as lignin biosynthesis encoding genes were upregulated in roots. Many genes for transporters, glycosyl, and other transferases as well as glycosylases were found to be differentially expressed in both organs. As no differentially expressed polyketide synthase gene homolog was found, the relative leaf and root 3,4-dihydroisocoumarin content was analysed by LC-MS measurement. Although Hydrangea species are known for their aluminium detoxification using phenylpropanoid-derived compounds, the levels of 3,4- dihydroisocoumarins were not enhanced. In this metabolite analysis, an organ- specific accumulation profile of hydrangenol, phyllodulcin, hydrangeic acid and their mono- and di-glycosides was figured out.

The Built Environment as a Social Determinant of Health.

The built environment encompasses buildings we live in; the distribution systems that provide us with water and electricity; and the roads, bridges, and transportation systems we use to get from place to place. It provides safety, health, and well-being and meaning to its dwellers, as a place to work, live, learn, play, and thrive. Poor-quality housing affects dwellers' health through toxins such as radon and lead, mold, cold indoor temperatures, and overcrowding. Physicians' practices should investigate their patients' diagnoses such as stress, depression, asthma, adverse childhood experiences, and anxiety, as potentially housing-related and make ameliorating recommendations or referrals.

A multidisciplinary transitional pain service to improve pain outcomes following trauma surgery: a preliminary report.

OBJECTIVES: Trauma (i.e., musculoskeletal injury from a blunt or penetrating force) can change the trajectory of a person's life. Patients often experience chronic pain, reduced quality of life, long-term opioid therapy, and psychiatric comorbidities after trauma surgery. This case report presents clinical outcomes of four patients who received postsurgical pain care in a transitional pain service (TPS) that provides long-term coordinated multimodal pain care, opioid tapering plans, and psychiatric care. METHODS: The Personalized Pain Program (PPP) measures prescription opioid use and patient-reported outcomes: pain severity and pain interference (Brief Pain Inventory), pain catastrophizing (Pain Catastrophizing Scale), insomnia severity (Insomnia Severity Index), physical and mental health functioning (SF-12 pre-COVID-19; SF-36 during COVID-19 pandemic) at initial and subsequent clinic visits. RESULTS: All four patients reduced their postsurgical opioid use with concurrent reductions in pain and improved functioning while receiving postoperative care in the PPP (average length of treatment: 2.8 years). Psychiatric co-treatment addressed the onset or exacerbation of mental health comorbidities following trauma. CONCLUSIONS: Long-term multidisciplinary pain care may improve post-trauma recovery and reduce risks of long-term opioid therapy and disability. Prospective studies are needed to evaluate the effectiveness of TPSs for patients undergoing trauma surgery.

Progression events defined by home-based assessment of motor function in multiple sclerosis: protocol of a prospective study.

Background: This study relates to emerging concepts of appropriate trial designs to evaluate effects of intervention on the accumulation of irreversible disability in multiple sclerosis (MS). Major starting points of our study are the known limitations of current definitions of disability progression by rater-based clinical assessment and the high relevance of gait and balance dysfunctions in MS. The study aims to explore a novel definition of disease progression using repeated instrumental assessment of relevant motor functions performed by patients in their home setting. Methods: The study is a prospective single-center observational cohort study with the primary outcome acquired by participants themselves, a home-based assessment of motor functions based on an RGB-Depth (RGB-D) camera, a camera that provides both depth (D) and color (RGB) data. Participants are instructed to perform and record a set of simple motor tasks twice a day over a one-week period every 6 months. Assessments are complemented by a set of questionnaires. Annual research grade assessments are acquired at dedicated study visits and include clinical ratings as well as structural imaging (MRI and optical coherence tomography). In addition, clinical data from routine visits is provided semiannually by treating neurologists. The observation period is 24 months for the primary endpoint with an additional clinical assessment at 27 month to confirm progression defined by the Expanded Disability Status Scale (EDSS). Secondary analyses aim to explore the time course of changes in motor parameters and performance of the novel definition against different alternative definitions of progression in MS. The study was registered at Deutsches Register für Klinische Studien (DRKS00027042). Discussion: The study design presented here investigates disease progression defined by marker-less home-based assessment of motor functions against 3-month confirmed disease progression (3 m-CDP) defined by the EDSS. The technical approach was chosen due to previous experience in lab-based settings. The observation time per participant of 24, respectively, 27 months is commonly conceived as the lower limit needed to study disability progression. Defining a valid digital motor outcome for disease progression in MS may help to reduce observation times in clinical trials and add confidence to the detection of progression events in MS.

The use of telemedicine for perioperative pain management during the COVID-19 pandemic.

INTRODUCTION: Using a human factors engineering approach, the Johns Hopkins Personalized Pain Program adopted telemedicine for perioperative pain management in response to the COVID-19 pandemic. This study examines the impact of telemedicine adoption on the quality and outcomes of perioperative pain management. METHODS: A mixed-methods study with a convergent parallel design was conducted. From June 2017 to December 2021, 902 patients participated in the Personalized Pain Program. Quantitative data on daily opioid consumption, pain severity and interference, physical and mental health status, and patient satisfaction and engagement were continuously collected with all patients using chart review and patient surveys. Beginning 23 March 2020, the Personalized Pain Program transitioned to telemedicine. A pre-post quasi-experimental design was used to examine the impact of telemedicine. In addition, qualitative interviews were conducted with 3 clinicians and 17 patients to explore their experience with telemedicine visits. RESULTS: The monthly number of new patients seen in the Personalized Pain Program did not significantly change before and after telemedicine adoption. Compared to patients having in-person visits before the pandemic, patients having telemedicine visits during the pandemic achieved comparable improvements in daily opioid consumption, pain severity and interference, and physical health status. While telemedicine helped overcome many challenges faced by the patients, the limitations of telemedicine were also discussed. CONCLUSION: The COVID-19 pandemic stimulated the use of telemedicine. To facilitate telemedicine adoption beyond the pandemic, future research is needed to examine best practices for telemedicine adoption and provide additional evidence on the effectiveness of telemedicine.