Transcatheter Aortic Valve Implantation Using the Evolut FX+ Platform With Optimal Diamond-Coronary Alignment.

We present one of the inaugural transcatheter aortic valve implantation procedures using the latest Medtronic platform, Evolut FX+. Successful coronary angiography was achieved within 28 seconds and 1 minute 49 seconds for the left and right coronary arteries, respectively. Postoperative cardiac computed tomography scan demonstrated optimal commissural and diamond-coronary alignment.

The effect of visual cues at different heights on sit-to-stand movements in people with and without low back pain.

BACKGROUND: Investigating movement strategies that can be utilized to avoid pain-provocation could enhance the management of low back pain episodes. OBJECTIVE: To assess the effect of visual cues at different heights on the kinematics of sit-to-stand movements, as well as perceived difficulty and pain levels. DESIGN: Cross-over design comparing individuals with low back pain to healthy controls. METHODS: 26 asymptomatic controls and 15 individuals with chronic, recurrent low back pain performed 5 sets of 5 sit-to-stand movements. High, middle, and low visual cues were used during sets 2-4. Spinal sagittal plane range of motion, peak spinal flexion and extension angles, and trunk centre of mass velocity were obtained from kinematic data. RESULTS: The low cue led to significantly more head and lumbar spine flexion, while the high cue led to significantly more head and thoracic spine extension and increased thoracic spine range of motion. The low back pain group demonstrated a significantly lower vertical trunk centre of mass velocity than the control group during the high cue trials. There was a significant association between higher perceived difficulty scores and lower trunk centre of mass velocity for the low back pain group. Pain scores were not significantly different between cue conditions. CONCLUSION: Visual cues can be used to temporarily change the spinal kinematics of sit-to-stand movements in people with and without low back pain. This could be helpful in clinical practice to encourage more, or less, movement in specific spinal regions, and avoid pain provocation to facilitate functional rehabilitation.

Effect of machine learning models on clinician prediction of postoperative complications: the Perioperative ORACLE randomised clinical trial.

BACKGROUND: Anaesthesiologists might be able to mitigate risk if they know which patients are at greatest risk for postoperative complications. This trial examined the impact of machine learning models on clinician risk assessment. METHODS: This single-centre, prospective, randomised clinical trial enrolled surgical patients aged ≥18 yr. Anaesthesiologists and nurse anaesthetists providing remote telemedicine support reviewed electronic health records with (assisted group) or without (unassisted group) reviewing machine learning predictions. Clinicians predicted the likelihood of postoperative 30-day all-cause mortality and postoperative acute kidney injury (AKI) within 7 days. The primary outcome was area under the receiver operating characteristic curve (AUROC) for clinician predictions of mortality and AKI, comparing AUROCs between assisted and unassisted assessments. RESULTS: We analysed 5071 patients (mean [range] age: 58 [18-100] yr; 52% female) assessed by 89 clinicians. Of these, 98 (2.2%) patients died within 30 days of surgery and 450 (11.1%) patients sustained AKI. Clinician predictions agreed with the models more strongly in the assisted vs unassisted group (weighted kappa 0.75 vs 0.62 for death, mean difference: 0.13 [95% CI 0.10-0.17]; and 0.79 vs 0.54 for AKI, mean difference: 0.25 [95% CI 0.21-0.29]). Clinical prediction of death was similar between the assisted (AUROC 0.793) and unassisted (AUROC 0.780) groups (mean difference: 0.013 [95% CI -0.070 to 0.097]; P=0.76). Prediction of AKI had an AUROC of 0.734 in the assisted group vs 0.688 in the unassisted group (difference 0.046 [95% CI -0.003 to 0.091]; P=0.06). CONCLUSIONS: Clinician performance was not improved by machine learning assistance. Further work is needed to clarify the role of machine learning in real-time perioperative risk stratification. CLINICAL TRIAL REGISTRATION: NCT05042804.

Recent Outcomes Research in Helicopter Emergency Medical Services: A Scoping Review of Publication Year 2023 Additions to the Helicopter Outcomes Assessment Research Database.

OBJECTIVE: The purpose of this scoping review was to identify and characterize helicopter emergency medical services (HEMS) outcomes literature from 2023, with the goal of describing updates to the Critical Care Transport Collaborative Outcomes Research Effort HEMS Outcomes Assessment Research Database (HOARD). METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, a multireviewer approach was used to source and review articles published or in preprint databases from 2023. The articles included assessed a patient-centered outcome for HEMS versus a non-HEMS control group. Article characteristics included the journal impact factor (JIF), diagnostic group (trauma or nontrauma), and geographic origin. Categoric analyses comparing 2023 studies with HOARD studies from the previous decade (2013-2022) were executed with the Fisher exact test; nonnormal JIF data were described using median and interquartile range and analyzed (vs 2013-2022) with rank sum testing. RESULTS: Of the initial records (N = 4,486), 4,410 were screened out, leaving 76 for full-text review. Of these, 58 were discarded, and 18 were classified as eligible for addition to HOARD. Most studies (14/18, 78%) focused on trauma, and an equally high proportion (14/18, 78%) came from North America. The median JIF was 2.4 (interquartile range, 1.2-3.6). Compared with HOARD studies from the previous decade, 2023 studies were similar with respect to diagnostic focus (P = .779), geographic origin (P = .171), and JIF (P = .531). CONCLUSION: This scoping review provides information on 18 HEMS outcomes studies new to the evidence base in 2023.

Proceedings: Sixth International Futures of Aviation Medicine Symposium.

In June 2024, leaders in aviation medicine from across the United States, Canada, and Europe met for the sixth Leonardo Helicopters/Association of Critical Care Transport: The Path to High Reliability Futures of Aviation Medicine Symposium in Miami, FL. The symposia, now held every few years, grew from the 2003 Air Medical Leadership Congress: Setting the Healthcare Agenda for the Air Medical Community. The meetings' goal is to gather leaders to distill, debate, and synthesize the state of the science while identifying, refining, and outlining conditions facilitating favorable evolution in civilian aviation medicine. Structured as thematic panel presentations followed by interactive all-attendee roundtable discussions, the gatherings build and expand an international network of thought leaders and proven doers. Meeting attendees have a common goal-accelerating learning and practice among early and developed systems moving toward a shared worldwide agenda for the future of aviation transport medicine.

Impact of systolic dominant pulmonary venous flow morphology on outcomes after mitral transcatheter edge-to-edge repair.

BACKGROUND: The prognostic significance of intraprocedural pulsed-wave Doppler analysis of pulmonary venous flow (PVF) during mitral transcatheter edge-to-edge repair (TEER) remains understudied. We aimed to investigate the prognostic value of systolic dominant-PVF (SD-PVF) morphology post-TEER. METHODS: In a retrospective analysis from December 2019 to December 2022, patients undergoing mitral TEER were categorized into SD-PVF and systolic blunting (SB)-PVF groups based on post-TEER morphology. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization at 1 year. We investigated the association of PVF morphology post-TEER with the primary endpoint at 1 year using Cox regression and compared the prognostic accuracy of PVF variables through receiver operating characteristic (ROC) curve analysis. RESULTS: Among 187 patients (mean age 76.4 ± 10.5 years, 51.3% primary etiology), residual mitral regurgitation (MR) ≤mild was observed in 147 (82.4%) patients and 105 (56.2%) had SD-PVF post-TEER. Patients with SD-PVF had a lower incidence of >2+ residual MR after clip deployment, at 30 days (2.1% vs. 13.1%; p = 0.005) and at 1 year (1.4% vs. 9%; p = 0.08). SD-PVF post-TEER was independently associated with the primary endpoint (HR = 0.59, 95% CI = 0.39-0.87; p = 0.009). ROC curve analysis of the prognostic accuracy of SD-PVF demonstrated an AUC of 0.64 (95% CI = 0.54-0.73), comparable to other quantitative measures of PVF. CONCLUSION: Assessing PVF morphology after clip deployment offers a simple prognostic tool for patients undergoing mitral TEER. Multicenter cohorts will be necessary to further investigate its prognostic value.

Utilizing citizen science data to rapidly assess changing associations between wild birds and avian influenza outbreaks in poultry.

High pathogenicity avian influenza virus (HPAIV) is a rapidly evolving virus causing significant economic and environmental harm. Wild birds are a key viral reservoir and an important source of viral incursions into animal populations, including poultry. However, we lack a thorough understanding of which species drive incursions and whether this changes over time. We explored associations between the abundances of 152 avian species and outbreaks of highly pathogenic avian influenza (HPAI) in poultry premises across Great Britain between October 2021 and January 2023. Spatial generalized additive models were used, with species abundance distributions sourced from eBird. Associations were investigated at the species-specific level and across species aggregations. During autumn/winter, associations were generally strongest with waterbirds such as ducks and geese; however, we also found significant associations in groups such as non-native gamebirds and rapid change in species-specific associations over time. Our results demonstrate the value of citizen science to rapidly explore wild species as potential facilitators of disease incursions into well-monitored populations, especially in regions where viral surveillance in wild species is limited. This can be a critical step towards prioritizing targeted surveillance that could inform species-specific biosecurity measures; particularly for HPAIV, which has undergone sudden shifts in host range and continues to rapidly evolve.

The Human Pathogen Mycobacterium tuberculosis and the Fish Pathogen Mycobacterium marinum Trigger a Core Set of Late Innate Immune Response Genes in Zebrafish Larvae.

Zebrafish is a natural host of various Mycobacterium species and a surrogate model organism for tuberculosis research. Mycobacterium marinum is evolutionarily one of the closest non-tuberculous species related to M. tuberculosis and shares the majority of virulence genes. Although zebrafish is not a natural host of the human pathogen, we have previously demonstrated successful robotic infection of zebrafish embryos with M. tuberculosis and performed drug treatment of the infected larvae. In the present study, we examined for how long M. tuberculosis can be propagated in zebrafish larvae and tested a time series of infected larvae to study the transcriptional response via Illumina RNA deep sequencing (RNAseq). Bacterial aggregates carrying fluorescently labeled M. tuberculosis could be detected up to 9 days post-infection. The infected larvae showed a clear and specific transcriptional immune response with a high similarity to the inflammatory response of zebrafish larvae infected with the surrogate species M. marinum. We conclude that M. tuberculosis can be propagated in zebrafish larvae for at least one week after infection and provide further evidence that M. marinum is a good surrogate model for M. tuberculosis. The generated extensive transcriptome data sets will be of great use to add translational value to zebrafish as a model for infection of tuberculosis using the M. marinum infection system. In addition, we identify new marker genes such as dusp8 and CD180 that are induced by M. tuberculosis infection in zebrafish and in human macrophages at later stages of infection that can be further investigated.

Synergistic Effects of Time-Restricted Feeding and Resistance Training on Body Composition and Metabolic Health: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis examined the synergistic impact of time-restricted feeding (TRF) combined with resistance training (RT) (TRF + RT) on body composition and metabolic health in adults, contrasting it with habitual eating patterns (CON) and RT (CON + RT). METHODS: Adhering to PRISMA guidelines, five databases were searched up to 28 April 2024. Randomized controlled trials or crossover trials assessing the effects of TRF + RT for at least 4 weeks in adults were selected. Data were pooled as standardized mean differences (SMDs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs). The risk of bias was evaluated using the revised Cochrane risk-of-bias tool. RESULTS: Seven studies with 164 participants were included in the final analysis. TRF + RT significantly reduced body mass (WMD -2.90, 95% CI: -5.30 to -0.51), fat mass (WMD -1.52, 95% CI: -2.30 to -0.75), insulin (SMD -0.72, 95% CI: -1.24 to -0.21), total cholesterol (WMD -9.44, 95% CI: -13.62 to -5.27), low-density lipoprotein cholesterol (LDL-C) (WMD -9.94, 95% CI: -13.47 to -6.41), and energy intake (WMD -174.88, 95% CI: -283.79 to -65.97) compared to CON + RT. No significant changes were observed in muscle mass, strength, or other metabolic markers. CONCLUSIONS: TRF + RT, in contrast to CON + RT, significantly improved body composition, insulin, and cholesterol levels without affecting muscle mass or strength.

Value of Engagement in Digital Health Technology Research: Evidence Across 6 Unique Cohort Studies.

BACKGROUND: Wearable digital health technologies and mobile apps (personal digital health technologies [DHTs]) hold great promise for transforming health research and care. However, engagement in personal DHT research is poor. OBJECTIVE: The objective of this paper is to describe how participant engagement techniques and different study designs affect participant adherence, retention, and overall engagement in research involving personal DHTs. METHODS: Quantitative and qualitative analysis of engagement factors are reported across 6 unique personal DHT research studies that adopted aspects of a participant-centric design. Study populations included (1) frontline health care workers; (2) a conception, pregnant, and postpartum population; (3) individuals with Crohn disease; (4) individuals with pancreatic cancer; (5) individuals with central nervous system tumors; and (6) families with a Li-Fraumeni syndrome affected member. All included studies involved the use of a study smartphone app that collected both daily and intermittent passive and active tasks, as well as using multiple wearable devices including smartwatches, smart rings, and smart scales. All studies included a variety of participant-centric engagement strategies centered on working with participants as co-designers and regular check-in phone calls to provide support over study participation. Overall retention, probability of staying in the study, and median adherence to study activities are reported. RESULTS: The median proportion of participants retained in the study across the 6 studies was 77.2% (IQR 72.6%-88%). The probability of staying in the study stayed above 80% for all studies during the first month of study participation and stayed above 50% for the entire active study period across all studies. Median adherence to study activities varied by study population. Severely ill cancer populations and postpartum mothers showed the lowest adherence to personal DHT research tasks, largely the result of physical, mental, and situational barriers. Except for the cancer and postpartum populations, median adherences for the Oura smart ring, Garmin, and Apple smartwatches were over 80% and 90%, respectively. Median adherence to the scheduled check-in calls was high across all but one cohort (50%, IQR 20%-75%: low-engagement cohort). Median adherence to study-related activities in this low-engagement cohort was lower than in all other included studies. CONCLUSIONS: Participant-centric engagement strategies aid in participant retention and maintain good adherence in some populations. Primary barriers to engagement were participant burden (task fatigue and inconvenience), physical, mental, and situational barriers (unable to complete tasks), and low perceived benefit (lack of understanding of the value of personal DHTs). More population-specific tailoring of personal DHT designs is needed so that these new tools can be perceived as personally valuable to the end user.

Pulmonary Vein Systolic Flow Reversal and Outcomes in Patients From the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Trial.

Background: The implications of pulmonary vein (PV) flow patterns in patients with heart failure (HF) and mitral regurgitation (MR) are uncertain. We examined PV flow patterns in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial (NCT01626079), in which patients with HF and moderate-to-severe or severe functional MR were randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip device plus guideline-directed medical therapy (GDMT) vs. GDMT alone. We sought to evaluate the prognostic utility of baseline PV systolic flow reversal (PVSFR) in HF patients with severe MR and to determine whether the presence of PVSFR can discriminate patients most likely to benefit from TEER in COAPT trial patients. Methods: Patients were categorized by the echocardiographic core laboratory-assessed baseline presence of PVSFR. Two-year outcomes were examined according to PVSFR and treatment. Results: Baseline PV flow patterns were evaluable in 526/614(85.7%) patients, 48.9% of whom had PVSFR. Patients with PVSFR had more severe MR, reduced stroke volume and cardiac output, greater right ventricular dysfunction, and worse hemodynamics. By multivariable analysis, PVSFR was not an independent predictor of 2-year all-cause death, or heart failure hospitalization (HFH). The reductions in the 2-year rates of all-cause death and HFH with TEER compared with GDMT alone were similar in patients with and without PVSFR (Pinteraction = 0.40 and 0.12, respectively). The effect of TEER on improving Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance were also independent of PVSFR. Conclusions: In the COAPT trial, PVSFR identified HF patients with severe MR and more advanced heart disease. Patients with and without PVSFR had consistent reductions in mortality, HFH, and improved quality-of-life and functional capacity after TEER. Clinical Trial Registration: ClinicalTrial.gov IdentifierNCT01626079.

Auranofin is lethal against feline Tritrichomonas foetus in vitro but ineffective in cats with naturally occurring infection.

Protozoal diarrhea caused by Tritrichomonas foetus (blagburni) is a prevalent, lifelong, and globally distributed burden in domestic cats. Treatment is limited to the use of 5-nitroimidazoles and treatment failure is common. The repurposed gold salt compound auranofin has killing activity against diverse protozoa in vitro but evidence of efficacy in naturally occurring protozoal infections is lacking. This exploratory study investigated the efficacy and safety of auranofin for treatment of cats with naturally occurring, 5-nitroimidazole-resistant, T. foetus infection. The minimum lethal concentration (MLC) of auranofin against 5 isolates of feline T. foetus was determined under aerobic conditions in vitro. Healthy cats and cats with T. foetus infection were treated with immediate release auranofin (range, 0.5-3 mg/cat for 7 days) or guar gum-coated auranofin capsules (0.5 or 3 mg/cat for 7 days). Adverse effects were monitored by clinical signs and clinicopathologic testing. Efficacy was determined by fecal consistency score, bowel movement frequency, and single-tube nested PCR of feces for T. foetus rDNA. Fecal samples were assayed for concentrations of auranofin, known and predicted metabolites of auranofin, gold containing molecules, and total gold content using HPLC, LC-MS, ion mobility-MS, and ICP-MS, respectively. Auranofin was effective at killing isolates of feline T. foetus at MLC ≥ 1 µg/ml. Treatment of cats with T. foetus infection with either immediate release auranofin or a colon-targeted guar gum-coated tablet of auranofin did not eradicate infection. Treatment failure occurred despite fecal concentrations of gold that met or exceeded the equivalent MLC of auranofin. Neither auranofin, known or predicted metabolites of auranofin, nor any gold-containing molecules >100 Da could be detected in fecal samples of treated cats. Adverse effects associated with auranofin treatment were common but minor. These studies identify that in vitro susceptibility test results of auranofin may not translate to treatment effectiveness in vivo even when achieving gold concentrations equivalent to the MLC of auranofin in the target environment. These studies further establish the absence of any predicted or unpredicted gold containing metabolites in feces after oral administration of auranofin.

Discharge instruction comprehension by older adults in the emergency department: A systematic review and meta-analysis.

INTRODUCTION: Older adults are at high risk of adverse health outcomes in the post-emergency department (ED) discharge period. Prior work has shown that discharged older adults have variable understanding of their discharge instructions which may contribute to these outcomes. To identify discharge comprehension gaps amenable to future interventions, we utilize meta-analysis to determine patient comprehension across five domains of discharge instructions: diagnosis, medications, self-care, routine follow-up, and return precautions. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, two reviewers sourced evidence from databases including Medline (PubMed), EMBASE, Web of Science, CINAHL, and Google Scholar (for gray literature). Publications or preprints appearing before April 2024 were included if they focused on geriatric ED discharge instructions and reported a proportion of patients with comprehension of at least one of five predefined discharge components. Meta-analysis of eligible studies for each component was executed using random-effects modeling to describe the proportion of geriatric ED cases understanding the discharge instructions; where appropriate we calculated pooled estimates, reported as percentages with 95% confidence interval (CI). RESULTS: Of initial records returned (N = 2898), exclusions based on title or abstract assessment left 51 studies for full-text review; of these, seven constituted the study set. Acceptable heterogeneity and absence of indication of publication bias supported pooled estimates for proportions comprehending instructions on medications (41%, 95% CI 31%-50%, I2 = 43%), self-care (81%, 95% CI 76%-85%, I2 = 43%), and routine follow-up (76%, 95% CI 72%-79%, I2 = 25%). Key findings included marked heterogeneity with respect to comprehending two discharge parameters: diagnosis (I2 = 73%) and return precautions (I2 = 95%). CONCLUSIONS: Older patients discharged from the ED had greater comprehension of self-care and follow-up instructions than about their medications. These findings suggest that medication instructions may be a priority domain for future interventions.

Challenges in reliable preoperative blood ordering: A qualitative interview study.

BACKGROUND: Presurgical blood orders are important for patient safety during surgery, but excess orders can be costly to patients and the healthcare system. We aimed to assess clinician perceptions on the presurgical blood ordering process and perceived barriers to reliable decision-making. METHODS: This descriptive qualitative study was conducted at a single large academic medical center. Semi-structured interviews were conducted with surgeons, anesthesiologists, nurse anesthetists, nurse practitioners working in preoperative assessment clinics, and transfusion medicine physicians to assess perceptions of current blood ordering processes. Interview responses were analyzed using an inductive open coding approach followed by thematic analysis. RESULTS: Twenty-three clinicians were interviewed. Clinicians felt that the current blood ordering process was frequently inconsistent. One contributor was a lack of information on surgical transfusion risk, related to lack of experience in ordering clinicians, insufficient communication between stakeholders, high turnover in academic settings, and lack of awareness of the maximum surgical blood ordering schedule. Other contributors included differing opinions about the benefits and harms of over- and under-preparing blood products, leading to variation in transfusion risk thresholds between clinicians, and disagreement about the safety of emergency-release blood. CONCLUSION: Several barriers to reliable decision-making for presurgical blood orders exist. Future efforts to improve ordering consistency may benefit from improved information sharing between stakeholders and education on safe transfusion practices.

Patients with type 1 diabetes are at elevated risk of developing new hypertension, chronic kidney disease and diabetic ketoacidosis after COVID-19: Up to 40 months' follow-up.

AIM: The aim was to investigate whether COVID-19 increases new incidence of hypertension (HTN), chronic kidney disease (CKD) and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) up to 40 months post-infection. MATERIALS AND METHODS: Three groups of patients from the Montefiore Health System in the Bronx (1 March 2020 to 1 July 2023) were studied: T1D patients hospitalized for COVID-19 (H-COVID-19, n = 511), T1D patients with COVID-19 but not hospitalized for COVID-19 (NH-COVID-19, n = 306) and T1D patients without a positive COVID-19 test on record (non-COVID-19, n = 1547). COVID-19 patients were those with a positive polymerase-chain-reaction test on record, and non-COVID-19 patients were either tested negative or not tested on record. Cumulative incidences and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed with adjustment for competing risks. RESULTS: Compared to non-COVID-19 patients, both H-COVID-19 (unadjusted 19.72% vs. 3.14%, p < 0.001; aHR = 7.55 [3.33, 17.06], p < 0.001) and NH-COVID-19 (10.26% vs. 3.14%, p = 0.004; aHR = 5.08 [2.19, 11.78], p < 0.001) patients were more likely to develop new HTN. Compared to non-COVID-19 patients, both H-COVID-19 (11.41% vs. 1.14%, p < 0.001; aHR = 9.76 [4.248, 22.25], p < 0.001) and NH-COVID-19 (7.69% vs. 1.14%, p < 0.001; aHR = 6.54 [2.91, 14.67], p < 0.001) patients were more likely to develop new CKD. Compared to non-COVID-19 patients, both H-COVID-19 (4.09% vs. 1.06%, p < 0.001; aHR = 12.24 [4.09, 36.59], p < 0.001) and NH-COVID-19 (3.06% vs. 1.06%, p = 0.035; aHR = 12.94 [4.09, 40.89], p < 0.001) patients were more likely to develop new DKA at follow-up. CONCLUSION: T1D patients with COVID-19 are at higher risk of developing new HTN, CKD and DKA compared to T1D patients without COVID-19.

Role of volume and inoculum in MIC assessment: a study with meropenem and Klebsiella pneumoniae.

OBJECTIVES: Pharmacodynamic parameters evaluated under conditions that simulate an infection site volume and microbial load might reveal hidden risks of resistance selection and subsequent treatment failure. The study aimed to investigate the predictive potential of MICs determined at various conditions on the antimicrobial effect and emergence of resistance. METHODS: We assessed meropenem MICs (microdilution: 0.2 mL, 5 × 105 cfu/mL; macrodilution: 2 mL, 5 × 105 cfu/mL), MICHVs (220 mL, 5 × 105 cfu/mL), MICHIs (0.2 mL, 5 × 107 cfu/mL) and MICHVIs (220 mL, 5 × 107 cfu/mL) for five Klebsiella pneumoniae strains and analysed these values alongside the results of experiments in a dynamic in vitro model. A clinically relevant meropenem dosing regimen was simulated and the starting bacterial inocula were 106 and 108 cfu/mL. RESULTS: The effectiveness of meropenem agreed with MICHVs for the 106 cfu/mL inoculum and with MICHIs or MICHVIs for the 108 cfu/mL inoculum. Strains characterized as resistant according to these values grew during meropenem exposure, and resistant mutants were selected. CONCLUSIONS: Our results suggest that MICHV-based parameters may be suitable for predicting antibacterial effects and the risk of resistance development when the inoculum is 106 cfu/mL, while MICHI- or MICHVI-based parameters are suitable for these purposes when the inoculum is 108 cfu/mL. Also, the correlation between resistance selection and the MICHI-based parameter was as high as one that corresponds with a mutant prevention concentration (MPC)-based parameter; this suggests that the MPC can be replaced by the more easily determined alternative parameter MICHI.

Headache-related disability as a function of migraine aura: A daily diary study.

OBJECTIVE: To examine the unique role of migraine aura in predicting day-to-day levels of headache-related disability. BACKGROUND: Migraine symptoms and psychological variables contribute to headache-related disability. Migraine aura may be associated with more severe symptom profiles and increased risk of psychiatric comorbidities, but the impact of aura on daily functioning is unknown. The present study sought to evaluate the role of migraine aura in predicting same-day and subsequent-day migraine-related disability while accounting for demographic, headache, and psychological variables. METHODS: This was an observational prospective cohort study among 554 adults with migraine. For each participant, data on migraine symptoms and psychological variables were collected daily for 90 days using the N-1 Headache™ digital app (N = 11,156 total migraine days). Analyses assessed whether the presence of aura predicted daily ratings of migraine-related disability independently of other headache and psychological variables. Given the number of predictors examined, statistical significance was set at p < 0.01. RESULTS: The mean (standard deviation, range) patient-level Migraine Disability Assessment questionnaire score across days of the migraine episode was 1.18 (1.03, 0-3). Aura was significantly associated with higher disability ratings on all days of the migraine episode (odds ratio [OR] 1.40, 99% confidence interval [CI] 1.13-1.74; p < 0.001). This relationship remained unchanged after adjusting for patient-level variables (OR 1.40, 99% CI 1.13-1.73; p < 0.001) and day-level psychological variables (OR 1.39, 99% CI 1.12-1.73; p < 0.001) but was fully negated after controlling for day-level headache variables (OR 1.19, 99% CI 0.95-1.49; p = 0.039). Aura on the first day of the episode was associated with increased odds of allodynia (OR 1.87, 99% CI 1.22-2.86; p < 0.001), phonophobia (OR 1.62, 99% CI 1.17-2.25; p < 0.001), photophobia (OR 1.89, 99% CI 1.37-2.59; p < 0.001), and nausea/vomiting (OR 1.54, 99% CI 1.17-2.02; p < 0.001) on all days of the episode, but not episode duration (p = 0.171), peak severity (p = 0.098), or any examined psychological variables (sleep duration [p = 0.733], sleep quality [p = 0.186], stress [p = 0.110], anxiety [p = 0.102], or sadness [p = 0.743]). CONCLUSION: The presence of aura is predictive of increased headache-related disability during migraine episodes, but this effect is attributable to associated non-pain symptoms of migraine.

Cross-Sectional Analysis of Outer Retinal Tubulation in Inherited Retinal Diseases: A Multicenter Study.

PURPOSE: This study aims to explore genetic variants that potentially lead to outer retinal tubulation (ORT), estimate the prevalence of ORT in these candidate genes, and investigate the clinical etiology of ORT in patients with inherited retinal diseases (IRDs), with respect to each gene. DESIGN: Retrospective cohort study. METHODS: A retrospective cross-sectional review was conducted on 565 patients with molecular diagnoses of IRD, confirming the presence of ORT as noted in each patient's respective spectral-domain optical coherence tomography (SD-OCT) imaging. Using SD-OCT imaging, the presence of ORT was analyzed in relation to specific genetic variants and phenotypic characteristics. Outcomes included the observed ORT frequencies across 2 gene-specific cohorts: non-retinal pigment epithelium (RPE)-specific genes, and RPE-specific genes; and to investigate the analogous characteristics caused by variants in these genes. RESULTS: Among the 565 patients included in this study, 104 exhibited ORT on SD-OCT. We observed ORT frequencies among the following genes from our patient cohort: 100% (23/23) for CHM, 100% (2/2) for PNPLA6, 100% (4/4) for RCBTB1, 100% for mtDNA [100% (4/4) for MT-TL1 and 100% (1/1) for mtDNA deletion], 100% (1/1) for OAT, 95.2% (20/21) for CYP4V2, 72.7% (8/11) for CHM female carriers, 66.7% (2/3) for C1QTNF5, 57.1% (8/14) for PROM1, 53.8% (7/13) for PRPH2, 42.9% (3/7) for CERKL, 28.6% (2/7) for CDHR1, 20% (1/5) for RPE65, 4% (18/445) for ABCA4. In contrast, ORT was not observed in any patients with photoreceptor-specific gene variants, such as RHO (n = 13), USH2A (n = 118), EYS (n = 70), PDE6B (n = 10), PDE6A (n = 4), and others. CONCLUSIONS: These results illustrate a compelling association between the presence of ORT and IRDs caused by variants in RPE-specific genes, as well as non-RPE-specific genes. In contrast, IRDs caused by photoreceptor-specific genes are typically not associated with ORT occurrence. Further analysis revealed that ORT tends to manifest in IRDs with milder intraretinal pigment migration (IPM), a finding that is typically associated with RPE-specific genes. These findings regarding ORT, genetic factors, atrophic patterns in the fundus, and IPM provide valuable insight into the complex etiology of IRDs. Future prospective studies are needed to further explore the association and underlying mechanisms of ORT in these contexts.