Emergency department (ED) patients with cellulitis requiring intravenous antibiotics may be eligible for outpatient parenteral antibiotic therapy (OPAT). The primary objective was to determine ...whether implementation of an OPAT clinic results in decreased hospitalizations and return ED visits for patients receiving OPAT. We conducted an interrupted time series study involving adults with cellulitis presenting to two EDs and treated with intravenous antibiotics. The intervention was the OPAT clinic, which involved follow up at 48–96 h with an infectious disease physician to determine the need for ongoing intravenous antibiotics (implemented January 1, 2014). The primary outcomes were hospital admission and return ED visits within 14 days. Secondary outcomes were treatment failure (admission after initiating OPAT) and adverse peripheral line or antibiotic events. We used an interrupted time series design with segmented regression analysis over one-year pre-intervention and one-year post-intervention. 1666 patients were included. At the end of the study period, there was a non-significant 12% absolute increase in hospital admissions (95% CI − 1.6 to 25.5%;
p
= 0.084) relative to what would have been expected in the absence of the intervention, but a significant 40.7% absolute reduction in return ED visits (95% CI 25.6–55.9%;
p
< 0.001). Treatment failure rates were < 2% and adverse events were < 6% in both groups. Implementation of an OPAT clinic significantly reduced return ED visits for cellulitis, but did not reduce hospital admission rates. An ED-to-OPAT clinic model is safe, and has a low rate of treatment failures.
Lactate dehydrogenase (LDH) has a crucial role in maintaining ATP production as the terminal enzyme in anaerobic glycolysis. This study will determine the effect of posttranslational modifications ...(PTMs) on the activity of LDH in the foot muscle and hepatopancreas of an estivating snail,
Otala lactea
. LDH in foot muscle of
O
.
lactea
was purified to homogeneity and partially purified in hepatopancreas in a two-step and three-step process, respectively. The kinetic properties and stability of these isoforms were determined where there was a significant difference in K
m
and I
50
values with pyruvate and urea separately in foot muscle; however, hepatopancreas exhibited significant differences in K
m
and I
50
in salt between control and stress. Interestingly, hepatopancreas has a higher affinity for pyruvate in the control state whereas foot muscle has a higher affinity for its substrate in the estivated state. PTMs of each isoform were identified using immunoblotting and dot blots, which prove to be significantly higher in the control state. Overall, foot muscle LDH enters a low phosphorylation state during estivation allowing more efficiency in consuming pyruvate with higher thermal stability but less structural stability. Hepatopancreas LDH becomes dephosphorylated in the estivating snail that decreases the efficiency of the enzyme in the forward direction; however, the snail has an increased tolerance to the presence of salt when water becomes scarce. Such tissue-specific regulations indicate the organism’s ability to reduce energy consumption when undergoing metabolic depression.
Congenital indifference to pain (CIP) is a rare condition in which patients have severely impaired pain perception, but are otherwise essentially normal. We identified and collected DNA from ...individuals from nine families of seven different nationalities in which the affected individuals meet the diagnostic criteria for CIP. Using homozygosity mapping and haplotype sharing methods, we narrowed the CIP locus to chromosome 2q24–q31, a region known to contain a cluster of voltage‐gated sodium channel genes. From these prioritized candidate sodium channels, we identified 10 mutations in the SCN9A gene encoding the sodium channel protein Nav1.7. The mutations completely co‐segregated with the disease phenotype, and nine of these SCN9A mutations resulted in truncation and loss‐of‐function of the Nav1.7 channel. These genetic data further support the evidence that Nav1.7 plays an essential role in mediating pain in humans, and that SCN9A mutations identified in multiple different populations underlie CIP.
Pyruvate kinase (PK) is responsible for the final reaction in glycolysis. As PK is a glycolytic control point, the analysis of PK posttranslational modifications (PTM) and kinetic changes reveals a ...key piece of the reorganization of energy metabolism in an anoxia tolerant vertebrate.
To explore PK regulation, the enzyme was isolated from red skeletal muscle and liver of aerobic and 20-hr anoxia-exposed red eared-slider turtles (
). Kinetic analysis and immunoblotting were used to assess enzyme function and the corresponding covalent modifications to the enzymes structure during anoxia.
Both muscle and liver isoforms showed decreased affinity for phosphoenolpyruvate substrate during anoxia, and muscle PK also had a lower affinity for ADP.
values for the inhibitors ATP and lactate were lower for PK from both tissues after anoxic exposure while
L-alanine was only reduced in the liver. Both isozymes showed significant increases in threonine phosphorylation (by 42% in muscle and 60% in liver) and lysine methylation (by 43% in muscle and 70% in liver) during anoxia which have been linked to suppression of PK activity in other organisms. Liver PK also showed a 26% decrease in tyrosine phosphorylation under anoxia.
Anoxia responsive changes in turtle muscle and liver PK coordinate with an overall reduced activity state. This reduced affinity for the forward glycolytic reaction is likely a key component of the overall metabolic rate depression that supports long term survival in anoxia tolerant turtles. The coinciding methyl- and phospho- PTM alterations present the mechanism for tissue specific enzyme modification during anoxia.
Status and Prospects of Aptamers as Drug Components Mattice, Christopher M. C.; DeRosa, Maria C.
BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy,
06/2015, Letnik:
29, Številka:
3
Journal Article
Recenzirano
The unique properties of nucleic acid aptamers and their suitability to therapeutic applications have attracted the attention of researchers for more than 2 decades. Aptamers exhibit significant ...advantages relative to antibody-based therapeutics and can serve dual roles as either the therapeutic agent itself or a targeting modality. Despite this intense research interest, aptamers have been slow to reach the clinic, partly due to practical limitations that can be overcome by rational chemical modifications and ingenious aptamer selection approaches. This review highlights the latest efforts to use aptamers in therapeutic applications, the key properties of aptamers that can be exploited, the aptamers that are currently in clinical trials, as well as speculation on the future of aptamers in the field of nanomedicine.
Acute atrial fibrillation (AF)/flutter (AFL) is a common emergency department (ED) presentation. In 2021, an updated version of CAEP's Acute AF/AFL Best Practices Checklist was published, seeking to ...guide management. We assessed the alignment with and safety of application of the Checklist, regarding stroke prevention and disposition.
This health records review included adults presenting to two tertiary care academic EDs between January and August 2022 with a diagnosis of acute AF/AFL. Patients were excluded if their initial heart rate was < 100 or if they were hospitalized. Data extracted included: demographics, CHADS-65 score, clinical characteristics, ED treatment and disposition, and outpatient prescriptions and referrals. Our primary outcome was the proportion of patient encounters with one or more identified safety issues. Each case was assessed according to seven predetermined criteria from elements of the CAEP Checklist and either deemed "safe" or to contain one or more safety issues. We used descriptive statistics with 95% confidence intervals.
358 patients met inclusion criteria. The mean age was 66.9 years, 59.2% were male and 77.4% patients had at least one of the CHADS-65 criteria. 169 (47.2%) were not already on anticoagulation and 99 (27.6%) were discharged home with a new prescription for anticoagulation. The primary outcome was identified in 6.4% (95% CI 4.3-9.5) of encounters, representing 28 safety issues in 23 individuals. The safety concerns included: failure to prescribe anticoagulation when indicated (n = 6), inappropriate dosing of a direct oral anticoagulant (DOAC) (n = 2), inappropriate prescription of rate or rhythm control medication (n = 9), and failure to recommend appropriately timed follow-up for new rate control medication (n = 11).
There was a very high level of ED physician alignment with CAEP's Best Practices Checklist regarding disposition and stroke prevention. There are opportunities to further improve care with respect to recommendation of anticoagulation and reducing inappropriate prescriptions of rate or rhythm medications.
Brunham LR, Tietjen I, Bochem AE, Singaraja RR, Franchini PL, Radomski C, Mattice M, Legendre A, Hovingh GK, Kastelein JJP, Hayden MR. Novel mutations in scavenger receptor BI associated with high ...HDL cholesterol in humans.
The scavenger receptor class B, member 1 (SR‐BI), is a key cellular receptor for high‐density lipoprotein (HDL) in mice, but its relevance to human physiology has not been well established. Recently a family was reported with a mutation in the gene encoding SR‐BI and high HDL cholesterol (HDL‐C). Here we report two additional individuals with extremely high HDL‐C (greater than the 90th percentile for age and gender) with rare mutations in the gene encoding SR‐BI. These mutations segregate with high HDL‐C in family members of each proband and are associated with a 37% increase in plasma HDL‐C in heterozygous individuals carrying them. Both mutations occur at highly conserved positions in the large extracellular loop region of SR‐BI and are predicted to impair the function of the SR‐BI protein. Our findings, combined with the prior report of a single mutation in the gene encoding SR‐BI, further validate that mutations in SR‐BI are a rare but recurring cause of elevated HDL‐C in humans.
Acute atrial fibrillation and flutter (AF/AFL) are common arrhythmias treated in the emergency department (ED). The 2021 CAEP Best Practices Checklist provides clear recommendations for management of ...patients with acute AF/AFL. This study aimed to evaluate physician compliance to Checklist recommendations for risk assessment and ED management of AF/AFL.
This health records review assessed the management of adult patients presenting to two tertiary care EDs for management of acute AF/AFL from January to August, 2022. All ECGs demonstrating AF/AFL with a heart rate greater than 100 were compiled to capture primary and secondary causes. All visits were assessed for rate and rhythm control management, adverse events, return to ED, and safety criteria. Study physicians classified safety criteria from the Checklist into high and moderate concerns. The primary outcome was the proportion of cases with safety concerns and adverse events occurring during management in the ED. Data were analyzed using simple descriptive statistics.
We included 429 patients with a mean age of 67.7 years and 57.1% male. ED management included rate control (20.4%), electrical (40.1%), and pharmacological (20.1%) cardioversion. Adverse events occurred in 9.5% of cases: 12.5% in rate control, 13.4% in electrical cardioversion, and 6.9% in pharmacologic cardioversion. Overall, 7.9% of cases had management safety concerns. Moderate safety concerns occurred in 4.9% of cases including failure to attain recommended heart rate at time of discharge (3.9%). Severe concerns were identified in 3.0% of cases including failure to cardiovert unstable patients (1.2%). The 30-day return-to-ED rate was 16.5% secondary to AF/AFL.
ED management of AF/AFL was consistent with the CAEP Checklist and was safe overall. Opportunities for optimizing care include attaining recommended targets during rate control, avoidance of calcium channel and beta blockers in patients with systolic dysfunction, and earlier cardioversion for clinically unstable patients.
Abstract
OBJECTIVES
Data regarding enhanced recovery after thoracic surgery (ERATS) are sparse and inconsistent. This study aims to evaluate the effects of implementing an enhanced ERATS programme on ...postoperative outcomes, patient experience and quality of life (QOL).
METHODS
We conducted a prospective, longitudinal study evaluating 9 months before (pre-ERATS) and 9 months after (post-ERATS) a 3-month implementation of an ERATS programme in a single academic tertiary care centre. All patients undergoing major thoracic surgeries were included. The primary outcomes included length of stay (LOS), adverse events (AEs), 6-min walk test scores at 4 weeks, 30-day emergency room visits (without admission) and 30-day readmissions. The process-of-care outcomes included time to ‘out-of-bed’, independent ambulation, successful fluid intake, last chest tube removal and removal of urinary catheter. Perioperative anaesthesia-related outcomes were examined as well as patient experience and QOL scores.
RESULTS
The pre-ERATS group (n = 352 patients) and post-ERATS group (n = 352) demonstrated no differences in demographics. Post-ERATS patients had improved LOS (4.7 vs 6.2 days, P < 0.02), 6-min walk test scores (402 vs 371 m, P < 0.05) and 30-day emergency room visits (13.7% vs 21.6%, P = 0.03) with no differences in AEs and 30-day readmissions. Patients experienced shorter mean time to ‘out-of-bed’, independent ambulation, successful fluid intake, last chest tube removal and urinary catheter removal. There were no differences in postoperative analgesia administration, patient satisfaction and QOL scores.
CONCLUSIONS
ERATS implementation was associated with improved LOS, expedited feeding, ambulation and chest tube removal, without increasing AEs or readmissions, while maintaining a high level of patient satisfaction and QOL.
Surgical interventions for thoracic cancer are among the most challenging procedures, particularly for patients with limited physiological reserve 1, 2.
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