-
CJEM Jan 2023Up to 3% of all Emergency Department (ED) visits are due to skin and soft tissue infections such as non-purulent cellulitis. The current treatment failure rate is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Up to 3% of all Emergency Department (ED) visits are due to skin and soft tissue infections such as non-purulent cellulitis. The current treatment failure rate is approximately 20%. Evidence is lacking regarding the optimal outpatient management of cellulitis.
OBJECTIVES
To evaluate the feasibility of a randomized trial comparing high-dose (1000 mg) to standard-dose (500 mg) cephalexin to treat ED patients with cellulitis.
METHODS
A parallel arm double-blind randomized controlled pilot trial conducted at two EDs in Canada. Eligible participants were adults (age ≥ 18 years) presenting to the ED with non-purulent cellulitis and determined by the treating emergency physician to be eligible for outpatient management with oral antibiotics. Participants were randomized to high-dose or standard-dose cephalexin four times daily for 7 days. The primary feasibility outcome was participant recruitment rate (target ≥ 35%). The preliminary primary effectiveness outcome was oral antibiotic treatment failure.
RESULTS
Of 134 eligible participants approached for trial participation, 69 (51.5%, 95% CI 43.1 to 59.8%) were recruited and randomized. After excluding three randomized participants due to an alternate diagnosis, 33 participants were included in each arm. Nineteen eligible cases (14.2%) were missed. Loss to follow-up was 6.1%. Treatment failure occurred in four patients (12.9%) in the standard-dose arm versus one patient (3.2%) in the high-dose arm. A greater proportion had minor adverse events in the high-dose arm. No patients had an unplanned hospitalization within 14 days.
CONCLUSION
This pilot randomized controlled trial comparing high-dose to standard-dose cephalexin for ED patients with cellulitis demonstrated a high participant recruitment rate and that a full-scale trial is feasible. High-dose cephalexin had fewer treatment failures but with a higher proportion of minor adverse effects. The findings of this pilot will be used to inform the design of a future large trial.
TRIAL REGISTRATION
This trial was registered at ClinicalTrials.gov (NCT04471246).
Topics: Adult; Humans; Adolescent; Cephalexin; Cellulitis; Pilot Projects; Anti-Bacterial Agents; Soft Tissue Infections
PubMed: 36592299
DOI: 10.1007/s43678-022-00433-7 -
Nuclear Medicine Communications Aug 2022The purpose of this study was to investigate image quality and lesion detectability of half-dose (1.85 MBq/kg) 18 F-fluorodeoxyglucose (FDG) total-body positron...
PURPOSE
The purpose of this study was to investigate image quality and lesion detectability of half-dose (1.85 MBq/kg) 18 F-fluorodeoxyglucose (FDG) total-body positron emission tomography/computed tomography (PET/CT) for colorectal cancer, full-dose (3.7 MBq/kg) 18 F-FDG serving as a reference.
METHODS
Fifty patients confirmed to have colorectal cancer who underwent total-body PET/CT with half-dose 18 F-FDG were included. Another 50 colorectal cancer patients with 3.70 MBq/kg 18 F-FDG activity were selected for the full-dose group. PET images in the half-dose group were scanned for 15 min and split into 1-, 2-, 3-, 4- and 10-min duration groups, denoted G1, G2, G3, G4 and G10, respectively. In the full-dose group, PET scanning was performed for 5 min, reconstructed with the first 0.5, 1, 2 and 5 min intervals, defined as G0.5', G1', G2' and G5', respectively. Subjective image quality was assessed with 5-point Likert scales. Objective image quality parameters included maximum standardized uptake values (SUV max) , mean standardized uptake values (SUV mean )and signal-to-noise ratio (SNR) of the liver, blood pool and muscle and SUV max and tumor-to-background ratio (TBR) of lesions.
RESULTS
In the two groups, the G3 and G2' images met clinical diagnosis requirements in terms of subjective image quality, with scores ≥3. There were no differences in terms of subjective and objective image quality between the groups (G1 and G0.5', G2 and G1', G4 and G2' and G10 and G5'). In the half-dose group, 56 colorectal lesions in 50 patients confirmed by surgical pathology were clearly visible in all groups. The number of FDG-avid lymph nodes was 37 in G1, 38 in G2 and 39 in the remaining half-dose groups. The number of missed metastatic liver lesions was 1 both in G1 and G2.
CONCLUSIONS
Total-body PET/CT with half-dose was feasible for diagnosing and staging colorectal cancer compared with full-dose 18 F-FDG PET/CT. Moreover, for half-dose total-body PET/CT, a 3-min scan duration could maintain image quality and lesion detectability.
Topics: Colorectal Neoplasms; Fluorodeoxyglucose F18; Humans; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 35634804
DOI: 10.1097/MNM.0000000000001589 -
MMWR. Morbidity and Mortality Weekly... Mar 2021In December 2020, two COVID-19 vaccines (Pfizer-BioNTech and Moderna) received Emergency Use Authorization from the Food and Drug Administration.* Both vaccines require...
In December 2020, two COVID-19 vaccines (Pfizer-BioNTech and Moderna) received Emergency Use Authorization from the Food and Drug Administration.* Both vaccines require 2 doses for a completed series. The recommended interval between doses is 21 days for Pfizer-BioNTech and 28 days for Moderna; however, up to 42 days between doses is permissible when a delay is unavoidable. Two analyses of COVID-19 vaccine administration data were conducted among persons who initiated the vaccination series during December 14, 2020-February 14, 2021, and whose doses were reported to CDC through February 20, 2021. The first analysis was conducted to determine whether persons who received a first dose and had sufficient time to receive the second dose (i.e., as of February 14, 2021, >25 days from receipt of Pfizer-BioNTech vaccine or >32 days from receipt of Moderna vaccine had elapsed) had received the second dose. A second analysis was conducted among persons who received a second COVID-19 dose by February 14, 2021, to determine whether the dose was received during the recommended dosing interval, which in this study was defined as 17-25 days (Pfizer-BioNTech) and 24-32 days (Moderna) after the first dose. Analyses were stratified by jurisdiction and by demographic characteristics. In the first analysis, among 12,496,258 persons who received the first vaccine dose and for whom sufficient time had elapsed to receive the second dose, 88.0% had completed the series, 8.6% had not received the second dose but remained within the allowable interval (≤42 days since the first dose), and 3.4% had missed the second dose (outside the allowable interval, >42 days since the first dose). The percentage of persons who missed the second dose varied by jurisdiction (range = 0.0%-9.1%) and among demographic groups was highest among non-Hispanic American Indian/Alaska Native (AI/AN) persons (5.1%) and persons aged 16-44 years (4.0%). In the second analysis, among 14,205,768 persons who received a second dose, 95.6% received the dose within the recommended interval, although percentages varied by jurisdiction (range = 79.0%-99.9%). Public health officials should identify and address possible barriers to completing the COVID-19 vaccination series to ensure equitable coverage across communities and maximum health benefits for recipients. Strategies to ensure series completion could include scheduling second-dose appointments at the first-dose administration and sending reminders for second-dose visits.
Topics: Adolescent; Adult; Aged; COVID-19; COVID-19 Vaccines; Female; Health Services Accessibility; Humans; Immunization Schedule; Male; Middle Aged; Time Factors; United States; Vaccination Coverage; Young Adult
PubMed: 33735162
DOI: 10.15585/mmwr.mm7011e2 -
British Journal of Clinical Pharmacology Jul 2023Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC) widely used for the long-term prevention of stroke in patients with non-valvular atrial fibrillation...
AIMS
Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC) widely used for the long-term prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). Adherence to NOAC therapy has been unsatisfactory and decreases over time. Remedial strategies are currently used to address the non-adherence events. Current recommendations, however, are generic and not well supported by evidence. The aim of this study was to explore appropriate remedial dosing regimens for non-adherent edoxaban-treated NVAF patients through Monte Carlo simulation.
METHODS
Six regimens were compared with the current recommendations of the European Heart Rhythm Association (EHRA) guide based on total deviation time. Both edoxaban plasma concentration and intrinsic Factor Xa activity were considered. Monte Carlo simulations were performed using RxODE based on a published population pharmacokinetic/pharmacodynamic (PK/PD) model.
RESULTS
The proposed remedial strategies were different than the EHRA recommendations and were related to the delay time. However, it was found that the missed dose can be administered immediately if the delay time is within 11 h. When the delay is between 12 and 19 h, a half dose followed by a regular dosing schedule is recommended. When the delay time exceeds 19 h, a full dose followed by a half dose is preferred.
CONCLUSION
PK/PD modelling and simulation are effective in developing and evaluating the remedial strategies of edoxaban, which can help maximise its therapeutic effect.
Topics: Humans; Atrial Fibrillation; Anticoagulants; Stroke; Pyridines; Factor Xa Inhibitors; Administration, Oral
PubMed: 35332559
DOI: 10.1111/bcp.15316 -
Endocrine Connections Nov 2023Insulin administration remains vital to the treatment of diabetes and although there have been advances in insulin delivery, evidence suggests that many people with... (Review)
Review
Insulin administration remains vital to the treatment of diabetes and although there have been advances in insulin delivery, evidence suggests that many people with diabetes on insulin therapy have suboptimal glycemic management. Recent advancements in insulin administration techniques include connected insulin devices, such as connected insulin pens and pen caps. In this review, we provide an overview of the literature on the use of connected insulin pens and pen caps to further elucidate the clinical benefits and drawbacks of these devices. We discuss the development of these devices, outlining the characteristics of insulin pens and pen caps with regulatory approvals. These devices have different features that can ease the burden of diabetes management, including automatic recording of insulin dose information, tracking of insulin-on-board, bolus calculators, and missed dose alerts. Despite the advantages of connected pens and pen caps, a small percentage of insulin users are currently using these devices, due to many factors, including lack of health-care professional awareness, initial training for prescribers, and setup of the device. Overcoming these barriers and publishing more data demonstrating the glycemic outcomes associated with these systems could improve diabetes management for people living with diabetes. As health-care systems become increasingly digital, connected insulin pens have the potential to allow a data-driven approach to diabetes management for people who are not interested in, cannot afford, or do not have intensive insulin regimens that might warrant use of insulin pumps or automated insulin delivery systems.
PubMed: 37610002
DOI: 10.1530/EC-23-0108 -
Vaccines Mar 2023Immunization has one of the highest coverage levels of any health intervention, yet there remain zero-dose children, defined as those who do not receive any routine...
Immunization has one of the highest coverage levels of any health intervention, yet there remain zero-dose children, defined as those who do not receive any routine immunizations. There were 18.2 million zero-dose children in 2021, and as they accounted for over 70% of all underimmunized children, reaching zero-dose children will be essential to meeting ambitious immunization coverage targets by 2030. While certain geographic locations, such as urban slum, remote rural, and conflict-affected settings, may place a child at higher risk of being zero-dose, zero-dose children are found in many places, and understanding the social, political, and economic barriers they face will be key to designing sustainable programs to reach them. This includes gender-related barriers to immunization and, in some countries, barriers related to ethnicity and religion, as well as the unique challenges associated with reaching nomadic, displaced, or migrant populations. Zero-dose children and their families face multiple deprivations related to wealth, education, water and sanitation, nutrition, and access to other health services, and they account for one-third of all child deaths in low- and middle-income countries. Reaching zero-dose children and missed communities is therefore critical to achieving the Sustainable Development Goals commitment to "leave no one behind".
PubMed: 37112693
DOI: 10.3390/vaccines11040781 -
Vaccines Feb 2023Reaching zero-dose (ZD) children, operationally defined as children who have not received a first dose of the diphtheria, tetanus, and pertussis (DTP1) vaccine, is...
Reaching zero-dose (ZD) children, operationally defined as children who have not received a first dose of the diphtheria, tetanus, and pertussis (DTP1) vaccine, is crucial to increase equitable immunisation coverage and access to primary health care. However, little is known about the approaches already taken by countries to improve immunisation equity. We reviewed all Health System Strengthening (HSS) proposals submitted by Gavi-supported countries from 2014 to 2021 inclusively and extracted information on interventions favouring equity. Pro-equity interventions were mapped to an analytical framework representing Gavi 5.0 programmatic guidance on reaching ZD children and missed communities. Data from keyword searches and manual screening were extracted into an Excel database. Open format responses were analysed using inductive and deductive thematic coding. Data analysis was conducted using Excel and R. Of the 56 proposals included, 51 (91%) included at least one pro-equity intervention. The most common interventions were conducting outreach sessions, tailoring the location of service delivery, and partnerships. Many proposals had "bundles" of interventions, most often involving outreach, microplanning and community-level education activities. Nearly half prioritised remote-rural areas and only 30% addressed gender-related barriers to immunisation. The findings can help identify specific interventions on which to focus future evidence syntheses, case studies and implementation research and inform discussions on what may or may not need to change to better reach ZD children and missed communities moving forward.
PubMed: 36851218
DOI: 10.3390/vaccines11020341 -
Journal of Medical Signals and Sensors 2023Virtual wedge (VW) is used in radiotherapy to compensate for missing tissues and create a uniform dose distribution in tissues. According to TECDOC-1583 and technical...
BACKGROUND
Virtual wedge (VW) is used in radiotherapy to compensate for missing tissues and create a uniform dose distribution in tissues. According to TECDOC-1583 and technical reports series no. 430, evaluating the dose calculation accuracy is essential for the quality assurance of treatment planning systems (TPSs). In this study, the dose calculation accuracy of the collapsed cone superposition (CCS) algorithm in the postmastectomy radiotherapy of the chest wall for breast cancer was evaluated by comparing the calculated and measured dose in VW fields.
METHODS
Two tangential fields with the typical VW angles were planned using ISOgray TPS in a thorax phantom. The CCS algorithm was used for dose calculation at 6 and 15 MV photon beams. The obtained dose distributions from EBT3 film spaces and TPS were evaluated using the gamma index.
RESULTS
The measured and calculated dose values using VW in a heterogeneous medium with different beam energies were in a good agreement with each other (acceptance rate: 88.0%-93.4%). The calculated and measured data did not differ significantly with an increase/decrease in wedge angle. In addition, the results demonstrated that ISOgray overestimated and underestimated the dose of the soft tissue and lung in the planned volume, respectively.
CONCLUSIONS
According to the results of gamma index analysis, the calculated dose distribution using VW model with the CCS algorithm in a heterogeneous environment was within acceptable limits.
PubMed: 37622042
DOI: 10.4103/jmss.jmss_7_22 -
European Journal of Drug Metabolism and... Sep 2022Nonadherence to levetiracetam (LEV) use can result in subtherapeutic concentrations and increase the risk of the occurrence of seizures. The impact of missing LEV doses...
BACKGROUND AND OBJECTIVE
Nonadherence to levetiracetam (LEV) use can result in subtherapeutic concentrations and increase the risk of the occurrence of seizures. The impact of missing LEV doses on its pharmacokinetics and evidence of the appropriate remedial dose is lacking. This study has determined the influence of missed LEV doses on its pharmacokinetics and has explored the appropriate remedial dosage regimens.
METHODS
Monte Carlo simulation was used to assess the impacts of different remedial dosage regimens on LEV concentrations. Simulated LEV concentrations outside the individual therapeutic range were calculated for the compliance scenario and for each of the remedial dosage regimens. The percentage of deviation from the full compliance scenario was also calculated. The regimen with the lowest percentage of deviation was considered the most appropriate.
RESULTS
The suitable LEV remedial dose varied across the delay times. For one missed dose, a remedial regimen with a regular dose followed by the usual dose was suitable for a delay time of less than 6 h, while a replacement with a regular dose followed by a partial dose appeared to be appropriate for a delay time of 6 h and longer. This was justified based on the concerns of LEV toxicity when the remedial dose is close to the next scheduled dose. For two consecutive missed doses, a remedial dose with one and a half of the regular dose was suitable if the gap between that and the next dose was greater than 6 h.
CONCLUSIONS
The appropriate remedial dosage regimen for one and two consecutive missed doses of LEV have been proposed. These remedial regimens, however, should be applied with clinicians' judgment based on the clinical status of the patients.
Topics: Anticonvulsants; Computer Simulation; Humans; Levetiracetam; Monte Carlo Method; Piracetam; Seizures
PubMed: 35761145
DOI: 10.1007/s13318-022-00774-9 -
The Journal of Emergency Medicine Jan 2022Despite increasing trends of nonfatal opioid overdoses in emergency departments (EDs), population-based studies comparing prescription opioid dosing patterns before and...
BACKGROUND
Despite increasing trends of nonfatal opioid overdoses in emergency departments (EDs), population-based studies comparing prescription opioid dosing patterns before and after nonfatal opioid overdoses are limited.
OBJECTIVES
To evaluate characteristics of prescribing behaviors before and after nonfatal overdoses, with a focus on opioid dosage.
METHODS
Included were 5,395 adult residents of Tennessee discharged from hospital EDs after a first nonfatal opioid overdose (2016-2017). Patients were linked to eligible prescription records in the Tennessee Controlled Substance Monitoring Database. We estimated odds ratios (OR) and 95% confidence intervals (CI) to evaluate characteristics associated with filling opioid prescriptions 90 days before overdose and with high daily dose (≥ 90 morphine milligram equivalents) 90 days after overdose.
RESULTS
Among patients who filled a prescription both before and after an overdose, the percentage filling a low, medium, and high dose was 33.7%, 31.9%, and 34.4%, respectively, after an opioid overdose (n = 1,516). Most high-dose users before an overdose (>70%) remained high-dose users with the same prescriber after the overdose. Male gender, ages ≥ 35 years, and medium metro residence were associated with increased odds of high-dose filling after an opioid overdose. Patients filling overlapping opioid-benzodiazepine prescriptions and with > 7 days' supply had increased odds of filling high dose after an opioid overdose (OR 1.4, 95% CI 1.08-1.70 and OR 3.7, 95% CI 2.28-5.84, respectively).
CONCLUSIONS
In Tennessee, many patients treated in the ED for an overdose are still prescribed high-dose opioid analgesics after an overdose, highlighting a missed opportunity for intervention and coordination of care between ED and non-ED providers.
Topics: Adult; Analgesics, Opioid; Drug Overdose; Emergency Service, Hospital; Humans; Male; Patient Discharge; Prescriptions; Tennessee
PubMed: 34535302
DOI: 10.1016/j.jemermed.2021.07.050