Usual Range Research Articles

Distribution of Belin-Ambrosio indices using Pentacam HR for normal patients aged 6 to 21 years in the Riyadh area

Objectives: To ascertain the Belin-Ambrosio indices distribution for Saudi patients aged 6-21 years in Riyadh. Method: Participants in this prospective, cross-sectional, observational, multicenter study ranged in age from 6 to 21 years old and were seen in several no n-ophthalmic emergency departments in Riyadh, Saudi Arabia, in 2017. Scheimpflug corneal tomography system in rotation was used to measure the cornea. Following optometric exams, corneal imaging and KC index measurements were performed using the Pentacam Results: The study's 366 participants were examined once the exclusion criteria were applied. All children's mean and standard deviation (SD) age was 17.41±4.83 years (range: 6–21 years). All Belin-Ambrosio indices percentiles for pediatric, adolescence, and young adult groups are within normal ranges. A comparison between Belin-Ambrosio indices and age demonstrates that the age groups have a statistically significant difference following indices topo astig, BAD Db, BAD Dp, BAD Dt, BAD Da, BAD Dy, BAD D, ART Min, ART Max and ART Avg with p-value 0.05. Also, the correlation coefficient results show a statistically significant correlation between Belin-Ambrosio indices and age with the following indices: Topo Astig, BAD Db, BAD Dp, BAD Dt, BAD Da, BAD Dy, BAD D, ART Min, ART Max, and ART Avg with p-value 0.05 as the age increases BAD Dt and BAD Dy, ART Min, ART Max, and ART Avg decrease. Also, As the age increases, the Topo Astig, BAD Db, BAD Dp, BAD Da, and BAD D increase. The correlation coefficient ranges from 0.11 negative weak to 0.65 negative moderate, and from positive 0.13 to negative strong 0.78. Conclusion:The usual range was seen in the Belin-Ambrosio indices. The Belin-Ambrosio indices and age groups differed statistically significantly.

Effects of prescribed surface temperature and heat flux with electrical conductivity via microbial chemotaxis to enhance nanoparticle

The purpose of the current investigations in to explore the three-dimensional magnetohydrodynamic (MHD) Oldroyd-B nanofluid flow over an exponential stretchable surface with variable thermal conductivity. Impact of thermal radiation and gyrotactic motile organism also incorporated in the present study. A fluid that has tiny particles, also referred to as nanoparticles, scattered throughout a base fluid is called a nanofluid. These nanoparticles can be formed from metals, oxides, carbon-based compounds, or other nanomaterials, and their usual sizes range from 1 to 100 nanometers. Water, oil, ethylene glycol, or other common liquids can be used as the foundation fluid. Because of their improved physical qualities, greater heat transfer, and thermal conductivity, nanofluids have many uses in a variety of sectors. Two type of boundary conditions are associated here like prescribed surface temperature (PST) and prescribed heat flux (PHF). Exploring nanoparticles influence on a fluid viscoelasticity, and vice versa, advanced understanding of three-dimensional nanofluid flow over a porous, stretchable surface. The research also probed microorganisms' and reactions' impact on heat/mass transfer. Employing MATLAB and a similarity approach converted Navier-Stokes equations into ordinary differential equations. Outcomes included velocity profile, temperature profiles, concentration profiles, and microbe behavior. Thus, this significantly contributed to modelling collectors and thermal storage. The concentration profile flattens when the Schmidt number (Sc) is increased, indicating that the fluid flow behavior is clearly influenced. Moreover, these findings established ways to improve energy systems' efficiency by elucidating heat transport and fluid flow parameters. This enables sustainable energy solutions to tackle global challenges. The influence of various convergence parameters is illustrated through graphically and in the form of table. Also, our results are validated with the previously published data and found tremendous agreement.

Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) in a One-Year-Old Child: A Case Report and Literature Review

Introduction: Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) is a rare autosomal recessive metabolic disorder characterized by abnormal phosphate regulation and soft tissue calcifications. Early diagnosis is crucial for optimal management to prevent complications. Case Presentation: A one-year-old child presented with intermittent fevers and a gluteal mass. Ultrasound revealed a calcified abscess, and biopsy confirmed a pseudocyst. Further workup identified elevated blood calcium, phosphorus, and neutropenia. The patient was ultimately diagnosed with HFTC. Discussion: Early diagnosis of HFTC is challenging due to the rarity of the disease and the potential for non-specific initial symptoms. This case highlights the importance of considering HFTC in the differential diagnosis for a young child with unexplained soft tissue masses or skeletal abnormalities, even outside the usual age range. Conclusions: This case report emphasizes the need for a high index of suspicion for HFTC in pediatric patients with suggestive clinical features, regardless of age. Early diagnosis and prompt intervention are essential to improve long-term outcomes and prevent complications.

Titanium oxide hydrates as versatile polymer crosslinkers and molecular‐hybrid formers

AbstractMolecular hybrid materials based on widely available polymers crosslinked with an inorganic species have received increasing interest for their unique property sets outside of the usual range of commodity plastics and/or nanocomposites. Here, we provide a mini‐review on molecular hybrids based on metal oxide hydrates—compounds that readily react with, for example, hydroxylated polymers to form inorganic:organic materials systems with many desirable features and properties. Focusing on titanium oxide hydrates, we discuss here that such molecular hybrids can exhibit a broad refractive index range in addition to an increased glass transition temperature, mechanical stiffness and swelling resistance in comparison to the neat polymer, which illustrates that such hybrid systems offer a new, low‐cost, robust and versatile functional materials platform with great promise for, for example, solution‐processed photonics, catalysts and antimicrobial coatings. Generally, our mini‐review seeks to provide a concise and accessible overview of titanium oxide hydrate:polymer hybrid systems, focusing on their unique properties and processability as well as their broad and largely untapped potential as functional materials. © 2024 The Author(s). Polymer International published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Septic paravertebral abscess and inferior vena cava thrombosis complicated by uro-sepsis: Case report

Paravertebral abscess is an uncommon and potentially dangerous illness characterized by the buildup of pus in the anatomical area surrounding the spinal column. A 65-year-old female, who has diabetes and high blood pressure, came in with intense discomfort in her lower back that spreads to her lower limbs, making it difficult for her to move. She also has a high fever, excessive sweating, and has lost a large amount of weight. The blood tests indicate the following abnormalities: low Hb level of 9.6 g/dl, low MCV of 70 fl, elevated total white blood cell count of 15.8 × 109/L, elevated neutrophil count of 12.4 × 109/L, normal lymphocyte count of 2.8 × 109/L, high platelet count of 485 × 109/L, and elevated ESR of 110 mm/hr. The level of phosphatase was raised to 247 U/L, which is beyond the usual range of 40-150 U/L. The blood film reveals the presence of hypochromic microcytic red blood cells, which are indicative of iron deficiency anemia. There is also evidence of neutrophil leukocytosis in the white blood cells, with no immature cells observed. Additionally, an increase in platelets is observed in the film. The D-dimer level is 2009 ng/ml, which is within the normal range of less than 500 ng/ml. The CRP level is 48 gm/l, which is above the usual range of less than 6 gm/l. The bone marrow testing yielded normal results. The blood culture indicated the presence of Streptococcus epidermidis growth. Radiological tests revealed that a CE-MRI of the dorsal and lumbar spine indicated the presence of a para-aortic abscess together with septic thrombosis of the inferior vena cava. Paravertebral abscess is a critical emergent condition required a necessary therapy protocols to stabilize the patient status. The timing of intervention is crucial in cases of paravertebral abscess, as the existence of a mass can led to spinal cord compression.

Neoarchaean oxygen-based nitrogen cycle en route to the Great Oxidation Event.

The nitrogen isotopic composition of sedimentary rocks (δ15N) can trace redox-dependent biological pathways and early Earth oxygenation1,2. However, there is no substantial change in the sedimentary δ15N record across the Great Oxidation Event about 2.45 billion years ago (Ga)3, a prominent redox change. This argues for a temporal decoupling between the emergence of the first oxygen-based oxidative pathways of the nitrogen cycle and the accumulation of atmospheric oxygen after 2.45 Ga (ref. 3). The transition between both states shows strongly positive δ15N values (10-50‰) in rocks deposited between 2.8 Gaand 2.6 Ga, but their origin and spatial extent remain uncertain4,5. Here we report strongly positive δ15N values (>30‰) in the 2.68-Gyr-old shallow to deep marine sedimentary deposit of the Serra Sul Formation6, Amazonian Craton, Brazil. Our findings are best explained by regionally variable extents of ammonium oxidation to N2 or N2O tied to a cryptic oxygen cycle, implying that oxygenic photosynthesis was operating at 2.7 Ga. Molecular oxygen production probably shifted the redox potential so that an intermediate N cycle based on ammonium oxidation developed before nitrate accumulation in surface waters. We propose to name this period, when strongly positive nitrogen isotopic compositions are superimposed on the usual range of Precambrian δ15N values, the Nitrogen Isotope Event. We suggest that it marks the earliest steps of the biogeochemical reorganizations that led to the Great Oxidation Event.

A Study of Characteristics and Properties of Nano-metal Oxides (Zinc Oxide, Cadmium Oxide, Titanium Dioxide, Iron Oxide)

Nanotechnology is a rapidly developing scientific discipline with promise for enhancing human well-being via its applications in nanomedicine. It describes the technology used to accurately manipulate atoms and molecules to create new materials with dimensions that are on the nanoscale. The usual size range of nanoparticles (NPs) is 1-100 nm. Since nanoparticles are important in preventing infections, they can be used as therapeutic nanocarriers having antibacterial properties. This paper reviews the literature on the various production techniques, characteristics, and biological uses of several nano-metal oxides (iron oxide, titanium dioxide, zinc oxide, and cadmium oxide). The utilization of nanoparticles and their applications will grow due to the cost-effective ways available for biomodification. Because of their special qualities, nanoparticles are helpful in several scientific domains, including biology, materials science, engineering, electronics, and food science. Researchers have become interested in nanotechnology because of its benefits, particularly its potential uses in the healthcare system for improved diagnosis and treatment.

Digoxin treatment does not reinduce radioiodine uptake in radioiodine refractory non-medullary thyroid carcinoma.

Patients with non-medullary thyroid carcinoma (NMTC) that are refractory to radioactive iodine (RAI) have a poor prognosis. Strategies for restoring the ability to take up iodine, so-called redifferentiation, are promising but not suitable for all patients. Preclinical studies, in human cell lines just as in a murine model, have shown that the cardiac glycoside digoxin restored RAI uptake. This prospective single-center open-label study aimed to investigate whether treatment with digoxin could reinduce clinically relevant RAI uptake in patients with metastasized RAI-refractory NMTC. Eight patients with metastasized RAI-refractory NMTC were included between November 2022 and June 2023. Before treatment, a baseline [123I]NaI scintigraphy was performed. Thereafter, patients were treated with digoxin for 3 weeks. Starting doses depended on age and weight. For safety reasons, the usual therapeutic range was aimed for. After 1 week, the digoxin plasma concentration was measured, and the digoxin dose was adjusted if necessary. After 3 weeks of digoxin treatment, a second [123I]NaI scintigraphy was performed. RAI uptake was compared between the two scintigraphies. Seven patients completed the digoxin treatment and were evaluable. None of the seven patients showed clinically relevant RAI uptake after digoxin treatment. No digoxin-related serious adverse events occurred during this trial. Contrary to results from preclinical trials, in this trial, 3 weeks of digoxin treatment did not reinduce RAI uptake in patients with NMTC. This highlights essential challenges regarding the approach toward optimization of studies aimed to restore the RAI uptake and its therapeutic efficacy through drug repurposing.

Validation of HPLC and TLC analytical methods to determine radiochemical purity of 99mTc-cAbVCAM1-5, a new experimental radiotracer

Cardiovascular diseases, including fatal myocardial infarctions from atheromatous plaques, are the primary global mortality cause. Detecting stenotic atheromatous plaques is possible through coronary angiography, but vulnerable plaques with eccentric remodeling are undetectable with current diagnostic methods. Addressing this challenge, our group developed a radiopharmaceutical drug targeting vascular cell adhesion molecule 1 (VCAM-1), radiolabeled with technetium-99m. Given the absence of a monograph in the European Pharmacopoeia, and in order to draft the investigational medicinal product documentation, analytical methods had to be validated by high performance liquid chromatography (HPLC) and thin layer chromatography (TLC) to determine the radiochemical purity (RCP) of 99mTc-cAbVCAM1–5. This study therefore presents the results of the validation of analytical methods obtained in this context. The method validation followed the European Association of Nuclear Medicine (EANM) recommendations adapted from ICH Q2(R1), ensuring conformity with specificity, accuracy, repeatability and intermediate precision, linearity, robustness, quantification limit (LoQ), and range criteria. Regarding the results of specificity, both HPLC and TLC methods demonstrated excellent separation of 99mTc-cAbVCAM1–5 from impurities 99mTcO4-. Accuracy results indicated recovery percentages within the range of 99.52–101.40% for the HPLC and 99.51–101.97% for TLC, ensuring reliable measurements for each concentration of 99mTcO4-. Precision of the methods was validated by assessing repeatability and intermediate precision. Linearity was determined over the usual concentrations range and the correlation coefficient was greater than 0.99 for both methods. The limit of quantification was measured by diluting the 99mTcO4- to obtain a signal-to-noise ratio of around 10:1. Under these conditions, we obtained an LOQ of 2.10 MBq/mL for HPLC and 2Mbq/mL for TLC. In conclusion, the analytical methods developed in this study comply with EANM recommendations. This therefore allows us to correctly assess the radiochemical purity of 99mTc-cAbVCAM1–5, a new radiotracer targeting inflammation in vulnerable plaques.

His dark materials: Quantifying the problem of dust (particulate matter) in the agricultural landscape of California

The composition and amounts of dust or particulate matter (PM) vary greatly in the atmosphere and particulates can have major adverse impacts on human health. Since PM10 deposition to foliage can improve air quality, there have been a number of studies of PM10 amounts on the surface of urban vegetation. Much less is known about PM in agricultural areas, although PM10 can be harmful to vegetation and, for food crops, have the potential to be ingested. Here we have quantified PM across the agricultural landscape of California, measuring the amounts present on the foliage of 18 crops at 21 locations. The amounts of particulates present varied (0.17–6.9 gm-2) and PM loads on leaves in the south and east of the area were higher than those in the northern and westerly locations. Our findings suggest that the amounts of particulates on the surface of agricultural crops can be high; exceeding the usual range of values for urban areas. Our data indicate that agricultural crops grown in regions like California and the Mediterranean where summer rainfall is largely absent and drip rather than spray irrigation is used are more vulnerable to PM accumulation and to any adverse effects resulting from these deposits. Microscopic analysis of PM10 on foliage showed that in these agricultural areas wind-blown soil particles make up 74.2% of the PM10 present; this is thus a very significant source. A small number of microplastic particles (2.2%) were also identified on foliage. We suggest that PM and microplastics could impact food and forage quality and that more work is needed to examine PM deposition to crops and their range of impacts.

In Vitro and In Silico Explorations of the Protein Conformational Changes of Corynebacterium glutamicum MshA, a Model Retaining GT-B Glycosyltransferase.

MshA is a GT-B glycosyltransferase catalyzing the first step in the biosynthesis of mycothiol. While many GT-B enzymes undergo an open-to-closed transition, MshA is unique because its 97° rotation is beyond the usual range of 10-25°. Molecular dynamics (MD) simulations were carried out for MshA in both ligand bound and unbound states to investigate the effect of ligand binding on localized protein dynamics and its conformational free energy landscape. Simulations showed that both the unliganded "opened" and liganded "closed" forms of the enzyme sample a wide degree of dihedral angles and interdomain distances with relatively low overlapping populations. Calculation of the free energy surface using replica exchange MD for the apo "opened" and an artificial generated apo "closed" structure revealed overlaps in the geometries sampled, allowing calculation of a barrier of 2 kcal/mol for the open-to-closed transition in the absence of ligands. MD simulations of fully liganded MshA revealed a smaller sampling of the dihedral angles. The localized protein fluctuation changes suggest that UDP-GlcNAc binding activates the motions of loops in the 1-l-myo-inositol-1-phosphate (I1P)-binding site despite little change in the interactions with UDP-GlcNAc. Circular dichroism, intrinsic fluorescence spectroscopy, and mutagenesis studies were used to confirm the ligand-induced structural changes in MshA. The results support a proposed mechanism where UDP-GlcNAc binds with rigid interactions to the C-terminal domain of MshA and activates flexible loops in the N-terminal domain for binding and positioning of I1P. This model can be used for future structure-based drug development of inhibitors of the mycothiol biosynthetic pathway.

Assessment of Forward Head Posture in Information Technology Employees with Neck Pain: A Cross-Sectional Study

Background: Neck pain is the most common complaint that we deal with in orthopedics, most of which are information technology (IT) professionals. These individuals have vocational mismanagement which leads to high incidence of forward head posture (FHP).
 Methods: A cross-sectional study was carried out from January 2019 to June 2019 during which a total of 300 patients were taken into study. Clinical assessment of neck pain, head posture, range of motion (ROM), and radiological assessment of craniovertebral angle (CVA) and anterior head translation (AHT) was done.
 Results: Out of 300 patients, the majority of the patients were men. On average, men used computers for 9.6 hours compared to 9.2 hours for women. The average CVA was higher in women (58.8). The average AHT was more in men (22.9).
 Conclusion: As compared with the previous literature, our study showed that 84.3% of male and 92.91% of female participants had FHP. CVA was lower, while AHT was higher in both groups than the usual range. The mean AHT in our sample was 18.8 mm, which was found to be aberrant in the prior research studies. In our study, we have found a negative correlation between the CVA and AHT, resulting in FHP, which can furthermore lead to early changes of cervical spondylosis in IT employees, probably due to long hours of desktop usage resulting in fixed postural habit.

Defining the Parameters for Endovenous Microwave Ablation to Achieve Equivalence With Endovenous Laser Ablation, Using the Porcine Liver Model.

Endovenous microwave ablation (EMWA) is an endovenous thermoablation (EVTA) system to ablate incompetent truncal veins. Early results suggest that EMWA uses more power than endovenous laser ablation (EVLA) to get the same results. We aimed to define the parameters for EMWA, which give the same tissue ablation as EVLA, using the validated porcine liver model. EVLA (1470nm 600micron radial fibre) treatments were performed at 6W, 8W and 10W, at pullback speeds of 6, 7, 8 and 9s/cm, giving Linear Endovenous Energy Densities (LEEDs) between 36 - 90J/cm. Each combination of power and pullback was repeated 5 times. We then used EMWA in the same model. Powers of 35-75W and pullback speeds of 4-9s/cm were used (LEEDs 140-675J/cm). Ablation tracts from both devices were analysed by 2 blinded observers, noting thermal spread and carbonisation. For each commonly used parameter for EVLA, we identified a range of parameters for EMWA that produced similar tissue ablation in the porcine liver model. To keep the pullback speeds within the usual range, powers of 35-75W were needed with EMWA, with mean EMWA LEEDs 3.9 - 5.8 times higher than EVLA LEEDs. We found the quicker the pullback speed, the higher the multiple of EMWA LEED we needed to get the same effect. We have identified parameters for EMWA that gave equivalent tissue ablation in the porcine liver model to commonly used parameters used for EVLA. These need to be validated clinically, but as the model used has already been validated against clinical outcome in endovenous thermal ablation, there is little reason to suspect that these results would not be valid. As the power during EMWA is higher than EVLA, EVMA LEEDs are approximately 4-6 times higher than EVLA LEEDs to achieve the same thermal effect on the tissues.

The symptom perception processes of monitoring, awareness, and evaluation in patients with heart failure: a qualitative descriptive study.

Patients with heart failure (HF) experience various signs and symptoms and have difficulties in perceiving them. Integrating insights from patients who have engaged in the process of symptom perception is crucial for enhancing our understanding of the theoretical concept of symptom perception. This study aimed to describe how patients with HF perceive symptoms through the processes of monitoring, awareness, and evaluation and what influences the process. Using a qualitative descriptive design, we conducted in-person semi-structured interviews with a purposeful sample of 40 adults experiencing an unplanned hospitalization for a HF symptom exacerbation. We elicited how patients monitor, become aware of, and evaluate symptoms prior to hospitalization. Data were analysed using directed qualitative content analysis. One overarching theme and three major themes emerged. Patients demonstrated Body listening, which involved active and individualized symptom monitoring tactics to observe bodily changes outside one's usual range. Trajectory of bodily change involved the patterns or characteristics of bodily changes that became apparent to patients. Three subthemes-sudden and alarming change, gradual change, and fluctuating change emerged. Patients evaluated symptoms through an Exclusionary process, sequentially attributing symptoms to a cause through a cognitive process of excluding possible causes until the most plausible cause remained. Facilitators and barriers to symptom monitoring, awareness, and evaluation were identified. This study elaborates the comprehensive symptom perception process used by adults with HF. Tailored nursing interventions should be developed based on the factors identified in each phase of the process to improve symptom perception in HF.

Safe extraction of an impacted open safety pin from the esophagus: A case report

Background: Children commonly experience a tendency to ingest foreign bodies. Open safety pins in the esophagus are quite uncommon, nevertheless. Peak rates of such ingestion range between 6 and 12 months. Case Presentation: A 9-month-old girl was admitted to the ED with a history of having swallowed a safety pin attached to her underwear 3 hours earlier, as witnessed by her mother. There were no symptoms present at the time of the assessment. Her blood tests and vital signs were both in the usual range. Plain radiographs of the neck, chest, and abdomen showed an open safety pin (SP) impinged in the upper third of the esophagus pointing upwards. While the infant was being intubated under general anesthesia, esophagoscopy was completed with a rigid pediatric esophagoscope. By grasping the SP by its tail end, a pair of crocodile forceps were used to reverse and straighten the pin in the esophagus such that its open end was pointed caudally. During surgery, a nasogastric tube was inserted. Ampicillin and neomycin were given intravenously for six days. On the fourth postoperative day observed the removal of the nasogastric tube. On the seventh postoperative day, the girl was allowed to go home. Recovery went without incident. Conclusion: For the removal of open safety pins, simple extraction methods, rigid and flexible endoscopies with the proper forceps, as well as surgery, can be used. Parents should also receive advice regarding the presence of safety pins around their children.

Was There Any Greed After All? The Lack of Greedflation Evidence in Greek Economic Data

As Greece has been experiencing a 9.6% inflation in 2022 and 4.2% in 2023, a policy narrative has risen claiming that corporate profits are to blame for the price hikes. However, Greek economic data indicate that when precisely defined, corporate unit profits are within their usual range. Furthermore, publicly available data indicate that corporate mark-ups (price-to-cost ratios) are relatively stable and primarily driven by the increases in costs of goods sold, with a mild increase being attributed to temporary business support measures in force in 2021. In addition, there is the overlooked demand-side component of inflation, contributing up to 50% in price increases between 2021 and 2022, fueled by the country’s fiscal responses to the crises of COVID-19 and the energy crisis of 2021-2022, both of which were among the largest in the world relative to GDP. On top of that, spending of the funds available under the RRF, with Greece once again spending the most in the E.U. relative to its GDP, further contributes to the inflationary pressures. As a result, it is imperative that any government financial support against increasing prices must be better targeted to not work as an income boost, fueling demand side inflation, and that the RRF plan be quickly implemented to lower prices by increasing the country’s productivity, rather than providing widespread income support in the hope of lowering mark-ups and prices only by enforcing competition regulations, which may bring opposite results than those intended.

Acute and subchronic oral toxicity study of Camelina sativa oil in Wistar rats

ObjectiveThe aim of these studies was to ascertain if Camelina sativa oil is harmful in both the acute and subchronic states. MethodsWistar rats of both sexes were used in an acute toxicity test, and the fatal dosage (LD50) of oral Camelina sativa oil was greater than 27.6 g/kg bw. Rats were gavaged with Camelina sativa oil at dosages of 0.00, 0.92, 1.84, and 3.68 g/kg bw per day for 90 days. In addition, satellite groups were established in the control and high-dose groups for a 28-day recovery period. The following factors were assessed: mortality, clinical anomalies, body weight, food intake, hematological, serum biochemistry, urine, gross necropsy, and histology. ResultsThere were no observable toxicity-related changes in any of the three dosage groups. There is no toxicological relevance to the change in the high-dose hematological indicator PLT at the conclusion of the recovery period because it was within the usual range for this strain in our laboratory. The test material did not result in any pathological alterations, according to a pathological examination. ConclusionSince the results of the current study, the no-observed-adverse-effect-level (NOAEL) for Camelina sativa oil in rats has been determined to be greater than 3.68 g/kg bw.

Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial

Daily methadone maintenance or buprenorphine treatment is the standard-of-care (SoC) medication for opioid use disorder (OUD). Subcutaneously injected, extended-release buprenorphine (BUP-XR) may be more effective-but there has been no superiority evaluation. This pragmatic, parallel-group, open-label, multi-centre, effectiveness superiority randomised, controlled, phase 3 trial was conducted at five National Health Service community-based treatment clinics in England and Scotland. Participants (adults aged ≥ 18 years; all meeting DSM-5 diagnostic criteria for moderate or severe OUD at admission to their current maintenance treatment episode) were randomly assigned (1:1) to receive continued daily SoC (liquid methadone (usual dose range: 60-120mg) or sublingual/transmucosal buprenorphine (usual dose range: 8-24mg) for 24 weeks; or monthly BUP-XR (Sublocade;® two injections of 300mg, then four maintenance injections of 100mg or 300mg, with maintenance dose selected by response and preference) for 24 weeks. In the intent-to-treat population (senior statistician blinded to blinded to treatment group allocation), and with a seven-day grace period after randomisation, the primary endpoint was the count of days abstinent from non-medical opioids between days 8-168 (i.e., weeks 2-24; range: 0-161 days). Safety was reported for the intention-to- treat population. Adopting a broad societal perspective inclusive of criminal justice, NHS and personal social service costs, a trial-based cost-utility analysis estimated the Incremental Cost-effectiveness Ratio (ICER) per quality-adjusted life year (QALY) of BUP-XR versus SoC at the National Institute for Health and Care Excellence threshold. The study was registered EudraCT (2018-004460-63) and ClinicalTrials.gov (NCT05164549), and is completed. Between Aug 9, 2019 and Nov 2, 2021, 314 participants were randomly allocated to receive SoC (n=156) or BUP-XR (n=158). Participants were abstinent from opioids for an adjusted mean of 104.37 days (standard error [SE] 9.89; range: 0-161 days) in the SoC group and an adjusted mean of 123.43 days (SE 4.76; range: 24-161 days) in the BUP-XR group (adjusted incident rate ratio [IRR] 1.18, 95% confidence interval [CI] 1.05-1.33; p-value 0.004). The incidence of any adverse event was higher in the BUP-XR group than the SoC group (128 [81.0%] of 158 participants versus 67 [42.9%] of 156 participants, respectively-most commonly rapidly-resolving (mild-moderate range) pain from drug administration in the BUP-XR group (121 [26.9%] of 450 adverse events). There were 11 serious adverse events (7.0%) in the 158 participants in the BUP-XR group, and 18 serious adverse events (11.5%) in the 156 participants in the SoC group-none judged to be related to study treatment. The BUP-XR treatment group had a mean incremental cost of £1033 (95% central range [CR]-1189 to 3225) and was associated with a mean incremental QALY of 0.02 (95% CR 0.00-0.05), and an ICER of £47,540 (0.37 probability of being cost-effective at the £30,000/QALY gained willingness-to-pay threshold). However, BUP-XR dominated the SoC among participants who were rated more severe at study baseline, and among participants in maintenance treatment for more that 28 days at study enrolment. Evaluated against the daily oral SoC, monthly BUP-XR is clinically superior, delivering greater abstinence from opioids, and with a comparable safety profile. BUP-XR was not cost-effective in a base case cost-utility analysis using the societal perspective, but it was more effective and less costly (dominant) among participants with more severe OUD, or those whose current treatment episode was longer than 28 days. Further trials are needed to evaluate if BUP-XR is associated with better clinical and health economic outcomes over the longer term. Indivior.

Motion Analysis of a Frontal Plane Adaptable Prosthetic Foot.

ABSTRACT Introduction An objective of designing a prosthetic foot is to achieve the natural adaptability of the foot and ankle on various surfaces and different forms of gait. Frontal plane position of the foot relative to the shank changes with many functional aspects of gait, such as turning, stairs, and walking on uneven ground. Prosthetic foot designs have variable frontal plane adaptability. An investigation foot with a linkage with ±10° of frontal plane motion was developed to improve frontal plane response under various conditions. The purpose of this study was to compare the kinematics of locked and unlocked conditions of a frontal plane adaptable prosthetic foot and the person’s usual foot while walking forward on a level surface, on an unstable rock surface, and sidestep, using a crossover design. These different conditions result in changes in frontal plane motion in the anatomical foot and ankle, and the current study evaluates whether there are similar trends in prosthetic feet. Materials and Methods People were included if they had a unilateral below-knee amputation, intact residual limb skin, were over 16 years old, and were able to walk more than 400 m on level ground without using a walking aid and without an increase in pain. The control group was people without amputations who completed the procedures once. Participants with amputations completed forward walking on level ground, on an unstable rock surface, and sidestep with their usual foot. Then after 2 weeks of accommodation, participants repeated these tests with the investigational foot unlocked and locked. Motion analysis data were collected with a 12-camera optically based system. Primary outcomes were sagittal and frontal plane motions of the foot relative to the shank. In addition, step length, step width, and stride velocity were obtained from the kinematic measures. Paired t-tests were used for statistical inference for individual participant comparisons. Unpaired t-tests were used for comparisons between the controls and people with amputations. Results Twenty-one people with amputations and 10 controls completed the tests. Participants with amputation had 16 different usual feet. There was a wide variation in usual foot motion during forward walking, whereas investigational foot conditions showed less variability. During level walking, control subjects had more frontal plane motion than any of the foot conditions, and the unlocked had more frontal plane motion than the usual foot and locked condition. Walking across an unstable rock surface showed similar trends, with control participants having more sagittal and frontal plane ankle motion compared with any prosthetic foot condition. Also, the unlocked had statistically greater frontal plane motion than the usual foot or locked condition. Sidestep results were also consistent with other gait tests. The control participants’ sagittal plane ankle range of motion was significantly more than the prosthetic sagittal plane motion for all foot conditions, whether the prosthetic side was leading or trailing. There was significantly more frontal plane motion with the unlocked than the usual foot and locked condition when the prosthetic foot was trailing or leading. Discussion and Conclusions Wide variation in usual foot range of motions in the frontal and sagittal planes confirmed the need for additional controls when considering the effect of the linkage alone. The unlocked had increased frontal plane ranges of motion compared with the locked and the majority of usual foot for all gait conditions, including level walking. This finding demonstrated that people with amputations were functionally using the additional range of motion provided by the linkage. However, control subjects used more range of motion in both the sagittal and frontal planes for the unstable rock surface and sidestepping. Increased frontal plane range of motion did not translate into improved stride length and velocity, step width, or center of mass deviations. Clinical Relevance The person-specific functional activities should be considered when choosing a prosthetic foot. A prosthesis with frontal plane motion may be applicable for a person who moves in a sidestep pattern or on uneven ground.

THU001 Novel Interactive Text-messaging Curriculum For Endocrinology Board Review

Abstract Disclosure: P. Majety: None. A. Ajayi: None. A. Modest: None. M. Vamvini: Grant Recipient; Self; MV was supported by F32-DK126432, and Joslin Diabetes Center P&F. J. Freed: None. Background: The ABIM certification exam is one of the measures to ensure that physicians have the clinical skills for good care delivery. The five-year average pass rate for the ABIM Endocrinology & Metabolism subspecialty exam is 86%, relatively lower when compared to other subspecialties. The pass rate for first time test takers significantly decreased from a usual range of 84-91% over 2017-2020 to a nadir of 74% in 2021 compared to a mean of 84% for other medicine subspecialties. This represents the lowest pass rate in 2021 for any internal medicine subspecialty exam. Objectives: The primary purpose of our study was to assess the feasibility of a unique text messaging curriculum for endocrinology fellows and its utility in improving their knowledge. We also assessed their study habits and resources available to them for ABIM subspecialty exam preparation. Methods: In 2021, endocrinology fellows from 51 programs across the country were invited to participate in our curriculum. They completed a pre-test, joined a texting group via Remind application and received 1 multiple choice question daily (total n = 78). At the end of curriculum, fellows received a post-test questionnaire, and a feedback survey. After 15 weeks, they completed a post-test and survey. Paired results from pre- and post-test were compared. Results: A total of 89 fellows from 27 programs responded. Of these, 82 fellows, predominantly females (n=60; 73%), filled out the pre-test. On an average, 42 fellows (SD = 12) responded to the questions daily. Thirty fellows completed the post-test. The median number of correct responses on the pre-test was 5 (IQR 3-6), compared to 8 (IQR 6-9) in the post-test. There was a significant improvement (p-value <0.0001) in fellows’ performance in the post-test when compared with the pre-test following our intervention.Final feedback survey was filled out by 33 of them. Ninety-seven percent responded that they use question banks as a resource for exam preparation followed by PowerPoint presentations (52%), journals (48%), online videos (39%), textbooks (33%) and lecture notes (33%). 23 fellows (70%) preferred mobile friendly question bank applications; 5 fellows (15%) preferred online question banks available through company websites only. None of them preferred paper-based question banks.Nineteen of the 33 fellows (58%) found the curriculum very useful. 17 fellows (52%) said it served as a discussion tool sometimes, while 9 fellows (27%) said they used it as a discussion tool often. Thirty two out of 33 fellows (97%) responded that they would like to continue to receive a question daily for the rest of their fellowship. Conclusions: Text-messaging based curriculum for exam preparation is feasible and can improve test performance. Fellows find receiving a daily high yield multiple choice question via text-message as a useful tool for exam preparation. Presentation: Thursday, June 15, 2023