Injection Interval Research Articles

Pharmacokinetic Correlates of Once-Monthly Paliperidone Palmitate-Related Adverse Drug Reactions.

The objective of this study was to investigate associations between pharmacokinetic correlates and once-monthly paliperidone palmitate (PP1M)-related adverse drug reactions (ADRs). Plasma concentrations and dose-adjusted plasma concentrations ('concentration-by-dose' [C/D]) of paliperidone from a naturalistic therapeutic drug monitoring database of PP1M-treated patients were compared between patients with ADRs, classified according to the Udvalg for Kliniske Undersogelser side-effect rating scales categories, and patients without ADRs. Analyses included non-parametric tests and a logistic regression model with a significance level set at 0.05. In 172 patients, we found no differences in sex, age, smoking, body mass index, PP1M dose, paliperidone plasma concentrations, and C/D values (p > 0.05) between 44 patients with and 128 patients without PP1M-related ADRs. We did not detect differences when specifying for different types of ADRs (p > 0.05). Injection intervals were shorter in patients with vs patients without ADRs (p = 0.03). The logistic regression did not report effects for sex, plasma concentrations, or C/D values (p > 0.05). Post hoc analyses in male patients receiving PP1M every 28 weeks reported higher paliperidone concentrations and C/D values in patients with vs without ADRs (p = 0.049 and p = 0.022). Within the group of male patients, we found an odds ratio of 3.07 for PP1M-associated ADRs in patients with C/D values above 7.7 (ng/mL)/(mg/day). Our findings did not reveal distinct patterns of paliperidone concentrations in patients with PP1M-related ADRs. However, male patients receiving PP1M every 28 days with C/D values higher than 7.7 (ng/mL)/(mg/day) showed a higher risk for ADRs, implying that therapeutic drug monitoring may be useful in assessing the risk of PP1M-related ADRs.

Optimal injection interval for testosterone undecanoate treatment of hypogonadal and transgender men.

ObjectiveTo define the optimized inter-injection interval of injectable testosterone undecanoate (TU) treatment for hypogonadal and transmen based on individual dose titration in routine clinical practice.Design and methodsA prolective observational study of consecutive TU injections in men undergoing testosterone replacement therapy for pathological hypogonadism or masculinization of female-to-male transgender (transmen) subject to individual dosing titration to achieve a stable replacement regimen.ResultsFrom 2006 to 2019, 6899 injections were given to 325 consecutive patients. After excluding the 6-week loading dose, 6300 injections were given to 297 patients who had at least three and a median of 14 injections. The optimal injection interval (mean of last three injection intervals) had a median of 12.0 weeks (interquartile range 10.4–12.7 weeks). The interval was significantly influenced by age and body size (body surface area, BSA) but not by diagnosis or trough serum LH, FSH, and SHBG. Longer (≥14 weeks; 68/297, 23%), but not shorter (≤10 weeks; 22/297, 7.4%), intervals were weakly correlated with age but not diagnosis or other covariables. Low blood hemoglobin increased with trough serum testosterone to reach plateau once testosterone was about 10 nmol/L or higher.ConclusionOptimal intervals between TU injection after individual titration resulted in the approved 12-week interval in 70% of patients with only minor influence for clinical application of BSA and not of trough serum LH, FSH, and SHBG. Individually optimized inter-injection interval did not differ between men with primary or secondary hypogonadism or transmen.

Consensus d’experts français sur les critères de choix d’un traitement de 1re intention dans la DMLA néovasculaire et importance du ratio bénéfice/risque à long terme

Choosing a first-line treatment to optimize long-term outcomes is a major challenge for treating patients with neovascular age-related macular degeneration (AMD). The development of several new molecules makes it critical to identify the relevant factors to consider so as to provide an optimal risk-benefit ratio when initiating a treatment in naïve patients with neovascular AMD. This paper proposes a consensus established with the Delphi method (which includes a gradation in a consensus based on an analysis of the convergence rate of answers) to provide criteria that guide the ophthalmologist's decision for treatment initiation and follow-up in neovascular AMD patients. Fourteen questions were submitted to 93 French retina experts. Thirteen (93%) of the questions reached a consensus (≥50% of answers consensual). The criteria recommended to take into account were both efficacy and onset of action of the molecules, their safety, and the ability to decrease injection frequency. The primary criterion of expected efficacy of a molecule is a combination of the gain in visual acuity and resorption of retinal fluid. With regard to safety, experts recommend tighter follow-up for molecules currently in development, and at every scheduled visit, patients should be screened to identify early any potential adverse effects such as intraocular inflammation, retinal vasculitis or vascular occlusion. Experts also emphasize the importance of the packaging of the biological, with a preference toward prefilled syringes. Injection frequency is a key factor, and the authors recommended aiming for a maximal injection interval of 12 to 16 weeks. The stability of that maximum interval is also an important factor to consider in treatment selection.

PND37 Cost-Effectiveness of BoNT-A Products for Treatment of Pediatric Spasticity in the United Kingdom

For children with impaired motor function, pain, or other functional difficulties attributable to focal spasticity, the UK National Institute for Health and Clinical Excellence guidelines recommend treatment with botulinum neurotoxin type A (BoNT-A). Two BoNT-A products are licensed for pediatric use in the United Kingdom: abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A), but these treatments differ in terms of doses, costs, and injection frequencies. The objective of this analysis was to evaluate the average expenditure per response obtained with aboBoNT-A or onaBoNT-A for managing pediatric spasticity of the upper (ULS) and lower (LLS) limbs. Cost-effectiveness analyses were conducted for BoNT-A treatment of ULS and LLS in the UK. Effectiveness was defined as response to therapy and was based on data from systematic literature reviews and meta-analyses of randomized controlled trials. BoNT-A dose was based on product label and the average weight of a pediatric (6-year-old) patient in the UK. Injection interval was based on clinical trial data, adjusted to consider differences in use observed in real-world studies of BoNT-A use in adult spasticity. Resource use for responders and non-responders was based on a survey of UK physicians treating pediatric LLS. Unit costs were informed by UK fee schedules. AboBoNT-A resulted in lower annual costs compared with onaBoNT-A for the management of ULS (£487 saved) and LLS (£429 saved). Results were driven by differences in injection intervals and a higher treatment response rate for people receiving aboBoNT-A compared with onaBoNT-A. Total cost per responder was lower for people receiving aboBoNT-A compared with onaBoNT-A (ULS: £37,880 vs. £50,100; LLS: £46,459 vs. £66,037). Results were robust to sensitivity analyses. AboBoNT-A may be a cost-effective choice for treatment of spasticity in children. These findings could help deliver more effective and efficient healthcare in the UK.

PND18 BoNT-As for Adult Spasticity and Cervical Dystonia: Cost-Effectiveness Analysis and the Cost of Response in the United Kingdom

For adults with spasticity or cervical dystonia (CD), treatment with botulinum neurotoxin type A (BoNT-A) has been shown to improve achievement of treatment goals. Considering the costs of available BoNT-A therapies could increase the efficiency of healthcare spending. The objective of this analysis was to evaluate the average expenditures per response obtained with abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) for spasticity and CD. Cost-effectiveness analyses were conducted to compare aboBoNT-A and onaBoNT-A for treatment of upper limb spasticity (ULS), lower limb spasticity (LLS), and CD, in the United Kingdom. Effectiveness was defined as response to therapy. Response rates and dosing were based on observational studies for ULS and CD. For LLS, real-world observational data were not available, so response rates were based on systematic literature reviews with meta-analysis of clinical trials and dosing based on UK product labels. BoNT-A treatment intervals were based on real-world data when available (ULS), or otherwise were assumed to follow similar patterns to those observed in clinical trials (LLS and CD). Resource use for responders and non-responders was based on a UK physician survey. Unit costs were informed by UK fee schedules. Compared with onaBoNT-A, aboBoNT-A resulted in lower annual costs per patient for the management of ULS, LLS, and CD (savings of £302, £584, and £422, respectively). Results were driven by differences in injection intervals and a higher treatment response rate for people receiving aboBoNT-A compared with onaBoNT-A. Total cost per responder was lower for patients receiving aboBoNT-A compared with onaBoNT-A (ULS: £43,266 vs £55,416; LLS: £98,962 vs £209,376; CD: £13,883 vs £21,817). Results were robust to sensitivity analyses. With high response rates and low costs, aboBoNT-A may be an efficient choice for treating adult spasticity and cervical dystonia in the UK.

Elevated Pre-injection Basal Luteinizing Hormone Concentrations are Common in Girls Treated for Central Precocious Puberty

Objective:A consensus on how to monitor girls with central precocious puberty (CPP) during gonadotropin-releasing hormone agonist (GnRHa) treatment is lacking. Increased, unstimulated basal luteinizing hormone (LH) concentrations have been suggested to indicate lack of suppression. The aim was to evaluate pre-injection basal LH concentrations during GnRHa (leuprorelin 3.75 mg) treatment every four weeks in girls with CPP.Methods:Medical records were reviewed for girls with CPP treated at a single center from 2014-2019. Clinical characteristics and laboratory findings during treatment were systematically recorded.Results:A total of 587 GnRHa pre-injection basal LH concentrations were analyzed in 74 girls. Basal LH was pubertal (≥0.3 IU/L) in 53.5% of blood samples and 87.8% of all girls had a pubertal basal LH concentration at least once. A GnRH test (n=29) was repeated in 23 girls due to suspicion of clinical progression, elevated basal LH or recordable estradiol concentrations. None had a stimulated LH >3.1 IU/L. The predictability of treatment suppression (specificity) of basal LH concentrations was 12.0% when compared to repeated GnRH stimulation tests. Despite shortening the GnRHa injection interval to three weeks, basal LH concentrations remained pubertal in 85.7% girls. A significant reduction in height standard deviation score (p<0.001) and bone age advance (p<0.001) was observed during treatment.Conclusion:Pre-injection basal LH remains at pubertal concentrations during treatment with leuprorelin 3.75 mg in girls with CPP. Clinical monitoring of pubertal progression is preferable to routine basal LH concentrations. Repeat GnRH stimulation testing should be regarded as the gold standard.

Exenatide Microspheres for Monthly Controlled-Release Aided by Magnesium Hydroxide.

GLP-1 receptor agonists are a class of diabetes medicines offering self-regulating glycemic efficacy and may best be administrated in long-acting forms. Among GLP-1 receptor agonists, exenatide is the one requiring the least dose so that controlled-release poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres may best achieve this purpose. Based on this consideration, the present study extended the injection interval of exenatide microspheres from one week of the current dosage form to four weeks by simply blending Mg(OH)2 powder within the matrix of PLGA microspheres. Mg(OH)2 served as the diffusion channel creator in the earlier stage of the controlled-release period and the decelerator of the self-catalyzed degradation of PLGA (by the formed lactic and glycolic acids) in the later stage due to its pH-responsive solubility. As a result, exenatide gradually diffused from the microspheres through Mg(OH)2-created diffusion channels before degradation of the PLGA matrix, followed by a mild release due to Mg(OH)2-buffered degradation of the polymer skeleton. In addition, an extruding–settling process comprising squeezing the PLGA solution through a porous glass membrane and sedimentation-aided solidification of the PLGA droplets was used to prepare the microspheres to ensure narrow size distribution and 95% encapsulation efficiency in an aqueous continuous phase. A pharmacokinetic study using rhesus monkey model confirmed the above formulation design by showing a steady blood concentration profile of exenatide with reduced CMAX and dosage form index. Mg(OH)2.

Lanadelumab Efficacy, Safety, and Injection Interval Extension in HAE: A Real-Life Study

Lanadelumab has been available in Germany for the prophylactic treatment of hereditary angioedema since February2019. To investigate real-life treatment outcome of lanadelumab and gain practical experience in adapting the therapy to individual patients. The study included 34 patients. In 24 patients with hereditary angioedema and 4 patients with angioedema due to acquired C1-inhibitor deficiency, the previous treatment was switched to lanadelumab. In 6 patients with hereditary angioedema, lanadelumab from the open-label Hereditary Angioedema Long-term Prophylaxis study was continued in regular care. During the transition, patients were monitored using the angioedema control test and the angioedema quality of life questionnaire. At the time at which patients became symptom-free, the dosage interval was increased gradually (+3 days). On average, the angioedema control test values improved from 7.5 (poorly controlled disease) to 14.9 (well-controlled disease), and all patients showed adequate disease control. All treated patients, except 1 outlier, scored angioedema quality of life questionnaire values representing only a slight reduction in quality of life (mean, 14 points). At the time point of data collection, 9 patients used an average fixed injection interval of 30 days. Twenty-two patients were symptom-free from the beginning of the treatment phase and intended to extend their injection interval from 30 to 32.5 days (median). We recommended reducing the initial dosing interval from 24 to 21 days (median) to 3 patients because of intermediately occurring symptoms. Gradual extension of injection intervals of lanadelumab presented in this study can minimize the burden oftherapy without losing efficacy.

POS0338 STEROID-SPARING EFFECT OF ANAKINRA IN GIANT-CELL ARTERITIS: A CASE SERIES WITH CLINICAL, BIOLOGICAL AND ICONOGRAPHIC LONG-TERM ASSESSMENTS

Background:The treatment of giant cell arteritis (GCA) relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-interleukin-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to interleukin-6, interleukin-1 also appears to play a significant role in GCA pathophysiology.Objectives:We report herein the efficacy of anakinra, an interleukin-1 receptor antagonist, in 6 GCA patients exhibiting corticosteroid dependence or resistance, specifically analyzing the outcome of aortitis in 4 of them, and including the long-term follow-up of 2 previously described patients (1).Methods:This retrospective study analyzed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis.Patients had to satisfy the following two criteria to be enrolled in this retrospective study. First, their diagnosis of GCA should be based on the fulfillment of at least 3 criteria of the American College of Rheumatology (ACR) for GCA or on the satisfaction of 2 of these criteria along with the demonstration of LVI on imaging. Second, patients should have received anakinra because of corticosteroid dependence or resistance.Corticosteroid dependence was defined as ≥2 relapses or the combination of 2 of the following criteria: a daily dose of oral prednisone &gt;20 mg/day (or 0.3 mg/kg) at 6 months; a daily dose of oral prednisone &gt;10 mg/day (or 0.2 mg/kg) at 12 months; and/or a treatment maintained &gt;24 months because of a relapsing disease course. Corticosteroid resistance was defined as persistent increased inflammatory parameters at month 3 despite a steroid dosage over 0.5 mg/kg.Results:After a median duration of anakinra therapy of 19 [18–32] months, all 6 patients exhibited complete clinical and biological remission. Among the 4 patients with large-vessel involvement, 2 had a disappearance of aortitis under anakinra, and 2 showed a decrease in vascular uptake. After a median follow-up of 56 [48–63] months, corticosteroids were discontinued in 4 patients, and corticosteroid dosage could be decreased to 5 mg/day in 2 patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 hours. Three patients experienced transient injection-site reactions, and 1 patient had pneumonia.Figure 1.Steroid dosages before and after the introduction of anakinra in 6 patients with giant-cell arteritis and corticosteroid dependence or resistance. The black arrow indicates the time of anakinra introduction.Conclusion:In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.

Anti-VEGF Treatment Patterns in Patients With Wet Age-Related Macular Degeneration in Clinical Practice.

To characterize on-label anti-vascular endothelial growth factor (VEGF) treatment patterns in patients with wet age-related macular degeneration (AMD) in clinical practice in the U.S. Retrospective cohort analysis using administrative claims data from the IQVIA Open Source Databases. Treatment-naïve patients in the U.S. who received one or more wet AMD-related anti-VEGF injection from July 1, 2013, to April 30, 2017, were included. The main outcome was the injection interval closest to Month 12. This study included 21,960 patients who initiated an anti-VEGF agent (ranibizumab, aflibercept, or bevacizumab): 5,489 initiated aflibercept and 4,253 initiated ranibizumab. Among ranibizumab, aflibercept, and all anti-VEGF eyes, 38.1% (n = 2,035), 33.5% (n = 3,262), and 40.0% (n = 12,505) of patient eyes had injection intervals of less than 8 weeks, respectively, at Month 12 with the mean (standard deviation) number of injections over 12 months being 8.0 (2.4), 7.6 (2.4), and 7.8 (2.5). A substantial proportion of patients receive injections more frequently than every 8 weeks within the first year of treatment. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:263-272.].

Platinum-Containing Supramolecular Drug Self-Delivery Nanomicelles for Efficient Synergistic Combination Chemotherapy.

Supramolecular drug self-delivery systems (SDSDSs) involving active drugs as building blocks linked by supramolecular interactions have been well defined as an advanced chemotherapy strategy. However, the lack of detecting release of drugs from SDSDSs at specific tumor sites inevitably leads to unsatisfactory therapeutic effects, owing to the lack of information regarding the administration of these drugs. In this work, predesigned platinum-containing supramolecular drug self-delivery nanomicelles (SDSDNMs) were employed to synchronously realize drug monitoring by computed tomography imaging, immediately reflecting the evolution of drug release and real-time treatment at the tumor site. The appropriate administration dosage (1.2 mg mL-1,100 μL) and the injection interval (once every 3 days) needed to guide the antitumor activity of SDSDNMs were then defined, thereby attaining the aim of efficient synergistic combination chemotherapy. In vivo tumor inhibition and histological analyses showed that SDSDNMs exhibited a strong tumor inhibition effect and good safety with respect to normal organs. Such a supramolecular drug self-delivery strategy with monitored functions may offer new potential opportunities for application in the field of synergistic combination chemotherapy.

Brolucizumab: a novel anti-VEGF humanized single-chain antibody fragment for treating w-AMD

ABSTRACT Introduction Wet age-related macular degeneration (w-AMD) represents the leading cause of visual impairment in the elderly in the developed countries. Intravitreal antivascular endothelial growth factor (VEGF) drugs are currently considered as the first-line treatment option for treating w-AMD; however, the frequent injection intervals have lit the way to investigate novel anti-VEGF agents allowing a more extended treatment regimen. Brolucizumab is a single-chain antibody fragment targeting all the isoforms of VEGF-A. Phase III HAWK and HARRIER trials have shown a longer durability and superior anatomical outcomes as compared with the standard of care by adopting a quarterly regimen for treating w-AMD. Brolucizumab has been approved in Europe, USA, and Japan for the management of w-AMD. Areas covered This article presents an overview of w-AMD and investigates the progress of brolucizumab through clinical trials. It offers insights into where brolucizumab may be placed in the current market of anti-VEGF agents and its potential advantages over the previous molecules adopted for treating w-AMD. Expert Opinion The possibility of administering brolucizumab with more dilated treatment intervals represents an important advantage to decrease the treatment burden and improve patient compliance. Brolucizumab represents a possible drug switching option in non-responding patients to other anti-VEGF drugs.

Current and emerging long-acting antipsychotics for the treatment of schizophrenia

ABSTRACT Introduction: In this review, the authors discuss the role of long-acting injectable antipsychotics (LAIs) for schizophrenia, focusing on the effectiveness and new perspectives introduced by such treatment strategy. Despite their promising pharmacokinetic features and their potential advantages in medication adherence, clinical outcomes, and medical costs, LAIs are not habitually presented as an option for patients, especially in the early phase of schizophrenia. Areas covered: This review explores the panorama of available LAIs for the treatment of schizophrenia, first-episode of psychosis, approved indications, medical costs, medication adherence, side effects, effectiveness and differences between first-generation (FGA)-LAIs and second-generation (SGA)-LAIs. Expert Opinion: LAIs differ in terms of specific indications, approved injection sites, needle size, injection volume, injection interval as well as potential drug–drug interactions, and commonly reported adverse reactions. The approved indications have expanded beyond schizophrenia to include bipolar and schizoaffective disorder. SGA-LAIs are often preferred to FGA-LAIs. FGA-LAIs although are less chosen in new patients due to the induction of cognitive and extrapyramidal side effects, even if, on the other hand, many SGA-LAIs are burden by hyperprolactinemia and weight gain. After a review of the available evidence, insight is provided into the potential and current therapeutic opportunities offered by LAI antipsychotic formulations.

Skin factor and potential formation damage from chemical and mechanical processes in a naturally fractured carbonate aquifer with implications to CO2 sequestration

In this study, we investigate formation damage due to acidization and water injection tests into the naturally fractured carbonate Middle Duperow Formation at Kevin Dome, Montana, potentially diminishing the chance of a future successful Geological Carbon Sequestration (GCS) project. Multiple well-test analytical models, correlated with core description and lithology data, are used to determine flow behavior and communication between the water injection interval and surrounding formations. An improved three-dimensional (3D) geologic model with dual-continuum matrix and fracture properties is constructed based on most recent seismic, core, and water sample measurements. Brine injection is simulated to verify the interpretation from the analytical models, followed by CO2 injection simulation. Geochemical calculations are performed to understand the in-situ processes that led to formation damage. Our findings suggest: (1) there are two possible scenarios that could lead to a positive total effective skin factor and permeability decline: partial penetration and formation damage; (2) analytical models indicate a positive total skin factor, contradicting results of a previous study suggesting that the well was mildly stimulated; (3) numerical simulation supports the formation damage hypothesis by matching the pressure buildup observed during the latter two brine injection tests; (4) several mechanical and chemical processes may have occurred during injection to clog the matrix/fracture system: anhydrite fines migration and/or calcite precipitation. We then make preventative suggestions for future GCS projects into carbonate reservoirs and remediation recommendations for GCS operation at the Kevin Dome.

Real-World Treatment Patterns in a Population With Neovascular AMD Treated With Anti-VEGF Agents.

To characterize mean number of injections, injection type, and injection frequency during the first year of treatment; assess factors significantly related to injection interval; and identify predictive factors related to patient outcomes. A retrospective, noncomparative, nonrandomized cohort study of ocular treatment with intravitreal injections of bevacizumab, ranibizumab, and aflibercept in eyes with neovascular age-related macular degeneration (nAMD). Data from January 1, 2012, through March 31, 2018, were systematically extracted from the electronic medical record system at Cole Eye Institute. Eligible patients had three or more injections within the first 12 months of treatment and received no prior injections. Patients received an average 8.12 ± 2.45 injections, and 45% of patients received injections at an interval of 8 weeks or less (≤q8 weeks), 33% received injections at 8 to 12 weeks (q8-12 weeks), and 22% received injections at greater than 12 weeks (>q12 weeks). Age (P = .007) and initial central subfield thickness (CST) (P = .043) had statistically significant trend relationships (P = .007) with injection interval, whereas younger patients and patients with higher CST measurements tended to have shorter injection intervals. Injection interval was a significant predictor of visual acuity (VA) and CST. Patients receiving injections at q8-12 weeks were more likely to have better VA outcomes than patients with injection intervals at ≤q8 weeks (odds ratio [OR] = 1.66 [1.16, 2.37]; P = .005). Patients receiving injections at >q12 weeks did not show a significant improvement in VA (P = .06) and were more likely to have worse CST outcomes than patients receiving injections at ≤q8 weeks (OR = 1.95 [1.17, 3.26]; P = .011). A significant portion of patients receive injections at an interval longer than every 8 weeks. Age and baseline CST had a significant relationship with injection interval. Injection interval was a significant predictor of VA and CST at 1 year. Patients with an injection interval of >q12 weeks tended to have less VA improvement and CST reduction compared to the ≤q8 weeks and q8-12 weeks groups. These findings suggest an extended injection interval >q12 weeks may be at the expense of potential VA improvement. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:190-198.].

Application of Botulinum Toxin in Patients with Secondary Otalgia Caused by Bruxism.

AimThe aim of this study was to determine the effectiveness of botulinum toxin administration in patients who consulted the otolaryngology clinic with secondary otalgia caused by bruxism.IntroductionBotulinum toxin can be applied to the hypertrophic muscles in patients who suffer from facial asymmetry even though they do not experience pain. Injection intervals and the condition of the muscles should be monitored as botulinum toxin applications to the muscles may result in decreased muscle strength and chewing difficulties.MethodsThis prospective study was conducted with bruxism patients at Private Kesan Hospital otorhinolaryngology outpatient clinic between August 2019 and December 2019. The diagnosis was based on the anamnesis and physical examination of the patient. The Visual Analogue Scale was used to evaluate patients’ pain levels throughout the treatment.ResultsA total of 37 patients, between 19 and 51 years old, 22 (59.46%) females and 15 (40.54%) males, who consulted to the otolaryngology clinic in Private Kesan Hospital between August 2019 and December 2019 with a diagnosis of otalgia caused by bruxism were included in the study. Nine patients (24.3%) had facial asymmetry due to masseter muscle hypertrophy. The average age of the participants was 34.00 ± 9.13 years old. Two weeks after the application of botulinum toxin, patients’ complaints subsided. In patients with facial asymmetry, it was observed that asymmetry decreased after the 2nd month and noticeably improved after the 4th month.DiscussionBruxism should be considered in the differential diagnosis of patients with ear pain. Botulinum toxin can be applied in patients who do not respond adequately to classical treatments such as medical treatments, chewing training, neck and facial muscle relaxation techniques, psychological support, and dental splint applications.

Parametric imaging of dual-time window [18F]flutemetamol and [18F]florbetaben studies

Optimal pharmacokinetic models for quantifying amyloid beta (Aβ) burden using both [18F]flutemetamol and [18F]florbetaben scans have previously been identified at a region of interest (ROI) level. The purpose of this study was to determine optimal quantitative methods for parametric analyses of [18F]flutemetamol and [18F]florbetaben scans. Forty-six participants were scanned on a PET/MR scanner using a dual-time window protocol and either [18F]flutemetamol (N=24) or [18F]florbetaben (N=22). The following parametric approaches were used to derive DVR estimates: reference Logan (RLogan), receptor parametric mapping (RPM), two-step simplified reference tissue model (SRTM2) and multilinear reference tissue models (MRTM0, MRTM1, MRTM2), all with cerebellar grey matter as reference tissue. In addition, a standardized uptake value ratio (SUVR) was calculated for the 90–110 min post injection interval. All parametric images were assessed visually. Regional outcome measures were compared with those from a validated ROI method, i.e. DVR derived using RLogan. Visually, RPM, and SRTM2 performed best across tracers and, in addition to SUVR, provided highest AUC values for differentiating between Aβ-positive vs Aβ-negative scans ([18F]flutemetamol: range AUC=0.96–0.97 [18F]florbetaben: range AUC=0.83–0.85). Outcome parameters of most methods were highly correlated with the reference method (R2≥0.87), while lowest correlation were observed for MRTM2 (R2=0.71–0.80). Furthermore, bias was low (≤5%) and independent of underlying amyloid burden for MRTM0 and MRTM1. The optimal parametric method differed per evaluated aspect; however, the best compromise across aspects was found for MRTM0 followed by SRTM2, for both tracers. SRTM2 is the preferred method for parametric imaging because, in addition to its good performance, it has the advantage of providing a measure of relative perfusion (R1), which is useful for measuring disease progression.

The role of bacterial urease activity on the uniformity of carbonate precipitation profiles of bio-treated coarse sand specimens

Protocols for microbially induced carbonate precipitation (MICP) have been extensively studied in the literature to optimise the process with regard to the amount of injected chemicals, the ratio of urea to calcium chloride, the method of injection and injection intervals, and the population of the bacteria, usually using fine- to medium-grained poorly graded sands. This study assesses the effect of varying urease activities, which have not been studied systematically, and population densities of the bacteria on the uniformity of cementation in very coarse sands (considered poor candidates for treatment). A procedure for producing bacteria with the desired urease activities was developed and qPCR tests were conducted to measure the counts of the RNA of the Ure-C genes. Sand biocementaton experiments followed, showing that slower rates of MICP reactions promote more effective and uniform cementation. Lowering urease activity, in particular, results in progressively more uniformly cemented samples and it is proven to be effective enough when its value is less than 10 mmol/L/h. The work presented highlights the importance of urease activity in controlling the quality and quantity of calcium carbonate cements.

Simulating a Controlled CO2 Release Experiment in a Shallow Fault Zone in Western Australia

Geological and dynamic modelling studies are routinely performed to design and interpret field test experiments. These studies help with the planning of well location, well operations and monitoring strategies, as well as with a range of different test activities. After the test, the new interpretations of the experiment observations are then integrated with previous knowledge and reconciled with the assumption that was first tested. Often, the results of a test are significantly different from what was anticipated (hence the purpose of testing). In this work, we examine such an example and put in perspective the impact of the first modelling study on the interpretation of the test. The CSIRO In-Situ Laboratory Project (In-Situ Lab) is located at the eastern edge of the South West Hub CCS Flagship project (SW Hub) in Western Australia, which has been identified as a potential area for commercial-scale CO2 storage. A first test at the In-situ Lab has evaluated the ability to monitor and detect unwanted leakage of CO2 from a storage complex in the shallow subsurface. The In-Situ Lab is also collocated within a major fault zone. Prior to a controlled-release test, a numerical simulation study was undertaken to inform the optimal location for a monitoring well, the vertical location of the downhole instrumentation, and to ensure breakthrough of CO2 occurred within the project timeframe. Based on the likely extent of the CO2 plume for an injection volume of 40 tonnes, the observation well ISL OB-1 was located at 7 m from the injection well to maximise the likelihood the CO2 plume would be intersected. The CO2 plume was predicted to migrate vertically for at least 20 m above the injection interval. Due to the resolution of the existing seismic and limited well data, large uncertainty existed regarding the detailed fault zone geometry, and, more specifically, how disaggregation and drag has impacted the contiguity and slope of lithostratigraphic layers within the fault zone. In other words, it was not clear to what extent the relatively low-permeability paleosols would form baffles for the migration of CO2. Also, it was not known whether sub-seismic faults, if present, would act as vertical barriers or conduits to CO2 migration. During a controlled-release test, 38 tonnes of gaseous CO2 were injected in February 2019, and the gas was monitored by a wide range of downhole and surface monitoring technologies. A higher than expected bottomhole pressure was observed. CO2 reached the ISL OB-1 monitoring well after approximately 1.5 days. Observations suggest that the fault zone did not alter the CO2 migration along bedding at the scale and depth of the controlled release experiment. No vertical CO2 migration was detected beyond the perforated injection interval. The injectivity was lower than predicted from core measurements and prior modelling. Also, contrary to prior model predictions, the plume did not migrate vertically across the paleosol overlying the injection interval. Post-injection reservoir simulations calibrated to the observed pressure and CO2 distribution data confirm that (1) a vertical segregation exists just above the injection interval, and (2) local overpressure are due to a combination of wellbore damage, mud invasion at the injection well and, to a lesser extent, reservoir compartmentalisation.

Anti-fouling effect by internal air injection in plate-type ceramic membrane fabricated for the treatment of agro-industrial wastewater

The ceramic microfiltration membrane which composed of membrane body having macro pore and active layer having micro pore was fabricated successfully by the process including the sintering of tape-casted and laminated mixture of zirconia and polyvinyl butyral binder, and re-sintering after screen coating of zirconia. The average pore size and porosity of the fabricated membrane were 0.1855 μm and 40 %, respectively. A novel membrane microfiltration system adopting the fabricated ceramic membrane was also devised for the treatment of agro-industrial wastewater, and the effects of external air sparging and internal air injection were investigated. A significant improvement of permeability by external air sparging was not observed, and the permeate flux was about 20 L/m2/h. Despite the abnormal biomass status resulted from low water temperature and poor maintenance of facility, however, the system operated at the initial TMP of 0.4 bar and internal air injection intervals of 5 min showed excellent permeability of 100 L/m2/h. In addition, although several periodic internal air injections with inverse pressure was carried out, structural defects of fabricated ceramic membrane were not observed. Thus, it confirmed that the anti-fouling effect by optimum back-flushing strategy in fabricated ceramic membrane was effective for stability enhancement of agro-industrial complex wastewater treatment process suffering from maintenance.