Monitoring subsurface changes by tracking direct-wave amplitudes and traveltimes in continuous DAS VSP data

Instrumenting wells with distributed acoustic sensors (DAS) and illuminating them with passive or active seismic sources allows precise tracking of temporal variations of direct-wave traveltimes and amplitudes, which can be used to monitor variations in formation stiffness and density. This approach has been tested by tracking direct-wave amplitudes and traveltimes as part of a CCS project where a 15 kt supercritical CO2 injection was monitored with continuous offset VSPs using nine permanently mounted surface orbital vibrators (SOVs) acting as seismic sources and several wells instrumented with DAS cables cemented behind the casing. The results show a significant (from 15 to 30%) increase of strain amplitudes within the CO2 injection interval, and travetime shifts of 0.3 to 0.4 ms below this interval, consistent with full-wave 1.5D numerical simulations and theoretical predictions. The results give independent estimates of the CO2 plume thickness and P-wave velocity reduction within it.

Short-Term Outcomes following “Switching” to Monthly Ranibizumab in Neovascular Age-Related Macular Degeneration Showing Insufficient Response to Bimonthly Aflibercept

Background/Objectives. To evaluate the efficacy of switching to monthly ranibizumab in neovascular age-related macular degeneration (nAMD) showing an insufficient response to bimonthly aflibercept. Subjects/Methods. A total of 13 nAMD eyes showing an insufficient treatment response to three successive aflibercept injections were enrolled through a retrospective chart review. After switching, three consecutive monthly intravitreal ranibizumab injections were performed. The main outcome measurements included the best-corrected visual acuity (BCVA), central retinal thickness (CRT), presence of intraretinal fluid (IRF), and subretinal fluid (SRF) using optical coherence tomography (OCT) and were measured every month. Results. CRT and logMAR VA were 349.62 ± 223.51 μm and 0.50 ± 0.23 at the baseline and 274.69 ± 148.77 μm and 0.46 ± 0.24, 311.54 ± 192.90 μm and 0.45 ± 0.20 at 1 month after the first and third ranibizumab injections, respectively. The CRT decrease during three ranibizumab injections was statistically significant (38.08 ± 69.52 μm, p = 0.033 ). Change in VA was not statistically significant. The percentage of eyes with SRF was 100% at baseline and 53.8%, 76.9%, and 69.2% one month after each ranibizumab injections. The percentage of eyes with IRF was 38.5% at baseline and 23.1%, 23.1%, and 15.4%, respectively, after switching. Conclusion. Switching to monthly ranibizumab in nAMD showing an insufficient response to bimonthly aflibercept led to immediate anatomical improvement. It can be considered in countries where the healthcare insurance system limits the minimum injection interval of aflibercept.

Revisiting the Classical Experiment in Earthquake Control at the Rangely Oil Field, Colorado, 1970, Using a Coupled Flow and Geomechanical Model

ABSTRACT The injection experiment conducted at the Rangely oil field, Colorado, was a pioneering study that showed qualitatively the correlation between reservoir pressure increases and earthquake occurrence. Here, we revisit this field experiment using a mechanistic approach to investigate why and how the earthquakes occurred. Using data collected from decades of field operations, we build a geological model for the Rangely oil field, perform reservoir simulation to history match pore-pressure variations during the experiment, and perform geomechanical simulations to obtain stresses at the main fault, where the earthquakes were sourced. As a viable model, we hypothesize that pressure diffusion occurred through a system of highly permeable fractures, adjacent to the main fault in the field, connecting the injection wells to the area outside of the injection interval where intense seismic activity occurred. We also find that the main fault in the field is characterized by a friction coefficient μ ≈ 0.7—a value that is in good agreement with the classical laboratory estimates conducted by Byerlee for a variety of rock types. Finally, our modeling results suggest that earthquakes outside of the injection interval were released tectonic stresses and thus should be classified as triggered, whereas earthquakes inside the injection interval were driven mostly by anthropogenic pore-pressure changes and thus should be classified as induced.

Real-World Dosing of OnabotulinumtoxinA and IncobotulinumtoxinA for Cervical Dystonia and Blepharospasm: Results from TRUDOSE and TRUDOSE II

The real-world use of onabotulinumtoxinA and incobotulinumtoxinA for cervical dystonia and blepharospasm treatment was assessed in two separate retrospective studies using identical protocols (TRUDOSE and TRUDOSE II). The studies were conducted in Mexico, Norway, and United Kingdom and designed to evaluate dose utilization of the two botulinum toxins in clinical practice. Eighty-three patients treated with both onabotulinumtoxinA and incobotulinumtoxinA for ≥2 years for each botulinum toxin were included, (52, cervical dystonia; 31, blepharospasm). All patients switched from onabotulinumtoxinA to incobotulinumtoxinA for administrative/financial reasons. A range of dose ratios (incobotulinumtoxinA to onabotulinumtoxinA) was reported; with the majority of dose ratios being >1. The mean dose ratio was >1 regardless of the study site or underlying clinical condition. The inter-injection interval was significantly longer for onabotulinumtoxinA versus incobotulinumtoxinA when assessed for all patients (15.5 vs. 14.3 weeks; p = 0.006), resulting in fewer onabotulinumtoxinA treatments over the study time period. Consistent with product labeling, no single fixed-dose ratio exists between incobotulinumtoxinA and onabotulinumtoxinA. The dosage of each should be individualized based on patient needs and used as per product labeling. These real-world utilization data may have pharmacoeconomic implications.

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

Objective: To 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 Methods: 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. Results: From 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. Conclusion: Optimal 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 age and body size (BSA) and not of trough serum LH, FSH and SHBG. Individually optimised inter-injection interval did not differ between men with primary or secondary hypogonadism or transmen.

Nonlinear Changes in Botulinum Toxin Treatment of Task-Specific Dystonia during Long-Term Treatment

Botulinum toxin (BoTX) is the standard treatment for task-specific dystonias (TSDs) such as musician’s dystonia (MD). Our aim was to assess the long-term changes in BoTX treatment in a highly homogeneous and, to our knowledge, largest group of MD patients with respect to the following parameters: (1) absolute and (2) relative BoTX dosage, (3) number of treated muscles, and (4) inter-injection interval. We retrospectively assessed a treatment period of 20 years in 233 patients, who had received a cumulative dose of 68,540 MU of BoTX in 1819 treatment sessions, performed by two neurologists. Nonlinear correlation was used to analyze changes in the parameters over the course of repeated treatments. Post-hoc we applied a median-split to classify two subgroups (high-BoTX, low-BoTX) depending on the total amount of BoTX needed during treatment. Across all patients, we found a decrease of dosage for the first approximately 25 treatments with an increase afterwards. The number of muscles and inter-injection intervals increased with time with a discrete decrease of inter-injection intervals after about 35 treatments. Subgroup differences were observed in the amount of BoTX and inter-injection intervals, with continuously increasing inter-injection intervals and decreasing BoTX dosage in the low-BTX group. Both groups showed a continuously increasing number of injected muscles. In summary, we found nonlinear changes of BoTX dosage and inter-injection intervals and a continuously increasing number of injected muscles with treatment duration in TSD-patients. Furthermore, we, for the first time, identified two subgroups with distinct differences. Increasing inter-injection intervals and decreasing BoTX dosages in the low-BoTX group indicated improvement of symptoms with continued treatment. Continually increasing BoTX dosages with unchanged inter-injection intervals in the high-BoTX group indicated deterioration.

Outcome of Switching Anti-VEGF Agents at Fixed Intervals to Treat Eyes With Macular Edema Secondary to Branch Retinal Vein Occlusion

ObjectiveTo determine whether switching intravitreal injections of ranibizumab or aflibercept to the other will affect the interval of subsequent injections in patients with macular edema secondary to branch retinal vein occlusion (BRVO).ResultsThe medical charts of 16 eyes of 16 patients were reviewed. After injections of ranibizumab or aflibercept for >3 times/year, the type of anti-vascular endothelial growth factor agent was switched. A comparison was made of the average injection interval for the one year before switching and the interval of the first two injections post-switching. In the group that switched from ranibizumab to aflibercept (R to A group, n=8), the interval before was 85.4±6.6 days which was significantly increased to 125.9±23.2 days post-switching (P=0.0013). In the A to R group (n=8), a significant shortening from 103.9±11.8 days before to 85.9±12.6 days was observed (P=0.007). In the R to A group, the central retinal thickness at a recurrence was 522.1±79.6 µm which decreased significantly to 419.3±64.5 µm post-switching (P=0.005). The results suggest that the intervals can be different between ranibizumab and aflibercept in patients with macular edema secondary to BRVO who required repeat injections.

Filter Cake Breaker Evaluation Scaled Up From Laboratory to Field Conditions

This article, written by JPT Technology Editor Judy Feder, contains highlights of paper SPE 199260, “Filter Cake Breaker Evaluation for Water Injectors: Scale Up From Laboratory to Field Deployment,” by Pavithiran Chandran, SPE, Arunesh Kumar, SPE, and Iain Cameron, BP, et al., prepared for the 2020 SPE International Conference and Exhibition on Formation Damage Control, Lafayette, Louisiana, 19–21 February. The paper has not been peer reviewed. The complete paper describes the test procedures adopted for evaluating various filter cake breaker formulations and the work conducted to develop the systems to be ready for use in two North Sea fields (Field A and Field B). Water injection wells were planned to provide pressure support to oil producers in the two fields, and water-based drilling fluids were selected to drill the reservoir sections for both. The average permeability is 1000 md for Field A and 50–100 md for Field B. A laboratory study was commissioned to evaluate and optimize filter cake breaker systems for use in water injectors to efficiently remove external and internal filter cake to attain matrix injection without the need for backflow to clean the sandface. Introduction Field A was commissioned to drill 18 producers and seven water injectors from a semisubmersible drilling rig. Most of the injector wells are high-inclination, long openhole sections. Fluid density of 1.24–1.48 specific gravity (SG) (10.3–12.3 ppg) was required for wellbore stability. The Field B development plan included drilling 26 producers and 10 water injectors with an average injection rate target of 40,000 B/D of treated, produced water per well. Most wells are high-inclination to reduce the risk of direct fracture communication between wells. Injectivity indexes of 10–30 BWPD/psi were anticipated. The ability to include backflow/gas-lift capacity in the injector wells to assist cleanup was not included in the operational plan; therefore, direct injection was the preferred design standard. The injection interval in Field A features high-permeability (approximately 1000-md) zones; the Field B injection interval is considered a low-to-mid-permeability (approximately 100-md) zone. Injection of warm produced water into naturally occurring fractures in Field B injector wells yields poorer performance than when cooler fluids such as seawater are used. Higher downhole temperature and longer fluid residence time in the wellbore on Field B could increase the temperature of the injection fluid and thermally contract the natural fractures. Poor initial injectivity with produced water was identified as a potential risk on these wells, because this could lead to subsequent complications with seawater injection into these zones. Reservoir Drilling Fluid (RDF) Design and Selection Water-based RDF was chosen to drill the reservoir section of the water injectors on the basis of its ability to reduce operational complexity in terms of fluids preparation, displacement design, and screen running issues. RDF fluids typically contain a brine phase to achieve required density, xanthan polymer for viscosity, starch for filtration control, sized calcium carbonates for a bridging package, and specialized chemicals to address specific well challenges such as shale inhibitors and lubricants. Water-based RDF is more amenable than invert emulsion fluids to stimulation treatments for cleanup of filter cake and remediation of near-wellbore damage. However, water-based fluids can pose other operational issues such as increased torque and drag and potential for differential sticking, especially while drilling long horizontal wells, as was planned for both fields. A lubricant was included in the fluid used on Field B to manage torque-and-drag issues.

Outcomes of a 2-year treat-and-extend regimen with aflibercept for diabetic macular edema

This prospective, open-label, single-arm, non-randomized clinical trial, assessed the efficacy of a 2-year treat-and-extend (T&E) regimen involving intravitreal aflibercept injection (IAI), with the longest treatment interval set to 16 weeks, and adjunct focal/grid laser in diabetic macula edema (DME) patients. We examined 40 eyes (40 adults) with fovea-involving DME from 8 Japanese centers between April 2015 and February 2017. Participants received IAI with an induction period featuring monthly injections and a subsequent T&E period featuring 8–16-week injection interval, adjusted based on optical coherence tomography findings. The primary endpoints were mean changes in the best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Thirty patients (75%) completed the 2-year follow-up. The mean BCVA and CST changed from 60.5 ± 15.6 letters and 499.2 ± 105.6 µm at baseline to 66.6 ± 17.1 letters (P = 0.217) and 315.2 ± 79.0 µm (P < 0.001), respectively, after 2 years. The treatment interval was extended to 12 and 16 weeks in 6.7% and 66.7% of patients, respectively, at the end of 2 years. The T&E aflibercept regimen with the longest treatment interval set to 16 weeks, with adjunct focal/grid laser may be a rational 2-year treatment strategy for DME.