Changes in Initial Opioid Prescribing Practices After the 2016 Release of the CDC Guideline for Prescribing Opioids for Chronic Pain.

Importance: The Centers for Disease Control and Prevention (CDC) released the "Guideline For Prescribing Opioids For Chronic Pain" (hereafter, CDC guideline) in 2016, but its association with prescribing practices for patients who are opioid naive is unknown. Objective: To estimate changes in initial prescribing rates, duration, and dosage practices to patients who are opioid naive after the release of the CDC guideline. Design, Setting, and Participants: This cohort study used 6 sequential cohorts to estimate preguideline trends in prescribing among patients who were opioid naive, project that trend forward, and compare it with postguideline prescribing practices. Participants included commercially insured adults without current cancer or hospice care diagnoses and with no past-year opioid claims in the US from 2011 to 2017. All adjusted models were controlled for patient demographics and state-fixed effects. Data were analyzed from January 2020 to May 2021. Exposures: The release of the CDC guideline. Main Outcomes and Measures: Indicators of any opioid prescription fills during a 9-month period, the number of days' supply of the initial prescription, and the binary indicator of whether the initial prescription was for 50 or more morphine milligram equivalents (MMEs) per day. Results: There were 12 870 612 eligible unique patients across cohorts (mean [SD] age in 2016, 51.2 [18.7] years; 6 553 458 [50.9%] women); and the mean (SD) age of the cohorts increased annually, from 48.7 (17.9) years in the April 2011 to December 2012 cohort to 51.9 (19.2) years in the April 2016 to December 2017 cohort. The postguideline prescribing prevalence was 532 962 of 5 834 088 individuals (9.1%), which exceeded that projected from the preguideline trend, estimated at 9.0% (95% CI, 9.0%-9.1%). Among patients receiving prescriptions during follow-up, adjusted mean days' supply was 4.7% (95% CI, 4.3%-5.1%) lower in the first year after release of the guideline and 9.8% (95% CI, 9.3%-10.3%) lower in the second year after release, compared with the expected rate from the preguideline trend. The adjusted odds of receiving a high-dose (ie, ≥50 MME/d) initial prescription were lower in the first year (odds ratio, 0.97; 95% CI, 0.96-0.98) and in the second year (odds ratio, 0.94; 95% CI, 0.93-0.96) after the release of the CDC guideline compared with the odds expected from the preguideline trend. Conclusions and Relevance: This cohort study found that patients who were opioid naive continued to initiate opioid therapy after the release of opioid prescribing guidelines by the CDC, but trends in prescribing duration reversed and decreased, after increasing in each of 4 preguideline cohorts examined. High-dose prescribing rates were already decreasing, but those trends accelerated after the CDC guideline release. These results suggest that nonmandatory, evidence-based guidelines from trusted sources were associated with prescribing practices. Guideline-concordant care has potential to improve pain management and reduce opioid-related harms.

Multiple-Choice versus Open-Ended Questions in Advanced Clinical Neuroanatomy: Using a National Neuroanatomy Assessment to Investigate Variability in Performance Using Different Question Types.

Methods of assessment in anatomy vary across medical schools in the United Kingdom (UK) and beyond; common methods include written, spotter, and oral assessment. However, there is limited research evaluating these methods in regards to student performance and perception. The National Undergraduate Neuroanatomy Competition (NUNC) is held annually for medical students throughout the UK. Prior to 2017, the competition asked open-ended questions (OEQ) in the anatomy spotter examination, and in subsequent years also asked single best answer (SBA) questions. The aim of this study is to assess medical students' performance on, and perception of, SBA and OEQ methods of assessment in a spotter style anatomy examination. Student examination performance was compared between OEQ (2013-2016) and SBA (2017-2020) for overall score and each neuroanatomical subtopic. Additionally, a questionnaire explored students' perceptions of SBAs. A total of 631 students attended the NUNC in the studied period. The average mark was significantly higher in SBAs compared to OEQs (60.6% vs. 43.1%, P < 0.0001)-this was true for all neuroanatomical subtopics except the cerebellum. Students felt that they performed better on SBA than OEQs, and diencephalon was felt to be the most difficult neuroanatomical subtopic (n = 38, 34.8%). Students perceived SBA questions to be easier than OEQs and performed significantly better on them in a neuroanatomical spotter examination. Further work is needed to ascertain whether this result is replicable throughout anatomy education.

Assessment of miniaturized ultrasound-powered implants: an in vivo study.

OBJECTIVE: Therapeutic applications of implantable active medical devices have improved the quality of patient life. Numerous on-going research in the field of neuromodulation and bioelectronic medicine are exploring the use of these implants for treating diseases and conditions. Miniaturized implantable medical devices that are wirelessly powered by ultrasound (US) can be placed close to the target sites deep inside the body for effective therapy with less invasiveness. In this study, we assessed the long-term in vivo performance of miniaturized US powered implants (UPI) using a rodent model. APPROACH: Prototype UPI devices were implanted in rodents and powered wirelessly using an unfocused US transmitter over 12 weeks, and the corresponding device output was recorded. Structural integrity of UPI before and after implantation was studied using scanning electron microscopy (SEM). We also conducted qualitative histological assessment of skin and muscle surrounding the UPI and compared it to naïve control and US exposed tissues. MAIN RESULTS: We found that it is feasible to power UPI devices wirelessly with US over long-term. The encapsulation of UPIs did not degrade over time and the tissues surrounding the UPI were comparable to both naïve control and US exposed tissues. SIGNIFICANCE: This study is the first to assess the long-term performance of miniaturized UPI devices using a rodent model over 12-weeks. The set of tests used in this study can be extended to assess other US-powered miniaturized implants.

Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences.

Exposure of the brain to high-intensity stress waves creates the potential for long-term functional deficits not related to thermal or cavitational damage. Possible sources of such exposure include overpressure from blast explosions or high-intensity focused ultrasound (HIFU). While current ultrasound clinical protocols do not normally produce long-term neurological deficits, the rapid expansion of potential therapeutic applications and ultrasound pulse-train protocols highlights the importance of establishing a safety envelope beyond which therapeutic ultrasound can cause neurological deficits not detectable by standard histological assessment for thermal and cavitational damage. In this study, we assessed the neuroinflammatory response, behavioral effects, and brain micro-electrocorticographic (µECoG) signals in mice following exposure to a train of transcranial pulses above normal clinical parameters. We found that the HIFU exposure induced a mild regional neuroinflammation not localized to the primary focal site, and impaired locomotor and exploratory behavior for up to 1 month post-exposure. In addition, low frequency (δ) and high frequency (ß, γ) oscillations recorded by ECoG were altered at acute and chronic time points following HIFU application. ECoG signal changes on the hemisphere ipsilateral to HIFU exposure are of greater magnitude than the contralateral hemisphere, and persist for up to three months. These results are useful for describing the upper limit of transcranial ultrasound protocols, and the neurological sequelae of injury induced by high-intensity stress waves.

Assessment of Enhanced Thermal Effect Due to Gold Nanoparticles during MR-Guided High-Intensity Focused Ultrasound (HIFU) Procedures Using a Mouse-Tumor Model.

An in vivo study was conducted using a mouse tumor model, to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers. Tumors were grown using melanoma tumor cells (B16/F10) subcutaneously on the right flanks of mice (C57Bl/6J). Physiologically relevant concentrations (0 and 0.125%) of gNPs were directly injected into the tumors. Sonications at acoustic powers of 10 and 30 W were performed for a duration of 16 s inside a magnetic-resonance system. Temperature increases and lesion volumes were calculated and compared for procedures with and without gNPs. Histopathology study was conducted using a cleaved caspase 3 antibody and hematoxylin and eosin staining after removing the tumors from the mice. For an acoustic power of 30 W, end-of-sonication temperature increases of 25.4 ± 3.8 °C (0% gNP) and 42.2 ± 4.6 °C (0.125% gNP) were measured. Using cleaved caspase 3 antibody, it was observed that more than 1% of nuclei are affected in the case of 0.125% and 30 W but only 0.01% of nuclei are affected in the 0% case. For 30 W and a gNP concentration of 0.125%, a lesion volume of 0.33 ± 0.22 mm3 was obtained, while no lesion was observed without gNP's.

Assessment of Gold Nanoparticle-Mediated-Enhanced Hyperthermia Using MR-Guided High-Intensity Focused Ultrasound Ablation Procedure.

High-intensity focused ultrasound (HIFU) has gained increasing popularity as a noninvasive therapeutic procedure to treat solid tumors. However, collateral damage due to the use of high acoustic powers during HIFU procedures remains a challenge. The objective of this study is to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers, thereby reducing the likelihood of collateral damage. Phantoms containing tissue-mimicking material (TMM) and physiologically relevant concentrations (0%, 0.0625%, and 0.125%) of gNPs were fabricated. Sonications at acoustic powers of 10, 15, and 20 W were performed for a duration of 16 s using an MR-HIFU system. Temperature rises and lesion volumes were calculated and compared for phantoms with and without gNPs. For an acoustic power of 10 W, the maximum temperature rise increased by 32% and 43% for gNPs concentrations of 0.0625% and 0.125%, respectively, when compared to the 0% gNPs concentration. For the power of 15 W, a lesion volume of 0, 44.5 ± 7, and 63.4 ± 32 mm3 was calculated for the gNPs concentration of 0%, 0.0625%, and 0.125%, respectively. For a power of 20 W, it was found that the lesion volume doubled and tripled for concentrations of 0.0625% and 0.125% gNPs, respectively, when compared to the concentration of 0% gNPs. We conclude that gNPs have the potential to locally enhance the heating and reduce damage to healthy tissue during tumor ablation using HIFU.

The FCTC's evidence-based policies remain a key to ending the tobacco epidemic.

With the dramatic reduction in tobacco use in developed nations, a growing number of public health leaders have called for what they describe as an 'endgame' strategy and the need for new policies to achieve that goal. In moving forward, it is important not to lose sight of the policies that have been the underpinnings of successful tobacco reduction efforts to date, nor should we allow any discussion of new strategies to decrease the emphasis on fully implementing the Framework Convention on Tobacco Control (FCTC). Any 'endgame' strategy should carefully build on the evidence-based strategies that have proven so effective and not be based on the false premise that the policies embraced by the FCTC are incapable of reducing tobacco use far below current levels or to a level where tobacco caused disease is no longer a major public health problem.

A theoretical assessment of a thermal technique to measure acoustic power radiated by ultrasound transducers.

The parameters affecting the temperature rise in an insonified absorber are studied computationally. Finite-element and analytical solutions are obtained for the transient energy equation in a cylindrical absorber. When the ultrasound beam radius is less than the radius of the absorber, the temperature field is seen to be considerably more complex than when the absorber cross section is uniformly heated. Circumstances in which power predictions based upon uniform heating would result in appreciable error are identified. The rise time required to achieve equilibrium is studied as a function of operational parameters, including absorber geometry and thermal properties as well as ultrasound beamwidth and frequency. The rise time is seen to increase approximately as the square of the absorber length, while optimized temperature rise increases linearly with absorber length, demonstrating a tradeoff in ultrasound power determination via equilibrium temperature measurements: longer lengths produce higher sensitivity, but also longer times before measurements can be made. A transient technique that may bypass this tradeoff is suggested.