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Cureus May 2024Introduction Persistent postoperative pain leads to impaired patient recovery and delays in discharge of patients. The aim was to compare the efficacy of 0.5%...
Introduction Persistent postoperative pain leads to impaired patient recovery and delays in discharge of patients. The aim was to compare the efficacy of 0.5% bupivacaine to two varying concentrations of ropivacaine, specifically 0.5% and 0.75%, along with fentanyl as a continuous epidural infusion in providing adequate pain relief for patients subjected to infraumbilical surgeries. Materials and methods A prospective randomized comparative study was carried out on 150 patients and was divided into three groups, namely group B, group R, and group RP. Group B indicates (0.5% bupivacaine), group R means (0.5% ropivacaine), and finally, group RP means (0.75% ropivacaine); the three groups had 50 patients each. Group B was administered an epidural infusion of bupivacaine at a concentration of 0.5%, group R was given 0.5% ropivacaine, and group RP was treated with 0.75% ropivacaine; all three groups included 40 mcg fentanyl. The duration of the motor and sensory blockade and the time needed for the first rescue analgesia after the stoppage of epidural infusion were assessed in all three groups. The data were statistically analyzed using the ANOVA, "post hoc Tukey," and chi-square tests. Results Comparison of the duration of motor and sensory blockade among all three groups showed that group RP (0.75% ropivacaine with 2 mcg/cc fentanyl) had the longest duration of 328.8 and 406 minutes, and the difference was statistically significant (p < 0.001). Comparison of the time of stoppage of epidural infusion to the requirement of first rescue analgesia showed that the group that received 0.75% ropivacaine with 40 mcg fentanyl had the highest value of 258.6 minutes and was statistically significant (p < 0.001). Conclusion Epidural intraoperative infusion of 0.75% ropivacaine with fentanyl offers better postoperative pain relief as compared to both 0.5% bupivacaine and 0.5% ropivacaine with fentanyl.
PubMed: 38827008
DOI: 10.7759/cureus.59477 -
Cureus Mar 2024Objectives An observational, retrospective, longitudinal, and analytical study aimed to evaluate the effectiveness of the erector spinae plane (ESP) block in managing...
Objectives An observational, retrospective, longitudinal, and analytical study aimed to evaluate the effectiveness of the erector spinae plane (ESP) block in managing pain in patients with vertebral fractures secondary to tumoral activity. This study included patients treated at the Pain Clinic who underwent ESP block. The objectives were to describe demographic characteristics, oncological diagnosis, vertebral fracture features, imaging techniques, medications used, and the level of ESP block. Additionally, pain levels were assessed using a numerical analog scale, and the consumption of opioid analgesic medications before and after the ESP block, during follow-up consultations, along with patient satisfaction. Methodology This retrospective, observational, and analytical study was conducted at the Pain Clinic of the National Cancer Institute of Mexico. Patients with vertebral fractures secondary to tumor activity were included, with data collected from March 2020 to September 2023. A consecutive non-probabilistic sampling method was employed, and specific inclusion and exclusion criteria were applied. Data were analyzed using descriptive statistics and the Wilcoxon signed-rank test for quantitative variables, with a significance level of p ≤ 0.05. IBM SPSS Statistics v. 26.0 (IBM Corp., Armonk, NY) software was utilized. Results A sample comprising 16 individuals was obtained, with an equal distribution between males and females. Fracture levels displayed variation, with L3 (12.5%) and T6 (12.5%) being the most prevalent. The ESP approach was primarily conducted using ultrasound (68.8%), while fluoroscopy and computed tomography were utilized in 25.0% and 6.3% of cases, respectively. Predominantly, methylprednisolone and ropivacaine (75.0%) were administered, with phenol used in 18.8% and a combination of methylprednisolone and bupivacaine in 6.3%. Patient satisfaction levels were reported at 81.3% (satisfied or very satisfied). Statistically significant disparities were noted between baseline and incidental pain reduction and oral opioid equivalent dosage in milligrams of morphine per day (MME/day) before and after ESP block (p ≤ 0.05). Conclusions This research provides promising preliminary evidence supporting the effectiveness of ESP block for pain management in vertebral fractures secondary to tumoral activity, enhancing the quality and safety of care for oncology patients. The absence of complications, significant improvement in pain, and reduction in opioid dependence underscore the clinical relevance of this therapeutic approach. An observational, retrospective, longitudinal, and analytical study aimed to evaluate the effectiveness of the ESP block in managing pain in patients with vertebral fractures secondary to tumoral activity. This study included patients treated at the Pain Clinic who underwent ESP block. The objectives were to describe demographic characteristics, oncological diagnosis, vertebral fracture features, imaging techniques, medications used, and the level of ESP block. Additionally, pain levels were assessed using a numerical analogue scale, and the consumption of opioid analgesic medications before and after the ESP block, during follow-up consultations, along with patient satisfaction.
PubMed: 38586726
DOI: 10.7759/cureus.55599 -
Journal of the American Heart... Jul 2023Background Splanchnic nerve modulation (SNM) is an emerging procedure to reduce cardiac filling pressures in heart failure. Although the main contributor to reduction in... (Clinical Trial)
Clinical Trial
Background Splanchnic nerve modulation (SNM) is an emerging procedure to reduce cardiac filling pressures in heart failure. Although the main contributor to reduction in cardiac preload is thought to be increased venous capacitance in the splanchnic circulation, supporting evidence is limited. We examined changes in venous capacitance surrogates pre- and post-SNM. Methods and Results This is a prespecified analysis of a prospective, open-label, single-arm interventional study evaluating the effects of percutaneous SNM with ropivacaine in chronic heart failure with elevated filling pressures at rest and with exercise. Patients underwent cardiopulmonary exercise testing with invasive hemodynamic assessment pre- and post-SNM. Blood pressure changes with modified Valsalva maneuver and hemoconcentration, pre- and post-SNM were compared using a repeated measures model. Inferior vena cava diameter and collapsibility (>50% decrease in size with inspiration), and presence of bendopnea pre- and post-SNM were also compared. Fifteen patients undergoing SNM (age 58 years, 47% women, 93% with left ventricular ejection fraction ≤35%) were included. After SNM, changes in systolic blood pressure during Valsalva (peak-to-trough) were greater (41 versus 48 mm Hg, =0.025). Exercise-induced hemoconcentration was unchanged (0.63 versus 0.43 g/dL, =0.115). Inferior vena cava diameter was reduced (1.59 versus 1.30 cm, =0.034) with higher collapsibility (33% versus 73%, =0.014). Bendopnea was less (47% versus 13%, =0.025). Conclusions SNM resulted in increased venous capacitance, associated decreased cardiac preload, and decreased bendopnea. Minimally invasive measures of venous capacitance could serve as markers of successful SNM. Long-term effects of SNM on venous capacitance warrant further investigation for heart failure management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03453151.
Topics: Female; Humans; Male; Middle Aged; Heart Failure; Prospective Studies; Splanchnic Nerves; Stroke Volume; Ventricular Function, Left
PubMed: 37449573
DOI: 10.1161/JAHA.122.028780 -
European Review For Medical and... Nov 2023The aim of this study was to compare the efficacy and safety of ultrasound-guided stellate ganglion block (SGB) with different volumes of 0.375% ropivacaine on sleep... (Comparative Study)
Comparative Study
OBJECTIVE
The aim of this study was to compare the efficacy and safety of ultrasound-guided stellate ganglion block (SGB) with different volumes of 0.375% ropivacaine on sleep quality in patients with insomnia.
PATIENTS AND METHODS
A total of 80 patients who were selected to undergo SGB for the treatment of insomnia were enrolled. The patients were divided into saline control group, and low-volume (4 mL), medium-volume (6 mL), and high-volume (8 mL) ropivacaine injection groups according to the random table method. The treatment included 7 blocks with once every three days. The left and right stellate ganglions are alternately blocked. The onset and maintenance time of Horner syndrome, the degree of carotid artery dilation and blood flow velocity before and 20 minutes after the first block, the occurrence of complications such as drug crossing of the midline of the artery and hoarse throat were recorded, and the improvement of sleep disorders was evaluated with the Pittsburgh Sleep Quality Index Scale.
RESULTS
Horner syndrome occurred in 100% of all volumes of ropivacaine block. The ipsilateral internal carotid artery was dilated and was accompanied by increased blood flow. The degree of dilation and increase in blood flow were not affected by the volumes of drug injection. There were no serious complications in any group, but the incidences of hoarseness and dysphagia were higher in the medium- and high-volume groups than those in the low-volume group (all p < 0.05). Compared with the low- and medium-volume groups, the high-volume group had a faster onset of action, longer maintenance time, and the highest chance of the drug crossing the artery (all p < 0.05). Compared to those before the pre-block and in the control groups, insomnia was improved in all volume groups after the block with nonsignificant intergroup differences.
CONCLUSIONS
4 mL of 0.375% ropivacaine for ultrasound-guided SGB is sufficient to improve the sleep quality of insomnia patients, whose overall risk is lower than block with 6 mL or 8 mL of ropivacaine.
Topics: Humans; Anesthetics, Local; Autonomic Nerve Block; Horner Syndrome; Ropivacaine; Sleep Initiation and Maintenance Disorders; Sleep Quality; Stellate Ganglion
PubMed: 37975347
DOI: 10.26355/eurrev_202311_34298 -
PloS One 2024Effective labor pain management is crucial for parturient well-being, as it can improve the delivery experience of pregnant women and reduce anxiety and tension. This... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Effective labor pain management is crucial for parturient well-being, as it can improve the delivery experience of pregnant women and reduce anxiety and tension. This systematic review and network meta-analysis compared the efficacy and safety of various analgesics, classified by drug category and individual treatment methods, for labor pain control.
METHODS
A comprehensive literature search was conducted in Pubmed, EMBASE, Cochrane Library, and Web of Science databases. All searches commenced from the database's inception to the date of the literature search (May 31, 2023). The Cochrane Risk of Bias 2 tool assessed study bias risk. Network meta-analyses using a random-effects model and odds ratios (ORs) with 95% confidence intervals (CIs) were performed.
RESULTS
Fifteen randomized controlled trials evaluating analgesic interventions in ASA I or II parturients were included. Combination therapies (OR: 5.81; 95% CI, 3.76-7.84; probability: 60%) and non-opioid analgesics (OR: 5.61; 95% CI, 2.91-8.30; probability: 39.2%) were superior to placebo for labor pain relief. Specifically, dexmedetomidine/ropivacaine/sufentanil (OR: 7.32; 95% CI, 2.73-11.89; probability: 40.6%) and dexmedetomidine/ropivacaine (OR: 6.50; 95% CI, 2.51-10.33; probability: 11.9%) combinations, bupivacaine/fentanyl and ropivacaine/sufentanil combinations, and remifentanil monotherapy showed improved analgesic efficacy versus placebo. Dexmedetomidine/ropivacaine reduced parturient nausea and vomiting versus alternatives.
CONCLUSION
Non-opioids, opioids and combinations thereof effectively relieved labor pain. In addition, dexmedetomidine/ropivacaine combination demonstrated analgesic efficacy and lower nausea and vomiting incidence.
Topics: Humans; Pregnancy; Female; Analgesics, Opioid; Labor Pain; Network Meta-Analysis; Pain Management; Analgesics, Non-Narcotic; Randomized Controlled Trials as Topic; Dexmedetomidine
PubMed: 38889108
DOI: 10.1371/journal.pone.0303174 -
Journal of Pain Research 2023Multiple regional nerve blocks proved no additional benefit in total laparoscopic hysterectomy in multimodal analgesia, as postoperative pain may mainly originate from...
PURPOSE
Multiple regional nerve blocks proved no additional benefit in total laparoscopic hysterectomy in multimodal analgesia, as postoperative pain may mainly originate from the vaginal cuff. Theoretically, caudal block can relieve pain from the vaginal cuff by a sacral spinal nerve block. We aimed to verify whether a caudal block with ropivacaine and morphine can achieve an analgesic effect without additional adverse effects after a total laparoscopic hysterectomy.
PATIENTS AND METHODS
Forty-eight patients undergoing total laparoscopic hysterectomy were randomly allocated to receive preoperative caudal block with 20 mL of mixture including 0.25% ropivacaine and 2 mg morphine (caudal block group) or sham block (sham group). The primary outcome was the postoperative 24 h cumulative sufentanil consumption.
RESULTS
Median (IQR) sufentanil consumption in the first 24 postoperative hours of the caudal block group and the sham group was 0.00 (0.00 to 0.05) μg/kg vs 0.13 (0.04 to 0.21) μg/kg, respectively, p < 0.001. The majority of patients felt that visceral pain was more intense than incisional pain at 1, 6, 12, and 24 h post-surgery in the sham group (95.8% at 1 h, 95.8% at 6 h, 95.8% at 12 h, and 75% at 24 h post-surgery). Compared to the sham group, the caudal block reduced visceral pain scores at rest and during movement at 1 h (p < 0.001), 6 h (p < 0.001), 12 h (p < 0.001), and 24 h (p < 0.001) post-surgery. Intraoperative remifentanil consumption was significantly lower in the caudal block group than in the sham group (p = 0.004). There were no significant differences in other secondary outcomes between the two groups.
CONCLUSION
A caudal block with ropivacaine and morphine could provide a satisfactory analgesic effect for 24 h postoperatively without additional adverse effects after total laparoscopic hysterectomy.
PubMed: 37817757
DOI: 10.2147/JPR.S426820 -
EClinicalMedicine Sep 2023Convincing clinical evidence regarding completely opioid-free postoperative pain management using erector spinae plane block (ESPB) in patients undergoing open major...
Analgesic efficacy of an opioid-free postoperative pain management strategy versus a conventional opioid-based strategy following open major hepatectomy: an open-label, randomised, controlled, non-inferiority trial.
BACKGROUND
Convincing clinical evidence regarding completely opioid-free postoperative pain management using erector spinae plane block (ESPB) in patients undergoing open major hepatectomy (OMH) is lacking. Herein, we aimed to compare the postoperative analgesic efficacy of the visualised continuous opioid-free ESPB (VC-ESPB) and conventional intravenous opioid-based postoperative pain management in hepatocellular carcinoma (HCC) patients undergoing OMH.
METHODS
This open-label, randomised, controlled, non-inferiority trial enrolled patients with HCC undergone open major hepatectomy in Fujian Provincial Hospital and compared the postoperative analgesic efficacy of VC-ESPB (VC-ESPB group) and conventional intravenous opioid-based pain management regimen (conventional group). Patients were randomly assigned (1:1) to VC-ESPB group and conventional group. Patients were not masked to treatment allocation. The VC-ESPB group was treated with intermittent injections of 0.25% ropivacaine (bilateral, 30 mL each side) given every 12 h through catheters placed in the space of erector spinae and an opioid-free intravenous pump (10-mg tropisetron diluted to 100 mL with 0.9% normal saline [NS]) for postoperative pain management. The conventional group did not receive ESPB and was treated with a conventional intravenous opioid-based pump (2.5-μg/kg sufentanil and 10-mg tropisetron diluted to 100 mL with 0.9% NS). Patients in the VC-ESPB group underwent magnetic resonance imaging (MRI) to identify local anaesthetic diffusion after ESPB was performed under ultrasound guidance. The primary outcome was postoperative analgesic efficacy, which was indicated by the cumulative area under the curve (AUC) of the pain visual analogue scale scores (range, 0-10; a higher score indicates more pain) obtained at rest and at movement until 48 h postoperatively after leaving the post-anaesthesia care unit (PACU). Herein, an AUC of 26.5 was set as the noninferiority margin, which needed to be satisfied for both cumulative AUC at rest and cumulative AUC at movement. Per protocol participants were included in primary and safety analyses. This trial was registered with ChiCTR.org.cn (ChiCTR1900026583).
FINDINGS
Between October 30, 2019, and May 1, 2023, 106 patients were enrolled and randomly assigned to the VC-ESPB group (n = 53) and the conventional group (n = 53). After the dropout (n = 5), a total of 101 patients (VC-ESPB group, n = 50; conventional group, n = 51) were analysed. Both the level of cumulative AUC (at rest: 160.08 ± 38.00 164.94 ± 31.00; difference [90% CI], -4.861 [-16.308, 6.585]) and cumulative AUC (at movement: 209.64 ± 28.98 212.59 ± 33.11; difference [90% CI], -2.948 [-13.236, 7.339]) were similar between the VC-ESPB and control groups within the first postoperative 48 h. The upper limit of the 90% CIs for the difference in cumulative ACUP at rest and at movement did not reach the upper inferiority margin (26.5). During the first postoperative 48 h, the rate of nonsteroidal anti-inflammatory drug rescue analgesia was similar between the VC-ESPB group and conventional group (n = 16, 32.0% n = 11, 21.6%; = 0.236). Treatment-related death was not observed in the VC-ESPB group (n = 0, 0%) and conventional group (n = 0, 0%). In VC-ESPB group, local site paralysis (n = 1, 2.0%) was observed in one patient and rash (n = 1, 2.0%) was observed in another patient. One patient in the conventional group was observed with rash preoperatively (n = 1, 2.0%). The VC-ESPB group had significantly lower rates of postoperative nausea (n = 2, 4.0%, n = 9, 17.6%, = 0.028), vomiting (n = 1, 2.0% n = 8, 15.7%, = 0.031) and lower incidence of major complications (n = 4, 8.0% n = 6, 11.8%; = 0.033).
INTERPRETATION
This study demonstrates the noninferiority of VC-ESPB when compared with the conventional opioid-based approach for postoperative pain management after OMH, suggesting that it is feasible to achieve opioid-free postoperative pain management for OMH.
FUNDING
The Joint Funds for the Innovation of Science and Technology, Fujian Province, China; the Youth Scientific Research Project of Fujian Provincial Health Commission; the Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare; and the Key Clinical Specialty Discipline Construction Program of Fujian, China.
PubMed: 37692074
DOI: 10.1016/j.eclinm.2023.102188 -
European Journal of Medical Research Apr 2024There have been no reports on the successful implementation of stellate ganglion block (SGB) in mice.
BACKGROUND
There have been no reports on the successful implementation of stellate ganglion block (SGB) in mice.
OBJECTIVES
This study aims to investigate a new method for implementing SGB in mice by placing them in a supine position with abducted upper limbs and touching the trachea and sternoclavicular joint with the hand.
METHODS
Fifty BABL/C mice, 8-10 weeks, were selected and randomly divided into four groups: control group (n = 5); SGB-R group (n = 15); SGB-L group (n = 15); and SGB-L + R (group n = 15). SGB was administered with 0.15% ropivacaine solution in a volume of 0.1 mL. The control group received equal volumes of saline. Horner's syndrome, heart rate, and complications such as brachial plexus block, vascular injury, pneumothorax, local anesthetic toxicity, and death were observed.
RESULTS
Horner's syndrome developed in 100% of SGB surviving mice; no difference was seen in the time to onset (100.4 ± 13.4 vs 96.7 ± 12.4, mean ± SD, seconds) and duration (264.1 ± 40.5 vs 296.3 ± 48.0, mean ± SD, min) of Horner's syndrome in the left and right SGB (P > 0.05). Compared with the control group (722 [708-726], median [IQR], bpm), the heart rate was significantly slowed down in the right SGB (475 [451.5-491], median [IQR], bpm) (P < 0.05). While the heart rate was slowed down after performing the left SGB, the difference was not statistically significant (P > 0.05). The overall complication rate was 18.4%, with a brachial plexus block rate of 12.3%, a vascular injury rate of 4.6%, and a mortality rate of 1.5%, as well as no local anesthetic toxicity (includes bilateral implementation of SGB) or pneumothorax manifestations were found.
CONCLUSIONS
This method allows for the successful implementation of SGB in a mouse model.
Topics: Animals; Mice; Anesthetics, Local; Horner Syndrome; Pneumothorax; Stellate Ganglion; Vascular System Injuries
PubMed: 38576012
DOI: 10.1186/s40001-024-01815-6 -
European Journal of Anaesthesiology Sep 2023Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively. (Meta-Analysis)
Meta-Analysis
The postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve and field blocks: A systematic review and meta-analysis, with trial sequential analysis.
BACKGROUND
Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively.
OBJECTIVES
To compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks.
DESIGN
A systematic review and meta-analysis with trial sequential analysis.
DATA SOURCES
MEDLINE, Embase and Web of Science, among others, up to June 2022.
ELIGIBILITY CRITERIA
We retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h.
RESULTS
Twenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I2 = 87%, P < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I2 = 82%, P = 0.001 and -0.7 (-1.1 to -0.3), I2 = 80%, P < 0.001, respectively. There were no differences in interval morphine consumption at 24 h ( P = 0.15), 48 h ( P = 0.15) and 72 h ( P = 0.07). The quality of evidence was moderate.
CONCLUSIONS
There is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.
Topics: Humans; Anesthetics, Local; Pain, Postoperative; Bupivacaine; Analgesics; Morphine; Peripheral Nerves; Analgesics, Opioid
PubMed: 37038770
DOI: 10.1097/EJA.0000000000001833 -
Anesthesiology and Pain Medicine Feb 2024Spinal anesthesia is considered to be the safest method of anesthesia for cesarean sections in patients with preeclampsia. Patients with preeclampsia are at an increased...
BACKGROUND
Spinal anesthesia is considered to be the safest method of anesthesia for cesarean sections in patients with preeclampsia. Patients with preeclampsia are at an increased risk of experiencing severe hypotension following spinal anesthesia, which could have more profound and deleterious effects on both the fetus and the mother. However, bupivacaine, the most commonly used drug, can induce severe hypotension even at low doses. The purpose of this study is to minimize post-spinal hypotension in both the mother and the fetus.
OBJECTIVES
To determine and compare the reduction in hypotension following spinal anesthesia in patients with preeclampsia between the ropivacaine and bupivacaine groups.
METHODS
In a randomized clinical trial, a total of 90 parturients with preeclampsia undergoing spinal anesthesia were enrolled and randomly divided into 2 groups: One receiving ropivacaine and the other receiving bupivacaine. The dose of spinal ropivacaine was 15 mg of a 0.5% solution, and the dose of bupivacaine was also 15 mg of a 0.5 % solution. Hemodynamic parameters, including systolic and diastolic blood pressure and heart rate, were recorded following the administration of spinal anesthesia. Pain scores and the time until the return of motor movement were also documented.
RESULTS
For statistical analysis, the -test, Chi-square, and ANOVA tests were utilized to compare the groups. Demographic variables, including maternal age, gestational age, parity, and gravidity, were not significantly different between the 2 groups. The trend of mean systolic blood pressure (SBP) was significantly lower in the bupivacaine group compared to the ropivacaine group at all measured time points in the study (P < 0.05). The amount of ephedrine used after spinal anesthesia was significantly different at 2 and 4 minutes in the ropivacaine group compared to the bupivacaine group (P = 0.012, P = 0.025). Post-operative pain scores at 1 hour in recovery were not significantly different between the ropivacaine and bupivacaine groups (P = 0.015). The time to knee movement was also significantly shorter in the ropivacaine group compared to the bupivacaine group (P < 0.001).
CONCLUSIONS
Ropivacaine reduces the incidence of hypotension in spinal anesthesia compared to bupivacaine for cesarean section in patients with preeclampsia. This is attributed to a lower occurrence of spinal-induced hypotension, improved hemodynamic control, reduced ephedrine usage, and faster patient ambulation. A future study could focus on investigating different dosages of both drugs with a larger number of participants.
PubMed: 38737589
DOI: 10.5812/aapm-142646