Prepacked Take-Home Analgesia in Outpatient Hand Surgery Reduces Opioid Dispensation.

BACKGROUND: Adequate postoperative pain treatment is important for quality of life, patient satisfaction, rehabilitation, function, and total opioid consumption, and might lower both the risk of chronic postoperative pain and the costs for society. Prolonged opioid consumption is a well-known risk factor for addiction. Previous studies in upper extremity surgery have shown that total opioid consumption is a third of the amount prescribed, which can be explained by package size. The aim of this study was to examine whether implementation of prepacked takehome analgesia bags reduced the quantity of prescribed and dispensed opioids. MATERIAL AND METHODS: We introduced prepacked take-home analgesia bags for postoperative pain treatment in outpatient surgery. The bags came in two sizes, each containing paracetamol, etoricoxib, and oxycodone. The first 147 patients who received the prepacked analgesia bags were included in the study, and received a questionnaire one month after surgery covering self-assessed pain (visual analog scale of 0-10) and satisfaction (0-5), as well as opioid consumption. Prescription data after introducing the analgesia bags were compared with data before the bags were introduced. RESULTS: Of the 147 patients included in the study, 58 responded. Compared to standard prescription (small bag group: 14 oxycodone immediate release capsules (5 mg), large bag group: additional 28 oxycodone extended release tablets (5 mg), based on the smallest available package), the patients in the small analgesia bag group received 50% less oxycodone and 67% less for the large bag group. Patients with small bags consumed a median of 0.0 mg oxycodone and those with large bags consumed a median of 25.0 mg oxycodone. The median satisfaction was 5.0 (range: 2-5) and the median pain score was acceptable at the first postoperative day. Prescription data showed a significant reduction of 60.0% in the total amount of prescribed opioids after the introduction of prepacked analgesia bags. CONCLUSIONS: The introduction of prepacked analgesia bags dramatically reduced the quantity of opioids prescribed after outpatient hand surgery. Patient satisfaction was high and the postoperative pain level was acceptable. KEY WORDS: analgesia, hand surgery, opioids, outpatint surgery, wrist surgery.

Comparison of analgesic effectiveness between nefopam and propacetamol in living kidney donors following rectus sheath block after hand-assisted living donor nephrectomy: a prospective, randomized controlled trial.

BACKGROUND: Nefopam and propacetamol are the most commonly used analgesics in postoperative multimodal analgesic regimens. Distinct mechanisms are involved in each drug's anti-nociceptive effects. No studies have compared pain relief efficacy between the two drugs in patients undergoing transplantation surgery. Here, we investigated whether the administration of nefopam or propacetamol to healthy living kidney donors who underwent rectus sheath block (RSB) for parietal pain could reduce the subsequent opioid dose necessary to produce adequate analgesia. METHODS: This prospective, randomized controlled trial included 72 donors undergoing elective hand-assisted living donor nephrectomy into two groups: propacetamol (n = 36) and nefopam (n = 36). Intraoperative RSB was performed in all enrolled donors. The primary outcome was the total volume of intravenous opioid-based patient-controlled analgesia (PCA) used on postoperative day 1 (POD 1). Additionally, the Numeric Rating Scale scores for flank (visceral) and umbilicus (parietal) pain at rest and during coughing were compared, and the Korean adaptation of the Quality of Recovery-15 Questionnaire (QoR-15 K) was evaluated on POD 1. RESULTS: Both groups had similar preoperative and intraoperative characteristics. On POD 1, the total amount of PCA infusion was significantly lower in the nefopam group than in the propacetamol group (44.5 ± 19.3 mL vs. 70.2 ± 29.0 mL; p < 0.001). This group also reported lower pain scores at the flank and umbilical sites and required fewer rescue doses of fentanyl in the post-anesthesia care unit. However, pain scores and fentanyl consumption in the ward were comparable between groups. The QoR-15 K scores were similar between groups; there were substantial improvements in breathing, pain severity, and anxiety/depression levels in the nefopam group. The incidences of postoperative complications, including sweating and tachycardia, were similar between groups. CONCLUSION: Compared with propacetamol, nefopam provides a greater analgesic effect for visceral pain and enhances the effects of blocks that reduce the opioid requirement in living kidney donors with parietal pain managed by RSB. TRIAL REGISTRATION: The trial was registered prior to patient enrollment in the clinical trial database using the Clinical Research Information Service (registration no. KCT0007351 , Date of registration 03/06/2022).

Use of electronic health record data to examine administrations of pro re nata analgesics during hip fracture post-acute care.

PURPOSE: Medications prescribed to older adults in US skilled nursing facilities (SNF) and administrations of pro re nata (PRN) "as needed" medications are unobservable in Medicare insurance claims. There is an ongoing deficit in our understanding of medication use during post-acute care. Using SNF electronic health record (EHR) datasets, including medication orders and barcode medication administration records, we described patterns of PRN analgesic prescribing and administrations among SNF residents with hip fracture. METHODS: Eligible participants resided in SNFs owned by 11 chains, had a diagnosis of hip fracture between January 1, 2018 to August 2, 2021, and received at least one administration of an analgesic medication in the 100 days after the hip fracture. We described the scheduling of analgesics, the proportion of available PRN doses administered, and the proportion of days with at least one PRN analgesic administration. RESULTS: Among 24 038 residents, 57.3% had orders for PRN acetaminophen, 67.4% PRN opioids, 4.2% PRN non-steroidal anti-inflammatory drugs, and 18.6% PRN combination products. The median proportion of available PRN doses administered per drug was 3%-50% and the median proportion of days where one or more doses of an ordered PRN analgesic was administered was 25%-75%. Results differed by analgesic class and the number of administrations ordered per day. CONCLUSIONS: EHRs can be leveraged to ascertain precise analgesic exposures during SNF stays. Future pharmacoepidemiology studies should consider linking SNF EHRs to insurance claims to construct a longitudinal history of medication use and healthcare utilization prior to and during episodes of SNF care.

Recommended dosages of analgesic and sedative drugs in intensive care result in a low incidence of potentially toxic blood concentrations.

Background: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated. Methods: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS). Results: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations. Conclusion: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.

Can Multimodal Analgesia Reduce Postoperative Opioid Consumption in Patients Undergoing Shoulder Arthroscopy? A Retrospective Study.

AIM: The aim of this study was to investigate whether multimodal analgesia can decrease postoperative opioid usage in patients undergoing shoulder arthroscopy. METHODS: Patients diagnosed with subacromial impingement syndrome who underwent acromioplasty at our institution between October 2022 and November 2023 were retrospectively analyzed. Patients were divided into an observation group and a control group based on postoperative pain management methods. The control group received intravenous self-controlled electronic analgesia (sufentanil injection 1 µg/kg + butorphanol injection 4 mg + 0.9% NaCl injection to 100 mL), while the observation group received multimodal analgesia (ropivacaine subacromial pump 3 mL/h, combined with oral celecoxib and acetaminophen). Visual Analog Scale (VAS) scores were recorded preoperatively and at various postoperative time points, and opioid usage, length of hospital stay, and analgesia-related complications within 1 week postoperatively were compared between groups. The 36-item Short Form Health Survey (SF-36) scores and the Constant-Murley score (CMS), were also assessed 1 day and 1 week after treatment. RESULTS: One hundred thirty-two patients were included in the study, 66 in the observation group and 66 in the control group. In the control group, there were 46 males and 20 females, with a mean age of 55.47 ± 11.42 years and in the observation group 44 males and 22 females, with a mean age of 56.13 ± 12.19 years The observation group consistently reported significantly lower pain intensity compared to the control group at 8 h (T1), 24 (T2), and 48 h (T3) after surgery (p < 0.05). Additionally, the observation group exhibited significantly lower opioid usage and complication rates compared to the control group (p < 0.05). SF-36 scores and CMS scores were significantly higher in the observation group 1 week after treatment compared to the control group (p < 0.05). CONCLUSIONS: Following shoulder arthroscopy, multimodal analgesia effectively reduces opioid consumption, lowers complication rates, and provides effective short-term pain relief. This approach carries significant implications for improving patient outcomes.

[Actual Access and Usage of Antipyretic Analgesics before and after COVID-19 Vaccination: Pharmacist's Roles in Promoting Proper Use of Medicines during the Infodemic].

An overwhelming surge of information regarding preparedness for postvaccination side effects had caused widespread confusion approximately since April 2021, when the coronavirus disease 2019 (COVID-19) vaccination had started for the general population in Japan. Notably, this resulted in a remarkably increased shortage of OTC acetaminophen formulations. The aim of this study was to elucidate the actual responses of the public in such an environment, how individuals acquired and understood information related to the management of postvaccination side effects, and how they obtained and used antipyretic analgesics before and after COVID-19 vaccination. We conducted a web-based survey in January 2022, targeting 400 individuals aged ≥20 years, who had received two COVID-19 vaccine doses, and excluded qualified professionals such as physicians and pharmacists. The results revealed that 67% of the respondents had obtained antipyretic analgesics in anticipation of adverse effects after vaccination, whereas 38% had taken these medicines before and/or after the second vaccination. Possible misappropriation of medicines from others, preventive administration, and lack of dosage and administration confirmation are the problems identified in medication acquisition and usage. Additionally, avoidance of antipyretic analgesics based on information without scientific evidence was observed. This study revealed no small amount of inappropriate use of medicines in situations, such as the COVID-19 pandemic, where there is an "infodemic" of mixed-quality information. Pharmacists, as experts in medication, should play a crucial role in promoting appropriate medication usage by consistently staying updated with the latest scientific evidence and proactively supporting OTC drug selection and counseling medication.

Effects of nano zinc oxide and nano chitosan on the taste masking paracetamol granules.

OBJECTIVE: The purpose of this study is to investigate the taste masking of Paracetamol granules in the range of 250-850 µm, coated by two nanocomposites prepared from Eudragit® E100, nanozinc oxide, and nanochitosan, respectively, from 1 to 5% by the weight of the granules. METHODS: In this study, Paracetamol granules were coated in several formulas with two different types of nanocomposites (polymeric and mineral) on two sizes of granules to reduce bitter taste and with the FBC method and pH-sensitive polymers (Eudragit® E100). RESULTS: The effect of nanoparticles (Nano zinc oxide and Nanochitosan) on taste-masking Paracetamol was studied with dissolution-coated granules in vitro by simulating in the oral (pH 6.8) range. Based on the results of the studies, the rate of drug release was confirmed by the taste test, and the formulated granule with 5% nano-chitosan (F14) had the best bitter taste mask function of all samples. These results were also confirmed by scanning electron microscopy (SEM) analysis, which showed a smoother and more stable surface than the samples obtained from other formulations. CONCLUSION: In the comparison of the release of two types of nanocomposites in the dissolution test, it was shown that the type B granules of Paracetamol's 5% nano-chitosan-coated granule (F14) were released 99% less than Paracetamol's 5% nano-ZnO-coated granule (F11). and Paracetamol's 1% nano-chitosan-coated granule (F12) was released 91% less than Paracetamol's 1% nano-ZnO-coated granule (F9). The results showed that nano-chitosan-coated granules have better coverage of bitter taste instead of nano-ZnO.

Forecasting the effect of water gastric emptying patterns on model drug release in an in vitro glass-bead flow-through system.

Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an in vitro glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.

Effectiveness and safety of prehospital analgesia with nalbuphine and paracetamol versus morphine by paramedics - an observational study.

BACKGROUND: Despite the development of various analgesic concepts, prehospital oligoanalgesia remains very common. The present work examines prehospital analgesia by paramedics using morphine vs. nalbuphine + paracetamol. METHODS: Patients with out-of-hospital-analgesia performed by paramedics from the emergency medical services of the districts of Fulda (morphine) and Gütersloh (nalbuphine + paracetamol) were evaluated with regards to pain intensity at the beginning and the end of prehospital treatment using the Numeric-Rating-Scale for pain (NRS), sex, age, and complications. The primary endpoint was achievement of adequate analgesia, defined as NRS < 4 at hospital handover, depending on the analgesics administered (nalbuphine + paracetamol vs. morphine). Pain intensity before and after receiving analgesia using the NRS, sex, age and complications were also monitored. RESULTS: A total of 1,808 patients who received out-of-hospital-analgesia were evaluated (nalbuphine + paracetamol: 1,635 (90.4%), NRS-initial: 8.0 ± 1.4, NRS-at-handover: 3.7 ± 2.0; morphine: 173(9.6%), NRS-initial: 8.5 ± 1.1, NRS-at-handover: 5.1 ± 2.0). Factors influencing the difference in NRS were: initial pain intensity on the NRS (regression coefficient (RK): 0.7276, 95%CI: 0.6602-0.7950, p < 0.001), therapy with morphine vs. nalbuphine + paracetamol (RK: -1.2594, 95%CI: -1.5770 - -0.9418, p < 0.001) and traumatic vs. non-traumatic causes of pain (RK: -0.2952, 95%CI: -0.4879 - -0.1024, p = 0.002). Therapy with morphine (n = 34 (19.6%)) compared to nalbuphine + paracetamol (n = 796 (48.7%)) (odds ratio (OR): 0.274, 95%CI: 0.185-0.405, p < 0.001) and the initial NRS score (OR:0.827, 95%CI: 0.771-0.887, p < 0.001) reduced the odds of having an NRS < 4 at hospital handover. Complications occurred with morphine in n = 10 (5.8%) and with nalbuphine + paracetamol in n = 35 (2.1%) cases. Risk factors for complications were analgesia with morphine (OR: 2.690, 95%CI: 1.287-5.621, p = 0.008), female sex (OR: 2.024, 95%CI: 1.040-3.937, p = 0.0379), as well as age (OR: 1.018, 95%CI: 1.003-1.034, p = 0.02). CONCLUSIONS: Compared to morphine, prehospital analgesia with nalbuphine + paracetamol yields favourable effects in terms of analgesic effectiveness and a lower rate of complications and should therefore be considered in future recommendations for prehospital analgesia.

Fully Biodegradable Elastomer-Based Device for Oral Macromolecule Delivery.

Oral devices, such as foil-type devices, show great potential for the delivery of poorly permeable macromolecules by enabling unidirectional release of the loaded pharmaceutical composition in close proximity to the epithelium in the small intestine or colon. However, one of the primary concerns associated with the use of foil-type devices so far has been the utilization of nonbiodegradable elastomers in the fabrication of the devices. Therefore, research into biodegradable substitute materials with similar characteristics enables drug delivery in a sustainable and environmentally friendly manner. In this study, a biodegradable elastomer, polyoctanediol citrate (POC), was synthesized via a one-pot reaction, with subsequent purification and microscale pattern replication via casting. The microstructure geometry was designed to enable fabrication of foil-type devices with the selected elastomer, which has a high intrinsic surface free energy. The final elastomer was demonstrated to have an elastic modulus ranging up to 2.2 ± 0.1 MPa, with strain at failure up to 110.1 ± 1.5%. Devices were loaded with acetaminophen and enterically coated, demonstrating 100% release at 2.5 h, following dissolution for 1 h in 0.1 M hydrochloric acid and 1.5 h in pH 6.8 phosphate-buffered saline. The elastomer demonstrated promising properties based on mechanical testing, surface free energy evaluation, and degradation studies.

Low doses of acetaminophen produce antidepressive-like effects through the opioid system in mice.

Acetaminophen (paracetamol) is one of the most popular analgesics for the management of fever and pain but few reports have investigated its antidepressant-like effect. Moreover, the role of the opioidergic pathway has been indicated in depression pathophysiology. This study aimed to examine the involvement of the opioid receptors in the antidepressant-like effect of acetaminophen after acute and sub-chronic administration using mice forced swimming test (FST). Our finding showed that administration of acetaminophen (50 and 100 mg/kg, i.p.) 30 min before the FST produced an antidepressant effect which was reduced by naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). Moreover, we observed that acetaminophen in higher doses (200 and 400 mg/kg) was ineffective. Also, the response of the non-effective dose of acetaminophen (25 mg/kg) was potentiated by the non-effective dose of morphine (0.1 mg/kg) in the FST that was antagonized by naloxone. Also, in contrast to morphine (10 mg/kg), acetaminophen (100 mg/kg, i.p.) induced neither tolerance to the anti-immobility behavior nor withdrawal syndrome after repeated administration. In addition, RT-PCR showed that hippocampal mu- and kappa-opioid receptor mRNA expression increased in mice after repeated administration of acetaminophen; however, morphine therapy for 6 days did not affect kappa-opioid receptor expression. Our findings demonstrated that acetaminophen in lower doses but not high doses revealed an antidepressant-like activity without inducing tolerance and withdrawal syndromes. Moreover, the observed effect of acetaminophen may be via altering the opioid system, particularly hippocampal mu- and kappa-receptors.

Tramadol-paracetamol for postoperative pain after spine surgery - A randomized, double-blind, placebo-controlled study.

OBJECTIVES: Multimodal pain management is one component in enhanced recovery after surgery protocol. Here we evaluate the efficacy of tramadol-paracetamol in acute postoperative pain and pain outcome at 12 months after spine surgery in randomized, double-blind, placebo-controlled trial. METHODS: We randomized 120 patients undergoing spine surgery to receive, for add-on pain management, two tramadol-paracetamol 37.5 mg/325 mg (n = 61) or placebo tablets (n = 59) twice a day for 5 postoperative days. In the hospital, multimodal pain management consisted of dexketoprofen and oxycodone. After discharge, patients were prescribed ibuprofen 200 mg, maximum 1,200 mg/day. Pain, analgesic use, and satisfaction with pain medication were followed up with the Brief Pain Inventory questionnaire before surgery and at 1 and 52 weeks after surgery. The primary outcome was patients' satisfaction with pain medication 1 week after surgery. RESULTS: At 1 week after surgery, patients' satisfaction with pain medication was similarly high in the two groups, 75% [interquartile range, 30%] in the placebo group and 70% [40%] in the tramadol-paracetamol group (p = 0.949) on a scale: 0% = not satisfied, 100% = totally satisfied. At 1 week, ibuprofen dose was lower in the placebo group 200 mg [1,000] compared to the tramadol-paracetamol group, 800 mg [1,600] (p = 0.016). There was no difference in the need for rescue oxycodone. Patients in the tramadol-paracetamol group had more adverse events associated with analgesics during the first postoperative week (relative risk = 1.8, 95% confidence interval, 1.2-2.6). CONCLUSION: Add-on pain treatment with tramadol-paracetamol did not enhance patients' satisfaction with early pain management after back surgery.

Efficacy and safety of simple analgesics for acute treatment of episodic tension-type headache in adults: a network meta-analysis.

OBJECTIVE: Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults. METHODS: We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554. RESULTS: We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity I2 between the studies was low. CONCLUSIONS: Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).

To our knowledge, this is the first network meta-analysis comparing the available data on adult patients with episodic tension-type headache (ETTH) treated with different simple analgesics recommended by the current guidelines.Ibuprofen (400 mg) and diclofenac-K (12.5 mg, 25 mg) are potentially the most effective and safe treatment options, supported by high-quality evidence.

Spray drying Eudragit® E-PO with acetaminophen using 2- and 3-fluid nozzles for taste masking.

Conventional spray drying using a 2-fluid nozzle forms matrix microparticles, where drug is distributed throughout the particle and may not effectively mask taste. In contrast, spray drying using a 3-fluid nozzle has been reported to encapsulate material. The objective of this study was to spray dry Eudragit® E-PO (EE) with acetaminophen (APAP), a water-soluble model drug with a bitter taste, using 2- and 3-fluid nozzles for taste masking. Spray drying EE with APAP, however, resulted in yields of ≤ 13 %, irrespective of nozzle configuration. Yields improved when Eudragit® L 100-55 (EL) or Methocel® E6 (HPMC) was used in the inner fluid stream of the 3-fluid nozzle or in place of EE for the 2-fluid nozzle. Drug release from microparticles prepared with the 2-fluid nozzle was relatively rapid. Using EE in the outer fluid stream of the 3-fluid nozzle resulted in comparatively slower drug release, although drug release was observed, indicating that encapsulation was incomplete. Results from these studies also show that miscible polymers used in the two fluid streams mix during the spray drying process. In addition, findings from this study indicate that the polymer used in the inner fluid stream can impact drug release.

Pain Reduction of Ibuprofen Sodium Dihydrate Alone and in Combination with Acetaminophen in an Untreated Endodontic Pain Model: A Randomized, Double-blind Investigation.

INTRODUCTION: Most pain studies have been based on a postsurgical, third molar model using ibuprofen (IBU)/acetaminophen (APAP). Studies have found quicker onset of pain relief with a newer formulation of IBU - ibuprofen sodium dihydrate (ISD). The purpose of this study was to compare pain reduction of ISD/APAP to ISD in an acute endodontic pain model of untreated patients experiencing moderate to severe pain with symptomatic apical periodontitis. METHODS AND MATERIALS: In this double-blind randomized study, 64 adult emergency patients in acute moderate to severe pain, a pulpal diagnosis of symptomatic irreversible pulpitis or necrosis, and symptomatic apical periodontitis participated. Each patient randomly received either one dose of 768 mg ISD/1000 mg APAP or one dose of 768 mg ISD. Pain intensity scores were recorded every 15 minutes over 240 minutes using the Heft-Parker VAS along with time to first sign of pain relief, time to meaningful pain relief, and time to 50% pain relief also recorded. The data were analyzed statistically. RESULTS: Both ISD and ISD/APAP groups showed a progressive decrease in pain from baseline to 120 minutes after medication administration. Afterward, a relative plateau was seen in the patients' pain. There was no difference in the VAS scores between the ISD and ISD/APAP at any given time point, time to first sign of pain relief, time to meaningful pain relief, and time to 50% pain relief. CONCLUSIONS: The addition of APAP to ISD for pain control in an untreated endodontic pain model did not differ significantly from ISD alone.

Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial.

BACKGROUND: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass. METHODS: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%. RESULTS: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%). CONCLUSIONS: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.

Implementing Change: Sustaining Enhanced Recovery After Surgery Protocols in Pediatric Surgery Using Iterative Assessments.

INTRODUCTION: While Enhanced Recovery After Surgery (ERAS) protocols are becoming more common in pediatric surgery, there is still little published about protocol compliance and sustainability. METHODS: This is a prospective observational study to evaluate the compliance of an ERAS protocol for pectus repair at a large academic children's hospital. Our primary outcome was overall protocol compliance at 1-y postimplementation of the ERAS protocol. Our comparison group included all pectus repairs for 2 y before protocol implementation. RESULTS: Overall protocol compliance at 12 mo was 89%. Of the 16 pectus repairs included in the ERAS protocol group, 94% (n = 15) and 94% (n = 15) received preoperative acetaminophen and gabapentin, respectively, which was significantly greater than the historical control group (P < 0.001). For the intraoperative components analyzed, only the intrathecal morphine was significantly different than historical controls (100% versus 49%, P < 0.001). Postoperatively, the time from operating room to return to normal diet was shorter for the ERAS group (0.53 d versus 1.16 d, P < 0.001). There was no significant difference in readmission rates between the two groups. CONCLUSIONS: ERAS protocol compliance varies based on phase of care. Solutions to sustain protocols depend on the institution and the patient population. However, the utilization of implementation science fundamentals was invaluable in this study to identify and address areas for improvement in protocol compliance. Other institutions may adapt these strategies to improve protocol compliance at their centers.

Fixed-time interval vs on-demand oral analgesia after vaginal delivery: a randomized controlled trial.

BACKGROUND: Scheduled administration of analgesics was proven superior to on-demand dosing following cesarean deliveries. However, this protocol was not compared after vaginal delivery. OBJECTIVE: To compare the efficacy of a fixed- vs on-demand analgesic protocol for the management of pain in the first 24 hours after a vaginal delivery. STUDY DESIGN: This randomized, prospective, controlled trial was conducted at a single tertiary medical center between June 1, 2020 and June 30, 2022. Vaginally delivered patients were randomly assigned to receive oral analgesics (paracetamol 1 g + ibuprofen 400 mg) either every 6 hours for the first 24 hours postpartum (scheduled analgesia group) or as needed (on-demand group). Pain level during the first 24 hours postdelivery was measured using a 10-point visual analog scale. RESULTS: A total of 200 patients were randomized 1:1 to the 2 cohorts. Baseline and delivery characteristics, including oxytocin augmentation, epidural anesthesia, episiotomy rate, and neonatal birthweight, were comparable between groups. Patients in the scheduled group received more paracetamol and ibuprofen doses in the first 24 hours (2.9±1.3 and 2.9±1.2 doses vs 0.8±1.1 and 0.7±1.1 doses, respectively; P<.001). Pain score was comparable between study groups (5.31±1.92 vs 5.29±1.67; P=.626) even after subanalysis for primiparity, episiotomy, and vacuum-assisted delivery (P>.05). However, patients on a fixed treatment schedule were more likely to breastfeed their baby (98% vs 88%; P=.006) as than those receiving treatment on demand. In addition, they were more satisfied with their labor and delivery experience, as evaluated by Birth Satisfaction Scale questionnaires quality control (37.9±4.7 vs 31.1±5.2; P=.0324), patient attributes (35.0±5.1 vs 30.3±6.3; P=.0453), and stress experienced (58.1±8.5 vs 50.1±8.3; P=.0398). No side effects or adverse outcomes were reported in either group. CONCLUSION: A scheduled analgesic protocol for postpartum pain management following vaginal delivery revealed similar pain scores compared with an on-demand protocol, although it was associated with higher breastfeeding rates and higher maternal satisfaction.

AI-driven design of customized 3D-printed multi-layer capsules with controlled drug release profiles for personalized medicine.

Personalized medicine aims to effectively and efficiently provide customized drugs that cater to diverse populations, which is a significant yet challenging task. Recently, the integration of artificial intelligence (AI) and three-dimensional (3D) printing technology has transformed the medical field, and was expected to facilitate the efficient design and development of customized drugs through the synergy of their respective advantages. In this study, we present an innovative method that combines AI and 3D printing technology to design and fabricate customized capsules. Initially, we discretized and encoded the geometry of the capsule, simulated the dissolution process of the capsule with classical drug dissolution model, and verified it by experiments. Subsequently, we employed a genetic algorithm to explore the capsule geometric structure space and generate a complex multi-layer structure that satisfies the target drug release profiles, including stepwise release and zero-order release. Finally, Two model drugs, isoniazid and acetaminophen, were selected and fused deposition modeling (FDM) 3D printing technology was utilized to precisely print the AI-designed capsule. The reliability of the method was verified by comparing the in vitro release curve of the printed capsules with the target curve, and the f2 value was more than 50. Notably, accurate and autonomous design of the drug release curve was achieved mainly by changing the geometry of the capsule. This approach is expected to be applied to different drug needs and facilitate the development of customized oral dosage forms.