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Objectives: This study compared the effects of leukocyte platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF) on patients' quality of life and the healing of palatal wounds after free gingival graft harvesting. Method and materials: After free gingival graft harvesting, palatal donor sites of 36 patients were assigned to one of three groups: L-PRF group, A-PRF group, or palatal stent + periodontal pack group (control group). Wound healing was evaluated by H2O2 test. Pain was evaluated by visual analog scale and number of analgesics consumed. For patient quality of life, the Oral Health Impact Profile-14 (OHIP-14) questionnaire was utilized. Results: Complete epithelialization was higher in the control group on day 7 than in the test groups (P < .05). Complete epithelialization was achieved in all groups 14 days postoperatively. Visual analog scale scores for pain and the number of analgesic tablets consumed were similar in all groups (P > .05). OHIP-14 total scores were similar in all study groups at 7 days postoperatively (P > .05). OHIP-14 total and physical pain score was lower in the L-PRF group than the A-PRF group at 14 days postoperatively (P < .05). Conclusion: Aside from the slight superiority of L-PRF over A-PRF, it can be concluded that both PRF procedures have similar effects on palatal wound healing and quality of life. [ABSTRACT FROM AUTHOR]

BackgroundPain is ubiquitous, yet understudied. The objective of this study was to analyze inequities in pain assessment and management for hospitalized older adults focusing on demographic and geriatric-related variables.MethodsThis was a retrospective cohort study from January 2013 through September 2021 of all adults 65 years or older on the general medicine service at UCSF Medical Center. Primary exposures included (1) demographic variables including race/ethnicity and limited English proficiency (LEP) status and (2) geriatric-related variables including age, dementia or mild cognitive impairment diagnosis, hearing or visual impairment, end-of-life care, and geriatrics consult involvement. Primary outcomes included (1) adjusted odds of numeric pain assessment versus other assessments and (2) adjusted opioids administered, measured by morphine milligram equivalents (MME).ResultsA total of 15,809 patients were included across 27,857 hospitalizations with 1,378,215 pain assessments, with a mean age of 77.8 years old. Patients were 47.4% White, 26.3% with LEP, 49.6% male, and 50.4% female. Asian (OR 0.75, 95% CI 0.70-0.80), Latinx (OR 0.90, 95% CI 0.83-0.99), and Native Hawaiian or Pacific Islander (OR 0.77, 95% CI 0.64-0.93) patients had lower odds of a numeric assessment, compared with White patients. Patients with LEP (OR 0.70, 95% CI 0.66-0.74) had lower odds of a numeric assessment, compared with English-speaking patients. Patients with dementia, hearing impairment, patients 75+, and at end-of-life were all less likely to receive a numeric assessment. Compared with White patients (86 MME, 95% CI 77-96), Asian patients (55 MME, 95% CI 46-65) received fewer opioids. Patients with LEP, dementia, hearing impairment and those 75+ years old also received significantly fewer opioids.ConclusionOlder, hospitalized, general medicine patients from minoritized groups and with geriatric-related conditions are uniquely vulnerable to inequitable pain assessment and management. These findings raise concerns for pain underassessment and undertreatment.

INTRODUCTION: Post-operative prescription opioid use is a known risk factor for persistent opioid use. Despite the increased utilization of robotic-assisted surgery (RAS) for inguinal hernia repair (IHR), little is known whether this minimally invasive approach results in less opioid consumption. In this study, we compare long-term opioid use between RAS versus laparoscopic (Lap) versus open surgery for IHR. METHODS: A retrospective cohort study of opioid-naïve patients who underwent outpatient primary IHR was conducted using the Merative™ MarketScan® (Previously IBM MarketScan®) Databases between 2016 and 2020. Patients not continuously enrolled 180 days before/after surgery, who had malignancy, pre-existing chronic pain, opioid dependency, or invalid prescription fill information were excluded. Among patients exposed to opioids peri-operatively, we assessed long-term opioid use as any opioid prescription fill within 90 to 180 days post-surgery. Secondary outcomes were controlled substance schedule II/III opioid fill, and high-dose opioid fill defined as > 50 morphine milligram equivalent per day. An Inverse-probability of treatment weighted logistic regression was used to compare outcomes between groups with p-value of

Objectives: This study examined the impact of injectable plateletrich fibrin (iPRF) and concentrated growth factor on postoperative pain, edema, trismus, and quality of life in impacted mandibular third molar surgery. The primary aim of this study was to minimize common sequelae following third molar surgery by using iPRF and concentrated growth factor. The secondary objective was to compare the postoperative effects of these products. Method and materials: This study represents a single-center, randomized prospective clinical trial conducted at the Ordu University Faculty of Dentistry. It involved patients who underwent third molar surgery for various reasons between July and October 2022. The predictor variables were the use of concentrated growth factor and i-PRF. They were categorized as concentrated growth factor, i-PRF, and control groups. The outcome variables include pain levels and analgesic consumption measured on a visual analog scale, distances between predetermined anatomical points, maximum mouth opening capacity, and data from the postoperative symptom severity (PoSSe) scale. Some statistical tests were performed with a 95% confidence interval, which was considered significant. Results: Total analgesic use was notably lower in the concentrated growth factor group (P = .044). Concentrated growth factor and iPRF outperformed the control group in all edema measurements by postoperative day 7 (tragus–pogonion, lateral canthus–angulus, tragus–commissura; P < .05). Concentrated growth factor significantly reduced trismus on days 2 and 7. Quality of life was notably higher in the concentrated growth factor group than in the control group (P = .026), although iPRF group differences were not significant. Conclusion: The results indicate that concentrated growth factor has a limited impact on postoperative pain, but significantly reduces edema, trismus, and enhances quality of life. The iPRF group experienced positive effects on pain, edema, and trismus, although the statistically significant differences observed with concentrated growth factor highlight its potential for use instead of iPRF after third molar surgery. An increased sample size is essential for more comprehensive results [ABSTRACT FROM AUTHOR]

Objective: Currently, there is no established treatment protocol to treat interdental papillary loss. This research aimed to evaluate the outcomes of interdental papillary reconstruction using minimally invasive surgery, with injectable hyaluronic acid gel. Method and materials: Seventeen patients were included, each with five sites of class 1 papillary recession (40 sites in the maxilla and 45 sites in the mandible). Subperiosteal tunneling was performed through a horizontal incision made apical to the base of the papilla without penetrating it. The free gingival sulcus was sealed by 000 retraction cord. A total of 0.2 to 0.6 mL hyaluronic acid was injected gradually. The incision was sutured with poly-glycolic sutures. Treated sites underwent clinical and digital evaluation at three follow-up time points (1 month, 3 months, and 6 months). Results: The interdental papillary defect height in the maxillary sites significantly reduced by 60%, 66%, and 42% at 1,3, and 6 months, respectively. In mandibular sites, the reduction was 54%, 55%, and 40% at the same follow-up time points. Regarding interdental papillary defect surface area in the maxilla, the reduction was 65%, 71%, and 45% at 1, 3, and 6 months. In the mandible, a reduction of 60%, 64%, and 48% was noticed at the same time points. Regarding patients' pain level score, during the day of surgery, 16 patients reported pain; the average pain score out of 10 was 3.94, and 11 patients (64.7%) needed to take analgesics. The pain generally subsided in the following days. At the day of treatment, 12 out of the 17 patients (70.6%) reported mild difficulty in speaking and eating. No complication, hypersensitivity, or allergy was noted in any patient. Conclusion: Subperiosteal tunneling with hyaluronic acid injection demonstrates clinical improvements in papilla height and papillary recession surface area reduction after 3 months of follow-up, with reduction in improvement after 6 months. Clinical significance: Adjunctive use of hyaluronic acid injection with minimally invasive surgery in interdental papillary management may improve clinical and esthetic outcomes. [ABSTRACT FROM AUTHOR]

Pain and inflammation contribute immeasurably to reduced quality of life, yet modern analgesic and anti-inflammatory therapeutics can cause dependence and side effects. Here, we screened 1444 plant extracts, prepared primarily from native species in California and the United States Virgin Islands, against two voltage-gated K+ channels - T-cell expressed Kv1.3 and nociceptive-neuron expressed Kv7.2/7.3. A subset of extracts both inhibits Kv1.3 and activates Kv7.2/7.3 at hyperpolarized potentials, effects predicted to be anti-inflammatory and analgesic, respectively. Among the top dual hits are witch hazel and fireweed; polymodal modulation of multiple K+ channel types by hydrolysable tannins contributes to their dual anti-inflammatory, analgesic actions. In silico docking and mutagenesis data suggest pore-proximal extracellular linker sequence divergence underlies opposite effects of hydrolysable tannins on different Kv1 isoforms. The findings provide molecular insights into the enduring, widespread medicinal use of witch hazel and fireweed and demonstrate a screening strategy for discovering dual anti-inflammatory, analgesic small molecules.

OBJECTIVE: To evaluate the role of psychosocial well-being on perioperative pain and opioid use among patients with cleft lip and palate (CLP) undergoing alveolar bone grafting (ABG). DESIGN: Retrospective review. SETTING: Tertiary level craniofacial clinic. PARTICIPANTS: 34 patients with CLP (median age: 11.7 years), including 25 (73.5%) unilateral CLP and 9 (26.5%) bilateral CLP, who underwent ABG from 2015 to 2022. INTERVENTIONS: ABG using iliac crest bone graft. Patients were prospectively administered four patient-reported psychosocial instruments from the Patient-Reported Outcomes Measurement Information System. MAIN OUTCOME MEASURES: Perioperative opioid use in morphine equivalent dosage/kilogram, patient-reported pain scores, and length of hospital stay after ABG. RESULTS: Patient-reported anxiety (r = 0.41, p = 0.02) and depressive symptoms (r = 0.35, p = 0.04) correlated to higher perioperative opioid usage. Multivariable regression models including psychosocial scores, total acetaminophen usage, length of surgery, and other simultaneous surgeries were developed for total opioid usage, patient-reported pain, and length of hospital stay. Patient-reported anxiety was independently predictive of higher perioperative opioid use (β=0.36, p = 0.01) and higher pain scores (β=0.39, p = 0.02), but not length of hospital stay. CONCLUSIONS: We identified an association for patient-reported anxiety and perioperative opioid use and pain in a CLP cohort undergoing ABG. Future considerations in preoperative patient and family consultation may be indicated in patients self-reporting higher anxiety in an effort to minimize perioperative opioid usage.

The intensifying global opioid crisis, majorly attributed to fentanyl (FT) and its analogs, has necessitated the development of rapid and ultrasensitive remote/on-site FT sensing modalities. However, current approaches for tracking FT exposure through wastewater-based epidemiology (WBE) are unadaptable, time-consuming, and require trained professionals. Toward developing an extended in situ wastewater opioid monitoring system, we have developed a screen-printed electrochemical FT sensor and integrated it with a customized submersible remote sensing probe. The sensor composition and design have been optimized to address the challenges for extended in situ FT monitoring. Specifically, ZIF-8 metal-organic framework (MOF)-derived mesoporous carbon (MPC) nanoparticles (NPs) are incorporated in the screen-printed carbon electrode (SPCE) transducer to improve FT accumulation and its electrocatalytic oxidation. A rapid (10 s) and sensitive square wave voltammetric (SWV) FT detection down to 9.9 µgL-1 is thus achieved in aqueous buffer solution. A protective mixed-matrix membrane (MMM) has been optimized as the anti-fouling sensor coating to mitigate electrode passivation by FT oxidation products and enable long-term, intermittent FT monitoring. The unique MMM, comprising an insulating polyvinyl chloride (PVC) matrix and carboxyl-functionalized multi-walled carbon nanotubes (CNT-COOH) as semiconductive fillers, yielded highly stable FT sensor operation (> 95% normalized response) up to 10 h in domestic wastewater, and up to 4 h in untreated river water. This sensing platform enables wireless data acquisition on a smartphone via Bluetooth. Such effective remote operation of submersible opioid sensing probes could enable stricter surveillance of community water systems toward timely alerts, countermeasures, and legal enforcement.

BACKGROUND: The pleiotropic effects of the melanocortin system show promise in overcoming limitations associated with large variations in opioid analgesic effectiveness observed in equine practice. Of particular interest is variation in the melanocortin-1-receptor (MC1R) gene, which dictates pigment type expression through its epistatic interaction with the agouti signalling protein (ASIP) gene. MC1R has previously been implicated in opioid efficacy in other species; however, this relationship is yet to be explored in horses. In this study, analgesic effectiveness was scored (1-3) based on noted response to dura penetration during the performance of cerebrospinal fluid centisis after sedation and tested for association with known genetic regions responsible for pigmentation variation in horses. RESULTS: The chestnut phenotype was statistically significant (P < 0.05) in lowering analgesic effectiveness when compared to the bay base coat colour. The 11bp indel in ASIP known to cause the black base coat colour was not significant (P>0.05); however, six single nucleotide polymorphisms (SNPs) within the genomic region encoding the ASIP gene and one within MC1R were identified as being nominally significant (P

BACKGROUND: Patients with limited English proficiency (LEP) may have worse health outcomes and differences in processes of care. Language status may particularly affect situations that depend on communication, such as symptom management or end-of-life (EOL) care. OBJECTIVE: The objective of this study was to assess whether opioid prescribing and administration differs by English proficiency (EP) status among hospitalized patients receiving EOL care. METHODS: This single-center retrospective study identified all adult patients receiving comfort care on the general medicine service from January 2013 to September 2021. We assessed for differences in the quantity of opioids administered (measured by oral morphine equivalents [OME]) by patient LEP status using multivariable linear regression, controlling for other patient and medical factors. RESULTS: We identified 2652 patients receiving comfort care at our institution during the time period, of whom 1813 (68%) died during the hospitalization. There were no significant differences by LEP status in terms of mean OME per day (LEP received 30.8 fewer OME compared to EP, p = .91) or in the final 24 h before discharge (LEP received 61.7 more OME compared to EP, p = .80). CONCLUSION: LEP was not associated with differences in the amount of opioids received for patients whose EOL management involved standardized order sets for symptom management at our hospital.

BACKGROUND: The number of older adults entering opioid treatment programs (OTPs) to treat opioid use disorder (OUD) is increasing. However, the lived experiences of aging in OTPs have not been examined. OBJECTIVE: To explore the aging experience with OUD and barriers to medical care for older adults who receive care in OTPs. DESIGN: From November 2021 to July 2022, we conducted 1-to-1, semi-structured qualitative interviews in English and Spanish, audio-recorded, transcribed, systematically coded, and analyzed to identify key themes regarding the challenges of aging with OUD and managing chronic diseases. PARTICIPANTS: Thirty-six adults aged ≥ 55 enrolled in OTPs in San Diego, California. APPROACH: A descriptive qualitative approach was used. Major themes and subthemes were identified through thematic analysis until thematic saturation was reached. KEY RESULTS: All participants were on methadone and had a mean age of 63.4 (SD 5.1) years; 11 (30.6%) identified as female, 14 (39%) as Hispanic/Latino, and 11 (36%) as Black, with a mean duration of methadone treatment of 5.6 years. Chronic diseases were common, with 21 (58.3%) reporting hypertension, 9 (25%) reporting untreated hepatitis C, and 32 (88.9%) having ≥ 2 chronic diseases. Three major themes emerged: (1) avoidance of medical care due to multiple intersectional stigmas, including those related to drug use, substance use disorder (SUD) treatment, ageism, and housing insecurity; (2) increasing isolation with aging and loss of family and peer groups; (3) the urgent need for integrating medical and aging-focused care with OUD treatment in the setting of increasing health and functional challenges. CONCLUSIONS: Older adults with OUD reported increasing social isolation and declining health while experiencing multilevel stigma and discrimination. The US healthcare system must transform to deliver age-friendly care that integrates evidence-based geriatric models of care incorporated with substance use disorder treatment and addresses the intersectional stigma this population has experienced in healthcare settings.

Background and Aims: Anterior cruciate ligament (ACL) repair is a common sports-related surgery requiring early rehabilitation. Injection between the popliteal artery and the capsule of the knee (iPACK) provides analgesia to the posterior knee and, when combined with adductor canal block (ACB), can provide complete analgesia for knee surgery. A 4-in-1 block, a single injection, has been studied for analgesia in TKR but not ACL repair. This study was done with the objective of comparing the postoperative analgesia of iPACK + ACB versus 4-in-1 block in ACL repair. Methods: The study was conducted on 184 participants undergoing ACL repair in the age group of 18-70 years. Patients were randomly allocated to iPACK +ACB or 4-in-1 block. After the preoperative and intraoperative protocol, a guided nerve block was performed. The duration of motor blockade of spinal anaesthesia and pain scores were monitored using the visual analogue scale (VAS), and the time for first rescue analgesia was noted at 3, 6, 12, 24, and 36 hours. An independent sample t-test was used to find the association of all quantitative variables, and a Chi-square test was used to find the association of categorical variables with both groups of patients (P < 0.05). Results: VAS scores were statistically similar between the two groups at 3, 6, 12, and 24 hours but were significantly less at 36 hours in group B (P < 0.001). The time to perform the regional block was lower in group B, a single injection technique (P < 0.001). None of the patients showed muscle weakness in the postoperative period and could cooperate reasonably with physiotherapy. Conclusion: The 4-in-1 block provides non-inferior analgesia compared to the established iPACK plus ACB for arthroscopic ACL surgery. Keywords: Analgesia, anterior cruciate ligament, muscle weakness, nerve block, visual analog scale, Author(s): Ritesh Roy [1]; Gaurav Agarwal (corresponding author) [2]; Priyanka Ahuja [3]; Ankita Mohta [2] INTRODUCTION Anterior cruciate ligament (ACL) injury, the most common sports-related injury of the knee, has [...]

OBJECTIVES: Patients receiving chiropractic spinal manipulation (CSM) for low back pain (LBP) are less likely to receive any opioid prescription for subsequent pain management. However, the likelihood of specifically being prescribed tramadol, a less potent opioid, has not been explored. We hypothesised that adults receiving CSM for newly diagnosed radicular LBP would be less likely to receive a tramadol prescription over 1-year follow-up, compared with those receiving usual medical care. DESIGN: Retrospective cohort study. SETTING: US medical records-based dataset including >115 million patients attending academic health centres (TriNetX, Inc), queried 9 November 2023. PARTICIPANTS: Opioid-naive adults aged 18-50 with a new diagnosis of radicular LBP were included. Patients with serious pathology and tramadol use contraindications were excluded. Variables associated with tramadol prescription were controlled via propensity matching. INTERVENTIONS: Patients were divided into two cohorts dependent on treatment received on the index date of radicular LBP diagnosis (CSM or usual medical care). PRIMARY AND SECONDARY OUTCOME MEASURES: Risk ratio (RR) for tramadol prescription (primary); markers of usual medical care utilisation (secondary). RESULTS: After propensity matching, there were 1171 patients per cohort (mean age 35 years). Tramadol prescription was significantly lower in the CSM cohort compared with the usual medical care cohort, with an RR (95% CI) of 0.32 (0.18 to 0.57; p

PURPOSE: The pupil displays chaotic oscillations, also referred to as pupillary unrest in ambient light (PUAL). As pain has previously been shown to increase pupillary unrest, the quantitative assessment of PUAL has been considered a possible tool to identify and quantify pain. Nevertheless, PUAL is affected by various states, such as vigilance, cognitive load, or emotional arousal, independent of pain. Furthermore, systematically applied opioids are known to reduce PUAL, thus potentially limiting its usefulness to detect pain or changes in pain intensity. To test the hypothesis that PUAL can reliably identify changes in pain intensity in a clinical setting, we measured PUAL in patients experiencing substantial pain relief when regional anesthesia interventions were applied after surgery. METHODS: We conducted an observational study at an academic surgery centre following institutional review board approval. Eighteen patients with unsatisfactory pain control following surgery underwent regional anesthesia procedures to improve pain control. We used infrared pupillometry to assess pupillary unrest before and after the regional block. We then compared the changes in pupillary unrest with the changes in pain scores (numeric rating scale [NRS], range 0-10). RESULTS: Eighteen patients received epidural anesthesia (n = 14) or peripheral nerve blocks (n = 4), resulting in improvement of mean (standard deviation [SD]) NRS pain scores from 7.2 (1.7) to 1.9 (1.8) (difference in means, -2.2; 95% confidence interval [CI], -6.3 to -4.1; P

The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role and synaptic mechanisms of descending noradrenergic signaling remain unclear. Here, we establish that noradrenergic neurons of the locus coeruleus (LC) are essential for supraspinal opioid antinociception. While much previous work has emphasized the role of descending serotonergic pathways, we find that opioid antinociception is primarily driven by excitatory output from the ventrolateral periaqueductal gray (vlPAG) to the LC. Furthermore, we identify a previously unknown opioid-sensitive inhibitory input from the rostroventromedial medulla (RVM), the suppression of which disinhibits LC neurons to drive spinal noradrenergic antinociception. We describe pain-related activity throughout this circuit and report the presence of prominent bifurcating outputs from the vlPAG to the LC and the RVM. Our findings substantially revise current models of the DPMS and establish a supraspinal antinociceptive pathway that may contribute to multiple forms of descending pain modulation.

BACKGROUND: Buprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients. METHODS: We conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics. RESULTS: There were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation. CONCLUSIONS: Withdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients withdrawal experiences.

People who nonmedically use drugs (PWUD) face intricate social issues that suppress self-actualization, communal integration, and overall health and wellness. Strengths-based approaches, an under-used pedagogy and practice in addiction medicine, underscore the significance of identifying and recognizing the inherent and acquired skills, attributes, and capacities of PWUD. A strengths-based approach engenders client affirmation and improves their capacity to reduce drug use-related harms by leveraging existing capabilities. Exploring this paradigm, we conducted and analyzed interviews with 46 PWUD who were clients at syringe services programs in New York City and rural southern Illinois, two areas with elevated rates of opioid-related morbidity and mortality, to assess respondents perceived strengths. We located two primary thematic modalities in which strengths-based ethos is expressed: individuals (1) being and advocate and resource for harm reduction knowledge and practices and (2) engaging in acts of continuous self-actualization. These dynamics demonstrate PWUD strengths populating and manifesting in complex ways that both affirm and challenge humanist and biomedical notions of individual agency, as PWUD refract enacted, anticipated, and perceived stigmas. In conclusion, programs that blend evidence-based, systems-level interventions on drug use stigma and disenfranchisement with meso and micro-level strengths-based interventions that affirm and leverage personal identity, decision-making capacity, and endemic knowledge may help disrupt health promotion cleavages among PWUD.

BACKGROUND: Opioid use after revision total hip arthroplasty (rTHA) has not been well characterized. The purpose of this study was to characterize preoperative, perioperative, and postoperative opioid use during rTHA. METHODS: Patients undergoing revision THA from 2010 to 2018 were screened for opioid use 3 months before revision surgery and tracked 24 months postoperatively. Patients were categorized as naïve or tolerant. Opioid prescriptions and average morphine milligram equivalents (MME) were compared between the two groups. RESULTS: One hundred twenty-four of 247 patients (50%) in the tolerant group averaged a preoperative MME of 23.7 mg/day. Postoperatively, tolerant patients received significantly higher daily MME at all time points, including at 3 months 31.4 versus 18.1 mg/day (P < 0.001), 6 months 19.9 versus 2.95 mg/day (P < 0.001), 12 months 14.3 versus 3.5 mg/day (P < 0.001), and 24 months 10.7 versus 2.17 mg/day (P < 0.001). Tolerant patients were more likely to have a prescription at 6 months (44% versus 22%), 12 months (41.4% versus 24%), and 24 months (38% versus 19.3%) (P < 0.001, P = 0.002, P < 0.001, respectively). DISCUSSION: Opioid-tolerant patients had higher postoperative MME requirements for longer recovery duration. Both groups reduced opioid use at 3 months and plateaued at 6 months. These findings can help the revision surgeon counsel patients and expectations.

Fentanyl-mixed and substituted heroin is well-documented, but less is known about unintentional fentanyl use among people using stimulants. To determine the prevalence of and racial and ethnic disparities in unintentional fentanyl use among people experiencing a medically attended opioid overdose, we reviewed 448 suspected non-fatal overdose cases attended by a community paramedic overdose response team in San Francisco from June to September 2022. We applied a case definition for opioid overdose to paramedic records and abstracted data on intended substance use prior to overdose. Among events meeting case criteria with data on intended substance use, intentional opioid use was reported by 57.3%, 98.0% of whom intended to use fentanyl. No intentional opioid use was reported by 42.7%, with most intending to use stimulants (72.6%), including methamphetamine and cocaine. No intentional opioid use was reported by 58.5% of Black, 52.4% of Latinx, and 28.8% of White individuals (p = 0.021), and by 57.6% of women and 39.5% of men (p = 0.061). These findings suggest that unintentional fentanyl use among people without opioid tolerance may cause a significant proportion of opioid overdoses in San Francisco. While intentional fentanyl use might be underreported, the magnitude of self-reported unintentional use merits further investigation to confirm this phenomenon, explore mechanisms of use and disparities by race and ethnicity, and deploy targeted overdose prevention interventions.

PURPOSE: The objective of this study was to perform a retrospective cohort analysis, in which we measured the association of an acute pain service (APS)-driven multimodal analgesia protocol that included preoperative intrathecal morphine (ITM) compared to historic controls (i.e., surgeon-driven analgesia protocol without ITM) with postoperative opioid use. METHODS: This was a retrospective cohort study in which the primary objective was to determine whether there was a decrease in median 24-h opioid consumption (intravenous morphine equivalents [MEQ]) among robotic nephrectomy patients whose pain was managed by the surgical team prior to the APS, versus pain managed by APS. Secondary outcomes included opioid consumption during the 24-48 h and 48-72 h period and hospital length of stay. To create matched cohorts, we performed 1:1 (APS:non-APS) propensity score matching. Due to the cohorts occurring at the different time periods, we performed a segmented regression analysis of an interrupted time series. RESULTS: There were 76 patients in the propensity-matched cohorts, in which 38 (50.0%) were in the APS cohort. The median difference in 24-h opioid consumption in the pre-APS versus APS cohort was 23.0 mg [95% CI 15.0, 31.0] (p

STUDY QUESTION: What is the efficacy and safety of long-term treatment (up to 2 years) with relugolix combination therapy (CT) in women with moderate to severe endometriosis-associated pain? SUMMARY ANSWER: For up to 2 years, treatment with relugolix CT improved menstrual and non-menstrual pain, dyspareunia, and function in women with endometriosis; after an initial decline of

The harmful side effects of opioid drugs such as respiratory depression, tolerance, dependence, and abuse potential have limited the therapeutic utility of opioids for their entire clinical history. However, no previous attempt to develop effective pain drugs that substantially ameliorate these effects has succeeded, and the current opioid epidemic affirms that they are a greater hindrance to the field of pain management than ever. Recent attempts at new opioid development have sought to reduce these side effects by minimizing engagement of the regulatory protein arrestin-3 at the mu-opioid receptor, but there is significant controversy around this approach. Here, we discuss the ongoing effort to develop safer opioids and its relevant historical context. We propose a new model that reconciles results previously assumed to be in direct conflict to explain how different signaling profiles at the mu-opioid receptor contribute to opioid tolerance and dependence. Our goal is for this framework to inform the search for a new generation of lower liability opioid analgesics.

American Indian/Alaska Native (AI/AN) communities are disproportionately affected by the opioid epidemic. AI/AN emerging adults (ages 18-25) in urban areas are at particularly high risk, with the overdose death rate among urban-dwelling AI/AN people 1.4 times higher than rural-dwelling AI/AN people. Despite these challenges, there are no evidence-based culturally tailored prevention or intervention programs to address opioid, alcohol and other drug use among urban AI/AN emerging adults. This study focused on understanding AI/AN emerging adults experiences with two culturally tailored programs addressing opioid, cannabis, and alcohol use as part of the randomized controlled trial for Traditions and Connections for Urban Native Americans (TACUNA) in order to enhance feasibility of this intervention. Using a convergent mixed methods design at 3-month follow-up, we collected satisfaction and experience ratings and written narratives (total n = 162; intervention n = 77; control n = 85) from a sample of urban-dwelling AI/AN emerging adults who participated in both programs. We analyzed data through simultaneous examination of qualitative and quantitative data. The quantitative ratings show that both programs were rated highly. The qualitative data contextualized these ratings, illustrating pathways through which specific components were perceived to cause desired or observed behavioral change in participants. Among the elements that mattered most to these participants were the convenience of the virtual format, having a comfortable and safe space to share personal stories, and learning new information about their social networks. Negative comments focused on workshop length and inconvenient scheduling. This is one of the first studies to explore participant satisfaction and experience with culturally tailored substance use programming among a historically marginalized and understudied population. It is important to consider the voices of urban-dwelling AI/AN people in program development because hidden factors, such as limited financial resources, limited time, and misalignment with cultural values may prevent existing programs from being feasible.

BACKGROUND: Both increases and decreases in patients prescribed daily opioid dose have been linked to increased overdose risk, but associations between 30-day dose trajectories and subsequent overdose risk have not been systematically examined. OBJECTIVE: To examine the associations between 30-day prescribed opioid dose trajectories and fatal opioid overdose risk during the subsequent 15 days. DESIGN: Statewide cohort study using linked prescription drug monitoring program and death certificate data. We constructed a multivariable Cox proportional hazards model that accounted for time-varying prescription-, prescriber-, and pharmacy-level factors. PARTICIPANTS: All patients prescribed an opioid analgesic in California from March to December, 2013 (5,326,392 patients). MAIN MEASURES: Dependent variable: fatal drug overdose involving opioids. Primary independent variable: a 16-level variable denoting all possible opioid dose trajectories using the following categories for current and 30-day previously prescribed daily dose: 0-29, 30-59, 60-89, or ≥90 milligram morphine equivalents (MME). KEY RESULTS: Relative to patients prescribed a stable daily dose of 0-29 MME, large (≥2 categories) dose increases and having a previous or current dose ≥60 MME per day were associated with significantly greater 15-day overdose risk. Patients whose dose decreased from ≥90 to 0-29 MME per day had significantly greater overdose risk compared to both patients prescribed a stable daily dose of ≥90 MME (aHR 3.56, 95%CI 2.24-5.67) and to patients prescribed a stable daily dose of 0-29 MME (aHR 7.87, 95%CI 5.49-11.28). Patients prescribed benzodiazepines also had significantly greater overdose risk; being prescribed Z-drugs, carisoprodol, or psychostimulants was not associated with overdose risk. CONCLUSIONS: Large (≥2 categories) 30-day dose increases and decreases were both associated with increased risk of fatal opioid overdose, particularly for patients taking ≥90 MME whose opioids were abruptly stopped. Results align with 2022 CDC guidelines that urge caution when reducing opioid doses for patients taking long-term opioid for chronic pain.

BackgroundIntraoperative opioid use has a positive relationship with postoperative nausea and vomiting (PONV), and opioid-free anaesthesia (OFA) might reduce PONV. We investigated whether OFA compared with opioid-based anaesthesia would reduce PONV during the first 2 postoperative days among patients undergoing thoracoscopic lung resection.MethodsIn this randomised controlled trial, 120 adult patients were randomly assigned (1:1, stratified by sex) to receive either OFA with esketamine, dexmedetomidine, and sevoflurane, or opioid-based anaesthesia with sufentanil and sevoflurane. A surgical pleth index (SPI) of 20-50 was applied for intraoperative analgesia provision. All subjects received PONV prophylaxis (dexamethasone and ondansetron) and multimodal analgesia (flurbiprofen axetil, ropivacaine wound infiltration, and patient-controlled sufentanil). The primary outcome was the occurrence of PONV during the first 48 h after surgery.ResultsThe median age was 53 yr and 66.7% were female. Compared with opioid-based anaesthesia, OFA significantly reduced the incidence of PONV (15% vs 31.7%; odds ratio [OR]=0.38, 95% confidence interval [CI], 0.16-0.91; number needed to treat, 6; P=0.031). Secondary and safety outcomes were comparable between groups, except that OFA led to a lower rate of vomiting (OR=0.23, 95% CI, 0.08-0.77) and a longer length of PACU stay (median difference=15.5 min, 95% CI, 10-20 min). The effects of OFA on PONV did not differ in the prespecified subgroups of sex, smoking status, and PONV risk scores.ConclusionsIn the context of PONV prophylaxis and multimodal analgesia, SPI-guided opioid-free anaesthesia halved the incidence of PONV after thoracoscopic lung resection, although it was associated with a longer stay in the PACU.Clinical trial registrationChinese Clinical Trial Registry (ChiCTR2200059710).

Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR). AgRP-specific MOR expression increases by energy surfeit and contributes to opioid-induced suppression of appetite. Conversely, its antagonists diminish suppression of AgRP neuron activity by food and satiety hormones. Mice with AgRP neuron-specific ablation of MOR expression have increased fat preference without increased motivation. These results suggest that post-ingestion release of endogenous opioids contributes to AgRP neuron inhibition to shape food choice through MOR signaling.

BACKGROUND: Opioid use remains a major public health issue, especially among young adults. Despite investment in harm reduction and supply-side strategies such as reducing overprescribing and safe medication disposal, little is known about demand-side issues, such as reasons for use and pathways to opioid use. Adolescents and young adults who struggle with opioid use disorder (OUD) are multifaceted individuals with varied individual histories, experiences, challenges, skills, relationships, and lives. METHODS: To inform the development of prevention strategies that hold promise for addressing opioid use, this study employs brief structured surveys and semi-structured in-depth interviews with 30 young adults (ages 18-29; 19 female, 23 White, 16 from Suburban areas) in recovery from OUD. For survey data, we used descriptive statistics to summarize the means and variance of retrospectively reported risk and protective factors associated with opioid use. For in-depth interview data, we used a combination of thematic analysis and codebook approaches to generate common themes and experiences shared by participants. RESULTS: Surveys revealed that the most endorsed risk factors pertained to emotions (emotional neglect and emotional abuse) followed by sexual abuse, physical abuse, and physical neglect. Themes generated from qualitative analyses reveal challenging experiences during adolescence, such as unaddressed mental health, social, and emotional needs, which were often reported as reasons for opioid initiation and use. Through surveys and interviews, we also identified positive assets, such as skills and social relationships that were present for many participants during adolescence. CONCLUSION: Implications include the need for universal prevention strategies that include emotion-focused interventions and supports alongside current harm reduction and environmental strategies to regulate prescriptions; the potential utility of more emotion-focused items being included on screening tools; and more voices of young people in recovery.

BACKGROUND: The overdose crisis driven by synthetic opioids continues to escalate in the USA. We evaluated the efficacy of multiple manufacturing lots of a fentanyl test strip (FTS) to detect fentanyl and fentanyl analogs and assessed cross-reactivity with possible interferences. METHODS: Drug standards were dissolved in water in a laboratory setting and serially diluted. Drug dilutions were tested using five different manufacturing lots of BTNX Rapid Response (20 ng/mL cutoff) lateral flow chromatographic immunoassay strips to assess lot-to-lot variability for FTS sensitivity and cross-reactivity for the analytes of interest. RESULTS: All five manufacturing lots cross-reacted with fentanyl and eleven fentanyl analogs. Diphenhydramine, lidocaine, MDMA, and methamphetamine were found to cause false positives with the strips. There was notable lot-to-lot variability in the sensitivity of the strips for fentanyl, fentanyl analogs, and known interferences. DISCUSSION: FTS remains an important overdose prevention tool, but lot-to-lot variability in performance complicates robust instructions that balance the prevention of false positives and false negatives. Continued lot-to-lot performance assessment is recommended to ensure health education for FTS remains accurate. More sophisticated drug checking technologies and services are needed in the community landscape to augment personal FTS use to facilitate informed consumption and overdose risk mitigation.

BackgroundThis study evaluated the real-world impact of acupuncture on analgesics and healthcare resource utilization among breast cancer survivors.MethodsFrom a United States (US) commercial claims database (25% random sample of IQVIA PharMetrics® Plus for Academics), we selected 18-63 years old malignant breast cancer survivors experiencing pain and ≥ 1 year removed from cancer diagnosis. Using the difference-in-difference technique, annualized changes in analgesics [prevalence, rates of short-term (

PURPOSE: Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery. METHODS: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1. RESULTS: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups. CONCLUSION: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052085).

ObjectiveMany persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood.Method and participantsStudy participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time.ResultsHPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14.ConclusionsWorsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation.

BackgroundWe aimed to characterize pain and analgesic use in a large contemporary cohort of patients with cirrhosis and to associate pain with unplanned health care utilization and clinical outcomes in this population.MethodsWe included all patients with cirrhosis seen in UCSF hepatology clinics from 2013 to 2020. Pain severity and location were determined using documented pain scores at the initial visit; "significant pain" was defined as moderate or severe using established cutoffs. Demographic, clinical, and medication data were abstracted from electronic medical records. Associations between significant pain and our primary outcome of 1-year unplanned health care utilization (ie, emergency department visit or hospitalization) and our secondary outcomes of mortality and liver transplantation were explored in multivariable models.ResultsAmong 5333 patients with cirrhosis, 32% had a nonzero pain score at their initial visit and 25% had significant (ie moderate/severe) pain. Sixty percent of patients with significant pain used ≥1 analgesic; 34% used opioids. Patients with cirrhosis with significant pain had similar Model for End-Stage Liver Disease-Sodium scores (14 vs. 13), but higher rates of decompensation (65% vs. 55%). The most common pain location was the abdomen (44%). Patients with abdominal pain, compared to pain in other locations, were more likely to have decompensation (72% vs. 56%). Significant pain was independently associated with unplanned health care utilization (adjusted odds ratio: 1.3, 95% CI: 1.1-1.5) and mortality (adjusted hazard ratio: 1.4, 95% CI: 1.2-1.6).ConclusionsPain among patients with cirrhosis is often not well-controlled despite analgesic use, and significant pain is associated with unplanned health care utilization and mortality in this population. Effectively identifying and treating pain are essential in reducing costs and improving quality of life and outcomes among patients with cirrhosis.

BackgroundThe rates of suicide and opioid use disorder (OUD) among pregnant and postpartum women continue to increase. This research characterized OUD and suicide attempts among Medicaid-enrolled perinatal women and examined prenatal OUD diagnosis as a marker for postpartum suicide attempts.MethodsData from Oregon birth certificates, Medicaid eligibility and claims files, and hospital discharge records were linked and analyzed. The sample included Oregon Medicaid women aged 15-44 who became pregnant and gave live births between January 2008 and January 2016 (N = 61,481). Key measures included indicators of suicide attempts (separately for any means and opioid poisoning) and OUD diagnosis, separately assessed during pregnancy and the one-year postpartum period. Probit regression was used to examine the overall relationship between prenatal OUD diagnosis and postpartum suicide attempts. A simultaneous equations model was employed to explore the link between prenatal OUD diagnosis and postpartum suicide attempts, mediated by postpartum OUD diagnosis.ResultsThirty-three prenatal suicide attempts by any means were identified. Postpartum suicide attempts were more frequent with 58 attempts, corresponding to a rate of 94.3 attempts per 100,000. Of these attempts, 79% (46 attempts) involved opioid poisoning. A total of 1,799 unique women (4.6% of the sample) were diagnosed with OUD either during pregnancy or one-year postpartum with 53% receiving the diagnosis postpartum. Postpartum suicide attempts by opioid poisoning increased from 55.5 per 100,000 in 2009 to 105.1 per 100,000 in 2016. The rate of prenatal OUD also almost doubled over the same period. Prenatal OUD diagnosis was associated with a 0.15%-point increase in the probability of suicide attempts by opioid poisoning within the first year postpartum. This increase reflects a three-fold increase compared to the rate for women without a prenatal OUD diagnosis. A prenatal OUD diagnosis was significantly associated with an elevated risk of postpartum suicide attempts by opioid poisoning via a postpartum OUD diagnosis.ConclusionsThe risk of suicide attempt by opioid poisoning is elevated for Medicaid-enrolled reproductive-age women during pregnancy and postpartum. Women diagnosed with prenatal OUD may face an increased risk of postpartum suicides attempts involving opioid poisoning.

Background: Older head and neck cancer (HNC) survivors have concerning rates of potentially unsafe opioid prescribing. Identifying the specialties of opioid prescribers for HNC survivors is critical for targeting the settings for opioid safety interventions. This study hypothesized that oncology and surgery providers are primarily responsible for opioid prescriptions in the year after treatment but that primary care providers (PCPs) are increasingly involved in prescribing over time. Methods: Using linked Surveillance, Epidemiology, and End Results–Medicare data, a retrospective analysis was conducted of adults aged >65 years diagnosed between 2014 and 2017 with stage I–III HNC and who had ≥6 months of treatment‐free follow‐up through 2019. Starting at treatment completion, opioid fills were assigned to a prescriber specialty: oncology, surgery, primary care, pain management, or other. Prescriber patterns were summarized for each year of follow‐up. Multinomial logistic regression models captured the likelihood of opioids being prescribed by each specialty. Results: Among 5135 HNC survivors, 2547 (50%) had ≥1 opioid fill (median, 2.1‐year follow‐up). PCPs prescribed 47% of all fills (42%–55% each year). PCPs prescribed opioids to 45% of survivors with ≥1 opioid fill, which was a greater share than other specialties. PCPs prescribed longer supplies of opioids (median, 20 days/fill; median, 30 days/year) than oncologists or surgeons. The likelihood of an opioid being prescribed by an oncology provider was four times lower than that of it being prescribed by a PCP. Conclusions: PCP involvement in opioid prescribing remains high throughout HNC survivorship. Interventions to improve the safety of opioid prescribing should target primary care, as is typical for opioid reduction efforts in the noncancer population. Half of older head and neck cancer (HNC) survivors, who experience a high burden of pain after treatment completion, fill opioid prescriptions in the early years after treatment completion, and those who fill opioid prescriptions are most likely to have their opioids prescribed by a primary care provider. Further exploration of opioid safety among HNC survivors, and interventions to improve opioid safety, should focus largely on primary care settings in the early years after treatment completion. [ABSTRACT FROM AUTHOR]

Background: Pain is a common, severe symptom related to endometriosis. Despite this prominent feature, there is limited literature regarding its description and use of integrative treatment methods. Objective: We aimed to describe endometriosis-related pain characteristics, severity, and association with an integrative approach encompassing pharmacological and non-pharmacological methods. Methods: A cross-sectional descriptive correlational study was conducted using convenience sampling of adult women with endometriosis-related pain. Three questionnaires were utilized: a demographic and general health questionnaire, a visual analog pain scale (VAS), and the short-form McGill pain questionnaire (SF-MPQ). Results: Participants included 93 women with a mean general pain level of 6.2/10 (SD = 2.7) on the VAS. The total mean pain score on the SF-MPQ was 26.25/45 (SD = 10.1). Sixty-four women (68.8%) reported experiencing pain at the time of completion of the questionnaire (mean: 1.6/4, SD = 1.3). All participants utilized analgesia; those who used opioids reported a higher overall mean pain score of 2.3 (SD = 1.3) than patients who did not use opioids reported a mean of 1.4 (SD = 1.2; z = 9.59; P <.001). Present pain intensity was significantly higher for women using opioids than those not using opioids. In all, 77 women (82.8%) used integrative methods to alleviate the pain symptoms. Women who utilized nutritional therapy as part of the non-pharmacological method experienced lower mean (SD) overall pain (4.4 [2.5]) compared with patients who did not utilize nutritional therapy (6.75 [2.5]; P <.01). Conclusions: More studies are needed to find evidence-based treatment options for women for integrative pain relief for endometriosis-related pain. [ABSTRACT FROM AUTHOR]

Background: Pain is one of the common postoperative issues that impair recovery and quality of life in patients undergoing coronary artery bypass graft (CABG) surgery. It leads to prolonged recovery and sleep disturbances in patients. Aim: This study was conducted to examine the effect of eye mask use on sleep quality and pain in patients undergoing CABG surgery. Study Design: A double‐blind randomized trial design was employed. The study included 60 patients undergoing CABG surgery. They were divided into intervention and control groups through block randomization. Data were collected using a 'Demographic Characteristics Form', the 'Richards‐Campbell Sleep Questionnaire (RCSQ)' and a 'Visual Analogue Scale' (VAS) through face‐to‐face interviews. While patients in the control group received standard care throughout the night, patients in the intervention group received standard care and used eye mask. All patients were followed up for three nights. The CONSORT was used to report the study. Results: The main outcome of the study, the RCSQ score, was higher in the intervention group at baseline. The intervention group had higher RCSQ scores than the control group at time 1 and time 2. There were no differences between the groups in the secondary outcome, pain levels. The control group had higher pain scores at time 1 and time 2 than the intervention group. Conclusion: The use of an eye mask after CABG surgery is an effective, safe and simple nursing intervention to improve sleep quality and control pain. Relevance to Clinical Practice: Because the use of an eye mask is an independent and unique nursing intervention, nurses should be supported and allowed to practise it. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation is a core intervention in critical care, but may also lead to negative consequences. Therefore, ventilator weaning is crucial for patient recovery. Numerous weaning interventions have been investigated, but an overview of interventions to evaluate different foci on weaning research is still missing. Aim: To provide an overview of interventions associated with ventilator weaning. Study Design: We conducted a scoping review. A systematic search of the Medline, CINAHL and Cochrane Library databases was carried out in May 2023. Interventions from studies or reviews that aimed to extubate or decannulate mechanically ventilated patients in intensive care units were included. Studies concerning children, outpatients or non‐invasive ventilation were excluded. Screening and data extraction were conducted independently by three reviewers. Identified interventions were thematically analysed and clustered. Results: Of the 7175 records identified, 193 studies were included. A total of six clusters were formed: entitled enteral nutrition (three studies), tracheostomy (17 studies), physical treatment (13 studies), ventilation modes and settings (47 studies), intervention bundles (42 studies), and pharmacological interventions including analgesic agents (8 studies), sedative agents (53 studies) and other agents (15 studies). Conclusions: Ventilator weaning is widely researched with a special focus on ventilation modes and pharmacological agents. Some aspects remain poorly researched or unaddressed (e.g. nutrition, delirium treatment, sleep promotion). Relevance to Clinical Practice: This review compiles studies on ventilator weaning interventions in thematic clusters, highlighting the need for multidisciplinary care and consideration of various interventions. Future research should combine different interventions and investigate their interconnection. [ABSTRACT FROM AUTHOR]

Chronic pain is a constantly recurring and persistent illness, presenting a formidable healthcare challenge for patients and physicians alike. Current first‐line analgesics offer only low‐modest efficacy when averaged across populations, further contributing to this debilitating disease burden. Moreover, many recent trials for novel analgesics have not met primary efficacy endpoints, which is particularly striking considering the pharmacological advances have provided a range of highly relevant new drug targets. Heterogeneity within chronic pain cohorts is increasingly understood to play a critical role in these failures of treatment and drug discovery, with some patients deriving substantial benefits from a given intervention while it has little‐to‐no effect on others. As such, current treatment failures may not result from a true lack of efficacy, but rather a failure to target individuals whose pain is driven by mechanisms which it therapeutically modulates. This necessitates a move towards phenotypical stratification of patients to delineate responders and non‐responders in a mechanistically driven manner. In this article, we outline a bench‐to‐bedside roadmap for this transition to mechanistically informed personalised pain medicine. We emphasise how the successful identification of novel analgesics is dependent on rigorous experimental design as well as the validity of models and translatability of outcome measures between the animal model and patients. Subsequently, we discuss general and specific aspects of human trial design to address heterogeneity in patient populations to increase the chance of identifying effective analgesics. Finally, we show how stratification approaches can be brought into clinical routine to the benefit of patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Opioids are known to cause respiratory depression, aspiration, and to suppress the immune system. This study aimed to investigate the relationship between short- and long-term opioid use and the occurrence and clinical outcomes of pneumonia in South Korea. METHODS: The data for this population-based retrospective cohort analysis were obtained from the South Korean National Health Insurance Service. The opioid user group consisted of those prescribed opioids in 2016, while the non-user group, who did not receive opioid prescriptions that year, was selected using a 1:1 stratified random sampling method. The opioid users were categorized into short-term (1-89 d) and long-term (≥90 d) users. The primary end point was pneumonia incidence from January 1, 2017-December 31, 2021, with secondary end points including pneumonia-related hospitalizations and mortality rates during the study period. RESULTS: In total, 4,556,606 adults were enrolled (opioid group, 2,070,039). Opioid users had a 3% higher risk of pneumonia and an 11% higher risk of pneumonia requiring hospitalization compared to non-users. Short-term users had a 3% higher risk of pneumonia, and long-term users had a 4% higher risk compared to non-users (P < .001). Additionally, short-term users had an 8% higher risk of hospital-treated pneumonia, and long-term users had a 17% higher risk compared to non-users (P < .001). CONCLUSIONS: Both short- and long-term opioid prescriptions were associated with higher incidences of pneumonia and hospital-treated pneumonia. In addition, long-term opioid prescriptions were linked to higher mortality rates due to pneumonia. [ABSTRACT FROM AUTHOR]

Anterior Iliac crest bone harvesting (AICBH) is a common surgical procedure with applications in various medical specialties, but it is often accompanied by significant postoperative pain. Effective pain management is therefore essential for optimising patient outcomes. This systematic literature review aimed to evaluate the effectiveness of local donor site pain management interventions in AICBH procedures. It followed the Cochrane Handbook for Systematic Reviews of Interventions version 6.4 guidelines and adhered to the PRISMA 2020 statement for comprehensive and high-quality reporting. A comprehensive search was conducted across PubMed, Cochrane, and Embase to identify relevant studies. Inclusion criteria encompassed randomised controlled trials assessing pain management strategies in AICBH patients. The methodological quality of the included studies was assessed using the Jadad scale. Data extraction focused on medication types, administration modes, pain scores, and use of narcotics. Fourteen eligible studies were included. Methodological quality varied, with most studies demonstrating a low risk of bias. Medication types included amide and opioid groups, administered via single-shot injections or infusion systems. Results indicated that indwelling iliac crest catheters with bupivacaine showed significant postoperative reductions in pain scores and narcotics use compared with other techniques. The findings suggest that use of an indwelling catheter with bupivacaine is an effective pain management strategy for AICBH patients. However, heterogeneity among the studies and a lack of standardised methodologies pose limitations. Further homogeneous and standardised studies are therefore needed to strengthen the evidence base and inform clinical practice. [ABSTRACT FROM AUTHOR]

Background: Many patients with chronic obstructive pulmonary disease and fibrotic interstitial lung disease suffer from severe dyspnea and reduced quality of life, despite receiving optimal disease-modifying treatment for their illness. Studies have suggested that these patients may benefit from treatment with low-dose opioids. However, many patients decline opioid treatment. This has led to patients not receiving proper palliative treatment of their lung disease. Aim: To identify potential barriers that prevent patients from receiving adequate palliative care with opioids and enable doctors to address patients' concerns. Design: A qualitative study based on semi-structured interviews. Interviews were transcribed and thematic analysis was done using NVivo. Setting/Participants: Patients were recruited when scheduled for out-patient follow-up at Center for Rare Lung Diseases or at the COPD clinic, Aarhus University Hospital. Eligible patients were 18 years of age, did not currently receive opioids or had ever received opioids for dyspnea. Results: A total of 28 patients participated. One patient was excluded before final analysis of 27 patients. Four themes were identified: Fear of side-effects, Need for more information, Stigma of opioids association with severe illness and dying, and No discernible barriers. Furthermore, three sub-themes to Fear of side-effects were identified: Fear of addiction, concern for sedative effect, and fear for loss of mobility due to inability to drive a car. The most expressed concern was Fear of side-effects, especially addiction. Conclusions: Pre-conceived notions about opioids prevent some patients with chronic obstructive lung disease or interstitial lung disease from receiving palliative care for breathlessness. [ABSTRACT FROM AUTHOR]

The opioid epidemic continues to have a staggering impact on millions of individuals and families across all socioeconomic levels and communities. Recent studies suggest high numbers of patients presenting for surgery with reported opioid misuse and/or opioid use disorder (OUD). Anesthesiologists often lack basic education to treat patients suffering with OUD or patients in recovery from this treatable disease. This manuscript will provide a review of the American Society of Anesthesiology and Pain Medicine Multisociety Working Group Practice Advisory recommendations on existing OUD treatment barriers and perioperative management best practices; it will also demonstrate the benefits that greater involvement of the anesthesiologist can have in managing patients with OUD perioperatively. [ABSTRACT FROM AUTHOR]

Background: Dentin hypersensitivity (DH) is a common oral condition that is associated with severe dental pain. Pain relief is a key focus of the treatment of DH. The purpose of this study was to evaluate the blocking and antacid effects of gallic acid (GA) combined with sodium fluoride (NaF) on dentinal tubules in vitro. Methods: Ninety dentin discs from human third molars were treated with 6% citric acid for 2 min. Then, the surface morphologies of ten dentin discs were observed by scanning electron microscopy (SEM). The remaining samples were randomly divided into four groups: the NaF group, which was treated with 1000 ppm NaF; the GA group, which was treated with 4000 ppm GA; the GA + NaF group, which was treated with 1000 ppm NaF + 4000 ppm GA; and the blank group, which was treated with deionized water. The dentin permeability of each sample was measured with a water-filled system before processing and after 7 days of treatment. Dentin morphology and surface deposits were observed by SEM. Then, samples from the NaF, GA + NaF and blank groups were subjected to an acid challenge by incubation with 0.02% citric acid for 2 min. SEM and a water-filled system were used to evaluate the blocking and antacid effects of NaF and GA + NaF. Results: 1. NaF and GA + NaF significantly decreased dentin permeability. The effect of the GA + NaF treatment was more significant. After acid challenge, both groups still exhibited decreased dentin permeability compared with the initial assessment. 2. Compared with the NaF group, the GA + NaF group had more mineral deposits on the dentin surface and dentin tubules. After acid challenge, the deposits in the GA + NaF group were still clearly visible. Conclusion: The combined effect of GA and NaF on reducing dentin permeability by blocking open dentin tubules is better than that of NaF alone. After acid challenge, the GA + NaF treatment still had a better effect. [ABSTRACT FROM AUTHOR]

Background: Renal colic is characterized by severe pain that is highly disabling. Gabapentin, an antiepileptic medication, is often recommended as a first-line therapy for neuropathic pain. However, its effectiveness in managing somatic pain, which is defined as the result of activity by pain receptors in the deep tissues, such as renal colic pain, is not as well-established. Method: A phase 3 randomized clinical trial was conducted to evaluate the adjuvant analgesic effects of gabapentin on acute renal colic pain. Eligible patients participated in the study via random allocation to the control or gabapentin groups using the block randomization method. All patients received a shared regimen of ketorolac and rescue morphine as the conventional analgesic treatment for renal colic pain. Gabapentin was added as an adjuvant analgesic for the gabapentin group. Result: A total of 63 individuals with an average age of 41.35 ± 13.08, were enrolled and completed the study. At the time of admission, there were no significant differences between the baseline characteristics of two groups, with exception of weight. The gabapentin group showed a significantly higher percentage of patients with pain severity of less than 5 after 60 and 90 min, as well as a significantly lower percentage of morphine rescue requirement and total morphine intake (mg) and mg/kg. Conclusion: In cases of acute renal colic, gabapentin significantly decreases both the amount of morphine required and the degree of pain, indicating that it may be a useful adjutant to standard analgesic regimens. Treatment regimens that include gabapentin may help individuals manage their pain and become less reliant on opioids. [ABSTRACT FROM AUTHOR]

Spine procedures are commonly performed to diagnose and treat various spinal conditions, ranging from degenerative disc disease to vertebral fractures. These procedures often involve the use of pharmaceutical agents to enhance the efficacy of the intervention and improve patient outcomes. This review provides an overview of the pharmaceuticals commonly utilized in spine procedures, including corticosteroids, anesthetics, antibiotics, radiographic contrast, neurolytic agents, and materials used in kyphoplasty and vertebroplasty. This review summarizes the utilization of these pharmaceutical agents in spine procedures in an effort to optimize patient outcomes. Understanding the pharmacological properties and appropriate uses of these pharmaceuticals is essential for interventionalist and healthcare providers involved in the care of patients undergoing spinal interventions. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hydroxyurea (HU) is an effective medication used to reduce the frequency of painful crises associated with sickle cell disease (SCD). However, data describing its prevalence among SCD patients in the Eastern Region of Saudi Arabia are scarce. This is a multi-center, retrospective, cross-sectional study that aims to investigate the pattern of prescribing HU in SCD patients and to determine the association between prescribing HU and other co-prescribed medications used to manage SCD complications. Methods: Data were collected from patients who visited the hematology clinics of Al-Qatif Central Hospital (QCH) and King Fahad Hospital in Hofuf (KFHH) between June 2021 to May 2023. The data included demographics, prescribed medications, and recent laboratory test results, all of which were collected from patients' medical records. Descriptive statistics were utilized to assess the difference between HU users vs. non-users. A binary logistic regression model was used to determine the association between prescribing HU and co-prescribed medications used to manage SCD complications. The results are presented as the odds ratio (OR) and 95% confidence interval (95% CI). Results: This study included 2816 SCD patients with a 56% prevalence of HU prescription. HU was prescribed for young age groups more often compared to old age group patients. Young males were more likely to be prescribed with HU compared to females, and it becomes dominant in females after the age of 36. HU users were more likely to have paracetamol (69% vs. 53%, OR = 1.9, 95% CI 1.6–2.2), NSAIDs (50% vs. 35%, OR = 1.7, 95% CI 1.5–2), and opioids (41% vs. 37%, OR = 1.3, 95% CI 1.1–1.6) co-prescribed, and less often to have laxatives (8% vs. 5%, OR = 0.66, 95% CI 0.48–0.9) and anticoagulants (22% vs. 15%, OR = 0.56, 95% CI 0.46–0.68) co-prescribed compared to non-users. Conclusions: The pattern of prescribing HU, supported by the association findings, raises concerns about patients' compliance and adherence to HU therapy. Early health education, specifically to young female SCD patients, is warranted to increase the success rate of HU therapy. [ABSTRACT FROM AUTHOR]

Oleogels are semi-solid materials that consist primarily of liquid oil immobilized in a network of organized structural molecules, which provide stability and maintain the oil in the desired shape. Due to their structure, oleogels can stabilize large amounts of liquid, making them excellent carriers for active substances, both lipophilic and hydrophilic. This study presents the synthesis methodology and investigations of olive oil-based oleogels, which are among the healthiest and most valuable vegetable fats, rich in unsaturated fatty acids and antioxidants such as vitamin E. Two types of surfactants were used: TWEEN 80, which lowers surface tension and stabilizes emulsions, and SPAN 80, which acts in oil-dominated phases. The oleogels were enriched with lidocaine, an active substance commonly used as a pain reliever and local anesthetic. This research characterized the obtained oleogels regarding their medical applications, paying particular attention to the influence of surfactant type and amount as well as the active substance on their physicochemical properties. Structural analyses were also conducted using Fourier transform infrared (FTIR) spectroscopy, alongside rheological and sorption studies, and the wettability of the materials was evaluated. The stability of the obtained oleogels was verified using the MultiScan MS20 system, allowing for an assessment of their potential suitability for long-term pharmaceutical applications. The results indicated that SPAN-stabilized oleogels exhibited better stability and favorable mechanical properties, making them promising candidates for medical applications, particularly in pain relief formulations. [ABSTRACT FROM AUTHOR]

It remains unclear whether feedback from group III/IV muscle afferents is of continuous significance for regulating the pulmonary response during prolonged (>5 min), steady‐state exercise. To elucidate the influence of these sensory neurons on hyperpnoea, gas exchange efficiency, arterial oxygenation and acid–base balance during prolonged locomotor exercise, 13 healthy participants (4 females; 21 (3) years, V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$: 46 (8) ml/kg/min) performed consecutive constant‐load cycling bouts at ∼50% (20 min), ∼75% (20 min) and ∼100% (5 min) of V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ with intact (CTRL) and pharmacologically attenuated (lumbar intrathecal fentanyl; FENT) group III/IV muscle afferent feedback from the legs. Pulmonary responses were continuously recorded and arterial blood (radial catheter) periodically collected throughout the exercise. Pulmonary gas exchange efficiency was evaluated using the alveolar‐arterial PO2${{P}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ difference (A−aDO2${\mathrm{A - a}}{{D}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$). There were no differences in any of the variables of interest between conditions before the start of the exercise. Pulmonary ventilation was up to 20% lower across all intensities during FENT compared to CTRL exercise (P < 0.001) and this hypoventilation was accompanied by an up to 10% lower arterial PO2${{P}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and a 2–4 mmHg higher PCO2${{P}_{{\mathrm{C}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ (both P < 0.001). The exercise‐induced widening of A−aDO2${\mathrm{A - a}}{{D}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ was up to 25% larger during FENT compared to CTRL (P < 0.001). Importantly, the differences developed within the first minute of each stage and persisted, or further increased, throughout the remainder of each bout. These findings reflect a critical and time‐independent significance of feedback from group III/IV leg muscle afferents for continuously regulating the ventilatory response, gas exchange efficiency, arterial oxygenation and acid–base balance during human locomotion. Key points: Feedback from group III/IV leg muscle afferents reflexly contributes to hyperpnoea during short duration (i.e. <5 min) locomotor exercise.Whether continuous feedback from these sensory neurons is obligatory to ensure adequate pulmonary responses during steady‐state exercise of longer duration remains unknown.Lumbar intrathecal fentanyl was used to attenuate the central projection of group III/IV leg muscle afferents during prolonged locomotor exercise (i.e. 45 min) at intensities ranging from 50% to 100% of V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$.Without affecting the metabolic rate, afferent blockade compromised pulmonary ventilation and gas exchange efficiency, consistently impairing arterial oxygenation and facilitating respiratory acidosis throughout exercise.These findings reflect the time‐independent significance of feedback from group III/IV muscle afferents for regulating exercise hyperpnoea and gas exchange efficiency, and thus for optimizing arterial oxygenation and acid–base balance, during prolonged human locomotion. [ABSTRACT FROM AUTHOR]

Background: Headache disorders, including migraine, pose a significant burden globally, with varying prevalence rates across different regions. However, research on migraine in Nigeria and other low-income countries is limited. Understanding the prevalence, characteristics, and treatment outcomes of migraine in Nigeria is essential for informing healthcare policies and improving patient care. Methods: This systematic review and meta-analysis aimed to synthesize existing literature on migraine prevalence, characteristics, and treatment outcomes in Nigeria. Eligible studies were identified through comprehensive searches of multiple electronic databases and grey literature sources. Studies reporting migraine prevalence, diagnostic criteria, treatment modalities, and outcomes were included. Data extraction and quality assessment were performed following established guidelines. Results: Ten studies involving 7,768 participants met the inclusion criteria and were included in the meta-analysis. The pooled prevalence of migraine headache in Nigeria was calculated to be 16% (95% CI = 7–28), with significant heterogeneity observed among studies (I² = 99.35%, P < 0.001). Subgroup analysis revealed a higher prevalence of migraine among women compared to men. Common triggers for migraine included physical activity, sleep deprivation, mental and physical fatigue, and emotional stress. Treatment modalities varied, with simple analgesics, NSAIDs, ergotamine derivatives, and amitriptyline being commonly used. However, many participants reported inadequate pain relief or significant side effects, highlighting the need for improved management strategies. Conclusion: The findings of this systematic review and meta-analysis underscore the significant burden of migraine in Nigeria and the need for improved healthcare policies and interventions. Addressing gaps in access to specialized care and implementing more effective treatment regimens could help alleviate the burden of migraine on individuals and healthcare systems in Nigeria. Further research is needed to standardize diagnostic criteria and methodologies and provide more reliable prevalence estimates. [ABSTRACT FROM AUTHOR]