Site Pain Research Articles

Técnica de aplicación de la vacuna BCG y la presencia de reacciones adversas

The BCG vaccine is one of the first vaccines administered as part of the national immunization schedule, under the responsibility of nursing professionals. Its administration requires mastering the correct intradermal technique. Although it is considered one of the safest vaccines, it is not exempt from generating adverse reactions in the population. This study aimed to evaluate the BCG vaccine application technique associated with adverse reactions. Through a descriptive, correlational, and cross-sectional study at Health Center N°1, Riobamba-Ecuador, involving 8 licensed nurses, 2 nursing interns, and 31 children immunized with the BCG vaccine, two methodological instruments were implemented: an observation guide for BCG vaccine application and a survey to identify potential post-vaccination adverse effects, both validated by expert health professionals. The study revealed significant deficiencies in the vaccination procedure by nursing staff: 20% did not provide complete information about the process and post-vaccination care, 40% omitted hand disinfection prior to the procedure, 60% did not perform hand washing afterward, 30% did not adequately position the patient, and 30% failed to meet intradermal administration parameters. Regarding adverse reactions, the following were documented: injection site pain (12.9%), large pustule (9.7%), fever (3.2%), and keloid scar (3.2%), highlighting the need to improve vaccination and follow-up protocols. There is a correlation between the BCG vaccine application technique and the adverse reactions presented in immunized patients.

Exploring the Safety and Satisfaction of Patients Injected With Collagen Biostimulators-A Prospective Investigation Into Injectable Poly-l-Lactic Acid (PLLA).

Esthetic medicine has shifted significantly toward non-surgical procedures, with the collagen biostimulator poly-l-lactic acid (PLLA) becoming increasingly popular for facial rejuvenation. However, the safety and patient satisfaction associated with PLLA facial treatments remain largely unexplored. This study aimed to evaluate the safety profile of PLLA treatment and assess patient mid- and long-term satisfaction with the outcome. This prospective single-center study was conducted at Bravo Clinic in Rio de Janeiro from August 2023 to August 2024. The patients' mid and lower face was treated by injecting Rennova Elleva (a collagen biostimulator containing 210 mg of PLLA) into the zygomatic and pre-masseteric regions. All patients underwent monthly clinical evaluations for the first 150 days and kept diaries to self-record any adverse effects during the first 30 days. Patient satisfaction was measured using the Global Aesthetic Improvement Scale (GAIS) on days 90 and 150 post-injection. The study included 52 female patients [mean age: 49.87 ± 10.7 years; mean body mass index (BMI): 23.99 ± 3.5 kg/m2]. Patients reported mild to moderate injection site reactions, including redness, pain, hardening, swelling, lumps, bruises, and skin discoloration, with most symptoms resolving within a few days. Clinically, no major adverse events were noted, except for one small, painless nodulation that resolved without intervention. On post-injection Day 90, the average GAIS was rated at 2.32 ± 1.0. This rating remained stable at Day 150, with an average GAIS of 2.32 ± 0.8 (p = 0.862). Inverse correlations were identified between the duration of mild pain and GAIS (rs = -0.546, p = 0.035), as well as between the duration of mild bruises and GAIS (rs = -0.598, p = 0.019). The duration of moderate pain was significantly associated with age (rs = -0.894, p = 0.041). Rennova Elleva, a PLLA-based collagen biostimulator, is safe and well-tolerated with a low incidence of adverse effects. It provides long-lasting, satisfactory results for patients with mild to moderate facial sagging, rendering it an effective non-surgical option for enhancing facial esthetics.

Safety, effectiveness and immunogenicity of heterologous mRNA-1273 boost after prime with Ad26.COV2.S among healthcare workers in South Africa: The single-arm, open-label, phase 3 SHERPA study.

Limited studies have been conducted on the safety and effectiveness of heterologous COVID-19 vaccine boosting in lower income settings, especially those with high-HIV prevalence., The Sisonke Heterologous mRNA-1273 boost after prime with Ad26.COV2.S (SHERPA) trial evaluated a mRNA-1273 boost after Ad26.COV2.S priming in South Africa. SHERPA was a single-arm, open-label, phase 3 study nested in the Sisonke implementation trial of 500000 healthcare workers (HCWs). Sisonke participants were offered mRNA-1273 boosters between May and November 2022, when Omicron sub-lineages were circulating. Adverse events (AE) were self-reported, and co-primary endpoints (SARS-CoV-2 infections and COVID-19 hospitalizations or deaths) were collected through national databases. We used Cox regression models with booster status as a time-varying covariate to determine the relative vaccine effectiveness (rVE) of the mRNA-1273 booster among SHERPA versus unboosted Sisonke participants. Of 11248 SHERPA participants in the rVE analysis cohort (79.3% female, median age 41), 45.4% had received one and 54.6% two Ad26.COV2.S doses. Self-reported comorbidities included HIV (18.7%), hypertension (12.9%) and diabetes (4.6%). In multivariable analysis including 413161 unboosted Sisonke participants, rVE of the booster was 59% (95%CI 29-76%) against SARS-CoV-2 infection: 77% (95%CI 9-94%) in the one-Ad26.COV2.S dose group and 52% (95%CI 13-73%) in the two-dose group. Severe COVID-19 was identified in 148 unboosted Sisonke participants, and only one SHERPA participant with severe HIV-related immunosuppression. Of 11798 participants in the safety analysis, 228 (1.9%) participants reported 575 reactogenicity events within 7 days of the booster (most commonly injection site pain, malaise, myalgia, swelling, induration and fever). More reactogenicity events were reported among those with prior SARS-CoV-2 infections (adjusted odds ratio [aOR] 2.03, 95%CI 1.59-2.59) and less among people living with HIV (PLWH) (aOR 0.49, 95%CI 0.34-0.69). There were 115 unsolicited adverse events (AEs) within 28 days of vaccination. No related serious AEs were reported. In an immunogenicity sub-study, mRNA-1273 increased binding and neutralizing antibody titres and spike-specific T-cell responses 4 weeks after boosting regardless of the number of prior Ad26.COV2.S doses, or HIV status, and generated Omicron spike-specific cross-reactive responses. mRNA-1273 boosters after one or two Ad26.COV2.S doses were well-tolerated, safe and effective against Omicron SARS-CoV-2 infections among HCWs and PLWH. Trial registration: The SHERPA study is registered in the Pan African Clinical Trials Registry (PACTR): PACTR202310615330649 and the South African National Clinical Trial Registry (SANCTR): DOH-27-052022-5778.

Exploring the associations between the presence, characteristics, and biopsychosocial covariates of pain and lifetime depression in adolescents: A cross-sectional ABCD study analysis

IntroductionDepression and pain co-occur, even during adolescence. However, there is limited knowledge on the association between pain and lifetime depression, and which biopsychosocial measures are associated with this co-occurrence. MethodsCross-sectional analysis of the Adolescent Brain and Cognitive Development (ABCD) two-year follow-up. We explored associations between the presence and characteristics of past month pain (intensity, duration, activity limitations, and number of pain sites) and lifetime depression using logistic regression. We explored associations of brain structure, physical, behavioural, emotional, social, and cognitive measures with lifetime depression and past month pain compared to having had one or neither condition using multinomial logistic regression. ResultsA total of 5211 adolescents (mean age = 12.0 years) who had: (1) no lifetime mental ill-health and no pain (n = 3327); (2) pain only (n = 1407); (3) lifetime depressive disorder but no pain (n = 272); and (4) lifetime depressive disorder and pain (n = 205) were included. Pain presence was associated with lifetime depression (OR[95%CI]: 1.76 [1.45, 2.13], p < 0.001). Pain-related activity limitations (1.13 [1.06, 1.21], p < 0.001) and the number of pain sites (1.06 [1.02, 1.09], p < 0.001) were associated with lifetime depression. Various behavioural, emotional, social, and cognitive, but not brain structure or physical measures, were associated with lifetime depression and past month pain. LimitationsLongitudinal analyses should validate prognostic markers on predicting co-occurring depression and pain. ConclusionsResults support an association between the presence and characteristics of pain and lifetime depression during adolescence and could indicate the need for more integrated recognition and clinical care of youth experiencing both depression and pain.

Sleep and circadian rhythm disturbances as risk and progression factors for multiple chronic overlapping pain conditions: a protocol for a longitudinal study.

Chronic overlapping pain conditions (COPCs), such as chronic low back pain (cLBP) and fibromyalgia, frequently cooccur and incur substantial healthcare costs. However, to date, much focus has been placed on individual anatomically based chronic pain conditions, whereas little is known about the mechanisms underlying progression to multiple (more than 1) COPCs. This study aims to address the gap by investigating the role of common and modifiable risk factors, specifically sleep and circadian rhythm disturbances, in the development of multiple COPCs. The study will enroll 300 participants with cLBP, including 200 with cLBP only and 100 with cLBP plus other COPCs (ie, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and chronic headaches) and follow them up for 12 months. Sleep and circadian rhythms will be assessed using wireless sleep electroencephalography, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin, actigraphy, and sleep diaries. Pain amplification using quantitative sensory testing, psychological distress using validated self-report measures, and the number of pain sites using a pain body map will also be assessed. This research aims to (1) comprehensively characterize sleep/circadian disturbances in individuals with single and multiple COPCs using multimodal in-home assessments; (2) examine the associations between sleep/circadian disturbances, changes in pain amplification, and psychological distress; and (3) investigate the relationship among these factors and the progression in the number of pain sites, a proxy for multiple COPCs. The findings will provide insights into the mechanisms leading to multiple COPCs, potentially informing treatment and prevention strategies for these complex conditions.

Donor site morbidity of upper extremity flaps in head and neck reconstruction

ObjectiveThis retrospective cohort study aims to compare donor site morbidity of three commonly used upper extremity flaps used in head and neck reconstructive surgery: scapular tip free flap (STFF), radial forearm free flap (RFFF), and pectoralis major pedicled flap (PMPF). MethodsThe billing database of an urban, academic, tertiary otolaryngology practice was queried to identify patients who underwent STFF, RFFF, and PMPF from 2020 to 2023. The primary outcome was identification of donor site pain and need for physical therapy (PT) referral after undergoing reconstruction. ResultsSeventy-three patients (44 M:29F) underwent surgery that utilized upper extremity free or pedicled flaps. Patients undergoing free tissue transfer (FTT) were 5.455 times more likely to require PT referral compared to patients undergoing pedicled tissue transfer (PTT). Patients undergoing FTT were 3.417 times more likely to report donor site pain compared to patients undergoing PTT. There were no differences in post-operative PT referrals or post-operative donor site pain when comparing STFF or RFFF groups. Importantly, RFFF were primarily all fasciocutaneous flaps (33/35). ConclusionsThese findings have important implications when counselling patients regarding reconstructive options for complex head and neck surgery defects.

Phase I study of allogeneic monocyte-derived inflammatory dendritic cells in combination with pembrolizumab.

PD-1 checkpoint inhibition has revolutionized the care of cancer. A small portion of patients with stage IV cancer achieve durable control. But, early progression is common and dramatic control is achieved for only a minority. We hypothesized that ilixadencel, an allogeneic monocyte-derived dendritic cell product could be injected into tumor to potentiate PD-1 response and thus conducted a phase I study of pembrolizumab plus ilixadencel. Twenty-one patients were accrued. The most common treatment emergent adverse events were fatigue, injection site pain, anemia, weight decreased and hyponatremia, mostly grade 1-2. No dose limiting toxicities were observed and the recommended phase II dose was established at 10 million cells administered twice. Two unconfirmed responses were observed, with no confirmed responses.

Wide-margin excision of diffuse ankle's tendon sheath giant cell tumor in 24 patients:A mid-term study

Giant cell tumour of tendon sheath (TSGCT) is an uncommon soft tissue tumor, especially in its diffuse subtype (D-TSGCT), which is rare and associated with a high recurrence rate after treatment. This condition significantly affects joint function and quality of life. This retrospective study evaluated the clinical characteristics, surgical outcomes, and long-term follow-up of 24 patients who underwent wide-margin resection for ankle D-TSGCT from 2011 to 2018. The average patient age was 36.5 years, with common symptoms including palpable masses and ankle swelling. All patients received wide-margin resection, with a mean follow-up period of 75.7 months. Tumor recurrence occurred in five patients (21%), with complications included postoperative infections, surgical site pain, ankle instability, and stiffness. There was a significant improvement in the Musculoskeletal Tumor Society (MSTS) scores post-surgery. Additionally, the Foot and Ankle Ability Measure (FAAM) showed improvements in daily living and physical activities, though Ankle Joint Functional Assessment Tool (AJFAT) scores did not demonstrate significant change. These findings indicate that wide-margin resection is an effective treatment for D-TSGCT, preserving ankle function and demonstrating a low recurrence rate, although it may lead to ankle instability requiring careful postoperative monitoring and rehabilitation.

Disproportionality analysis of adverse events associated with asfotase alfa: a post-marketing study using the FDA Adverse Event Reporting System

ABSTRACT Background Asfotase alfa (AA) is an FDA-approved enzyme replacement therapy for hypophosphatasia (HPP). Limited real-world data on its adverse events (AEs) exist. This study evaluates AA-related AEs using the U.S. FDA’s Adverse Event Reporting System (FAERS) database. Methods Reports for AA were extracted from FAERS and analyzed per FDA guidelines. AEs were categorized using MedDRA version 26.1. Disproportionality analysis was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM) algorithms. Time-to-onset (TTO) was calculated, with a Weibull shape parameter test to assess risk over time. Results Out of 13,702,373 reports, 5,040 AA-related AEs were identified, with 198 significant preferred terms (PTs). Common AEs included injection site reactions and pain, with additional PTs for ear/labyrinth disorders and infections. The median onset for 234 AEs with reported times was 170 days (IQR 18–390 days). No significant differences in AEs were found across gender or age groups. Conclusion Most AEs align with known data, but newly identified ear/labyrinth disorders and infections require further investigation to enhance AA’s safety profile.

Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction over six months of treatment: A Phase 2, vehicle-controlled, randomized extension trial

PurposeTo determine the efficacy and safety of AZR-MD-001 (0.5 % and 1.0 %) ophthalmic ointment, relative to vehicle, over 3–6 months of treatment, in participants with meibomian gland dysfunction (MGD). MethodsThis was a Phase 2, randomized, vehicle-controlled, multicenter extension clinical trial. Eligible participants were adults with MGD (meibomian gland secretion score (MGS) ≤12 out of 15 glands) who discontinued all other dry eye or MGD treatments. Participants were randomized 1:1:1 to apply AZR-MD-001 1.0 %, 0.5 %, or vehicle to the lower eyelids, twice weekly. Key exploratory endpoints included the least-squared mean difference between groups in the change from baseline in clinical signs (meibomian gland yielding score; MGYLS) and symptoms (Ocular Surface Disease Index; OSDI), at clinic visits at Month 4.5 and 6, and safety measures from 36 months. ResultsParticipants (66.5 % female) were randomized, at baseline, to AZR-MD-001 0.5 % (n = 82), 1.0 % (n = 83), or vehicle (n = 80). Statistically significant improvements, compared to vehicle, were observed at Month 6 in MGYLS for both AZR-MD-001 groups (0.5 % group: 1.9, 95 % CI 0.9 to 2.8, P = 0.002; 1.0 % group: 1.1, 95 % CI 0.2 to 2.1, P = 0.026), and in OSDI score for the 0.5 % group (−4.5, 95 % CI -8.0 to −0.9, P = 0.0135). The most common adverse events for AZR-MD-001 were application site pain, superficial punctate keratitis and eye pain; most were mild to moderate in severity, and decreased in incidence over time. ConclusionsAZR-MD-001 (0.5 %) was efficacious in treating signs and symptoms of MGD over six months, with a lower observed incidence of new adverse events over time.

The disability profile in primary care may depend on the type of care and pain aspects.

OBJECTIVE: To investigate the relationship between sociodemographic factors, musculoskeletalpain and its characteristics, and the type of primary health care received with self-reported disability.METHODS: This is a cross-sectional study, interviewing individuals selected from spontaneous demand for health care in two types of care: health center and family health unit. Disability was investigated using the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 and characteristics of intensity, frequency, duration, number of pain sites, and regions. Measures of association between predictors and disability were performed with non-parametric statistical tests, whereas non-parametric regression models were presented for pain characteristics and for the general population.RESULTS: In total, 2.3% of family health users and 7.2% of health center users had severe levels ofdisability. Health center users had more self-reported disability than family health users (p &lt; 0.001). Fewer years of life (p = 0.034) and lower per capita income quintile (p = 0.014) were associated with greater disability. The most intense pain and pain in the greatest number of sites increased the disability score by 1.8 (95%CI = 1.0–2.6) and 6.3 (95%CI = 0.1–12.2) points, respectively. CONCLUSION: Users who had more disabilities sought care at walk-in health centers, had lower per capita income, presented musculoskeletal pain of worse intensity, and pain in a greater number of sites.

Multisite pain is longitudinally associated with an increased risk of fall among older adults with or at risk of knee osteoarthritis: data from the osteoarthritis initiative.

To examine the association between baseline multisite pain (two and three or more sites) and longitudinal risk of fall and recurrent falls among older adults with or at risk of knee osteoarthritis (OA). This prospective longitudinal cohort study included older adults with or at risk of knee OA. Fall, including the history of falls, number of falls, and recurrent falls, were assessed at baseline and during six follow-up visits at 12, 24, 36, 48, 72, and 96 months. Multisite pain was categorized into the following four categories: no pain, 1-site, 2-sites, ≥3-sites. This study included 2585 older adults. Baseline 2-sites (Odds Ratio [OR] 1.50, p = 0.018) and ≥ 3-sites (OR 1.89, p < 0.001) were significantly associated with increased risk of fall over time compared to no pain sites. Baseline 2-sites (Incidence Rate Ratio [IRR] 1.44, p = 0.024) and ≥ 3-sites (IRR 1.73, p < 0.001) were significantly associated with an increased number of falls over time. Only ≥3-sites were associated with the recurrent falls (OR 2.16, p = 0.003).Conclusions: Baseline multisite pain (≥3-sites) was longitudinally associated with increased fall incidence, number of falls, and recurrent falls over seven years of follow-up.

Ultrasound of Groin Pain in the Athlete.

Groin pain is a common cause of disability in athletes. Imaging is crucial in a clinical diagnosis, given the multiple associated etiologies. The main sites of groin pain are the adductors, iliopsoas muscles, inguinal ring, hip joint, and pubic symphysis. Although magnetic resonance imaging is the gold standard to image groin pain, ultrasound (US) offers excellent accuracy in pinpointing muscle injuries, inguinal disruption, and hernias. US requires a detailed knowledge of anatomical landmarks; imaging pitfalls, and pathologic patterns. We review the complex anatomy of the groin region, the sonographic appearance of the involved structures, and the strengths and weaknesses of US.

Evaluating the safety and efficacy of aminolevulinic acid 20% topical solution activated by blue light in the treatment of facial cutaneous squamous cell carcinoma in situ

Background: Cutaneous squamous cell carcinoma in situ (isSCC) is a common skin cancer occurring from sun exposure and often appears on the face. Treatment is primarily surgical but less invasive treatments are desirable. Currently, aminolevulinic acid for photodynamic therapy (ALA-PDT) is approved in the US and Canada for the treatment of single and multiple non-hyperkeratotic actinic keratoses of the face and scalp. This study evaluated the safety, tolerability, and efficacy of ALA-PDT for treatment of facial isSCC.Methods: Thirty-two patients with biopsy-confirmed isSCC on the face were recruited. Lesions 0.4–1.3 cm in diameter were included. Per the actinic keratosis treatment protocol, the lesion was debrided with a 4 x 4 gauze and ALA 20% topical solution was applied to the lesion and adjacent skin and incubated for 18–24 hours, followed by blue light therapy 16 minutes 40 seconds at 10 J/cm2. Patients underwent two treatments with ALA-PDT spaced 28 +/- 3 days apart. The area of the original lesion was excised eight weeks following the second treatment for histopathological assessment. The primary efficacy endpoint was the complete absence histologically of the isSCC at end of treatment. The secondary efficacy endpoint was the achievement of clinical clearance of the skin lesion. Safety assessment was done through adverse events and local skin reactions (LSRs; erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) and site pain within 15 minutes of each treatment session.Results: Of the 32 patients enrolled, two did not complete the study. No residual SCCis was detected in 30/30 (100%) patients. Clinical clearance was achieved in 30/30 (100%) of the patients by the end of treatment. None of the patients experienced related adverse events and only 2/30 (5%) experienced an AE of hypertension and was considered to be unrelated. The most common LSRs were erythema and scaling and were primarily mild, seen to occur immediately after both treatments and diminished over time. The average median ± SD immediate post-treatment pain score was 2.56 ± 2.15 on the VAS scale.Conclusion: The ALA-PDT protocol outlined in this study appears to be a very effective, safe and well-tolerated treatment option for isSCC on the face.

Results of a Phase 2 Multicenter Study Evaluating the Safety and Tolerability of VP-315, an Investigational Therapy for Basal Cell Carcinoma

Introduction VP-315 is an intratumorally injected, chemotherapeutic oncolytic peptide in development as a non-surgical immunotherapeutic agent to be utilized as first line therapy in a primary or neoadjuvant setting for patients with basal cell carcinoma (BCC). Objective In Part 2 of this study, the primary objective was to determine the optimal dosing regimen for VP-315 by exploring the effects of various dosing schemes on the safety and tolerability of VP-315 in a larger population of subjects with biopsy proven BCC. Methods Eighty-two (82) subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme: Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose). Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose). Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*). Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*). * Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later. Safety and tolerability were assessed by documenting the occurrence of Treatment Related Adverse Events (TRAEs), including those of special interest, Treatment Related Serious Adverse Events (TRSAEs), discontinuations due to AEs and expected treatment-related cutaneous reactions including tumor necrosis. Results All 82 subjects completed one of the VP-315 treatment regimens for BCC. TRAEs were mostly mild to moderate. AEs included injection site pain (mild 13.4%, moderate 12.2%, severe 1.2%), hypertension (mild 4.9%), hypotension (mild 4.9%), erythema (mild 1.2%, moderate 2.4%), and headache (mild 2.4%). Expected cutaneous reactions were observed. No TRSAEs were reported. Conclusion VP-315 treatment was shown to be safe and well-tolerated when administered once daily 2-3 times per week per tumor for up to 2 weeks using a split dose approach. Given its favorable safety profile, VP-315 warrants continued research as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting. Sponsored by Verrica Pharmaceuticals Inc.

Bimekizumab Safe and Effective Self-administration Using 2 mL Devices by Patients with Moderate to Severe Plaque Psoriasis: Results from Two Multicenter, Randomized, Open-label Studies

Introduction: Safe and effective self-injection of subcutaneous bimekizumab (BKZ) in patients with moderate to severe plaque psoriasis using a 1­ mL safety syringe (sy) or auto-injector (AI) has previously been associated with an overall positive patient experience.1 Here, the ability of patients to safely and effectively self-administer subcutaneous BKZ using a 2 mL sy or AI is reported. Methods: DV0002 (North America) and DV0006 (Germany, Hungary and Poland) were sub-studies of the phase 3 open-label extension (OLE) study, BE BRIGHT.1,2 Included patients received BKZ 320 mg every 4 weeks (Q4W) or Q8W based on treatment regimen and Psoriasis Area Severity Index (PASI) response at BE BRIGHT entry. Patients were randomized 1:1 to BKZ-sy-2 mL or BKZ-AI-2 mL, and performed self-injections (after training in the self-injection technique) at baseline and Wk8. Safe and effective self-injection defined as complete dose delivery of BKZ and absence of adverse events related to the device which led to study withdrawal. Primary and secondary objectives were to assess patients’ ability to safely and effectively self-administer BKZ at Wk8 and baseline, respectively. Other objectives included to evaluate patient experience of self-injection, using the injection site pain visual analog scale (VAS; 0 [no pain]–100 [worst possible pain]) and the Self-Injection Assessment Questionnaire (SIAQ; subscale scores ranged 0-10 [higher scores better]), and the post-use structural and mechanical integrity of each device. Data analyzed using two full analysis sets (BKZ-sy-2 mL and BKZ-AI-2 mL) and reported for the combined BKZ dose groups (BKZ Total) using observed cases. Results: In DV0002, 19 patients each were randomized to use BKZ-sy-2 mL and BKZ-AI-2 mL. All patients using BKZ-sy-2 mL (n=19) self-injected BKZ safely and effectively at baseline and Wk8. All (n=19) and 94.7% (n=18/19) of patients using BKZ-AI-2 mL self-injected BKZ safely and effectively at baseline and Wk8, respectively. In DV0006, 44 and 45 patients were randomized to use BKZ-sy-2 mL and BKZ-AI-2 mL, respectively. All patients using BKZ-sy-2 mL (n=44) and BKZ-AI-2 mL (n=45) safely and effectively self-injected BKZ at baseline and Wk8. In DV0002/6, median pre-injection and post-injection SIAQ scores were ≥7.5 across both devices, and &gt;9.0 for feelings about injections, self-image, and injection-site reactions subscales. In DV0002/6, low median VAS scores across both devices indicate variable but generally low pain. All devices maintained their structural and functional integrity post-use. One device deficiency complaint was received. Conclusions: A positive self-administration experience was associated with the 2 mL devices, as reported with 1 mL devices,1 providing patients with an option to self-administer a single injection of BKZ.

Musculoskeletal pain is associated with poor sleep quality and increased daytime sleepiness in dental students: a cross-sectional pilot study.

While a bidirectional relationship between sleep health and musculoskeletal (MSK)-pain have been established among chronic pain patients, few studies explored it among dental students. This cross-sectional study assessed the relationship of self-report MSK-pain with sleep health and psychological outcomes among dental students, and whether differences existed as a function of number and location of painful body-sites. Validated questionnaires were sent through REDCap to dental students at a predoctoral dental school, assessing presence, location (head, shoulder/neck, jaw, back, body), and intensity of MSK-pain, sleep health (risk of sleep apnea, insomnia severity symptoms, sleep quality, daytime sleepiness, and chronotype), and psychological outcomes (anxiety/depression). Differences between those with and without MSK-pain, and across participants with different number and location of painful sites were tested with t-tests and ANOVA, adjusting for age/gender. Out of 80 participants (82.5% females), 76.3% reported MSK-pain (68.9% in neck/shoulders). Those with MSK-pain scored significantly worse in sleep quality (7.7±3.7 vs. 4.8±2.1, p<.001), daytime sleepiness (6.1±4.2 vs. 3.3±2.7, p<.001). Those with >3 painful body-sites reported worse sleep quality (p=.006) and daytime sleepiness (p=.003) than pain-free controls. There were no differences on sleep and psychological outcomes as a function of number of painful body-sites. Those reporting back pain scored worse in insomnia (p=.037), daytime sleepiness (p=.002), and sleep quality (p=.006) than those without back pain. MSK-pain is prevalent among dental students and associated with worse sleep health. While number of painful sites may not influence sleep/psychological health, specific locations (e.g., back pain) were associated with worse sleep functioning.

A Single-Dose Study to Evaluate the Relative Bioavailability, Safety, and Tolerability of Monthly Extended-Release Buprenorphine at Alternative Injection Locations in Adult Participants with Opioid Use Disorder.

Buprenorphine extended-release monthly formulation (BUP-XR, SUBLOCADE®) is approved for treatment of moderate-to-severe opioid use disorder (OUD) following subcutaneous injection in the abdomen. This open-label pharmacokinetic study assessed three alternative injection locations (upper arm, thigh, buttocks) to offer additional flexibility considering the chronic nature of the disease and patient preferences. Following stabilization on 12/3 mg/day of sublingual buprenorphine/naloxone for ≥ 7 days, participants with moderate-to-severe OUD were randomized to receive a single 300-mg BUP-XR injection in the upper arm, thigh, buttocks, or abdomen (reference). Serial blood samples were taken to measure buprenorphine plasma concentrations over 28 days and assess buprenorphine relative bioavailability. Safety evaluations included treatment-emergent adverse events and assessments of injection site pain, tenderness, erythema, induration, and swelling. A total of 88 participants received a single subcutaneous injection of 300-mg BUP-XR in the upper arm (N = 21), thigh (N = 23), buttocks (N = 22), or abdomen (N = 22); 81/88 (92%) completed the study. Buprenorphine plasma exposure (area under the plasma concentration-time curve over 28 days) was comparable across injection site groups with mean buprenorphine plasma concentrations sustained at approximately 2 ng/mL (therapeutic target concentration) or above. Buprenorphine maximum plasma concentration (Cmax) was approximately 39% and 52% higher after injection in the upper arm and thigh, respectively, versus the abdomen, while comparable between buttocks and abdomen. Higher Cmax values were not associated with an increased incidence of adverse events. Safety and injection site tolerability were comparable across injection groups. These pharmacokinetic and safety findings support BUP-XR injection into the upper arm, thigh, and buttocks. Clinicaltrials.gov: NCT05704543.

Subcutaneous furosemide in heart failure: a systematic review.

Intravenous loop diuretics are the primary treatment for congestion in patients with decompensated heart failure (HF). Furosemide is the most commonly used loop diuretic and is licensed for administration either orally, intramuscularly or intravenously but not subcutaneously. Recently developed, pH-neutral, concentrated, 'skin-friendly' preparations of furosemide have been developed which allow subcutaneous administration. In this systematic review, we summarize and critically appraise the current evidence for subcutaneous furosemide in patients with HF. The electronic databases MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov registry were searched up to 31 December 2023. Of the 17 studies identified, 5 were randomised controlled trials (RCTs), 2 were non-randomised controlled studies, 3 were prospective observational cohort studies, and 7 were retrospective observational studies.All RCTs utilised novel pH-neutral, subcutaneous preparations of furosemide. Bioavailability of novel subcutaneous preparations were similar to intravenous furosemide 10mg/ml: 99.7% for an 8mg/ml preparation and 112% for a 30mg/ml preparation. Natriuresis and diuresis were also similar with novel subcutaneous and conventional intravenous furosemide. Adverse events of novel preparations included infusion site pain or discomfort, localised skin erythema and minimal swelling. All studies of conventional subcutaneous furosemide were non-randomised with very limited data re bioavailability or diuretic and natriuretic effect. Conventional subcutaneous furosemide was associated with substantial skin irritation (affecting 3-23% of patients), and skin infections requiring treatment with antibiotics (3-17%). Novel, pH-neutral preparations of subcutaneous furosemide achieved similar diuresis, natriuresis, and bioavailability to intravenous furosemide, and were well tolerated. Novel preparations may be a treatment option for patients with HF.

Analysis of tirzepatide in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and sex-specific subgroups.

Tirzepatide, a novel GIP and GLP1 agonist, has been extensively examined in clinical trials. However, specific data on its adverse drug events (ADEs) remain limited. This study aims to comprehensively assess real-world ADEs associated with tirzepatide by mining data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. ADE reports from the FAERS database were retrieved for the second quarter of 2022 through the first quarter of 2024. Significant associations between ADEs and tirzepatide were evaluated using proportional disproportionality analyses, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS). A total of 37,827 ADE reports associated with tirzepatide were identified, with 100 significantly disproportionate preferred terms (PTs) recognized by all four algorithms. The top five PTs with the highest reporting rates were incorrect dose administered, injection site pain, off-label use, nausea, and injection site hemorrhage. Additionally, unexpected signals such as starvation ketoacidosis were identified. The median time to onset for all ADEs was 23 days. Furthermore, sex-specific high-intensity signals were found, with males primarily experiencing gastrointestinal disorders and females experiencing general disorders and administration site conditions. This study provides valuable insights into the occurrence of ADEs following tirzepatide administration, potentially supporting clinical monitoring and risk identification efforts.