Implementation of an Electronic Medical Record Alert Significantly Increases Lung Cancer Screening Uptake.

INTRODUCTION: Lung cancer survival is significantly improved with early detection. However, lung cancer screening (LCS) uptake remains low despite national recommendations. Our aim was to determine whether implementation of an electronic medical record (EMR) alert and order set would increase LCS uptake. STUDY DESIGN: A query of current and former smokers identified 62,630 patients aged 50 and above in the primary care setting between January 1, 2021 and May 5, 2022. We randomly reviewed 3704 charts for LCS eligibility and recorded who received LCS in the form of low-dose computed tomography amongst the eligible patients. We collected demographic information including gender, race, primary language, ethnicity, zip code, and insurance. Data analysis was performed utilizing 2-proportional z tests. RESULTS: We identified 461 patients who were LCS eligible. Our overall LCS uptake was 19.9% (92/461). Three-time frames were analyzed: (1) prior to EMR alert implementation, (2) after implementation of EMR alert (January 7, 2021), and (3) after implementation of EMR alert and order set (March 3, 2021). Screening uptake was significantly improved with initiation of EMR alert (1/46 [2.2%] to 23/109 [21.1%]; P = .003). LCS uptake remained similarly high after subsequent order set implementation (23/109 [21.1%] and 68/306 [22.2%]; P = .72). Amongst the different demographics, age was significantly associated with screening uptake, with age ≥65 demonstrating statistically significant increased rates of screening (15.6% [41/263] for <65 vs 25.8% [51/198] for ≥65; P = .007). CONCLUSION: Implementation of EMR alerts significantly improves LCS uptake in the primary care setting. Such efforts should be considered in other hospital settings to improve LCS uptake.

Early versus delayed weight-bearing following operatively treated ankle fracture (WAX): a non-inferiority, multicentre, randomised controlled trial.

BACKGROUND: After surgery for a broken ankle, patients are usually instructed to avoid walking for 6 weeks (delayed weight-bearing). Walking 2 weeks after surgery (early weight-bearing) might be a safe and preferable rehabilitation strategy. This study aimed to determine the clinical and cost effectiveness of an early weight-bearing strategy compared with a delayed weight-bearing strategy. METHODS: This was a pragmatic, multicentre, randomised, non-inferiority trial including 561 participants (aged ≥18 years) who received acute surgery for an unstable ankle fracture in 23 UK National Health Service (NHS) hospitals who were assigned to either a delayed weight-bearing (n=280) or an early weight-bearing rehabilitation strategy (n=281). Patients treated with a hindfoot nail, those who did not have protective ankle sensation (eg, peripheral neuropathy), did not have the capacity to consent, or did not have the ability to adhere to trial procedures were excluded. Neither participants nor clinicians were masked to the treatment. The primary outcome was ankle function measured using the Olerud and Molander Ankle Score (OMAS) at 4 months after randomisation, in the per-protocol population. The pre-specified non-inferiority OMAS margin was -6 points and superiority testing was included in the intention-to-treat population in the event of non-inferiority. The trial was prospectively registered with ISRCTN Registry, ISRCTN12883981, and the trial is closed to new participants. FINDINGS: Primary outcome data were collected from 480 (86%) of 561 participants. Recruitment was conducted between Jan 13, 2020, and Oct 29, 2021. At 4 months after randomisation, the mean OMAS score was 65·9 in the early weight-bearing and 61·2 in the delayed weight-bearing group and adjusted mean difference was 4·47 (95% CI 0·58 to 8·37, p=0·024; superiority testing adjusted difference 4·42, 95% CI 0·53 to 8·32, p=0·026) in favour of early weight-bearing. 46 (16%) participants in the early weight-bearing group and 39 (14%) in the delayed weight-bearing group had one or more complications (adjusted odds ratio 1·18, 95% CI 0·80 to 1·75, p=0·40). The mean costs from the perspective of the NHS and personal social services in the early and delayed weight-bearing groups were £725 and £785, respectively (mean difference -£60 [95% CI -342 to 232]). The probability that early weight-bearing is cost-effective exceeded 80%. INTERPRETATION: An early weight-bearing strategy was found to be clinically non-inferior and highly likely to be cost-effective compared with the current standard of care (delayed weight-bearing). FUNDING: National Institute for Health and Care Research (NIHR), NIHR Barts Biomedical Research Centre, and NIHR Applied Research Collaboration Oxford and Thames Valley.

Research priorities for the management of major trauma: an international priority setting partnership with the James Lind Alliance.

OBJECTIVE: The objective of this study is to determine research priorities for the management of major trauma, representing the shared priorities of patients, their families, carers and healthcare professionals. DESIGN/SETTING: An international research priority-setting partnership. PARTICIPANTS: People who have experienced major trauma, their carers and relatives, and healthcare professionals involved in treating patients after major trauma. The scope included chest, abdominal and pelvic injuries as well as major bleeding, multiple injuries and those that threaten life or limb. METHODS: A multiphase priority-setting exercise was conducted in partnership with the James Lind Alliance over 24 months (November 2021-October 2023). An international survey asked respondents to submit their research uncertainties which were then combined into several indicative questions. The existing evidence was searched to ensure that the questions had not already been sufficiently answered. A second international survey asked respondents to prioritise the research questions. A final shortlist of 19 questions was taken to a stakeholder workshop, where consensus was reached on the top 10 priorities. RESULTS: A total of 1572 uncertainties, submitted by 417 respondents (including 132 patients and carers), were received during the initial survey. These were refined into 53 unique indicative questions, of which all 53 were judged to be true uncertainties after reviewing the existing evidence. 373 people (including 115 patients and carers) responded to the interim prioritisation survey and 19 questions were taken to a final consensus workshop between patients, carers and healthcare professionals. At the final workshop, a consensus was reached for the ranking of the top 10 questions. CONCLUSIONS: The top 10 research priorities for major trauma include patient-centred questions regarding pain relief and prehospital management, multidisciplinary working, novel technologies, rehabilitation and holistic support. These shared priorities will now be used to guide funders and teams wishing to research major trauma around the globe.

Momentary Factors and Study Characteristics Associated With Participant Burden and Protocol Adherence: Ecological Momentary Assessment.

BACKGROUND: Ecological momentary assessment (EMA) has become a popular mobile health study design to understand the lived experiences of dynamic environments. The numerous study design choices available to EMA researchers, however, may quickly increase participant burden and could affect overall adherence, which could limit the usability of the collected data. OBJECTIVE: This study quantifies what study design, participant attributes, and momentary factors may affect self-reported burden and adherence. METHODS: The EMA from the Phase 1 Family Matters Study (n=150 adult Black, Hmong, Latino or Latina, Native American, Somali, and White caregivers; n=1392 observation days) was examined to understand how participant self-reported survey burden was related to both design and momentary antecedents of adherence. The daily burden was measured by the question "Overall, how difficult was it for you to fill out the surveys today?" on a 5-item Likert scale (0=not at all and 4=extremely). Daily protocol adherence was defined as completing at least 2 signal-contingent surveys, 1 event-contingent survey, and 1 end-of-day survey each. Stress and mood were measured earlier in the day, sociodemographic and psychosocial characteristics were reported using a comprehensive cross-sectional survey, and EMA timestamps for weekends and weekdays were used to parameterize time-series models to evaluate prospective correlates of end-of-day study burden. RESULTS: The burden was low at 1.2 (SD 1.14) indicating "a little" burden on average. Participants with elevated previous 30-day chronic stress levels (mean burden difference: 0.8; P=.04), 1 in 5 more immigrant households (P=.02), and the language primarily spoken in the home (P=.04; 3 in 20 more non-English-speaking households) were found to be population attributes of elevated moderate-high burden. Current and 1-day lagged nonadherence were correlated with elevated 0.39 and 0.36 burdens, respectively (P=.001), and the association decayed by the second day (ß=0.08; P=.47). Unit increases in momentary antecedents, including daily depressed mood (P=.002) and across-day change in stress (P=.008), were positively associated with 0.15 and 0.07 higher end-of-day burdens after controlling for current-day adherence. CONCLUSIONS: The 8-day EMA implementation appeared to capture momentary sources of stress and depressed mood without substantial burden to a racially or ethnically diverse and immigrant or refugee sample of parents. Attention to sociodemographic attributes (eg, EMA in the primary language of the caregiver) was important for minimizing participant burden and improving data quality. Momentary stress and depressed mood were strong determinants of participant-experienced EMA burden and may affect adherence to mobile health study protocols. There were no strong indicators of EMA design attributes that created a persistent burden for caregivers. EMA stands to be an important observational design to address dynamic public health challenges related to human-environment interactions when the design is carefully tailored to the study population and to study research objectives.

HuD (ELAVL4) gain-of-function impairs neuromuscular junctions and induces apoptosis in in vitro and in vivo models of amyotrophic lateral sclerosis.

Early defects at the neuromuscular junction (NMJ) are among the first hallmarks of the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). According to the "dying back" hypothesis, disruption of the NMJ not only precedes, but is also a trigger for the subsequent degeneration of the motoneuron in both sporadic and familial ALS, including ALS caused by the severe FUS pathogenic variant P525L. However, the mechanisms linking genetic and environmental factors to NMJ defects remain elusive. By taking advantage of co-cultures of motoneurons and skeletal muscle derived from human induced pluripotent stem cells (iPSCs), we show that the neural RNA binding protein HuD (ELAVL4) may underlie NMJ defects and apoptosis in FUS-ALS. HuD overexpression in motoneurons phenocopies the severe FUSP525L mutation, while HuD knockdown in FUSP525L co-cultures produces phenotypic rescue. We validated these findings in vivo in a Drosophila FUS-ALS model. Neuronal-restricted overexpression of the HuD-related gene, elav, produces per se a motor phenotype, while neuronal-restricted elav knockdown significantly rescues motor dysfunction caused by FUS. Finally, we show that HuD levels increase upon oxidative stress in human motoneurons and in sporadic ALS patients with an oxidative stress signature. On these bases, we propose HuD as an important player downstream of FUS mutation in familial ALS, with potential implications for sporadic ALS related to oxidative stress.

Systems of Care Delivery and Optimization in the Intensive Care Unit.

As the volume and complexity of patients requiring intensive care grows, so do the barriers and challenges to the delivery of that care. This article summarizes these challenges, outlines strategies used to overcome them, and presents new developments and concepts within the care of the ICU patient.

Effects of Smoothing and Adaptive Filtering in Multifocal Electroretinography (mfERG).

(1) Background: mfERG testing is used to study the function of cone photoreceptors in the central retina. Various filters including "smoothing" (Smooth) and "adaptive data filtering" (Adapt) are used to simplify raw data. This study will seek to characterize the effect of data modification on raw patient data. (2) Methods: This was a retrospective study of patients with mfERG results at our institution. For each patient, raw mfERG data without filtering, with smooth level 4 modifier applied, and with adapt level 4 applied were collected and compared. (4) Conclusions: In all patients, smoothing and adaptive filter modifiers create statistically significant differences in both P1 latency and P1 amplitude values when compared to raw data. The impacts of these filters demonstrated in this study should impact physicians' decision making when interpreting mfERG results.

A retrospective analysis of frailty status on atrial fibrillation catheter ablation outcomes.

INTRODUCTION: Catheter ablation for atrial fibrillation (AF) reduces symptoms and improves the quality of life compared with medical treatment. It is unclear if frailty impacts on the outcome of catheter ablation in patients with symptomatic AF. We sought to evaluate the association between frailty as measured by the validated NHS electronic Frailty Index (eFI) and outcomes post-AF ablation. METHODS: Two hundred forty eight patients who had undergone AF ablation with a mean age of 72.9 ± 5.16 were included in the study retrospectively. The primary endpoint for success was defined as freedom from atrial arrhythmia lasting >30 s beyond the 3-month blanking periods. Frailty was based on the eFI, and the cohort split into four groups: fit (no frailty), mild, moderate and severe frailty. RESULTS: Frailty was categorized as fit (118/248; 47.6%), mild (66/248; 26.6%), moderate (54/248; 21.8%), and severe (10/248; 4.0%). Freedom from arrhythmia occurred in 167 of 248 (67.3%) patients after a mean follow-up of 25.8 +/- 17.3 months. Fit patients had significantly greater freedom from arrhythmia (92/118; 78%) compared to mild frailty (40/66; 60.6%, p-value = .020), moderate frailty (31/54; 57.4%, p-value = .006), or severe frailty (4/10; 40.0%, p-value < .001). There was also a significant difference in arrhythmia occurrence between patients with mild frailty and severe frailty (p-value = .044). CONCLUSION: Frailty is associated with poorer outcomes in patients undergoing AF ablation. The eFI may be used in the prognostic evaluation of AF ablation outcomes. Further studies are essential to confirm the findings of this study.

Congenital Midline Cervical Cleft (CMCC): Z-Plasty Versus Linear Cutaneous Repair.

Congenital midline cervical cleft (CMCC) is a rare congenital difference. Accurate diagnosis is important to ensure appropriate treatment. CMCC results in both functional and esthetic concerns addressed by surgical management. While the majority of reported CMCC cases have been treated with a z-plasty, the best method of repair has been debated in the literature. The authors present a case of CMCC and review of the literature.

Obstetric and perinatal outcomes of singleton pregnancies after blastocyst-stage embryo transfer compared with those after cleavage-stage embryo transfer: a systematic review and cumulative meta-analysis.

BACKGROUND: Extended embryo culture to blastocyst stage is widely used in IVF and is the default strategy in most clinics. The last decade has witnessed a growing interest in obstetric-perinatal outcomes following blastocyst transfer. Recent studies have challenged the conclusions of systematic reviews that associate risks of preterm birth (PTB) and large for gestational age (LGA) babies with blastocyst transfer. A higher proportion of blastocysts is transferred as frozen-thawed embryos, which may also have added implications. OBJECTIVE AND RATIONALE: The aim of this study was to conduct an updated systematic review of the obstetric-perinatal outcomes in singleton pregnancies following blastocyst-stage transfer compared to cleavage-stage transfer in IVF/ICSI cycles. Where deemed appropriate, data were combined in cumulative meta-analyses. SEARCH METHODS: Data sources from Medline, EMBASE, CINAHL, Web of Science, the Cochrane Central Register of Clinical Trials and the International Clinical Trials Registry Platform (ICTRP) (1980-2020) were searched using combinations of relevant keywords. Searches had no language restrictions and were limited to human studies. Observational studies and randomized controlled trials comparing obstetric-perinatal outcomes between singleton pregnancies after blastocyst-stage transfer and those after cleavage-stage transfer in IVF/ICSI cycles were sought. Two independent reviewers extracted data in 2 × 2 tables and assessed the methodological quality of the relevant studies using the Critical Appraisal Skills Programme scoring. Cumulative meta-analyses were carried out with independent analysis of pregnancies after fresh and frozen embryo transfers, using the Comprehensive Meta-Analysis software. If provided by included studies, adjusted effect sizes were combined in a sensitivity analysis. OUTCOMES: A total of 35 studies were included (n = 520 769 singleton pregnancies). Outcome data suggest singleton pregnancies following fresh blastocyst transfer were associated with higher risk of LGA (risk ratio (RR) 1.14; 95% CI 1.05-1.24) and very PTB (RR 1.17; 95% CI 1.08-1.26) compared to fresh cleavage-stage transfer. Singleton pregnancies following frozen blastocyst transfer were associated with higher risks of LGA (RR 1.17; 95% CI 1.08-1.27), PTB (RR 1.13; 95% CI 1.03-1.24) and caesarean section (RR 1.08; 95% CI 1.03-1.13) but lower risks of small for gestational age (RR 0.84, 95% CI 0.74-0.95) and perinatal mortality (RR 0.70; 95% CI 0.58-0.86). Increased risks of LGA and PTB after frozen blastocyst transfer persisted in the sensitivity analysis, which also showed a significantly increased risk of PTB after fresh blastocyst transfer. Cumulative meta-analyses revealed consistency in prevalence and magnitude of risks for a number of years. Data on other perinatal outcomes are still evolving. WIDER IMPLICATIONS: While the available evidence is predominantly reassuring in the context of blastocyst-stage embryo transfer, observational data suggest that blastocyst transfer is associated with a higher risk of LGA. This holds true irrespective of fresh or frozen transfer. Meta-analysis of adjusted data showed an increased risk of PTB with fresh and frozen blastocyst transfer. However, the quality of available evidence ranges from low to very low. Although blastocyst-stage embryo transfer remains the default position in most centres, based on individual risk profile we may need to consider cleavage-stage embryo transfer in some to mitigate the risk of LGA/PTB.

Research priorities for the management of complex fractures: a UK priority setting partnership with the James Lind Alliance.

OBJECTIVE: To determine research priorities for the management of complex fractures, which represent the shared priorities of patients, their families, carers and healthcare professionals. DESIGN/SETTING: A national (UK) research priority setting partnership. PARTICIPANTS: People who have experienced a complex fracture, their carers and relatives, and relevant healthcare professionals and clinical academics involved in treating patients with complex fractures. The scope includes open fractures, fractures to joints broken into multiple pieces, multiple concomitant fractures and fractures involving the pelvis and acetabulum. METHODS: A multiphase priority setting exercise was conducted in partnership with the James Lind Alliance over 21 months (October 2019 to June 2021). A national survey asked respondents to submit their research uncertainties which were then combined into several indicative questions. The existing evidence was searched to ensure that the questions had not already been sufficiently answered. A second national survey asked respondents to prioritise the research questions. A final shortlist of 18 questions was taken to a stakeholder workshop, where a consensus was reached on the top 10 priorities. RESULTS: A total of 532 uncertainties, submitted by 158 respondents (including 33 patients/carers) were received during the initial survey. These were refined into 58 unique indicative questions, of which all 58 were judged to be true uncertainties after review of the existing evidence. 136 people (including 56 patients/carers) responded to the interim prioritisation survey and 18 questions were taken to a final consensus workshop between patients, carers and healthcare professionals. At the final workshop, a consensus was reached for the ranking of the top 10 questions. CONCLUSIONS: The top 10 research priorities for complex fracture include questions regarding rehabilitation, complications, psychological support and return to life-roles. These shared priorities will now be used to guide funders and teams wishing to research complex fractures over the coming decade.

The long-term effect of thermal-guided second-generation cryoablation in paroxysmal and persistent atrial fibrillation.

BACKGROUND: Second-generation cryoballoon ablation is safe and effective in patients with paroxysmal (PAF) and persistent atrial fibrillation (AF). OBJECTIVE: This study aimed to assess the long-term clinical outcomes and freedom from AF in patients undergoing thermal-guided cryoablation without the use of an electrical mapping catheter. METHODS: All patients who had undergone thermal-guided second-generation cryoablation without electrical mapping between January 2015 and April 2018 at Eastbourne District General Hospital were retrospectively analysed. Success was defined as freedom from atrial arrhythmia lasting >30 s during the follow up period. RESULTS: The study included 234 patients with a mean age of 65.3 ± 10.6 years. There were 134 (57.0%) and 100 (42.7%) patients who had PAF and persistent AF respectively. Arrhythmia recurrence occurred in 38 of 134 (28.4%) PAF and 42 of 100 (42.0%) persistent AF patients after mean follow up of 40 ± 9.2 months. The patients with PAF had a significantly greater freedom from arrhythmia than patients with persistent AF (p = .040). The mean procedure time was 55.5 ± 12.2 min and the mean fluoroscopy time was 10.9 ± 4.8 min 73.5% of patients were discharged on the same day. CONCLUSION: Thermal-guided cryoablation is feasible, safe and results in freedom from arrhythmia in the majority of paroxysmal and persistent AF patients in the long term. Randomised controlled trials are required to confirm the findings of this study.

Case Series on 2g Tranexamic Acid Flush From the 75th Ranger Regiment Casualty Database.

Early tranexamic acid (TXA) administration for resuscitation of critically injured warfighters provides a mortality benefit. The 2019 Tactical Combat Casualty Care (TCCC) recommendations of a 1g drip over 10 minutes, followed by 1g drip over 8 hours, is intended to limit potential TXA side effects, including hypotension, seizures, and anaphylaxis. However, this slow and cumbersome TXA infusion protocol is difficult to execute in the tactical care environment. Additionally, the side effect cautions derive from studies of elderly or cardiothoracic surgery patients, not young healthy warfighters. Therefore, the 75th Ranger Regiment developed and implemented a 2g intravenous or intraosseous (IV/IO) TXA flush protocol. We report on the first six cases of this protocol in the history of the Regiment. After-action reports (AARs) revealed no incidences of post-TXA hypotension, seizures, or anaphylaxis. Combined, the results of this case series are encouraging and provide a foundation for larger studies to fully determine the safety of the novel 2g IV/IO TXA flush protocol toward preserving the lives of traumatically injured warfighters.

A New Contrast Sensitivity Test for Pediatric Patients: Feasibility and Inter-Examiner Reliability in Ocular Disorders and Cerebral Visual Impairment.

Purpose: Assess feasibility and interexaminer reliability of a new test of contrast sensitivity (CS) for pediatric populations. Methods: The Double Happy (DH) measures CS using a method similar to the Teller Acuity Cards. The schematic DH face is 16 degrees in diameter with features of 0.3 c/d and a channel frequency of 0.8 c/d. DH log10 CS is in 0.15 log unit steps, 0.05 to 2.1. Participants were 43 unselected patients, ages 2 to 18 years: 23 were diagnosed with ocular disorders only; 20 were diagnosed with cerebral visual impairment (CVI). Two examiners measured DH log10 CS. Visual acuity (VA) was also measured. Results: All 43 participants were tested for binocular DH log10CS. Cohen's kappa values for interexaminer reliability were fair. The between examiner ICC was +0.92 (P < 0.001). The mean difference between examiners was near zero, and the 95% CI was -0.44 to 0.45 log10CS. DH log10CS was near normal in the ocular disorder group and reduced in the CVI group. VA was reduced in both groups. DH log10 CS and VA were correlated (r = -0.65). DH log10 CS was a marginally better predictor of diagnosis than VA. Conclusions: DH log10CS test was successful in a diverse pediatric population diagnosed with ocular disorders or CVI. Interexaminer reliability was comparable to that of adults tested previously using the same stimuli and methods. Both CS and VA are reduced in CVI. Translational Relevance: CS and VA both should be tested in pediatric clinical populations, especially in those at risk of CVI.

Nuclear actin filaments in DNA repair dynamics.

Recent development of innovative tools for live imaging of actin filaments (F-actin) enabled the detection of surprising nuclear structures responding to various stimuli, challenging previous models that actin is substantially monomeric in the nucleus. We review these discoveries, focusing on double-strand break (DSB) repair responses. These studies revealed a remarkable network of nuclear filaments and regulatory mechanisms coordinating chromatin dynamics with repair progression and led to a paradigm shift by uncovering the directed movement of repair sites.

Life-long control of cytomegalovirus (CMV) by T resident memory cells in the adipose tissue results in inflammation and hyperglycemia.

Cytomegalovirus (CMV) is a ubiquitous herpesvirus infecting most of the world's population. CMV has been rigorously investigated for its impact on lifelong immunity and potential complications arising from lifelong infection. A rigorous adaptive immune response mounts during progression of CMV infection from acute to latent states. CD8 T cells, in large part, drive this response and have very clearly been demonstrated to take up residence in the salivary gland and lungs of infected mice during latency. However, the role of tissue resident CD8 T cells as an ongoing defense mechanism against CMV has not been studied in other anatomical locations. Therefore, we sought to identify additional locations of anti-CMV T cell residency and the physiological consequences of such a response. Through RT-qPCR we found that mouse CMV (mCMV) infected the visceral adipose tissue and that this resulted in an expansion of leukocytes in situ. We further found, through flow cytometry, that adipose tissue became enriched in cytotoxic CD8 T cells that are specific for mCMV antigens from day 7 post infection through the lifespan of an infected animal (> 450 days post infection) and that carry markers of tissue residence. Furthermore, we found that inflammatory cytokines are elevated alongside the expansion of CD8 T cells. Finally, we show a correlation between the inflammatory state of adipose tissue in response to mCMV infection and the development of hyperglycemia in mice. Overall, this study identifies adipose tissue as a location of viral infection leading to a sustained and lifelong adaptive immune response mediated by CD8 T cells that correlates with hyperglycemia. These data potentially provide a mechanistic link between metabolic syndrome and chronic infection.

Preliminary evidence that hydroxyurea is associated with attenuated peripheral sensitization in adults with sickle cell disease.

INTRODUCTION: Hydroxyurea (HU) is a drug that targets the underlying pathophysiology of sickle cell disease (SCD); however, it continues to be an underutilized treatment for adults. Previous research suggests that HU treatment can result in fewer hospital contacts for acute vaso-occlusive pain crises (VOC). Hydroxyurea's impact on non-VOC pain, however, is not well established. OBJECTIVES: This study examined whether HU moderated patterns of static and dynamic pain processing and clinical pain in SCD individuals. METHODS: Fifty-eight patients with SCD (N taking HU = 17) underwent quantitative sensory testing (QST) and completed twice daily symptom diaries for 12 weeks. Quantitative sensory testing established thermal threshold and tolerance, mechanical thresholds, and thermal and mechanical temporal summation of pain. RESULTS: Groups did not differ in age, sex, or opioid use. After controlling for morphine use, QST results showed that participants taking HU had higher heat and mechanical pain thresholds (static QST measures) but not thermal and mechanical temporal summation (dynamic QST measures). Participants taking HU also reported lower VOC pain compared with SCD participants not taking HU; however, HU did not moderate non-VOC clinical pain ratings. CONCLUSION: Findings cautiously suggest that HU acts on pain hypersensitivity and VOC pain, rather than inhibiting pain facilitation and non-VOC pain. These differences may reflect HU's influence on peripheral rather than central sensitization. Future research is warranted to replicate these findings in a larger sample and determine whether early HU administration can prevent peripheral sensitization in SCD individuals.