The Vitamin D Metabolite Ratio Is Associated With Volumetric Bone Density in Older Men.

CONTEXT: Serum 25-hydroxyvitamin D (25(OH)D) is the current marker of vitamin D adequacy, but its relationship with bone health has been inconsistent. The ratio of 24,25-dihydroxyvitamin D3 to 25(OH)D3 (vitamin D metabolite ratio or VMR) is a marker of vitamin D that has been associated with longitudinal changes in bone mineral density (BMD) and fracture risk. OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) provides information on bone health beyond standard dual-energy x-ray absorptiometry, in that it measures volumetric BMD (vBMD) as well bone strength. The relationship of the VMR with vBMD and bone strength remains unknown. METHODS: We evaluated the associations of the VMR and 25(OH)D3 with vBMD and bone strength in the distal radius and tibia, assessed by HR-pQCT in 545 older men participating in the Osteoporotic Fractures in Men (MrOS) Study. Primary outcomes were vBMD and estimated failure load (EFL, a marker of bone strength) at the distal radius and tibia. RESULTS: The mean age was 84 ± 4 years, 88.3% were White, and 32% had an estimated glomerular filtration rate <60 mL/min/1.73 m2. In adjusted models, each twofold higher VMR was associated with a 9% (3%, 16%) higher total vBMD and a 13% (5%, 21%) higher EFL at the distal radius. Results were similar at the distal tibia. 25(OH)D3 concentrations were not associated with any of the studied outcomes. CONCLUSION: Among older men, a higher VMR was associated with greater vBMD and bone strength while 25(OH)D3 was not. The VMR may serve as a valuable marker of skeletal health in older men.

Tendon Transfers to Improve Grip and Pinch in Patients with Sporadic Inclusion Body Myositis.

Background: Sporadic inclusion body myositis (sIBM) is a rare and slowly progressive skeletal muscle disease that can cause hand dysfunction, which is a major source of disability. Tendon transfers have been reliably used to improve function in other neuromuscular settings. Given that sIBM patients often present with flexion impairments and mostly functioning extensors, we investigated the potential opportunity for tendon transfer surgery to improve hand dysfunction in sIBM patients. Methods: We conducted a scoping review for studies of sIBM and tendon transfers, extracted descriptions of hand function and surgical technique, and recorded results in terms of hand function. We also conducted an institutional review board-approved survey with 470 participants to determine baseline patient-reported function and to determine participant perceptions and expectations for tendon transfer surgery to improve hand function in sIBM. Results: We identified three published case reports on tendon transfers in sIBM patients with subjectively improved grip and pinch strength, but standardized measures of hand function or quality-of-life were not reported. Within the surveyed cohort, half of participants reported that they would consider surgery, yet only 8% had been referred to a hand surgeon. Fifty four percent of participants reported that they would consider surgery if there would be 1-2 years of benefit after surgery. All participants who would consider surgery also had significant upper extremity disability. Discussion: Tendon transfer surgery has the potential to improve quality-of-life for sIBM patients, and there is significant patient interest in this approach. To objectively assess its efficacy, we propose conducting a surgical trial.

Development and Validation of Novel Free Vitamin D Equations: The Health Aging and Body Composition Study.

Vitamin D deficiency is prevalent in 25% of Americans. However, 25(OH)D may not be an accurate measure of vitamin D because the majority (85%-90%) of 25(OH)D is bound to vitamin D binding protein (VDBP), which varies by over 30% across individuals. Free 25(OH)D may be a better measure, but it is difficult to measure accurately and precisely. The existing free 25(OH)D estimating equation does not include VDBP phenotypes; therefore, new equations that include this variable may be more accurate. A total of 370 participants in the Health, Aging, and Body Composition Study, a cohort of healthy community-dwelling individuals aged 70-79 years old, underwent VDBP and vitamin D metabolite [25(OH)D, 24,25(OH)2D, 1,25(OH)2D, free 25(OH)D] measurements and were randomly allocated into equation development (two out of three) and internal validation (one out of three) groups. New equations were developed with multiple linear regression and were internally validated with Bland-Altman plots. The mean age was 75 ± 3 years, 53% were female, and the mean measured free 25(OH)D was 5.37 ± 1.81 pg/mL. Three equations were developed. The first equation included albumin, 25(OH)D3, 25(OH)D2, VDBP, 1,25(OH)2D3, and 24,25(OH)2D3. The second equation included all variables in Eq. (1) plus VDBP phenotypes. The third equation included albumin, 25(OH)D3, intact parathyroid hormone, and 1,25(OH)2D3. In internal validation, all three new equations predicted free 25(OH)D values within 30% and 15% of the measured free 25(OH)D concentrations in 76%-80% and 48%-52% of study participants, respectively. Equation (2) was the most precise, with a mean bias of 0.06 (95% limits of agreement -2.41 to 2.30) pg/mL. The existing equation estimated free 25(OH)D within 30% and 15% of measured free 25(OH)D in 43% and 22% of participants, respectively. Free 25(OH)D can be estimated with clinically available biomarkers as well as with more laboratory-intensive biomarkers with moderate precision. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Sheffield Shield Cricketers Live Longer than the Age-Matched General Australian Male Population.

Background/objectives: Previous studies have shown a trend that elite athletes tend to live longer than the general population, which has been attributed to the "healthy worker hire effect" and the health benefits of exercise. There have not been any previous studies looking at survival of elite cricketers with the general population as a reference cohort. This study aimed to compare the annual mortality rates of current and retired elite male Australian cricket players to that of the age-matched general Australian male population. Methods: Analysis of publicly accessible dates of birth, death, and cricket debut data for male Australian Sheffield Shield cricket players who played before 2022 and had not died before 1971. Included persons were Sheffield Shield players who lived primarily in Australia during and after their cricket careers. Death rates from 1971 to 2021 (inclusive) were compared to the general Australian male population. Results: 1824 Sheffield Shield players had not died prior to 1971 (798 had played before the 1971 season, 1026 debuting subsequently). There were 586 deaths in the 51 years of observations, compared to 825 expected deaths, giving a Standardized Mortality Ratio of 0.71 (95% CI 0.63-0.80). Conclusion: Elite Australian male Sheffield Shield cricket players outlive the general male population with lower death rates. This is probably due to a combination of the healthy worker hire effect and the health benefits of exercise. This study provides evidence that in terms of longevity, it is safe to play elite-level cricket in Australia.

The Vitamin D Metabolite Ratio (VMR) is a Biomarker of Vitamin D Status That is Not Affected by Acute Changes in Vitamin D Binding Protein.

BACKGROUND: 25-hydroxyvitamin D[25(OH)D] may be a poor marker of vitamin D status due to variability in levels of vitamin D binding protein (VDBP). The vitamin D metabolite ratio (VMR) is the ratio of 24,25-dihydroxyvitamin D[24,25(OH)2D3] to 25(OH)D3 and has been postulated to reflect vitamin D sufficiency independent of variability in VDBP. Therapeutic plasma exchange (TPE) is a procedure that removes plasma, including VDBP, and may lower bound vitamin D metabolite concentrations. Effects of TPE on the VMR are unknown. METHODS: We measured 25(OH)D, free 25(OH)D, 1,25-dihydroxyvitamin D[1,25(OH)2D], 24,25(OH)2D3, and VDBP in persons undergoing TPE, before and after treatment. We used paired t-tests to assess changes in these biomarkers during a TPE procedure. RESULTS: Study participants (n = 45) had a mean age of 55 ± 16 years; 67% were female; and 76% were white. Compared to pretreatment concentrations, TPE caused a significant decrease in total VDBP by 65% (95%CI 60,70%), as well as all the vitamin D metabolites-25(OH)D by 66% (60%,74%), free 25(OH)D by 31% (24%,39%), 24,25(OH)2D3 by 66% (55%,78%) and 1,25(OH)2D by 68% (60%,76%). In contrast, there was no significant change in the VMR before and after a single TPE treatment, with an observed mean 7% (-3%, 17%) change in VMR. CONCLUSIONS: Changes in VDBP concentration across TPE parallel changes in 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D3, suggesting that concentrations of these metabolites reflect underlying VDBP concentrations. The VMR is stable across a TPE session despite a 65% reduction in VDBP. These findings suggest that the VMR is a marker of vitamin D status independent of VDBP levels.

Dynamic peripheral nerve stimulation can produce cortical activation similar to punctate mechanical stimuli.

During contact, phasic and tonic responses provide feedback that is used for task performance and perceptual processes. These disparate temporal dynamics are carried in peripheral nerves, and produce overlapping signals in cortex. Using longitudinal intrafascicular electrodes inserted into the median nerve of a nonhuman primate, we delivered composite stimulation consisting of onset and release bursts to capture rapidly adapting responses and sustained stochastic stimulation to capture the ongoing response of slowly adapting receptors. To measure the stimulation's effectiveness in producing natural responses, we monitored the local field potential in somatosensory cortex. We compared the cortical responses to peripheral nerve stimulation and vibrotactile/punctate stimulation of the fingertip, with particular focus on gamma band (30-65 Hz) responses. We found that vibrotactile stimulation produces consistently phase locked gamma throughout the duration of the stimulation. By contrast, punctate stimulation responses were phase locked at the onset and release of stimulation, but activity maintained through the stimulation was not phase locked. Using these responses as guideposts for assessing the response to the peripheral nerve stimulation, we found that constant frequency stimulation produced continual phase locking, whereas composite stimulation produced gamma enhancement throughout the stimulus, phase locked only at the onset and release of the stimulus. We describe this response as an "Appropriate Response in the gamma band" (ARγ), a trend seen in other sensory systems. Our demonstration is the first shown for intracortical somatosensory local field potentials. We argue that this stimulation paradigm produces a more biomimetic response in somatosensory cortex and is more likely to produce naturalistic sensations for readily usable neuroprosthetic feedback.

Biomarkers predictive of response to pembrolizumab in head and neck cancer.

BACKGROUND: We performed an integrated biomarker evaluation in pembrolizumab-treated patients with R/M HNSCC enrolled in KEYNOTE-012 or KEYNOTE-055. The relationship between biomarkers and HPV status was explored. METHODS: We evaluated PD-L1 (combined positive score [CPS]), TMB, T-cell-inflamed gene expression profile (Tcellinf GEP), and HPV status. Associations between biomarkers were evaluated by logistic regression (ORR) and Cox regression (PFS, OS). RESULTS: Two hundred and fifty-seven patients (KEYNOTE-012, n = 106; KEYNOTE-055, n = 151) had TMB data available; of these, 254 had PD-L1 and 236 had Tcellinf GEP. TMB, PD-L1, and Tcellinf GEP were each significantly associated with ORR (p < 0.01). Kaplan-Meier curves at prespecified cutoffs generally showed PFS and OS separation in the anticipated direction for these biomarkers, except for OS and TMB. TMB did not correlate with PD-L1 or Tcellinf GEP (Spearman ρ = -0.03 and ρ = -0.13, respectively); PD-L1 and Tcellinf GEP were moderately correlated (Spearman ρ = 0.47). In multivariate models, TMB, PD-L1, and Tcellinf GEP were each independently predictive for ORR (p < 0.001). ORR was higher in patients with high versus low levels of biomarkers when dichotomized using prespecified cutoffs; patients with higher versus lower levels of TMB and PD-L1 or TMB and Tcellinf GEP had the highest ORRs. Within HPV subgroups, higher versus lower distributions of biomarkers (PD-L1, TMB, and Tcellinf GEP) were associated with response. HPV detection by p16-immunohistochemistry and WES showed good concordance (81%); results were generally similar by HPV status, regardless of the detection method. CONCLUSIONS: TMB and the inflammatory biomarkers PD-L1 and Tcellinf GEP, assessed alone or together, may be useful for characterizing clinical response to pembrolizumab in R/M HNSCC.

Prospective pre-operative 3-T MR neurography peripheral nerve mapping of upper extremity amputations implanted with FAST-LIFE electrode interfaces of robotic hands: technical report.

BACKGROUND AND PURPOSE: Fascicular targeting of longitudinal intrafascicular electrode (FAST-LIFE) interface enables hand dexterity with exogenous electrical microstimulation for sensory restoration, custom neural recording hardware, and deep learning-based artificial intelligence for motor intent decoding. The purpose of this technical report from a prospective pilot study was to illustrate magnetic resonance neurography (MRN) mapping of hand and nerve anatomy in amputees and incremental value of MRN over electrophysiology findings in pre-surgical planning of FAST-LIFE interface (robotic hand) patients. MATERIALS AND METHODS: After obtaining informed consent, patients with upper extremity amputations underwent pre-operative 3-T MRN, X-rays, and electrophysiology. MRN findings were correlated with electrophysiology reports. Descriptive statistics were performed. RESULTS: Five patients of ages 21-59 years exhibited 3/5 partial hand amputations, and 2/5 transradial amputations on X-rays. The median and ulnar nerve end bulb neuromas measured 10.1 ± 3.04 mm (range: 5.5-14 mm, median: 10.5 mm) and 10.9 ± 7.64 mm (2-22 mm, 9.75 mm), respectively. The ADC of median and ulnar nerves were increased at 1.64 ± 0.1 × 10-3 mm2/s (range: 1.5-1.8, median: 1.64 × 10-3 mm2/s) and 1.70 ± 0.17 × 10-3 mm2/s (1.49-1.98 × 10-3 mm2/s, 1.65 × 10-3 mm2/s), respectively. Other identified lesions were neuromas of superficial branch of the radial nerve and anterior interosseous nerve. On electrophysiology, 2/5 reports were unremarkable, 2/5 showed mixed motor-sensory neuropathies of median and ulnar nerves along with radial sensory neuropathy, and 1/5 showed sensory neuropathy of lateral cutaneous nerve of the forearm. All patients regained naturalistic sensations and motor control of digits. CONCLUSION: 3-T MRN allows excellent demonstration of forearm and hand nerve anatomy, altered diffusion characteristics, and their neuromas despite unremarkable electrophysiology for pre-surgical planning of the FAST-LIFE (robotic hand) interfaces.

Artificial Intelligence Enables Real-Time and Intuitive Control of Prostheses via Nerve Interface.

OBJECTIVE: The next generation prosthetic hand that moves and feels like a real hand requires a robust neural interconnection between the human minds and machines. METHODS: Here we present a neuroprosthetic system to demonstrate that principle by employing an artificial intelligence (AI) agent to translate the amputee's movement intent through a peripheral nerve interface. The AI agent is designed based on the recurrent neural network (RNN) and could simultaneously decode six degree-of-freedom (DOF) from multichannel nerve data in real-time. The decoder's performance is characterized in motor decoding experiments with three human amputees. RESULTS: First, we show the AI agent enables amputees to intuitively control a prosthetic hand with individual finger and wrist movements up to 97-98% accuracy. Second, we demonstrate the AI agent's real-time performance by measuring the reaction time and information throughput in a hand gesture matching task. Third, we investigate the AI agent's long-term uses and show the decoder's robust predictive performance over a 16-month implant duration. Conclusion & significance: Our study demonstrates the potential of AI-enabled nerve technology, underling the next generation of dexterous and intuitive prosthetic hands.

Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma.

BACKGROUND: To characterize genomic determinants of response to pembrolizumab in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 study. METHODS: Associations between biomarkers (tumor mutational burden (TMB), neoantigen load (NL), 18-gene T-cell-inflamed gene expression profile (TcellinfGEP), and PD-L1 combined positive score (CPS)) and clinical outcomes with pembrolizumab were assessed in patients with R/M HNSCC (n=192). Tumor human papillomavirus (HPV) status was also evaluated with the use of p16 immunohistochemistry and whole exome sequencing (WES; HPV+, mapping >20 HPV reads) in pretreatment tumor samples (n=106). RESULTS: TMB, clonality-weighted TMB, and TcellinfGEP were significantly associated with objective response (p=0.0276, p=0.0201, and p=0.006, respectively), and a positive trend was observed between NL and PD-L1 CPS and clinical response (p=0.0550 and p=0.0682, respectively). No correlation was observed between TMB and TcellinfGEP (Spearman ρ=-0.026) or TMB and PD-L1 (Spearman ρ=0.009); a correlation was observed between TcellinfGEP and PD-L1 (Spearman ρ=0.511). HPV status by WES and p16 immunohistochemistry showed concordance (84% Ò¡=0.573) among patients whose HPV results were available using both methods. CONCLUSIONS: TMB and inflammatory biomarkers (TcellinfGEP and PD-L1) may represent distinct and complementary biomarkers predicting response to anti-programmed death 1 therapies in HNSCC; further study of these relationships in randomized clinical trials is needed. TRIAL REGISTRATION NUMBER: NCT01848834.

Changes in antidepressant medication use in the workplace and sustainable employability: a qualitative study of experiences, strategies and solutions.

This study explores patients' experiences of how antidepressant medication transition events (ceasing, changing or reducing) affect employment and workplace functioning. An anonymous online survey was conducted with adults who had experienced antidepressant medication transition events (AMTEs). Data were analyzed using a hybrid inductive and deductive thematic analysis approach. While a majority of participants perceived many positive impacts of antidepressant medication on their workplace functioning, considerable negative effects during AMTEs were reported. Participants provided practical solutions to assist employers, policy and clinicians. Significant and detrimental impact of antidepressant medication changes occurred in the workplace. There is an urgent need to raise awareness of the vulnerability of people during AMTEs and to develop educational and supportive resources to assist clinicians and practitioners to support people during this vulnerable time.

Force balance in rapidly rotating Rayleigh-Bénard convection.

The force balance of rotating Rayleigh-Bénard convection regimes is investigated using direct numerical simulation on a laterally periodic domain, vertically bounded by no-slip walls. We provide a comprehensive view of the interplay between governing forces both in the bulk and near the walls. We observe, as in other prior studies, regimes of cells, convective Taylor columns, plumes, large-scale vortices (LSVs) and rotation-affected convection. Regimes of rapidly rotating convection are dominated by geostrophy, the balance between Coriolis and pressure-gradient forces. The higher-order interplay between inertial, viscous and buoyancy forces defines a subdominant balance that distinguishes the geostrophic states. It consists of viscous and buoyancy forces for cells and columns, inertial, viscous and buoyancy forces for plumes, and inertial forces for LSVs. In rotation-affected convection, inertial and pressure-gradient forces constitute the dominant balance; Coriolis, viscous and buoyancy forces form the subdominant balance. Near the walls, in geostrophic regimes, force magnitudes are larger than in the bulk; buoyancy contributes little to the subdominant balance of cells, columns and plumes. Increased force magnitudes denote increased ageostrophy near the walls. Nonetheless, the flow is geostrophic as the bulk. Inertia becomes increasingly more important compared to the bulk, and enters the subdominant balance of columns. As the bulk, the near-wall flow loses rotational constraint in rotation-affected convection. Consequently, kinetic boundary layers deviate from the expected behaviour from linear Ekman boundary layer theory. Our findings elucidate the dynamical balances of rotating thermal convection under realistic top/bottom boundary conditions, relevant to laboratory settings and large-scale natural flows.

A portable, self-contained neuroprosthetic hand with deep learning-based finger control.

Objective.Deep learning-based neural decoders have emerged as the prominent approach to enable dexterous and intuitive control of neuroprosthetic hands. Yet few studies have materialized the use of deep learning in clinical settings due to its high computational requirements.Approach.Recent advancements of edge computing devices bring the potential to alleviate this problem. Here we present the implementation of a neuroprosthetic hand with embedded deep learning-based control. The neural decoder is designed based on the recurrent neural network architecture and deployed on the NVIDIA Jetson Nano-a compacted yet powerful edge computing platform for deep learning inference. This enables the implementation of the neuroprosthetic hand as a portable and self-contained unit with real-time control of individual finger movements.Main results.A pilot study with a transradial amputee is conducted to evaluate the proposed system using peripheral nerve signals acquired from implanted intrafascicular microelectrodes. The preliminary experiment results show the system's capabilities of providing robust, high-accuracy (95%-99%) and low-latency (50-120 ms) control of individual finger movements in various laboratory and real-world environments.Conclusion.This work is a technological demonstration of modern edge computing platforms to enable the effective use of deep learning-based neural decoders for neuroprosthesis control as an autonomous system.Significance.The proposed system helps pioneer the deployment of deep neural networks in clinical applications underlying a new class of wearable biomedical devices with embedded artificial intelligence.Clinical trial registration: DExterous Hand Control Through Fascicular Targeting (DEFT). Identifier: NCT02994160.

Deep Learning-Based Approaches for Decoding Motor Intent From Peripheral Nerve Signals.

Previous literature shows that deep learning is an effective tool to decode the motor intent from neural signals obtained from different parts of the nervous system. However, deep neural networks are often computationally complex and not feasible to work in real-time. Here we investigate different approaches' advantages and disadvantages to enhance the deep learning-based motor decoding paradigm's efficiency and inform its future implementation in real-time. Our data are recorded from the amputee's residual peripheral nerves. While the primary analysis is offline, the nerve data is cut using a sliding window to create a "pseudo-online" dataset that resembles the conditions in a real-time paradigm. First, a comprehensive collection of feature extraction techniques is applied to reduce the input data dimensionality, which later helps substantially lower the motor decoder's complexity, making it feasible for translation to a real-time paradigm. Next, we investigate two different strategies for deploying deep learning models: a one-step (1S) approach when big input data are available and a two-step (2S) when input data are limited. This research predicts five individual finger movements and four combinations of the fingers. The 1S approach using a recurrent neural network (RNN) to concurrently predict all fingers' trajectories generally gives better prediction results than all the machine learning algorithms that do the same task. This result reaffirms that deep learning is more advantageous than classic machine learning methods for handling a large dataset. However, when training on a smaller input data set in the 2S approach, which includes a classification stage to identify active fingers before predicting their trajectories, machine learning techniques offer a simpler implementation while ensuring comparably good decoding outcomes to the deep learning ones. In the classification step, either machine learning or deep learning models achieve the accuracy and F1 score of 0.99. Thanks to the classification step, in the regression step, both types of models result in a comparable mean squared error (MSE) and variance accounted for (VAF) scores as those of the 1S approach. Our study outlines the trade-offs to inform the future implementation of real-time, low-latency, and high accuracy deep learning-based motor decoder for clinical applications.

Fascicle-Specific Targeting of Longitudinal Intrafascicular Electrodes for Motor and Sensory Restoration in Upper-Limb Amputees.

Multichannel longitudinal intrafascicular electrode (LIFE) interfaces provide optimized balance of invasiveness and stability for chronic sensory stimulation and motor recording/decoding of peripheral nerve signals. Using a fascicle-specific targeting (FAST)-LIFE approach, where electrodes are individually placed within discrete sensory- and motor-related fascicular subdivisions of the residual ulnar and/or median nerves in an amputated upper limb, FAST-LIFE interfacing can provide discernment of motor intent for individual digit control of a robotic hand, and restoration of touch- and movement-related sensory feedback. The authors describe their findings from clinical studies performed with 6 human amputee trials using FAST-LIFE interfacing of the residual upper limb.

Detailed Case Reports of Surgical Treatment for Intraneural Ganglion Cysts.

Intraneural ganglion cysts are nonneoplastic mucinous cysts that form by the accumulation of thick mucinous fluid in the epineurium of peripheral nerves. Symptoms arise from mechanical compression of adjacent nerve fascicles from the intraneural ganglion cyst, and include local or radiating pain, paresthesias, weakness, and muscle atrophy. METHODS: Retrospective review of three cases of symptomatic intraneural ganglion cysts affecting the upper and lower extremity. RESULTS: In our cases, the intraneural ganglion cysts were completely decompressed with resection of the articular branches, leading to improvement in the patient's symptoms. CONCLUSIONS: Treatment of intraneural ganglion cysts requires an understanding of the underlying anatomy and pathophysiology; accurate early diagnosis is important and can lead to timely treatment and better outcomes.

Quality of Life With Pembrolizumab for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: KEYNOTE-040.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) affects health-related quality of life (HRQoL); few treatments have demonstrated clinically meaningful HRQoL benefit. KEYNOTE-040 evaluated pembrolizumab vs standard of care (SOC) in patients with recurrent and/or metastatic HNSCC whose disease recurred or progressed after platinum-containing regimen. METHODS: Patients received pembrolizumab 200 mg or SOC (methotrexate, docetaxel, or cetuximab). Exploratory HRQoL analyses used European Organisation for Research and Treatment of Cancer (EORTC) 30 quality-of-life, EORTC 35-question quality-of-life head and neck cancer-specific module, and EuroQoL 5-dimensions questionnaires. RESULTS: The HRQoL population comprised 469 patients (pembrolizumab = 241, SOC = 228). HRQoL compliance for patients in the study at week 15 was 75.3% (116 of 154) for pembrolizumab and 74.6% (85 of 114) for SOC. The median time to deterioration in global health status (GHS) and QoL scores were 4.8 months with pembrolizumab and 2.8 months with SOC (hazard ratio = 0.79, 95% confidence interval [CI] = 0.59 to 1.05). At week 15, GHS / QoL scores were stable for pembrolizumab (least squares mean [LSM] = 0.39, 95% CI = -3.00 to 3.78) but worsened for SOC (LSM = -5.86, 95% CI = -9.68 to -2.04); the LSM between-group difference was 6.25 points (95% CI = 1.32 to 11.18; nominal 2-sided P = .01). A greater difference in the LSM for GHS / QoL score occurred with pembrolizumab vs docetaxel (10.23, 95% CI = 3.15 to 17.30) compared with pembrolizumab vs methotrexate (6.21, 95% CI = -4.57 to 16.99) or pembrolizumab vs cetuximab (-1.44, 95% CI = -11.43 to 8.56). Pembrolizumab-treated patients had stable functioning and symptoms at week 15, with no notable differences from SOC. CONCLUSIONS: GHS / QoL scores were stable with pembrolizumab but declined with SOC in patients at week 15, supporting the clinically meaningful benefit of pembrolizumab in recurrent and/or metastatic HNSCC.