Satellite imaging reveals increased proportion of population exposed to floods.

Flooding affects more people than any other environmental hazard and hinders sustainable development1,2. Investing in flood adaptation strategies may reduce the loss of life and livelihood caused by floods3. Where and how floods occur and who is exposed are changing as a result of rapid urbanization4, flood mitigation infrastructure5 and increasing settlements in floodplains6. Previous estimates of the global flood-exposed population have been limited by a lack of observational data, relying instead on models, which have high uncertainty3,7-11. Here we use daily satellite imagery at 250-metre resolution to estimate flood extent and population exposure for 913 large flood events from 2000 to 2018. We determine a total inundation area of 2.23 million square kilometres, with 255-290 million people directly affected by floods. We estimate that the total population in locations with satellite-observed inundation grew by 58-86 million from 2000 to 2015. This represents an increase of 20 to 24 per cent in the proportion of the global population exposed to floods, ten times higher than previous estimates7. Climate change projections for 2030 indicate that the proportion of the population exposed to floods will increase further. The high spatial and temporal resolution of the satellite observations will improve our understanding of where floods are changing and how best to adapt. The global flood database generated from these observations will help to improve vulnerability assessments, the accuracy of global and local flood models, the efficacy of adaptation interventions and our understanding of the interactions between landcover change, climate and floods.

Nutrient Intakes and Gastrointestinal Symptoms Among Esophagogastric Cancer Survivors up to 5 Years Post-Surgery.

A cross-sectional analysis explored nutritional intakes and gastrointestinal (GI) symptoms among esophagogastric cancer survivors up to 12, 13-36, and 37+ months post-surgery. Participants were identified from the Upper GI Cancer Registry at St James' Hospital, Ireland. The Short Nutritional Assessment Questionnaire, European Prospective Investigation of Cancer Food Frequency Questionnaire, World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score, and Gastrointestinal Symptoms Rating Scale assessed malnutrition risk, nutritional intake, adherence to (secondary) cancer prevention recommendations, and GI symptoms, respectively. Most (82.5%, n33) participants (n40) were male. Mean age was 65.5 ± 9.3 years. Time post-surgery ranged from 6-62 months. Half (50.0%, n20) had a BMI in the healthy range. A quarter (27.5%, n11) were at risk of malnutrition. Intakes of meat and meat products exceeded recommendations and intakes of fruits, vegetables, and fiber were below recommendations, with no significant between-group differences. The mean WCRF/AICR score was 3.6 ± 1.1, indicating adherence to 3.6 of 7 cancer prevention recommendations. It was not significantly different between subgroups. Minor to mild GI discomfort was reported, with no significant between-group differences in symptoms. As rates of long-term survivorship continue to increase, survivors must be supported to sustain behaviors that enhance quality of life and reduce secondary cancer risk.

Conversations about race in Black and White US families: Before and after George Floyd's death.

Research has shown that Black parents are more likely than White parents to have conversations about race with their children, but few studies have directly compared the frequency and content of these conversations and how they change in response to national events. Here we examine such conversations in the United States before and after the killing of George Floyd. Black parents had conversations more often than White parents, and they had more frequent conversations post-Floyd. White parents remained mostly unchanged and, if anything, were less likely to talk about being White and more likely to send colorblind messages. Black parents were also more worried than White parents-both that their children would experience racial bias and that their children would perpetrate racial bias, a finding that held both pre- and post-Floyd. Thus, even in the midst of a national moment on race, White parents remained relatively silent and unconcerned about the topic.

Relationship between clinical measures of hearing and clinical measures of vestibular function.

PURPOSE: Patients often have basic audiometry (BA) but not objective diagnostic tests of the vestibular system (VNG) when complaining of symptoms of a vestibular disorder. The relationship of BA results to VNG results is unknown. This study sought to determine if BA scores are related to impaired VNG scores. MATERIALS AND METHODS: We reviewed electronic medical records at a tertiary care center, for patients seen between 2015 and 2021 who had had both a BA and a VNG (n = 651). BA subtests were pure tone averages, word recognition, and tympanogram. VNG subtests were cervical vestibular evoked myogenic potentials, Dix-Hallpike maneuvers, and bi-thermal caloric tests. All tests were summarized as normal/abnormal. RESULTS: More subjects had abnormal BA than abnormal VNG scores. Age but not sex was significantly related to abnormal scores. High BP was a significant comorbidity in 15 % of the sample, more in patients with abnormal than normal VNG scores. Although the abnormal BA and abnormal VNG were significantly related, pure tone averages and tympanogram scores were not related to VNG subtests. Abnormal word recognition with both ears combined was significantly related to normal and abnormal bi-thermal caloric tests. CONCLUSIONS: If the clinician needs to know of any VNG impairment, in general, then performing a BA without a VNG might suffice. If the clinician needs information about the details of possible vestibular impairment, then a VNG should be performed.

Biomechanical and ergonomic risks associated with cervical musculoskeletal dysfunction amongst surgeons: A systematic review.

INTRODUCTION: Surgeons are at high risk of developing musculoskeletal symptoms due to a range of factors including, maladaptive positioning and surgical ergonomics. Cervical muscle strain and biomechanical load is most prevalent due to repetitive motions and prolonged static neck positioning. This issue is apparent through reports of prevalence between 10 and 74.4% among surgeons. The aim of this systematic review is to provide an objective assessment of the clinical evidence available and a descriptive analysis of the effects of kinematics and surgical ergonomics on the prevalence of surgeons' cervical musculoskeletal pain. METHODS: This is PRISMA-compliant systematic review of clinical studies assessing the prevalence of cervical musculoskeletal dysfunction in surgeons by searching PUBMED and Ovid EMBASE databases from inception to 19th October 2023. Study quality was graded according to the National Institutes of Health study quality assessment tools. RESULTS: A total of 9 studies were included in the final qualitative analysis. The use of loupes, open surgery and excessive neck flexion (>30°) were associated with cervical dysfunction. Comparison of study outcomes was challenging due to heterogeneity within study methods and the paucity of methodological quality. CONCLUSION: The current literature assessing ergonomic and biomechanical factors predisposing surgeons to cervical musculoskeletal dysfunction is insufficient to provide reliable guidance for clinicians. Although the literature identifies factors contributing to work-related cervical dysfunction, few attempt to evaluate interventions for improved surgical ergonomics. An objective assessment of interventions that prompt postural correction with the aim to improve neck pain in surgeon cohorts is warranted.

Juvenile idiopathic arthritis-associated genetic loci exhibit spatially constrained gene regulatory effects across multiple tissues and immune cell types.

Juvenile idiopathic arthritis (JIA) is an autoimmune, inflammatory joint disease with complex genetic etiology. Previous GWAS have found many genetic loci associated with JIA. However, the biological mechanism behind JIA remains unknown mainly because most risk loci are located in non-coding genetic regions. Interestingly, increasing evidence has found that regulatory elements in the non-coding regions can regulate the expression of distant target genes through spatial (physical) interactions. Here, we used information on the 3D genome organization (Hi-C data) to identify target genes that physically interact with SNPs within JIA risk loci. Subsequent analysis of these SNP-gene pairs using data from tissue and immune cell type-specific expression quantitative trait loci (eQTL) databases allowed the identification of risk loci that regulate the expression of their target genes. In total, we identified 59 JIA-risk loci that regulate the expression of 210 target genes across diverse tissues and immune cell types. Functional annotation of spatial eQTLs within JIA risk loci identified significant overlap with gene regulatory elements (i.e., enhancers and transcription factor binding sites). We found target genes involved in immune-related pathways such as antigen processing and presentation (e.g., ERAP2, HLA class I and II), the release of pro-inflammatory cytokines (e.g., LTBR, TYK2), proliferation and differentiation of specific immune cell types (e.g., AURKA in Th17 cells), and genes involved in physiological mechanisms related to pathological joint inflammation (e.g., LRG1 in arteries). Notably, many of the tissues where JIA-risk loci act as spatial eQTLs are not classically considered central to JIA pathology. Overall, our findings highlight the potential tissue and immune cell type-specific regulatory changes contributing to JIA pathogenesis. Future integration of our data with clinical studies can contribute to the development of improved JIA therapy.

Current trends in craniofacial reconstruction.

Reconstruction of the head and neck continues to pose a variety of difficult functional and aesthetic challenges to the plastic surgeon. While the surgical treatment for midfacial and skull base tumours continues to advance, the three-dimensional reconstruction predicaments continue to increase in complexity. Reconstructive strategies of the head and neck require the restoration of intricate skeletal architecture and large volumes of both internal and external soft tissue envelopes that can withstand adjuvant therapies. Vascularized bone grafts in combination with microsurgical techniques is the current trend of most reconstruction and has replaced local and pedicle flaps as the preferred modality for large defects. This article will focus on concise areas of difficulty in craniofacial reconstruction, including mandibular, midfacial, scalp and base of skull reconstruction. As our goals now move from flap survival to refinement, more complex and innovative reconstructions are executed. The problems with each modality are examined, and the frontiers of head and neck reconstruction are explored. With the potential combination of virtual surgery and tissue engineered biotechnology, we may someday be able to expand our reconstructive capabilities beyond free tissue transfer.

A rare case of intralesional haemorrhage of a benign aqueductal cyst after CSF diversion treatment. A case report and review of literature.

Benign cysts within the pure aqueductal region are a rare entity. Their critical location within the ventricular system presents a risk of potentially catastrophic outcomes. We present a case of a 68-year-old female who was transferred to our unit with an acute obstructive triventricular hydrocephalus caused by a benign cyst within the cerebral aqueduct. She became unconscious and had an urgent endoscopic third ventriculostomy (ETV). Post-operatively, the patient was recovering well but then developed a sudden onset severe headache accompanied by vomiting. Imaging revealed intracystic haemorrhage with expansion of lesion but there was no obstructive hydrocephalus due to CSF diversion performed 9 d prior. She was treated conservatively and continued to improve.

Engaging the Wisdom of Older Veterans to Enhance VA Healthcare, Research, and Services.

BACKGROUND: Stakeholder engagement helps ensure that research is relevant, clinical innovations are responsive, and healthcare services are patient-centered. OBJECTIVE: Establish and sustain a Veteran engagement board involving older Veterans and caregivers to provide input on aging-related research and clinical demonstration projects. DESIGN AND PARTICIPANTS: The Older Veteran Engagement Team (OVET)-a group of eight Veterans and one caregiver who range in age from 62 to 92-was formed in November 2017 and has met monthly since January 2018. The OVET provides feedback on topics that reflect the foci of the VA Eastern Colorado Geriatric Research Education and Clinical Center (GRECC) (e.g., physical functioning, hearing health, and emotional wellness/mental health). Ongoing evaluation documents the return on investment of Veteran engagement. MAIN MEASURES: The OVET member and provider/investigator meeting evaluations with longitudinal follow-up at 6 and 12 months. RESULTS: Return on investment of Veteran engagement is multi-faceted. For OVET, ROI ranges from grant support to improved healthcare quality/efficiency to social-emotional benefits. To date, funding awards total over $2.3 M for NIH and VA-funded projects to which OVET provided substantive feedback. Documented impacts on healthcare services include reductions in patient wait times, more appropriate utilization of services and increased patient satisfaction. Social-emotional benefits include generativity, as OVET members contribute to improving clinical and community-based supports for other Veterans. The OVET provides an opportunity for older Veterans to share their lived experience with trainees and early career investigators who are preparing for careers serving Veterans. CONCLUSION: The OVET is similar to other established stakeholder engagement groups; team members offer their individual viewpoints at any stage of research, clinical demonstration, or quality improvement projects. The OVET provides a mechanism for the voice of older Veterans and caregivers to shape aspects of individual projects. Importantly, these projects support patient-centered care and promote the characteristics of an age-friendly healthcare system.

Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour.

BACKGROUND: The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour. METHODS: UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated. p values < 0.05 were considered significant in analyses. RESULTS: Twenty-four UC patients were included (age [median, range]) 55 [21-72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression, p = 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (p = 0.015) and IL-12 / IL-23p40 (p = 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (p = 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (p = 0.016). CONCLUSION: Reduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.

Modification of hurling helmets causing penetrating upper limb injury: A case series demonstrating opportunity for improved player safety.

BACKGROUND: The games of hurling and camogie involve fast ball movement and a substantial physical contact with opposing players. The wearing of protective helmets with faceguards became obligatory 10 years ago and resulted in a significant reduction of craniofacial injuries. However since then a trend has emerged of players modifying helmets to improve comfort and vision. As officials are not yet required to perform pre-match checks, many players enter competition with defective protective equipment which poses a risk to both themselves and others. METHODS: We present 4 cases of penetrating upper limb injury in hurlers sustained as a result of helmet faceguards. These injuries were sustained during competitive play and the affected patients presented with portions of the faceguards embedded in their wounds. Each patient required admission to hospital and exploration of their wounds under general anaesthetic. CONCLUSIONS: This case series demonstrates the dangers of modification and damage to protective helmet faceguards used in hurling and camogie. We encourage helmet manufacturers to re-engage with players to ensure that current safety equipment meets the functional demands of the modern player while adhering to approved manufacturing standards. Mandatory helmet checks before competitive games would reduce the likelihood of penetrating upper limb injury to players.

Cost-effectiveness of duloxetine for knee OA subjects: the role of pain severity.

OBJECTIVE: Establish the impact of pain severity on the cost-effectiveness of generic duloxetine for knee osteoarthritis (OA) in the United States. DESIGN: We used a validated computer simulation of knee OA to compare usual care (UC) - intra-articular injections, opioids, and total knee replacement (TKR) - to UC preceded by duloxetine in those no longer achieving pain relief from non-steroidal anti-inflammatory drugs (NSAIDs). Outcomes included quality-adjusted life years (QALYs), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs). We considered cohorts with mean ages 57-75 years and Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain 25-55 (0-100, 100-worst). We derived inputs from published data. We discounted costs and benefits 3% annually. We conducted sensitivity analyses of duloxetine efficacy, duration of pain relief, toxicity, and costs. RESULTS: Among younger subjects with severe pain (WOMAC pain = 55), duloxetine led to an additional 9.6 QALYs per 1,000 subjects (ICER = $88,500/QALY). The likelihood of duloxetine being cost-effective at willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY was 40% and 54%. Offering duloxetine to older patients with severe pain led to ICERs >$150,000/QALY. Offering duloxetine to subjects with moderate pain (pain = 25) led to ICERs <$50,000/QALY, regardless of age. Among knee OA subjects with severe pain (pain = 55) who are unwilling or unable to undergo TKR, ICERs were <$50,600/QALY, regardless of age. CONCLUSIONS: Duloxetine is a cost-effective addition to knee OA UC for subjects with moderate pain or those with severe pain unable or unwilling to undergo TKR. Among younger subjects with severe pain, duloxetine is cost-effective at WTP thresholds >$88,500/QALY.

LC-MS/MS quantification of fat soluble vitamers - A systematic review.

Fat soluble vitamers (FSV) are several biochemically diverse micronutrients essential for healthy development, growth, metabolism, and cell regulation. We cannot synthesize FSV completely or at the required concentrations. Deficiency or excess of FSV can result in many health problems. Plasma is the most accessible sample matrix for the quantification of FSV. However, due to its complexity and other analytical challenges (e.g., FSV sensitivity to light, oxygen, heat, pH, chemical heterogeneity, standard availability), developing a method for the simultaneous quantification of multiple FSV at physiological concentrations has been challenging. In this systematic review, we examine the parameters and criteria used in existing Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) methods for FSV quantification to the extraction method, chromatographic resolution, matrix effects, and method validation as critical to a sensitive and robust method. We conclude that the final FSV method sensitivity is predominantly based on aforementioned criteria and future method development using LC-MS/MS will benefit from the application of this systematic review.

Secukinumab shows high and sustained efficacy in nail psoriasis: 2.5-year results from the randomized placebo-controlled TRANSFIGURE study.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, a cornerstone cytokine in psoriasis, has shown long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations. OBJECTIVES: To report the long-term (2·5-year) efficacy and safety of secukinumab in nail psoriasis. METHODS: TRANSFIGURE, a double-blind, randomized, placebo-controlled, parallel-group, multicentre phase IIIb study in 198 patients, investigated secukinumab 150 mg and 300 mg in patients with moderate-to-severe nail psoriasis. RESULTS: At week 16, the primary endpoint Nail Psoriasis Severity Index (NAPSI) was met, demonstrating superiority of secukinumab to placebo. The effect was sustained over 2·5 years with a large benefit for nail clearance, with mean NAPSI improvement of -73·3% and -63·6% with secukinumab 300 mg and 150 mg, respectively. At 2·5 years, secukinumab demonstrated sustained clinically significant reductions in total mean Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) quality-of-life (QoL) scores of -52·4% and -18·1%, and 70% and 71% of patients achieved a weighted NAPPA Patient Benefit Index global score of ≥ 2 with secukinumab 300 mg and 150 mg, respectively. Patients showed considerable improvements in the EuroQol 5-Dimension health status questionnaire at 2·5 years, reporting a decrease in pain and discomfort. No new safety findings were observed. CONCLUSIONS: Secukinumab demonstrated strong and clinically meaningful efficacy for up to 2·5 years in nail psoriasis, with significant sustained QoL improvements and a favourable safety profile.

Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800.

AIMS: Increases in antimicrobial resistance have meant that the antimicrobial potential of lantibiotics is now being investigated irrespective of the nature of the producing organism. The aim of this study was to investigate whether natural nisin variants produced by non-Generally Recognized as Safe (GRAS) strains, such as nisin H, nisin J and nisin P, could be expressed in a well-characterized GRAS host. METHODS AND RESULTS: This study involved cloning the nisin A promoter and leader sequence fused to nisin H, nisin J or nisin P structural gene sequences originally produced by Streptococcus hyointestinalis DPC 6484, Staphylococcus capitis APC 2923 and Streptococcus agalactiae DPC 7040, respectively. This resulted in their expression in Lactococcus lactis NZ9800, a genetically modified strain that does not produce nisin A. CONCLUSIONS: Induction of the nisin controlled gene expression system demonstrates that these three nisin variants could be acted on by nisin A machinery provided by the host strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Describes the first successful heterologous production of three natural nisin variants by a GRAS strain, and demonstrates how such systems could be harnessed not only for lantibiotic production but also in the expansion of their structural diversity and development for use as future biotherapeutics.

Toddlers learn and flexibly apply multiple possibilities.

The ability to consider multiple possibilities forms the basis for a wide variety of human-unique cognitive capacities. When does this skill develop? Previous studies have narrowly focused on children's ability to prepare for incompatible future outcomes. Here, we investigate this capacity in a causal learning context. Adults (N = 109) and 18- to 30-month olds (N = 104) observed evidence that was consistent with two hypotheses, each occupying a different level of abstraction (individual vs. relational causation). Results suggest that adults and toddlers identified multiple candidate causes for an effect, held these possibilities in mind, and flexibly applied the appropriate hypothesis to inform subsequent inferences. These findings challenge previous suggestions that the ability to consider multiple alternatives does not emerge until much later in development.

Estimating contextual effect in nonpharmacological therapies for pain in knee osteoarthritis: a systematic analytic review.

OBJECTIVE: Conduct a systematic review and use meta-analytic techniques to estimate the proportion of total treatment effect that can be attributable to contextual effects (PCE) in adults receiving nonpharmacological, nonsurgical (NPNS) treatments for knee osteoarthritis (OA). DESIGN: We reviewed the published literature to identify five frequently studied NPNS treatments for knee OA: exercise, acupuncture, ultrasound, laser, and transcutaneous electrical nerve stimulation (TENS). We searched for randomized controlled trials (RCTs) of these treatments and abstracted pre- and post-intervention pain scores for groups receiving placebo and active treatments. For each study we calculated the PCE by dividing the change in pain in the placebo group by the change in pain in the active treatment group. We log transformed the PCE measure and pooled across studies using a random effects model. RESULTS: We identified 25 studies for analysis and clustered the RCTs into two groups: acupuncture and topical energy modalities (TEM). 13 acupuncture studies included 1,653 subjects and 12 TEM studies included 572 subjects. The combined PCE was 0.61 (95% CI 0.46-0.80) for acupuncture and 0.69 (95% CI 0.54-0.88) for TEM. CONCLUSION: Our findings suggest that about 61% and 69% of the total treatment effect experienced by subjects receiving acupuncture and TEM treatments, respectively, for knee OA pain may be explained by contextual effects. Contextual effects may include the placebo effect, changes attributable to natural history, and effects of co-therapies. These data highlight the important role of contextual effects in the response to NPNS OA treatments.

Long-term clinical and economic outcomes of a short-term physical activity program in knee osteoarthritis patients.

OBJECTIVE: Physical activity (PA) in the US knee osteoarthritis (OA) population is low, despite well-established health benefits. PA program implementation is often stymied by sustainability concerns. We sought to establish parameters that would make a short-term (3-year efficacy) PA program a cost-effective component of long-term OA care. METHOD: Using a validated computer microsimulation (Osteoarthritis Policy Model), we examined the long-term clinical (e.g., comorbidities averted), quality of life (QoL), and economic impacts of a 3-year PA program, based upon the SPARKS (Studying Physical Activity Rewards after Knee Surgery) Trial, for inactive knee OA patients. We determined the cost, efficacy, and impact of PA on QoL and medical costs that would make a PA program a cost-effective addition to OA care. RESULTS: Among the 14 million with knee OA in the US, >4 million are inactive. Participation of 10% in the modeled PA program could save 200 cases of cardiovascular disease, 400 cases of diabetes, and 6,800 quality-adjusted life-years (QALYs). The program had an incremental cost-effectiveness ratio (ICER) of $16,100/QALY. Tripling PA program cost ($860/year) raised the ICER to $108,300/QALY; varying QoL benefits from PA yielded ICERs of $8,800/QALY-$99,900/QALY; varying background cost savings from PA did not qualitatively impact ICERs. Offering the PA program to any adults with knee OA (not only inactive) yielded $31,000/QALY. CONCLUSION: A PA program with 3-year efficacy in the knee OA population carried favorable long-term clinical and economic benefits. These results offer justification for policymakers and payers considering a PA intervention incorporated into knee OA care.

Multimode Storage of Quantum Microwave Fields in Electron Spins over 100 ms.

We report long coherence times (up to 300 ms) for near-surface bismuth donor electron spins in silicon coupled to a superconducting microresonator, biased at a clock transition. This enables us to demonstrate the partial absorption of a train of weak microwave fields in the spin ensemble, their storage for 100 ms, and their retrieval, using a Hahn-echo-like protocol. Phase coherence and quantum statistics are preserved in the storage.

Sustained efficacy of secukinumab in patients with moderate-to-severe palmoplantar psoriasis: 2·5-year results from GESTURE, a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Secukinumab has shown sustained efficacy and safety in several manifestations of psoriasis. OBJECTIVES: GESTURE investigated the long-term (2·5-year) safety and efficacy of 150 mg and 300 mg subcutaneous secukinumab in 205 patients with moderate-to-severe palmoplantar psoriasis. METHODS: GESTURE was a randomized, double-blind, placebo-controlled, multicentre, phase IIIb trial conducted across 15 countries. The study was 140 weeks long and consisted of four periods: screening (up to 4 weeks), treatment period 1 (16 weeks), treatment period 2 (116 weeks) and post-treatment follow-up (8 weeks). Eligible patients were aged ≥ 18 years with moderate-to-severe palmoplantar psoriasis and at least one plaque outside of the palms and soles. Efficacy was assessed via a palmoplantar Investigator's Global Assessment (ppIGA) and the palmoplantar Psoriasis Area and Severity Index (PASI). RESULTS: The primary end point, a ppIGA score of 0 or 1, was met at week 16. The effect was sustained over 2·5 years with 59% [95% confidence interval (CI) 43·5-74·1] and 53% (95% CI 35·1-69·6) of patients in the secukinumab 300 mg and 150 mg groups, respectively, achieving clear or almost clear palms and soles (ppIGA 0 or 1). At 2·5 years, the mean palmoplantar PASI percentage was reduced in both the secukinumab 300 mg group (-74·7%) and the secukinumab 150 mg group (-61·6%). A total of 17% (secukinumab 300 mg group) and 18% (secukinumab 150 mg group) of patients experienced no difficulty in hands and feet functionality, as indicated by the palmoplantar quality of life instrument overall scores. The safety profile was favourable. CONCLUSIONS: GESTURE revealed that secukinumab provides a strong and sustained response over 2·5 years in challenging-to-treat palmoplantar psoriasis.