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In chronic musculoskeletal conditions, the prognosis tends to be more informative than the diagnosis for the future course of the disease. Many studies have identified clusters of patients who seemingly share similar pain trajectories. In a dataset of low back pain (LBP) patients, pain trajectories have been identified, and distinct trajectory types have been defined, making it possible to create pattern recognition software that can classify patients into respective pain trajectories reflecting their condition. It has been suggested that the classification of pain trajectories may create clinically meaningful subgroups of patients in an otherwise heterogeneous population of patients with LBP. A software tool was created that combined the ability to recognise the pain trajectory of patients with a system that could create subgroups of patients based on their characteristics. This tool is primarily meant for researchers to analyse trends in large heterogeneous datasets without large losses of data. Prospective analysis of pain trajectories is not directly helpful for clinicians. However, the tool might aid in the identification of patient characteristics which have predictive capabilities of the most likely trajectory a patient might experience in the future. This will help clinicians to tailor their advice and treatment for a specific patient., (© 2024. The Author(s).)

Fractures are ubiquitous and can lead to the catastrophic material failure of materials. Although fracturing in a two-dimensional plane is well understood, all fractures are extended in and propagate through three-dimensional space. Moreover, their behaviour is complex. Here we show that the forward propagation of a fracture front occurs through an initial rupture, nucleated at some localized position, followed by a very rapid transverse expansion at velocities as high as the Rayleigh-wave speed. We study fracturing in a circular geometry that achieves an uninterrupted extended fracture front and use a fluid to control the loading conditions that determine the amplitude of the forward jump. We find that this amplitude correlates with the transverse velocity. Dynamic rupture simulations capture the observations for only a high transverse velocity. These results highlight the importance of transverse dynamics in the forward propagation of an extended fracture., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Water transfer in wood plays a major role during the life time of timber structures but the physics of the various processes involved, such as wetting and imbibition, is not fully understood. Here we show that the angle of contact of a water drop placed in contact with an air dry wood surface is initially larger than 90°, then the drop slowly spreads over the surface, while the apparent (macroscopic) contact angle decreases down to a few tens of degrees. We show that similar results are obtained with a model material, i.e. hydrogel, as soon as a perturbation is induced onto the line of contact. We demonstrate that for the gel the initial large apparent contact angle results from a strong deformation of the gel in a thin softened region below the line of contact resulting from the fast diffusion of water and swelling of this region. This phenomenon ensures a real (local) contact angle close to zero. The spreading then results from the progressive diffusion of water at farther distance and successive perturbations of the line of contact when the drop enters in contact with small liquid droplets dispersed along the surface (residues of the chemical reaction during gel preparation). It is suggested that a similar effect occurs for the water drop over a wood surface and explains the large initial contact angle and slow spreading: the line of contact is initially pinned thanks to a wood surface deformation resulting from the wood surface swelling due to water absorption, thus leading to a large contact angle; it will then unpin when the local conditions have changed as a result of water diffusion at further distance, allowing for a small displacement up to the next pinning point and so on.

Background: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies., Patients and Methods: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients)., Results: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality., Conclusions: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies., Clinical Trial Identifier: NCT04354701., Competing Interests: Disclosure JDA reports research funding to the institution from Tesaro, outside the submitted work. ZB reports nonfinancial support from Bristol Myers Squibb and grants from Genentech/imCORE, outside the submitted work. BB reports research funding to the institution from Boehringer Ingelheim, Bicycle Therapeutics, Syros Pharmaceuticals, and Ikena Oncology, all outside the submitted work. TB-S reports research funding to the institution from Agios, Arys, Boston Biomedical, Bayer, Amgen, Merck, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Array Biopharma, Genentech, Novartis, Mirati, Merus, AbGenomics, Incyte, Pfizer, BMS; consulting (to institution) for Ipsen, Array Biopharma, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, and Merck; consulting (to self) for AbbVie, Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo, Natera, Treos Bio, Celularity, Exact Science, Sobi, BeiGene, Xilis, Astra Zeneca, and Foundation Medicine; serving on Independent Data Monitoring Committee/Data and Safety Monitoring Board (to self) for AstraZeneca, Exelixis, Lilly, PanCAN, and 1Globe; positions on Scientific Advisory Board for Imugene, Immuneering, and Sun Biopharma; and inventions/patents (WO/2018/183488 and WO/2019/055687), all outside the submitted work. SB reports being on advisory boards for Bristol Meyers Squibb and Seattle Genetics. MAB reports personal fees from Exelixis, Bristol-Myers Squibb, Bayer, Eisai, Pfizer, AstraZeneca, Janssen, Genomic Health, Nektar, and Sanofi; grants from Xencor, Bayer, Bristol-Myers Squibb, Genentech/Roche, Seattle Genetics, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Peloton Therapeutics, and Pfizer, outside the submitted work. NB reports honoraria from Novartis, Pfizer, Roche, and Lilly, outside the submitted work. DWB reports research funding to the institution from Exelixis, Ayala, Merck, and Elevar, all outside the submitted work. DDC declares consulting or advisory role with Exelixis, outside the submitted work. TKC reports institutional and personal research support from Alexion, Analysis Group, AstraZeneca, Aveo, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Calithera, Cerulean, Corvus, Eisai, Exelixis, F. Hoffmann-La Roche, Foundation Medicine Inc., Genentech, GlaxoSmithKline, Ipsen, Lilly, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Roche, Roche Products Limited, Sanofi/Aventis, Takeda, Tracon; consulting/honoraria or advisory role with Alexion, Analysis Group, AstraZeneca, Aveo, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Cerulean, Corvus, Eisai, EMD Serono, Exelixis, Foundation Medicine Inc., Genentech, GlaxoSmithKline, Heron Therapeutics, Infinity Pharma, Ipsen, Jansen Oncology, IQVIA, Lilly, Merck, NCCN, Novartis, Peloton, Pfizer, Pionyr, Prometheus Labs, Roche, Sanofi/Aventis, Surface Oncology, Tempest, Up-to-Date; CME-related events (e.g. OncLive, PVI, MJH Life Sciences); stock ownership in Pionyr, Tempest; patents filed, royalties, or other intellectual properties related to biomarkers of immune checkpoint blockers; fees for travel, accommodations, expenses, medical writing in relation to consulting, advisory roles, or honoraria; and no speaker's bureau; also supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE and Program, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at DFCI. DBD reports consulting for Ipsen, Boehringer Ingelheim; ASCO Young Investigator Award from Conquer Cancer Foundation, outside the submitted work. AE reports grant support from AstraZeneca, outside the submitted work. DF reports research funding to the institution from Viracor-Eurofins and Astellas, all outside the submitted work. LAF reports clinical trial funding to the institution from BMS, EMD Serono, Pfizer, Merck KGaA, Array, Kartos, Merck, and Incyte, ECOG-ACRIN study funding from Array; and personal fees from Elsevier and Via Oncology, outside the submitted work. DBF reports honoraria from Castle Biosciences. SMG reports Honoraria from AstraZeneca, Merck, Genentech/Roche; consulting or advisory role with Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Xcovery, Boehringer Ingelheim, Novocure, Daiichi Sankyo, Novartis, Jazz Pharmaceuticals, Blueprint Medicines, Eli Lilly, Pfizer, Janssen Oncology; research funding (to self) from Merck, AstraZeneca; research funding (to institution) from Genentech/Roche, Merck, Blueprint Medicines, ARIAD/Takeda, Astellas Pharma, Lycera, Daiichi Sankyo, IMAB, Nektar, AstraZeneca, Pfizer, Amgen; travel, accommodations, expenses from Genentech/Roche, Merck; and other relationship from AstraZeneca, all outside the submitted work. MDG reports personal fees from Genentech, Pfizer, Astra Zeneca, Merck, Bristol Myers Squib, Dragonfly, Dracen, Seattle Genetics, and Astellas, outside the submitted work. PG reports consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Clovis Oncology, Dyania Health, Driver, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, Genzyme, GlaxoSmithKline, Heron Therapeutics, Immunomedics, Infinity Pharmaceuticals, Janssen, Merck, Mirati Therapeutics, Pfizer, Seattle Genetics, QED Therapeutics; research funding to institution from Merck, Mirati Therapeutics, Pfizer, Clovis Oncology, Bavarian Nordic, Immunomedics, Debiopharm, Bristol-Myers Squibb, QED Therapeutics, GlaxoSmithKline, and Kure It Cancer Research, all outside the submitted work. SG reports research funding to the institution from AstraZeneca and consulting/advisory role with Puma Biotechnology. SG reports consultancy fees from BMS, Merck, AstraZeneca, Seattle Genetics, Pfizer; and speaker fees from Seattle Genetics and Janssen, all outside the submitted work. TRH reports consulting or advisory role with Curium, ScioScientific, TERUMO, Lexicon, Ipsen, Advanced Accelerator; research funding from Ipsen, ArQule, Agios, Thermo Fisher Scientific, Basilea. BH reports research funding to the institution from Amgen, AbbVie, BI, Mirati, Merck, Eli-Lilly, AstraZeneca, BMS, Novartis, GSK, Pfizer, Advaxis, and Guardant Health; consulting/advisory role with Merck, BMS, Genentech, AstraZeneca, Amgen, Novartis, TPT, VI, Guardant Health; and honoraria from PER and OncLive, all outside the submitted work. JEH reports research funding from Regeneron and Dendreon; and travel, accommodations, and expenses from Genzyme. CH reports funding from the Henry Ford Cancer Institute supporting the current work; research funding to institution from Merck, Exelixis, Bayer, AstraZeneca, Genentech, Dendreon and Bausch; personal fees from Sanofi/Genzyme, Dendreon, Exelixis, Bristol Myers Squibb, Astellas, Medivation, Bayer, and Janssen Scientific, all outside the submitted work; and stock ownership by an immediate family member in Johnson and Johnson. DBJ reports advisory board participation for Array Biopharma, BMS, Catalyst Biopharma, Iovance, Jansen, Merck, Novartis, and OncoSec, and receives research funding from BMS and Incyte, all outside the submitted work. AK reports support to his institution from TESARO, Halozyme, Geistlich Pharma, Astellas Pharma, and Rafael Pharmaceuticals; and honoraria from OncLive, outside the submitted work. ARK (or an immediate family member) has currently or during the past 2 years owned stock or held an ownership interest in Merck, Sanofi, and BMS. VSK reports personal fees from Pfizer, Janssen, Dendreon, AstraZeneca, Seattle Genetics, and Clovis; grants (for institution) from Nektar, Novartis/Endocyte, Janssen, Clovis, and Prostate Cancer Foundation, all outside the submitted work. NMK reports personal fees from G1 Therapeutics, Invitae, Beyond Spring, Spectrum, BMS, Janssen, and Total Health, all outside the submitted work. PEL reports consulting/advisory role with Pfizer, Merck, Teva, BI, and Astra Zeneca, all outside the submitted work. AL-B reports personal fees from PSI CRO, Bayer, Blueprint, Astra-Zeneca, Medidata, Taiho, QED, Cardinal Health, BrightInsight, The Lynx Group, Boston Biomedical, Amgen, Bayer, Guardant, Natera, Eisai, Ipsen, and Merck; and stock options from Massive Bio, outside the submitted work. GdLL reports honoraria from Boehringer Ingelheim; consulting or advisory role for Pfizer and AstraZeneca; research funding from AstraZeneca; funding to his institution from Merck Sharp & Dohme, EMD Serono, AstraZeneca, Blueprint Medicines, Tesaro, Bavarian Nordic, NOVARTIS, G1 Therapeutics, Adaptimmune, BMS, GSK, AbbVie, Rgenix, Pfizer, Roche, Genentech, Lilly, and Janssen; travel, accommodations, and expenses from Boehringer Ingelheim, Pfizer, E.R. Squibb Sons, LLC, Janssen. GHL reports grants from AMGEN (institution); personal fees from G1 Therapeutics, TEVA, Samsung Bioepis, Beyond Spring, and Merck, outside the submitted work. RRM reports research funding from Bayer, Pfizer, Tempus; serves on Advisory Board for AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Exelixis, Janssen, Merck, Novartis, Pfizer, Sanofi, Tempus; is a consultant for Dendreon, Vividion; and serves on the molecular tumor board at Caris. RAM grants from Incyte, CTI, AbbVie, and Celgene; personal fees from Novartis, Genentech, Sierra Oncology, La Jolla, and Samus, outside the submitted work. VM has currently or during the past 2 years employment and stock or other ownership interest with Johnson & Johnson, all outside the submitted work. GN reports research funding to the institution from Novartis, all outside the submitted work. JN reports personal fees from AstraZeneca, Clovis Oncology; all outside the submitted work. CAP (or an immediate family member) has currently or during the past 2 years owned stock or held an ownership interest in Pfizer, Epizyme, Inovio, OPKO Health Inc, Roche. JMP reports grant from Dana-Farber/Harvard Cancer Center Breast SPORE Program, outside the submitted work. PP reports receiving payment for speakers' bureau from Novartis, Daichi Sankyo, Genentech, Seattle Genetics, and Pfizer, all outside the submitted work. NAP reports personal fees from Eli Lilly, Merck, BMS, Genentech, AstraZeneca, Inivata, and Regeneron, outside the submitted work. SP reports personal fees from AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics and Takeda, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp and Dohme, Novartis, Pfizer, and Takeda; nonfinancial support from Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Meyers Squibb, Clovis, F. Hoffmann-La Roche, Illumina, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer, and Sanofi; and personal fees from BioInvent (all fees to institution), outside the submitted work. DYR reports consulting/advisory role with and coverage of travel/accommodation expenses by Castle Biosciences, all outside the submitted work. BIR reports grants, personal fees, and nonfinancial support from Merck; grants and personal fees from BMS, Pfizer, Aveo, and Genentech; grants from Astra Zeneca; personal fees from Synthorx, 3D Medicines, Aravive, Surface Oncology, and Arrowhead Therapeutics; and other from PTC Therapeutics, outside the submitted work. RPR reports research grants to her institution from BMS and Janssen and has worked as a consultant/advisor and received honoraria from BMS and Janssen, all of which are outside the scope of submitted work. ALS reports travel support provided by Pfizer and Astellas. GKS reports personal fees from Apexigen, Array, Epizyme, GenCirq, Daiichi Sankyo, Fortress, Iovance Biotherapeutics, Bayer Pharmaceuticals, Pfizer Oncology, Array Advisory Board, Oncogenuity, Puretech, PTC Therapeutics, Ellipses Pharma, Concarlo; advisory board for Bionaut; grants from Astex; stock ownership in Pfizer, all outside the submitted work. SS reports stock and other ownership interests in Grand Rounds, Janssen, and Natera. YS reports honoraria from Boehringer Ingelheim, AstraZeneca, Novartis, and Eisai; consulting or advisory role with Pfizer, AstraZeneca, Novartis, Roche, Genentech, and Janssen, all outside the submitted work. MAT reports travel support from Syapse, Royalties from UpToDate, Connect MDS/AML Registry in Celgene (now owned by BMS), Myeloma Registry in Takeda; stock ownership in Doximity; personal fees from VIA Oncology (now owned by Elsevier ClinicalPath), Adaptive Advisory Board, and GSK; he is the local PI for Clinical Trials in AbbVie, BMS, CRAB CTC, Denovo, Research Network, Eli Lilly, LynxBio, Strata Oncology, and TG Therapeutics, all outside the submitted work. AKV reports research funding to the institution from BMS, MedPacto, Prelude, iOnctura, and Janssen; honoraria from Acceleron and Novartis; consulting/advisory role with Stelexis and Janssen; stock or other ownership in Stelexis; and an immediate family member with employment/leadership with CereXis, all outside the submitted work. DCV reports honoraria and speakers' bureau fees from CSL Behring, Merck Canada, Novartis Canada, Takeda, and UCB Biosciences GmbH, and travel accommodations from CSL Behring, and Avir Pharma, all outside the submitted work. He is supported by the Fonds de la recherche en santé du Québec (FRQS) Clinician-Scientist Junior 2 program. JLW reports grants from the National Cancer Institute during the conduct of the study; personal fees from Westat and IBM Watson Health; and other from HemOnc.org LLC, outside the submitted work. TMW-D reports stock and other ownership interests in High Enroll; honoraria from Physicians' Education Resource; consulting or advisory roles with Shattuck Labs, Rakuten Medical, Exicure; research funding from Merck, AstraZeneca/MedImmune, Bristol-Myers Squibb, GlaxoSmithKline, Caris Life Sciences, GlaxoSmithKline; travel, accommodations, expenses from Merck, Bristol-Myers Squibb, Bexion, AstraZeneca/MedImmune, Caris Life Sciences, Lilly, and Tesaro, all outside the submitted work. EW-B reports work in a consultant/advisor role for Astellas and BMS; funding support from Pfizer Global Medical Grants; other for Exelixis; and an immediate family member with stock ownership in Immunomedics and Nektar, all outside the submitted work. TZ reports research funding (to Duke) from Pfizer, Janssen, Acerta, AbbVie, Novartis, Merrimack, OmniSeq, PGDx, Merck, Mirati, Astellas, and Regeneron; consulting/speaking role with Genentech Roche, Exelixis, Genomic Health, and Sanofi Aventis; and serves on the consulting/advisory board for AstraZeneca, Bayer, Pfizer, Foundation Medicine, Janssen, Amgen, BMS, Calithera, Dendreon, and MJH Associates; stock ownership/employment (spouse) from Capio Biosciences, Archimmune Therapeutics, and Nanorobotics. AYZ has currently or during the past 2 years owned stock or held an ownership interest in Gilead Sciences. LZ reports personal fees from MERCK, outside the submitted work. All others have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: To evaluate the cost-effectiveness of a reduction in the number of routine radiographs in the follow-up of patients with ankle fractures., Methods: We performed an economic evaluation alongside the multicentre, randomised WARRIOR trial. Participants were randomised to a reduced imaging follow-up protocol (i.e. radiographs at week 6 and 12 follow-up obtained on clinical indication) or usual care (i.e. routine radiography at weeks 6 and 12). The Olerud & Molander Ankle Score (OMAS) was used to assess ankle function and the EQ-5D-3L was used to estimate Quality-Adjusted Life Years (QALYs). Costs and resource use were assessed using self-reported questionnaires and medical records, and analysed from a societal perspective. Multiple imputation was used for missing data, and data were analysed using seemingly unrelated regression analysis and bootstrapping., Results: In total, 246 patients had data available for analysis (reduced imaging = 118; usual care = 128). Fewer radiographs were obtained in the reduced imaging group (median = 4) compared with the usual-care group (median = 5). Functional outcome was comparable in both groups. The difference in QALYs was - 0.008 (95% CI:-0.06 to 0.04) and the difference in OMAS was 0.73 (95% CI:-5.29 to 6.76). Imaging costs were lower in the reduced imaging group (-€48; 95% CI:- €72 to -€25). All other cost categories did not statistically differ between the groups. The probability of the reduced imaging protocol being cost-effectiveness was 0.45 at a wiliness-to-pay of €20,000 per QALY., Conclusions: Reducing the number of routine follow-up radiographs has a low probability of being cost-effective compared with usual care. Functional outcome, health-related quality of life and societal costs were comparable in both groups, whereas imaging costs were marginally lower in the reduced imaging group. Given this, adherence to a reduced imaging follow-up protocol for those with routine ankle fractures can be followed without sacrificing quality of care, and may result in reduced costs., Trial Registration: The trial was registered on 26-05-2014 in the Netherlands Trial Registry, with reference number NL4477 ( www.trialregister.nl/trial/4477 ).

Background: The clinical consequences of routine follow-up radiographs for patients with ankle fracture are unclear, and their usefulness is disputed. The purpose of the present study was to determine if routine radiographs made at weeks 6 and 12 can be omitted without compromising clinical outcomes., Methods: This multicenter randomized controlled trial with a noninferiority design included 246 patients with an ankle fracture, 153 (62%) of whom received operative treatment. At 6 and 12 weeks of follow-up, patients in the routine-care group (n = 128) received routine radiographs whereas patients in the reduced-imaging group (n = 118) did not. The primary outcome was the Olerud-Molander Ankle Score (OMAS). Secondary outcomes were the American Academy of Orthopaedic Surgeons (AAOS) foot and ankle questionnaire, health-related quality of life (HRQoL) as measured with the EuroQol-5 Dimensions-3 Levels (EQ-5D-3L) and Short Form-36 (SF-36), complications, pain, health perception, self-perceived recovery, the number of radiographs, and the indications for radiographs to be made. The outcomes were assessed at baseline and at 6, 12, 26, and 52 weeks of follow-up. Data were analyzed with use of mixed models., Results: Reduced imaging was noninferior compared with routine care in terms of OMAS scores (difference [β], -0.9; 95% confidence interval [CI], -6.2 to 4.4). AAOS scores, HRQoL, pain, health perception, and self-perceived recovery did not differ between groups. Patients in the reduced-imaging group received a median of 4 radiographs, whereas those in the routine-care group received a median of 5 radiographs (p < 0.05). The rates of complications were similar (27.1% [32 of 118] in the reduced-imaging group, compared with 22.7% [29 of 128] in the routine-care group, p = 0.42). The types of complications were also similar., Conclusions: Implementation of a reduced-imaging protocol following an ankle fracture has no measurable negative effects on functional outcome, pain, and complication rates during the first year of follow-up. The number of follow-up radiographs can be reduced by implementing this protocol., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Background: Routine radiography in the follow-up of distal radial fractures is common practice, although its usefulness is disputed. The aim of this study was to determine whether the number of radiographs in the follow-up period can be reduced without resulting in worse patient outcomes., Methods: In this multicenter, prospective, randomized controlled trial with a non-inferiority design, patients ≥18 years old with a distal radial fracture could participate. They were randomized between a regimen with routine radiographs at 6 and 12 weeks of follow-up (usual care) and a regimen without routine radiographs at those time points (reduced imaging). Randomization was performed using an online registration and randomization program. The primary outcome was the Disabilities of the Arm, Shoulder and Hand (DASH) score. Secondary outcomes included the Patient-Rated Wrist/Hand Evaluation (PRWHE) score, health-related quality of life, pain, and complications. Outcomes were assessed at baseline and after 6 weeks, 3 months, 6 months, and 1 year of follow-up. Data were analyzed using mixed models. Neither the patients nor the health-care providers were blinded., Results: Three hundred and eighty-six patients were randomized, and 326 of them were ultimately included in the analysis. The DASH scores were comparable between the usual-care group (n = 166) and the reduced-imaging group (n = 160) at all time points as well as overall. The adjusted regression coefficient for the DASH scores was 1.5 (95% confidence interval [CI] = -1.8 to 4.8). There was also no difference between the groups with respect to the overall PRWHE score (adjusted regression coefficient, 1.4 [95% CI = -2.4 to 5.2]), quality of life as measured with the EuroQol-5 Dimensions (EQ-5D) (-0.02 [95% CI = -0.05 to 0.01]), pain at rest as measured with a visual analog scale (VAS) (0.1 [95% CI = -0.2 to 0.5]), or pain when moving (0.3 [95% CI = -0.1 to 0.8]). The complication rate was similar in the reduced imaging group (11.3%) and the usual-care group (11.4%). Fewer radiographs were made for the participants in the reduced-imaging group (median, 3 versus 4; p < 0.05)., Conclusions: This study shows that omitting routine radiography after the initial 2 weeks of follow-up for patients with a distal radial fracture does not affect patient-reported outcomes or the risk of complications compared with usual care., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Many phenomena of interest in nature and industry occur rapidly and are difficult and cost-prohibitive to visualize properly without specialized cameras. Here we describe in detail the virtual frame technique (VFT), a simple, useful, and accessible mode of imaging that increases the frame acquisition rate of any camera by several orders of magnitude by leveraging its dynamic range. The VFT is a powerful tool for capturing rapid phenomena where the dynamics facilitate a transition between two states, and are thus binary. The advantages of the VFT are demonstrated by examining such dynamics in five physical processes at unprecedented rates and spatial resolution: fracture of an elastic solid, wetting of a solid surface, rapid fingerprint reading, peeling of adhesive tape, and impact of an elastic hemisphere on a hard surface. We show that the performance of the VFT exceeds that of any commercial high-speed camera not only in rate of imaging but also in field of view, achieving a 65MHz frame rate at 4MPx resolution. Finally, we discuss the performance of the VFT with several commercially available conventional and high-speed cameras. In principle, modern cell phones can achieve imaging rates of over a million frames per second using the VFT.

Background: The added value of routine radiography in the follow-up of extremity fractures is unclear. The aim of this systematic review was to create an overview of radiography use in extremity fracture care and the consequences of these radiographs for the treatment of patients with these fractures., Materials and Methods: Studies were included if they reported on the use of radiography in the follow-up of extremity fractures and on its influence on treatment strategy, clinical outcome, or complications. A comprehensive search of electronic databases (i.e., PubMed, Embase, and Cochrane) was performed to identify relevant studies. Methodological quality was assessed with the Newcastle-Ottawa scale for cohort studies. Level of evidence was assessed using GRADE. The search, quality appraisal, and data extraction were performed independently by two researchers., Results: Eleven studies were included. All studies were retrospective cohorts. Of these, only two used a comparative design. Two of the included studies described fractures of both the upper and lower extremities, four studies concerned fractures of the lower extremity only, and five studies focused on fractures of the upper extremity. Pooling of data was not performed because of clinical heterogeneity. Eight studies reported on a change in treatment strategy related to radiography. Percentages ranged from 0 to 2.6%. The overall results indicated that radiographs in the follow-up of extremity fractures seldom alter treatment strategy, that the vast majority of follow-up radiographs are obtained without a clinical indication and that detection of a complication on a radiograph, in the absence of clinical symptoms, is unlikely. All included studies were regarded of a 'very low' level using GRADE., Conclusions: Based on current literature, the added value of routine radiography in the follow-up of extremity fractures seems limited. Results, however, should be interpreted with care, considering that available evidence is of a low level.

Hematopoietic cell transplantation (HCT) offers definitive management for a wide variety of malignant and nonmalignant diseases. Conditioning regimens and therapies used to prevent and treat GvHD are immune suppressive, often increasing the risk of developing fungal disease due to yeasts or molds. Antifungal prophylaxis may be useful in preventing morbidity and mortality during and after HCT. In this article, we review the epidemiology and current literature regarding strategies for prevention of invasive fungal disease (IFD) in the pre-engraftment and post-engraftment settings, and propose future direction for scientific discovery.

Background: Information on the course of neck pain (NP) and low back pain (LBP) typically relies on data collected at few time intervals during a period of up to 1 year., Methods: In this prospective, multicentre practice-based cohort study, patients consulting a chiropractor responded weekly for 52 weeks to text messages on their cell phones. Data from 448 patients (153 NP, 295 LBP) who had returned at least one set of answers in the first 26 weeks were used. Outcome measures were pain intensity (VAS) and functional outcome, assessed using four different questions: pain intensity, limitation in activities of daily living (ADL), number of days with pain in the previous week and number of days limited in ADL. Distinct patterns of pain were analysed with quadratic latent class growth analysis., Results: The final model was a 4-class model for NP and LBP. The 'recovering from mild baseline pain' is most common (76.3% of NP patients/58.3% of LBP patients) followed by the 'recovering from severe baseline pain' class (16.3% NP/29.8% LBP). They follow similar trajectories when considered over a period of 6 months. Pain at baseline, duration of complaints, functional status, limitations in ADL and the score on psychosocial scales were the variables that most contributed to distinguish between groups., Conclusions: Most patients with NP or LBP presenting in chiropractic care show a trajectory of symptoms characterized by persistent or fluctuating pain of low or medium intensity. Only a minority either experience a rapid complete recovery or develop chronic severe pain., Significance: Ninety percentage of patients with neck pain or low back pain presenting to chiropractors have a 30% improvement within 6 weeks and then show a trajectory of symptoms characterized by persistent or fluctuating pain of low or medium intensity. Only a minority either experience a rapid complete recovery or develop chronic severe pain., (© 2017 European Pain Federation - EFIC®.)

Introduction: The value of routine radiographs during follow-up after distal radius fractures is unclear. The aim of this study was to evaluate whether routine radiographs performed during the follow-up period in patients with a distal radius fracture influenced clinical decision making., Methods: This retrospective cohort study included patients aged ≥18 years who were treated for a distal radius fracture at four hospitals in The Netherlands in 2012. Demographic and clinical and radiographic characteristics were collected from medical records., Results: 1042 patients were included. In 121 (14%) of the 841 radiographs, a clinical indication was reported. Treatment was affected by 22 (2.6%) radiographs, including 11 (1.5%) radiographs that were categorized as routine, 9 (1.2%) of which led to prolonged cast immobilization and 2 (0.2%) to surgery for conservatively treated patients., Conclusion: Although it is common practice to take radiographs after distal radius fractures, the study results indicate that routine radiographs seldom affect treatment. This finding should be weighed against the high health care costs associated with these fractures. We hope that the results of our study will trigger the awareness among surgeons that in the current practice, many radiographs are taken on routine without influencing clinical decision making and can probably be omitted., Level of Evidence: Level III.

Background: Near-infrared imaging with indocyanine green (ICG) has been extensively investigated during laparoscopic cholecystectomy (LC). However, methods vary between studies, especially regarding patient selection, dosage and timing. The aim of this systematic review was to evaluate the potential of the near-infrared imaging technique with ICG to identify biliary structures during LC., Methods: A comprehensive systematic literature search was performed. Prospective trials examining the use of ICG during LC were included. Primary outcome was biliary tract visualization. Risk of bias was assessed using ROBINS-I. Secondly, a meta-analysis was performed comparing ICG to intraoperative cholangiography (IOC) for identification of biliary structures. GRADE was used to assess the quality of the evidence., Results: Nineteen studies were included. Based upon the pooled data from 13 studies, cystic duct (Lusch et al. in J Endourol 28:261-266, 2014) visualization was 86.5% (95% CI 71.2-96.6%) prior to dissection of Calot's triangle with a 2.5-mg dosage of ICG and 96.5% (95% CI 93.9-98.4%) after dissection. The results were not appreciably different when the dosage was based upon bodyweight. There is moderate quality evidence that the CD is more frequently visualized using ICG than IOC (RR 1.16; 95% CI 1.00-1.35); however, this difference was not statistically significant., Conclusion: This systematic review provides equal results for biliary tract visualization with near-infrared imaging with ICG during LC compared to IOC. Near-infrared imaging with ICG has the potential to replace IOC for biliary mapping. However, methods of near-infrared imaging with ICG vary. Future research is necessary for optimization and standardization of the near-infrared ICG technique.

Background: Chronic low back pain (LBP) is the leading cause of pain and disability, resulting in a major socioeconomic impact. The Cochrane Review which examined the effect of spinal manipulative therapy (SMT) for chronic LBP concluded that SMT is moderately effective, but was based on conventional meta-analysis of aggregate data. The use of individual participant data (IPD) from trials allows for a more precise estimate of the treatment effect and has the potential to identify moderators and/or mediators. The aim is (1) to assess the overall treatment effect of SMT for primary and secondary outcomes in adults with chronic LBP, (2) to determine possible moderation of baseline characteristics on treatment effect, (3) to identify characteristics of intervention (e.g., manipulation/mobilization) that influence the treatment effect, and (4) to identify mediators of treatment effects., Methods: All trials included in the Cochrane Review on SMT for chronic LBP will be included which were published after the year 2000, and the search will be updated. No restrictions will be placed on the type of comparison or size of the study. Primary outcomes are pain intensity and physical functioning. A dataset will be compiled consisting of individual trials and variables included according to a predefined coding scheme. Variables to be included are descriptive of characteristics of the study, treatment, comparison, participant characteristics, and outcomes at all follow-up periods. A one-stage approach with a mixed model technique based on the intention-to-treat principle will be used for the analysis. Subsequent analyses will focus on treatment effect moderators and mediators., Discussion: We will analyze IPD for LBP trials in which SMT is one of the interventions. IPD meta-analysis has been shown to be more reliable and valid than aggregate data meta-analysis, although this difference might also be attributed to the number of studies that can be used or the amount of data that can be utilized. Therefore, this project may identify important gaps in our knowledge with respect to prognostic factors of treatment effects., Systematic Review Registration: PROSPERO CRD42015025714.

Purpose: To evaluate the cost-effectiveness of manual therapy according to the Utrecht School (MTU) in comparison with physiotherapy (PT) in sub-acute and chronic non-specific neck pain patients from a societal perspective., Methods: An economic evaluation was conducted alongside a 52-week randomized controlled trial, in which 90 patients were randomized to the MTU group and 91 to the PT group. Clinical outcomes included perceived recovery (yes/no), functional status (continuous and yes/no), and quality-adjusted life-years (QALYs). Costs were measured from a societal perspective using self-reported questionnaires. Missing data were imputed using multiple imputation. To estimate statistical uncertainty, bootstrapping techniques were used., Results: After 52 weeks, there were no significant between-group differences in clinical outcomes. During follow-up, intervention costs (β:€-32; 95 %CI: -54 to -10) and healthcare costs (β:€-126; 95 %CI: -235 to -32) were significantly lower in the MTU group than in the PT group, whereas unpaid productivity costs were significantly higher (β:€186; 95 %CI:19-557). Societal costs did not significantly differ between groups (β:€-96; 95 %CI:-1975-2022). For QALYs and functional status (yes/no), the maximum probability of MTU being cost-effective in comparison with PT was low (≤0.54). For perceived recovery (yes/no) and functional status (continuous), a large amount of money must be paid per additional unit of effect to reach a reasonable probability of cost-effectiveness., Conclusions: From a societal perspective, MTU was not cost-effective in comparison with PT in patients with sub-acute and chronic non-specific neck pain for perceived recovery, functional status, and QALYs. As no clear total societal cost and effect differences were found between MTU and PT, the decision about what intervention to administer, reimburse, and/or implement can be based on the preferences of the patient and the decision-maker at hand., Trial Registration: ClinicalTrials.gov Identifier: NCT00713843.

Aim: To determine if psychosocial factors are associated with outcome in patients with neck pain or low back pain., Methods: In a prospective, multi-center chiropractic practice-based cohort study in Belgium and The Netherlands, 917 patients, of which 326 with neck pain and 591 with low back pain, completed self-administered questionnaires at baseline, following the second visit, and at 1, 3, 6 and 12 months. Psychosocial factors assessed at baseline were: distress, depression, anxiety and somatization via the Four Dimensional Symptom Questionnaire, patient's beliefs regarding the effect of physical activity and work on their complaint via the Fear Avoidance Beliefs Questionnaire, and social support via the Feij social support scale. Primary outcome measures were perceived recovery, pain intensity, and functional status which was measured with the Neck Disability Index and Oswestry Disability Index. A univariable regression analysis to estimate the relation between each psychological variable and outcome was followed by a multivariable multilevel regression analysis., Results: There were no differences in baseline patient characteristics between the patient population from Belgium and the Netherlands. Somatization scores are consistently associated with perceived recovery, functional status and pain for both neck pain and low-back pain. Depression was associated with poorer functioning in patients with LBP. There was a small association between fear and function and pain for patients with neck pain or low-back pain., Conclusion: Somatization was the only variable consistently found to be associated with diminished perceived recovery, higher degree of neck or low back disability, and increased neck or low back pain., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To establish an evidence-based recommendation for the pragmatic use of the Neck Disability Index-Dutch Version (NDI-DV) in primary care based on an assessment of the reliability, the responsiveness, and the interpretability of the NDI-DV., Study Design and Setting/methods: At baseline, the NDI-DV was completed by 337 patients with neck pain presenting to 97 chiropractic clinics in Belgium and the Netherlands. Three months after inclusion, 265 patients provided data to assess the responsiveness and interpretability. Reliability was assessed in 155 patients (retested after 10 days) by calculating the intra-class correlation coefficient for agreement (ICCagreement) and the measurement error (standard error of measurement, SEM), the latter resulting in the smallest detectable change (SDC). The minimal important change (MIC) was assessed by the anchor-based MIC distribution using self-reported perceived recovery as anchor. We tested interpretability by relating SDC to MIC., Results: The ICCagreement was 0.88. The SEMagreement was 1.95 resulting in a SDC of 5.40. The NDI-DV appeared to be responsive, being able to distinguish improved from stable patients with an area under the curve of 0.85. The MIC was 4.50., Conclusion: The NDI-DV has good reliability and responsiveness and may be used in clinical practice in Belgium and the Netherlands. A change score of 5 is important for patients, but has a 7 % chance to be due to measurement error.

The objective of this review was to determine the effectiveness of pharmacological interventions [i.e., non-steroid anti-inflammatory drugs (NSAIDs), muscle relaxants, antidepressants, and opioids] for non-specific chronic low-back pain (LBP). Existing Cochrane reviews for the four interventions were screened for studies fulfilling the inclusion criteria. Then, the literature searches were updated. Only randomized controlled trials on adults (≥18 years) with chronic (≥12 weeks) non-specific LBP and evaluation of at least one of the main clinically relevant outcome measures (pain, functional status, perceived recovery, or return to work) were included. The GRADE approach was used to determine the quality of evidence. A total of 17 randomized controlled trials was included: NSAIDs (n = 4), antidepressants (n = 5), and opioids (n = 8). No studies were found for muscle relaxants; 14 studies had a low risk of bias. The studies only reported effects on the short term (<3 months). The overall quality of the evidence was low. NSAIDs and opioids seem to lead to a somewhat higher relief in pain on the short term, as compared to placebo, in patients with non-specific chronic low back pain; opioids seem to have a small effect in improving function for a selection of patients who responded with an exacerbation of their symptoms after stopping their medication. However, both types of medication show more adverse effects than placebo. There seems to be no difference in effect between antidepressants and placebo in patients with non-specific chronic LBP.

We present a visualization of the predicted instability in ionic conduction from a binary electrolyte into a charge selective solid. This instability develops when a voltage greater than critical is applied to a thin layer of copper sulfate flanked by a copper anode and a cation selective membrane. The current-voltage dependence exhibits a saturation at the limiting current. With a further increase of voltage, the current increases, marking the transition to the overlimiting conductance. This transition is mediated by the appearing vortical flow that increases with the applied voltage.

We measure the spatial and temporal behavior of the true contact area A along a rough spatially extended interface between two blocks in frictional contact. Upon the application of shear the onset of motion is preceded by a discrete sequence of cracklike precursors, which are initiated at shear levels that are well below the threshold for static friction. These precursors arrest well before traversing the entire interface. They systematically increase in length with the applied shear force and significantly redistribute the true contact area along the interface. Thus, when frictional sliding occurs, the initially uniform contact area along the interface has already evolved to one that is highly nonuniform in space.

We perform quantitative measurements of the actual area of contact, A, formed by two rough solids that are subjected to different normal loading protocols. We show that microscopic motion, induced by Poisson contraction or expansion, produces a strong memory dependence of on the loading history with a large corresponding influence on the system's frictional strength. These effects, together with accompanying transient dynamics, are independent of humidity, loading rates, and material contrast across the interface.

Objective: To describe the use of rotational cervical manipulation in treating a patient who had undergone a traumatically induced dissection of the internal carotid artery and to review the literature on recurrent cervical artery dissections., Clinical Features: A 21-year-old woman with hemiparesis from an internal carotid artery dissection that occurred as the result of a motor vehicle accident had neck pain and headaches. Moderate range of motion restrictions in the neck were present along with articular restrictions to movement palpation., Intervention and Outcome: After a year of soft-tissue treatment, we obtained detailed, informed consent from the patient to attempt diversified manipulation to the neck. The patient described greater and more immediate relief and longer pain-free periods than could be achieved by soft-tissue treatment alone., Conclusion: Patients with previous cervical artery dissections may present with unrelated neck pain and headaches and request treatment. In selected cases, with complete informed consent, manipulation of the neck may relieve these symptoms. A review of published case reports on recurrent dissections suggests that trauma is not a significant factor in the second dissection. Care must be taken in extrapolating the results from this case to any other patient with a history of cervical artery dissection.

Complications of chiropractic adjustments or manipulations can be considered either benign or catastrophic. Although there are a number of papers on the more severe complications, the precipitation of benign and often reversible symptoms following chiropractic care has been largely ignored in the literature. This article discusses six cases where pain symptomatology was either aggravated or precipitated at a location other than the presenting complaints. Two potential causes of these complications are discussed: a) the use of long levers, which can exert force on nonsymptomatic joints in the extremities, and b) the manipulation of biomechanically dysfunctional but asymptomatic joints.

Cauda equina syndrome has been implicated as a potential complication of spinal manipulation. A review of the literature from 1911 to 1989 revealed ten reported cases of cauda equina syndrome in patients undergoing manipulation without anesthesia. This article presents three new cases where a temporal association was found between the onset of cauda equina symptoms and lumbar manipulation. The type of manipulation administered and the relationship between the treatment and symptoms is reviewed. In each of these cases both the chiropractic practitioner and the emergency room physician failed to comprehend the nature of the problem and take appropriate action. As a consequence, the patients went untreated for several days. This may have led to residual symptomatology. It is concluded that patients who present with bowel or bladder disturbances, leg weakness, or rectal and genital sensory changes after manipulation, be recognized as experiencing a cauda equina syndrome.

Increasing numbers of elderly patients are currently seeking chiropractic care. One condition commonly seen in the elderly is osteoporosis of the spine, which carries with it the risk of compression fractures. We present four cases in which patients were noted to have compression fractures following chiropractic adjustments. In each of these cases, serious questions are raised concerning the relationship between the adjustment and the occurrence of fracture. What is clear is that failure to diagnose a compression fracture, together with the application of adjustment into the area of fracture, can increase symptoms and prolong disability. It is recommended that patients with osteoporosis who have suffered a fall or injury be X rayed before treatment is given. In addition, special care should be exercised in elderly patients with osteoporosis.