Defining acute flares in knee osteoarthritis: a systematic review.

OBJECTIVE: To identify and critically synthesise definitions of acute flares in knee osteoarthritis (OA) reported in the medical literature. DESIGN: Systematic review and narrative synthesis. We searched Medline, EMBASE, Web of science and six other electronic databases (inception to July 2017) for original articles and conference abstracts reporting a definition of acute flare (or synonym) in humans with knee OA. There were no restrictions by language or study design (apart from iatrogenic-induced flare-ups, eg, injection-induced). Data extraction comprised: definition, pain scale used, flare duration or withdrawal period, associated symptoms, definition rationale, terminology (eg, exacerbation or flare), baseline OA severity, age, gender, sample size and study design. RESULTS: Sixty-nine articles were included (46 flare design trials, 17 observational studies, 6 other designs; sample sizes: 15-6085). Domains used to define flares included: worsening of signs and symptoms (61 studies, 27 different measurement tools), specifically increased pain intensity; minimum pain threshold at baseline (44 studies); minimum duration (7 studies, range 8-48 hours); speed of onset (2 studies, defined as 'sudden' or 'quick'); requirement for increased medication (2 studies). No definitions included activity interference. CONCLUSIONS: The concept of OA flare appears in the medical literature but most often in the context of flare design trials (pain increases observed after stopping usual treatment). Key domains, used to define acute events in other chronic conditions, appear relevant to OA flare and could provide the basis for consensus on a single, agreed definition of 'naturally occurring' OA flares for research and clinical application. PROSPERO REGISTRATION NUMBER: CRD42014010169

Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial

INTRODUCTION: Intensive care-acquired weakness is a common problem, leads to significant impairment in physical functioning and muscle strength, and is prevalent in individuals with sepsis. Early rehabilitation has been shown to be safe and feasible; however, commencement is often delayed due to a patient's inability to co-operate. An intervention that begins early in an intensive care unit (ICU) admission without the need for patient volition may be beneficial in attenuating muscle wasting. The eRiCC (early rehabilitation in critical care) trial will investigate the effectiveness of functional electrical stimulation-assisted cycling and cycling alone, compared to standard care, in individuals with sepsis. METHODS AND ANALYSIS: This is a single centre randomised controlled trial. Participants (n=80) aged ≥18 years, with a diagnosis of sepsis or severe sepsis, who are expected to be mechanically ventilated for ≥48 h and remain in the intensive care ≥4 days will be randomised within 72 h of admission to (1) standard care or (2) intervention where participants will receive functional electrical muscle stimulation-assisted supine cycling on one leg while the other leg undergoes cycling alone. Primary outcome measures include: muscle mass (quadriceps ultrasonography; bioelectrical impedance spectroscopy); muscle strength (Medical Research Council Scale; hand-held dynamometry) and physical function (Physical Function in Intensive Care Test; Functional Status Score in intensive care; 6 min walk test). Blinded outcome assessors will assess measures at baseline, weekly, at ICU discharge and acute hospital discharge. Secondary measures will be evaluated in a nested subgroup (n=20) and will consist of biochemical/histological analyses of collected muscle, urine and blood samples at baseline and at ICU discharge. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the relevant institution, and results will be published to inform clinical practice in the care of patients with sepsis to optimise rehabilitation and physical function outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12612000528853

How do people with knee osteoarthritis perceive and manage flares? A qualitative study

BackgroundAcute flares in people with osteoarthritis (OA) are poorly understood. There is uncertainty around the nature of flares, their impact, and how these are managed.AimExplore understandings and experiences of flares in people with knee OA, describe self-management and help-seeking strategiesDesign &amp; settingQualitative interview study of people with knee OA in England, United Kingdom.MethodSemi-structured interviews with 15 people with knee OA. Thematic analysis using constant comparison methods.ResultsWe identified four main themes: experiencing pain, consequences of acute pain, predicting and avoiding acute pain, and response to acute pain. People with OA described minor episodes which were frequent, fleeting, occurred during everyday activity, had minimal impact, and were generally predictable. This contrasted with severe episodes which were infrequent, had greater impact, and were less likely to be predictable. The latter generally led to feelings of low confidence, vulnerability and of being a burden. The term ‘flare’ was often used to describe the severe events but this was applied inconsistently and some would describe a flare as any increase in pain.Participants used numerous self-management strategies but tended to seek help when these had been exhausted, their symptoms led to emotional distress, disturbed sleep, or pain experience worse than usual. Previous experiences shaped whether people sought help and who they sought help from.ConclusionSevere episodes of pain are likely to be synonymous with flares. Developing a common language about flares will allow a shared understanding of these events, early identification and appropriate management.</jats:sec

Evidence for a crucial role of Paneth Cells in mediating the intestinal response to injury

The identification of the intestinal stem cell (ISC) markers Lgr5 and Bmi-1 has furthered our understanding of how they accomplish homeostasis in this rapidly self-renewing tissue. Recent work indicates that these markers identify a cycling Lgr5+ ISC which can be replaced by a quiescent Bmi-1+ ISC. Currently, there is little data on how these cells interact to control intestinal crypt homeostasis and regeneration. This interaction likely involves other differentiated cells within the niche as it has previously been demonstrated that the “stemness” of the Lgr5 ISC is closely tied to the presence of their neighboring Paneth cells. To investigate this, we used two conditional mouse models to delete the transcription factor β-catenin within the intestinal crypt. Critically these differ in their ability to drive recombination within Paneth cells and therefore allow us to compare the effect of deleting the majority of active ISCs in the presence or absence of the Paneth cells. After gene deletion, the intestines in the model in which Paneth cells were retained showed a rapid recovery and repopulation of the crypt-villus axis presumably from either a spared ISC or the hypothetical quiescent ISCs. However, in the absence of Paneth cells the recovery ability was compromised resulting in complete loss of intestinal epithelial integrity. This data indicates that the Paneth cells play a crucial role within the in vivo ISC niche in aiding recovery following substantial insult

The safety of paediatric surgery between COVID-19 surges:an observational study

Despite the ongoing coronavirus disease 2019 (COVID-19) pandemic, elective paediatric surgery must continue safely through the first, second and subsequent waves of disease. This study presents outcome data from a children's hospital in north-west England, the region with the highest prevalence of COVID-19 in England. Children and young people undergoing elective surgery isolated within their household for 14 days, then presented for real-time reverse transcriptase polymerase chain reaction testing for severe acute respiratory syndrome coronavirus disease-2 (SARS-CoV-2) within 72 h of their procedure (or rapid testing within 24 h in high-risk cases), and completed a screening questionnaire on admission. Planned surgery resumed on 26 May 2020; in the four subsequent weeks, there were 197 patients for emergency and 501 for elective procedures. A total of 488 out of 501 (97.4%) elective admissions proceeded, representing a 2.6% COVID-19-related cancellation rate. There was no difference in the incidence of SARS-CoV-2 among children and young people who had or had not isolated for 14 days (p > 0.99). One out of 685 (0.1%) children who had surgery re-presented to the hospital with symptoms potentially consistent with SARS-CoV-2 within 14 days of surgery. Outcomes were similar to those in the same time period in 2019 for length of stay (p = 1.0); unplanned critical care admissions (p = 0.59); and 14-day hospital re-admission (p = 0.17). However, the current cohort were younger (p = 0.037); of increased complexity (

Deep electronic states in ion-implanted Si

In this paper we present an overview of the deep states present after ion-implantation by various species into n-type silicon, measured by Deep Level Transient Spectroscopy (DLTS) and high resolution Laplace DLTS (LDLTS). Both point and small extended defects are found, prior to any anneal, which can therefore be the precursors to more detrimental defects such as end of range loops. We show that the ion mass is linked to the concentrations of defects that are observed, and the presence of small interstitial clusters directly after ion implantation is established by comparing their behaviour with that of electrically active stacking faults. Finally, future applications of the LDLTS technique to ion-implanted regions in Si-based devices are outlined.</p

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Triggers for acute flare in adults with, or at risk of, knee osteoarthritis: a web-based case-crossover study in community-dwelling adults.

OBJECTIVE: To identify proximate causes ('triggers') of flares in adults with, or at risk of, knee osteoarthritis (OA), estimate their course and consequences, and determine higher risk individuals. METHODS: In this 13-week web-based case-crossover study adults aged ≥40 years, with or without a recorded diagnosis of knee OA, and no inflammatory arthropathy who self-reported a knee flare completed a questionnaire capturing information on exposure to 21 putative activity-related, psychosocial and environmental triggers (hazard period, ≤72 hours prior). Comparisons were made with identical exposure measurements at four 4-weekly scheduled time points (non-flare control period) using conditional logistic regression. Flare was defined as a sudden onset of worsening signs and symptoms, sustained for ≥24 hours. Flare characteristics, course and consequence were analysed descriptively. Associations between flare frequency and baseline characteristics were estimated using Poisson regression. RESULTS: Of 744 recruited participants (mean age (SD) 62.1 (10.2) years; 61% female), 376 reported 568 flares (hazards) and provided 867 valid control period measurements. Thirteen exposures (8 activity-related, 5 psychosocial/environmental) were positively associated with flare onset within 24 hours (strongest odds ratio estimate, knee buckling: 9.06: 95% confidence interval [CI] 5.86, 13.99; weakest, cold/damp weather: 1.45: 95%CI 1.12, 1.87). Median flare duration was 5 days (IQR 3, 8), less common if older (incident rate ratio [IRR] 0.98: 95%CI 0.97, 0.99), more common if female (IRR 1.85: 95%CI 1.43, 2.39). CONCLUSIONS: Multiple activity-related, psychosocial and environmental exposures are implicated in triggering flares. This evidence can help inform prevention and acute symptom management for patients and clinicians

Outcome following surgery for colorectal cancer: analysis by hospital after adjustment for case-mix and deprivation

Outcome, adjusted for case-mix and deprivation, in 3200 patients undergoing resection for colorectal cancer in 11 hospitals in Central Scotland between 1991 and 1994 was studied. There were significant differences among individual hospitals in the proportion of elderly (P<0.001) and deprived (P<0.0001) patients, the mode (P=0.007) and stage (P<0.0001) at presentation, and the proportion of patients who underwent apparently curative resection (P<0.001). There were no significant differences in postoperative mortality. Cancer-specific survival at 5 years following apparently curative resection varied from 59 to 76%; cancer-specific survival at 2 years following palliative resection varied from 22 to 44%. The corresponding hazard ratios, adjusted for the above prognostic factors, for patients undergoing apparently curative resection varied among hospitals from 0.58 to 1.32; and the ratios for palliative resection varied from 0.73 to 1.26. This study demonstrates that, after adjustment for variations in case-mix and deprivation, significant differences in outcome among hospitals following resection for colorectal cancer persist