Outcomes of patients admitted with malignant small bowel obstruction: a subgroup multicentre observational cohort analysis.

INTRODUCTION AND PURPOSE OF THE STUDY: Small bowel obstruction (SBO) accounts for a substantial proportion of emergency surgical admissions. Malignancy is a common cause of obstruction, either due to a primary tumour or intra-abdominal metastases. However, little is known regarding the current treatment or outcomes of patients with malignant SBO. This study aimed to characterise the treatment of malignant SBO and identify areas for potential improvement and compare overall survival of patients with malignant SBO to patients with non-malignant SBO. MATERIALS AND METHODS: This was a subgroup analysis of a multicentre observational study of patients admitted with SBO. Details regarding these patients' diagnoses, treatments, and outcomes up to 1-year after admission were recorded. The primary outcome was overall survival in patients with malignant SBO. RESULTS: A total of 316 patients with small bowel obstruction were included, of whom 33 (10.4%) had malignant SBO. Out of the 33 patients with malignant SBO, 20 patients (60.6%) were treated with palliative intent although only 7 patients were seen by a palliative team during admission. Nutritional assessments were performed on 12 patients, and 11 of these patients received parenteral nutrition. 23 patients underwent surgery, with the most common surgical interventions being loop ileostomies (9 patients) and gastrointestinal bypasses (9 patients). 4 patients underwent right hemicolectomies, with a primary anastomosis formed and 1 patient had a right hemicolectomy with a terminal ileostomy. Median survival was 114 days, and no difference was seen in survival between patients treated with or without palliative intent. CONCLUSION: Malignant SBO is associated with significant risks of short-term complications and a poor prognosis. Consideration should be given to the early involvement of senior decision-makers upon patient admission is essential for optimal management and setting expectation for a realistic outcome.

Social network analysis reveals the failure of between-farm movement restrictions to reduce Salmonella transmission.

An increasing number of countries are investigating options to stop the spread of the emerging zoonotic infection Salmonella Dublin (S. Dublin), which mainly spreads among bovines and with cattle manure. Detailed surveillance and cattle movement data from an 11-yr period in Denmark provided an opportunity to gain new knowledge for mitigation options through a combined social network and simulation modeling approach. The analysis revealed similar network trends for noninfected and infected cattle farms despite stringent cattle movement restrictions imposed on infected farms in the national control program. The strongest predictive factor for farms becoming infected was their cattle movement activities in the previous month, with twice the effect of local transmission. The simulation model indicated an endemic S. Dublin occurrence, with peaks in outbreak probabilities and sizes around observed cattle movement activities. Therefore, pre- and postmovement measures within a 1-mo time window may help reduce S. Dublin spread.

Chinese family care partners of older adults in Canada have grit: A qualitative study.

AIM: To explain the process taken by Chinese family care partners of older adults in the Greater Toronto Area, Canada, to access health and social services in their communities. The research question was: What mechanisms and structures impact the agency of Chinese family care partners of older adults, in the process of assisting them to access health and social services? DESIGN: This qualitative study was informed by critical realism. METHODS: Chinese family care partners of older adults in the Greater Toronto Area, Canada, were interviewed from August 2020 to June 2021. Transcripts underwent thematic analysis. FINDINGS: Twenty-eight Chinese family care partners expressed a firm commitment to maintain caregiving conditions and to judiciously access health and social services. Their commitment was made up of three parts: (a) legislative and cultural norms of family, work, and society; (b) their perseverance to fill gaps with limited social and financial resources; (c) the quality of their relationship to, and illness trajectory of the older adults. The social structures created tension in how Chinese family care partners made decisions, negotiated resources, and ultimately monitored and coordinated timely access with older adults. CONCLUSION: Participants' commitment and perseverance were conceptualized as "grit," central to their agency to conform to legislative and cultural norms. Moreover, findings support grit's power to motivate and sustain family caregiving, in order for older adults to age in place as long as possible with finite resources. IMPLICATIONS FOR THE PROFESSION: This study highlights the importance of cultural awareness education for nurses, enabling continuity of care at a systems level and for a more resilient healthcare system. IMPACT: Family care partners' grit may be crucial for nurses to harness when together, they face limited access to culturally appropriate health and social services in a system grounded in values of equity and inclusion, as in Canada. REPORTING METHOD: When writing this manuscript, we adhered to relevant EQUATOR guidelines of the Consolidated Criteria for Reporting Qualitative Research (COREQ). PATIENT OR PUBLIC INVOLVEMENT AND ENGAGEMENT: No patient or public involvement.

Optical coherence tomography for presurgical delineation of basal cell carcinomas on the face-A comparison with histopathology.

BACKGROUND: To minimize the risk of incomplete excision of basal cell carcinomas (BCC) the macroscopic tumor margins should be adequately defined. Optical coherence tomography (OCT) is a non-invasive imaging tool that can provide structural and vascular information about skin cancer lesions. The study objective was to compare the presurgical delineation of facial BCC by clinical examination, histopathology, and OCT imaging in tumors undergoing full excision. METHODS: Ten patients with BCC lesions on the face were examined clinically, with OCT and histopathology at 3-mm intervals, from the clinical lesion border and beyond the resection line. The OCT scans were evaluated blinded and a delineation estimate of each BCC lesion was made. The results were compared to the clinical and histopathologic results. RESULTS: OCT evaluations and histopathology were in agreement in 86.6% of the collected data points. In three cases the OCT scans estimated a reduction of the tumor size compared to the clinical tumor border set by the surgeon. CONCLUSION: The results of this study support the notion that OCT can have a role in the clinical daily practice by aiding clinicians in delineating BCC lesions before surgery.

Real-world accuracy of computed tomography in patients admitted with small bowel obstruction: a multicentre prospective cohort study.

PURPOSE: Small bowel obstruction (SBO) is a common surgical emergency. Previous studies have shown the value computed tomography (CT) scanning in both confirming this diagnosis and identifying indications for urgent surgical intervention, such as strangulated bowel or closed loop obstructions. However, most of the literature is based on retrospective expert review of previous imaging and little data regarding the real-time accuracy of CT reporting is available. Here, we investigated the real-world accuracy of CT reporting in patients admitted with SBO. METHODS: This was a multicentre prospective study including consecutive patients admitted with SBO. The primary outcomes were the sensitivity and specificity of CT scanning for bowel obstruction with ischaemia and closed loop obstruction. Data were retrieved from the original CT reports written by on-call radiologists and compared with operative findings. RESULTS: One hundred seventy-six patients were included, all of whom underwent CT scanning with intravenous contrast followed by operative management of SBO. Bowel obstruction with ischaemia was noted in 20 patients, with a sensitivity and specificity of CT scanning of 40.0% and 85.5%, respectively. Closed loop obstructions were noted in 26 patients, with a sensitivity and specificity of CT scanning of 23.1% and 98.0%, respectively. CONCLUSIONS: The real-world accuracy of CT scanning appears to be lower than previously reported in the literature. Strategies to address this could include the development of standardised reporting schemas and to increase the surgeon's own familiarity with relevant CT features in patients admitted with SBO.

Cost-effectiveness of 12 weeks of supervised treatment compared to written advice in patients with knee osteoarthritis: a secondary analysis of the 2-year outcome from a randomized trial.

OBJECTIVE: To assess the 24-month cost-effectiveness of supervised treatment compared to written advice in knee osteoarthritis (OA). DESIGN: 100 adults with moderate-severe OA not eligible for total knee replacement (TKR) randomized to a 12-week individualized, supervised treatment (exercise, education, diet, insoles and pain medication) or written advice. Effectiveness was measured as change in quality-adjusted life years (QALYs) from baseline to 24 months, including data from baseline, 3, 6, 12 and 24 months, while healthcare costs and transfer payments were derived from national registries after final follow-up. Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. A sensitivity analysis resampling existing data was conducted and the probability of cost-effectiveness was estimated using a 22,665 Euros/QALY threshold. In a sensitivity analysis, cost-effectiveness was calculated for different costs of the supervised treatment (actual cost in study; cost in private practice; and in-between cost). RESULTS: Average costs were similar between groups (6,758 Euros vs 6,880 Euros), while the supervised treatment were close to being more effective (incremental effect (95% CI) of 0.075 (-0.005 to 0.156). In the primary analysis excluding deaths, this led the supervised treatment to be cost-effective, compared to written advice. The sensitivity analysis demonstrated that the results were sensitive to changes in the cost of treatment, but in all scenarios the supervised treatment was cost-effective (ICERs of 6,229 to 20,688 Euros/QALY). CONCLUSIONS: From a 24-month perspective, a 12-week individualized, supervised treatment program is cost-effective compared to written advice in patients with moderate-severe knee OA not eligible for TKR. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01535001.

Quantitative sensory testing in feline osteoarthritic pain - a systematic review and meta-analysis.

Quantitative sensory testing (QST) is a psychophysical test used to quantify somatosensory sensation under normal or pathological conditions including osteoarthritis (OA). OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of studies using QST in healthy and osteoarthritic cats, registered at Systematic Review Research Facility (#26-06-2017). DESIGN: Hierarchical models with random intercepts for each individual study extracted through the systematic review were fit to subject-level data; QST measures were contrasted between healthy and osteoarthritic cats. Four bibliographic databases were searched; quality and risk of bias assessment were performed using pre-established criteria. RESULTS: Six articles were included; most were of high quality and low risk of bias. Punctate tactile threshold (n = 70) and mechanical temporal summation (n = 35) were eligible for analysis. Cats with OA have lower punctate tactile threshold [mean difference (95%HDI): -44 (-60; -26) grams] and facilitated temporal summation of pain [hazard ratio (95%HDI): 5.32 (2.19; 14) times] when compared with healthy cats. The effect of sex and body weight on sensory sensitivity remained inconclusive throughout all analyses. Due to the correlation between age and OA status, it remains difficult to assess the effect of OA on sensory sensitivity, independently of age. CONCLUSIONS: Clear and transparent reporting using guidelines are warranted. Similar to people, centralized sensitization is a feature of OA in cats. Future studies should try to elucidate the age effect on feline OA. Research with natural OA in cats is promising with potential to benefit feline health and welfare, and improve translatability to clinical research.

Acquisition of a simple motor skill: task-dependent adaptation and long-term changes in the human soleus stretch reflex.

Changing the H reflex through operant conditioning leads to CNS multisite plasticity and can affect previously learned skills. To further understand the mechanisms of this plasticity, we operantly conditioned the initial component (M1) of the soleus stretch reflex. Unlike the H reflex, the stretch reflex is affected by fusimotor control, comprises several bursts of activity resulting from temporally dispersed afferent inputs, and may activate spinal motoneurons via several different spinal and supraspinal pathways. Neurologically normal participants completed 6 baseline sessions and 24 operant conditioning sessions in which they were encouraged to increase (M1up) or decrease (M1down) M1 size. Five of eight M1up participants significantly increased M1; the final M1 size of those five participants was 143 ± 15% (mean ± SE) of the baseline value. All eight M1down participants significantly decreased M1; their final M1 size was 62 ± 6% of baseline. Similar to the previous H-reflex conditioning studies, conditioned reflex change consisted of within-session task-dependent adaptation and across-session long-term change. Task-dependent adaptation was evident in conditioning session 1 with M1up and by session 4 with M1down. Long-term change was evident by session 10 with M1up and by session 16 with M1down. Task-dependent adaptation was greater with M1up than with the previous H-reflex upconditioning. This may reflect adaptive changes in muscle spindle sensitivity, which affects the stretch reflex but not the H reflex. Because the stretch reflex is related to motor function more directly than the H reflex, M1 conditioning may provide a valuable tool for exploring the functional impact of reflex conditioning and its potential therapeutic applications. NEW & NOTEWORTHY Since the activity of stretch reflex pathways contributes to locomotion, changing it through training may improve locomotor rehabilitation in people with CNS disorders. Here we show for the first time that people can change the size of the soleus spinal stretch reflex through operant conditioning. Conditioned stretch reflex change is the sum of task-dependent adaptation and long-term change, consistent with H-reflex conditioning yet different from it in the composition and amount of the two components.

Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis.

OBJECTIVE: Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of osteoarthritis (OA), of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type Col10 to assess its diagnostic value for radiographic knee OA. METHODS: A neo-epitope of Col10 was identified in urine samples from OA patients. A monoclonal antibody against the neo-epitope was produced in Balb/C mice. The enzyme responsible for the cleavage was identified. Immunohistochemical detection of this neo-epitope was performed on human OA cartilage. An immunoassay (Col10neo) was developed and quantified in two clinical studies: the C4Pain-003 and the NYU OA progression study. Receiver operating characteristic curve (ROC) curve analysis was carried out to evaluate the discriminative power of Col10neo between OA and rheumatoid arthritis (RA). RESULTS: A neo-epitope specific mAb was produced. The Cathepsin K-generated neo-epitope was localized to the pericellular matrix of chondrocytes, while its presence was extended and more prominent in superficial fibrillation in the cartilage with advanced degradation. In the C4Pain study, a higher level of Col10neo was seen in subjects with greater KL grade. The group of the highest tertile of Col10neo included more subjects with KL3-4. In the NYU study, Col10neo was statistically higher in OA than control or RA. ROC curve analysis revealed area under the curve was 0.88 (95% CI 0.81-0.94). CONCLUSION: Our findings indicate that Col10neo linked to hypertrophic chondrocytes could be used as a diagnostic biochemical marker for knee OA.

Antipruritic effects of transient heat stimulation on histaminergic and nonhistaminergic itch.

BACKGROUND: Chronic itch is notoriously difficult to treat. Counterstimuli are able to inhibit itch, but this principle is difficult to apply in clinical practice, and the mechanisms behind counterstimulation-induced itch suppression in humans are unclear. OBJECTIVES: Firstly, to analyse the stimulus-response effects of transient heat stimuli on histaminergic and nonhistaminergic itch, and secondly, to investigate whether the antipruritic effect depends on homotopic (peripheral mediation) or heterotopic (central mediation) counterstimulation relative to the itch provocation site. METHODS: Eighteen healthy volunteers participated (eight female, mean age 25·7 ± 0·8 years). Itch was evoked on premarked areas of the volar forearms, by either histamine (1% solution) or cowhage (35-40 spicules). In addition to the itch provocations (experiment 1), 5-s homotopic heat stimuli at 32, 40, 45 or 50 °C were applied. In experiment 2, heat stimuli were applied either homotopically, intrasegmentally (next to the provocation site) or extrasegmentally (dorsal forearm). Itch intensity was evaluated throughout the procedures using a digital visual analogue scale. RESULTS: Homotopic counterstimuli inhibited histaminergic itch by 41·3% at 45 °C (P < 0·01) and by 76·7% at 50 °C (P < 0·001). Cowhage-induced itch was less prone to counterstimulation and was significantly diminished only at 50 °C, by 43·6% (P = 0·009). Counterstimulations applied heterotopically were not able to inhibit itch significantly. CONCLUSIONS: Itch pathway-specific effects of counterstimuli were observed between homo- and heterotopic stimulation. Histaminergic itch was robustly inhibited by short-term homotopic noxious heat stimuli for up to 10 min. Nonhistaminergic itch was only weakly inhibited. The inhibitory effects exerted by the short-term heat stimuli only occurred following homotopic counterstimulation.

Update from a 12-Year Nationwide Fungemia Surveillance: Increasing Intrinsic and Acquired Resistance Causes Concern.

New data from the years 2012 to 2015 from the Danish National Fungemia Surveillance are reported, and epidemiological trends are investigated in a 12-year perspective (2004 to 2015). During 2012 to 2015, 1,900 of 1,939 (98%) fungal bloodstream isolates were included. The average incidence was 8.4/100,000 inhabitants, and this appears to represent a stabilizing trend after the increase to 10.1/100,000 in 2011. The incidence was higher in males than females (10.0 versus 6.8) and in patients above 50 years, and those changes were mainly driven by an increasing incidence among 80-to-89-year-old males (65.3/100,000 in 2014 to 2015). The proportion of Candida albicans isolates decreased from 2004 to 2015 (64.4% to 42.4%) in parallel with a doubling of the proportion of Candida glabrata isolates (16.5% to 34.6%, P < 0.0001). C. glabrata was more common among females (34.0% versus 30.4% in males). Following an increase in 2004 to 2011, the annual drug use stabilized during the last 2 to 3 years of that time period but remained higher than in other Nordic countries. This was particularly true for the fluconazole and itraconazole use in the primary health care sector, which exceeded the combined national levels of use of these compounds in each of the other Nordic countries. Fluconazole susceptibility decreased (68.5%, 65.2%, and 60.6% in 2004 to 2007, 2008 to 2011, and 2012 to 2015, respectively, P < 0.0001), and echinocandin resistance emerged in Candida (0%, 0.6%, and 1.7%, respectively, P < 0.001). Amphotericin B susceptibility remained high (98.7%). Among 16 (2.7%) echinocandin-resistant C. glabrata isolates (2012 to 2015), 13 harbored FKS mutations and 5 (31%) were multidrug resistant. The epidemiological changes and the increased incidence of intrinsic and acquired resistance emphasize the importance of continued surveillance and of strengthened focus on antifungal stewardship.

Total knee replacement and non-surgical treatment of knee osteoarthritis: 2-year outcome from two parallel randomized controlled trials.

OBJECTIVES: To compare 2-year outcomes of total knee replacement (TKR) followed by non-surgical treatment to that of non-surgical treatment alone and outcomes of the same non-surgical treatment to that of written advice. DESIGN: In two randomized trials, 200 (mean age 66) adults with moderate to severe knee osteoarthritis (OA), 100 eligible for TKR and 100 not eligible for TKR, were randomized to TKR followed by non-surgical treatment, non-surgical treatment alone, or written advice. Non-surgical treatment consisted of 12 weeks of supervised exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the mean score of the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, covering pain, symptoms, activities of daily living (ADL), and quality of life (QOL). RESULTS: Patients randomized to TKR had greater improvements than patients randomized to non-surgical treatment alone (difference of 18.3 points (95% CI; 11.3 to 25.3)), who in turn improved more than patients randomized to written advice (difference of 7.0 points (95% CI; 0.4 to 13.5)). Among patients eligible for TKR, 16 (32%) from the non-surgical group underwent TKR during 2 years and among those initially ineligible, seven patients (14%) from the non-surgical group and ten (20%) from the written advice group underwent TKR. CONCLUSIONS: TKR followed by non-surgical treatment is more effective on pain and function than non-surgical treatment alone, which in turn is more effective than written advice. Two out of three patients with moderate to severe knee OA eligible for TKR delayed surgery for at least 2 years following non-surgical treatment. TRIAL REGISTRATION: ClinicalTrials.gov numbers NCT01410409 and NCT01535001.

Acid-induced experimental knee pain and hyperalgesia in healthy humans.

Inflammation and the related acidity in peri-articular structures may be involved in pain generation and hyperalgesia in knee osteoarthritis. This study investigated pain and associated hyperalgesia provoked by infusion of acidic saline into the infrapatellar fat pad. Twenty-eight subjects participated in two sessions in which acidic saline (AS, pH 5) or neutral saline (NS, pH 7.4) were infused into the infrapatellar fat pad for 15 min. Pain intensity, pain area, mechanical and thermal sensitivity, and maximal voluntary knee extension force were recorded. Repeated infusions were performed in 14 subjects. Infusion of AS caused significantly higher pain intensity, larger pain areas, induced hyperalgesia around the infused knee, and reduced extension force. No significant pain facilitation or spreading of hyperalgesia was found after repeated infusions as compared with single infusions. Acidic saline infused into the infrapatellar fat pad provoked pain and localized mechanical hyperalgesia. Thus, this acid-induced pain model may mimic the early-stage responses to tissue injury of knee osteoarthritis.

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study.

OBJECTIVES: To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA). METHODS: Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced (DCE)-MRI prior to (TKR) and correlated with microscopic and macroscopic assessments of synovitis obtained intraoperatively. Multiple bivariate correlations were used with a pre-specified threshold of 0.70 for significance. Also, multiple regression analyses with different subsets of MRI-variables as explanatory variables and the histology score as outcome variable were performed with the intention to find MRI-variables that best explain the variance in histological synovitis (i.e., highest R2). A stepped approach was taken starting with basic characteristics and non-CE MRI-variables (model 1), after which CE-MRI-variables were added (model 2) with the final model also including DCE-MRI-variables (model 3). RESULTS: 39 patients (56.4% women, mean age 68 years, Kellgren-Lawrence (KL) grade 4) had complete MRI and histological data. Only the DCE-MRI variable MExNvoxel (surrogate of the volume and degree of synovitis) and the macroscopic score showed correlations above the pre-specified threshold for acceptance with histological inflammation. The maximum R2-value obtained in Model 1 was R2 = 0.39. In Model 2, where the CE-MRI-variables were added, the highest R2 = 0.52. In Model 3, a four-variable model consisting of the gender, one CE-MRI and two DCE-MRI-variables yielded a R2 = 0.71. CONCLUSION: DCE-MRI is correlated with histological synovitis in end-stage KOA and the combination of CE and DCE-MRI may be a useful, non-invasive tool in characterising synovitis in KOA.

Optimization and characterization of highly nonlinear fiber for broadband optical time lens applications.

We demonstrate simple and intuitive methods, for dispersion optimization and characterization of highly nonlinear fiber (HNLF) for use in four-wave-mixing (FWM) based time lens applications. A composite dispersion-flattened HNLF is optimized for high bandwidth time lens processing, by segmentation to mitigate FWM impairments due to dispersion fluctuations. The fiber is used for FWM conversion of 32 WDM-channels with 50 GHz spacing in a time lens, with -4.6 dB total efficiency, and <1 dB per-channel efficiency difference. The novel characterization method is based on two tunable continuous-wave lasers. The method is experimentally verified to predict the spectral output profile of time lenses for broadband multicarrier input, with detailed numerical simulations for support.

Increased mortality in a Danish cohort of young people with Type 1 diabetes mellitus followed for 24 years.

AIM: To determine the mortality rate in a Danish cohort of children and adolescents diagnosed with Type 1 diabetes mellitus compared with the general population. METHODS: In 1987 and 1989 we included 884 children and 1020 adolescents aged 20 years and under, corresponding to 75% of all Danish children and adolescents with Type 1 diabetes, in two nationwide studies in Denmark. Those who had participated in both investigations (n = 720) were followed until 1 January 2014, using the Danish Civil Registration System on death certificates and emigration. We derived the expected number of deaths in the cohort, using population data values from Statistics Denmark to calculate the standardized mortality ratio. Survival analysis was performed using Cox proportional hazards model. RESULTS: During the 24 years of follow-up, 49 (6.8%) patients died, resulting in a standardized mortality ratio of 4.8 (95% confidence interval 3.5, 6.2) compared with the age-standardized general population. A 1% increase in baseline HbA1c (1989), available in 718 of 720 patients, was associated with all-cause mortality (hazard ratio = 1.38; 95% confidence interval 1.2, 1.6; P < 0.0001). Type 1 diabetes with multiple complications was the most common reported cause of death (36.7%). CONCLUSION: We found an increased mortality rate in this cohort of children and adolescents with Type 1 diabetes compared with the general population. The only predictor for increased risk of death up to 24 years after inclusion was the HbA1c level in 1989. This emphasizes the importance of achieving optimal metabolic control in young people with Type 1 diabetes.

Antipruritic effect of pretreatment with topical capsaicin 8% on histamine- and cowhage-evoked itch in healthy volunteers: a randomized, vehicle-controlled, proof-of-concept trial.

BACKGROUND: Chronic itch is difficult to treat. Low-concentration topical capsaicin (0·006-0·05%) has previously been applied in itch therapy but evidence on its efficacy is contradictory. OBJECTIVES: This vehicle-controlled, double-blinded study investigated the effect of topical capsaicin 8% after 1- and 24-h application on evoked itch, neurogenic inflammation and itch-associated dysaesthesia. METHODS: Sixteen healthy volunteers (aged 22 ± 0·5 years, nine female) were treated with capsaicin for 1 h and 24 h, and vehicle for 24 h on each volar forearm. Subsequently, histamine (1%, administered prick test lancets) and cowhage (40-45 spicules) were applied to the pretreated areas. Evoked itch and pain intensities were recorded for 10 min using a visual analogue scale (0-10 cm), while sensitivity to touch-evoked itch was evaluated using von Frey filaments before and after itch provocations. Neurogenic inflammation was assessed using perfusion imaging. RESULTS: In the vehicle areas peak itch responses to histamine and cowhage were 4·67 ± 0·58 and 5·15 ± 0·71, respectively. Capsaicin pretreatment reduced peak itch responses to histamine and cowhage after 24-h pretreatment to 1·41 ± 0·58 (P = 0·003) and 0·81 ± 0·18, (P < 0·001), respectively. Capsaicin pretreatment for 1 h reduced only cowhage-induced itch (P = 0·023). Furthermore, 24-h capsaicin pretreatment abolished punctuate hyperknesis and lowered histamine-induced neurogenic inflammation but did not affect weal reactions. CONCLUSIONS: Topical capsaicin 8% pretreatment for 24 h reduced histaminergic and nonhistaminergic itch by about 75%, while a significant reduction (≈60%) was achieved for only nonhistaminergic itch in a standard 1-h treatment. Further investigations are needed to elucidate the clinical potential of high-concentration capsaicin as an antipruritic.

Visualization of haemophilic arthropathy in F8-/- rats by ultrasonography and micro-computed tomography.

INTRODUCTION: A major complication of haemophilia is haemophilic arthropathy (HA), a debilitating disorder with an incompletely defined pathobiology. High-resolution imaging may provide new knowledge about onset and progression of HA, and thereby support identification of new treatment opportunities. Recently, a F8-/- rat model of HA was developed. The size of the rat allows for convenient and high resolution imaging of the joints, which could enable in vivo studies of HA development. AIM: To determine whether HA in the F8-/- rat can be visualized using ultrasonography (US) and micro-computed tomography (µCT). METHODS: Sixty F8-/- and 20 wild-type rats were subjected to a single or two induced knee bleeds. F8-/- rats were treated with either recombinant human FVIII (rhFVIII) or vehicle before the induction of knee bleeds. Haemophilic arthropathy was visualized using in vivo US and ex vivo µCT, and the observations correlated with histological evaluation. RESULTS: US and µCT detected pathologies in the knee related to HA. There was a strong correlation between disease severity determined by µCT and histopathology. rhFVIII treatment reduced the pathology identified with both imaging techniques. CONCLUSION: US and µCT are suitable imaging techniques for detection of blood-induced joint disease in F8-/- rats and may be used for longitudinal studies of disease progression.

Intra-articular onabotulinumtoxinA in osteoarthritis knee pain: effect on human mechanistic pain biomarkers and clinical pain.

OBJECTIVES: OnabotulinumtoxinA (onabotA) attenuates peripheral nociceptive transduction and consequently neuronal firing. The aim of this mechanistic study was to evaluate the effect of intra-articular (IA) onabotA in patients with painful knee osteoarthritis (OA). METHOD: We conducted a double-blind, randomized, placebo-controlled, 12-week trial using a single ultrasound-guided IA injection of onabotA (200 U). Patients (N = 121) were randomized to receive onabotA (n = 61) or placebo (n = 60). Mechanistic pain biomarkers and clinical outcomes were used for profiling the effect. The biomarkers were pressure pain thresholds (PPTs) from the knee joint (localized sensitization) and extra-articular sites (widespread sensitization), and wind-up pain (central sensitization). Clinical assessments included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), average daily pain (ADP), patient global impression of change (GIC), and rescue medication. The painDETECT questionnaire (PD-Q) was used for subgrouping patients (nociceptive, neuropathic, and mixed/uncertain). RESULTS: The nociceptive and non-nociceptive groups were identical with respect to all baseline data. No significant differences in clinical efficacy parameters were found between onabotA and placebo in the entire population. The nociceptive group showed significant improvement after IA onabotA at week 8 for all WOMAC outcomes, ADP at weeks 9 and 10, and patient GIC at week 12, and significant reduction in rescue medication counts within each 14-day period at weeks 9 and 10. After 4, 8, and 12 weeks, significant correlations were obtained in the onabotA group between ADP (both the entire group and the nociceptive group) and various sensitization parameters. The nociceptive group showed pronounced effects on widespread sensitization. CONCLUSIONS: Intra-articular onabotA given to patients with nociceptive knee OA reduced pain sensitization together with improvement in pain and function.

Symptoms, diagnoses, and sporting consequences among athletes referred to a Danish sports cardiology clinic.

As the number of recreational athletes performing exercise and participating in competitions at a high-level increases, exercise-induced cardiac symptoms may become a more common problem, not least because recreational athletes often continue high-level exercise programs into advanced ages. We investigated the prevalence of cardiac symptoms and diagnoses among 201 athletes referred for cardiac evaluation at a Sports Cardiology Clinic in Denmark. To our knowledge, this is the first systematic study of athletes referred for suspected cardiac disease. The athletes were all well-trained recreational to elite athletes who participated in various sports with different training loads and a wide age span (13-66 years). All patients were referred by physicians, primarily their general practitioner (38%), and palpitations were the most common cardiac symptom (40%). Cardiac symptoms had a sensitivity of 86% in detecting cardiac disease and a specificity of 13%. Cardiac disease was diagnosed in 44% of the patients, and atrial fibrillation was the most prevalent diagnosis (7.5%). Cardiac diseases with therapeutic- or sports-related consequences for the patients were diagnosed in 28% of the population, but only 1% received a recommendation to avoid high-level sports indefinitely.