Summary
Background
Nonresponse and loss of response to anti‐TNF therapies in Crohn's disease represent significant clinical problems for which clear management guidelines are lacking.
Aim
To review ...the incidence, mechanisms and predictors of primary nonresponse and secondary loss of response to formulate practical clinical algorithms to guide management.
Methods
Through a systematic literature review, 503 articles were identified which fit the inclusion criteria.
Results
Primary nonresponse to anti‐TNF treatment affects 13–40% of patients. Secondary loss of response to anti‐TNF occurs in 23–46% of patients when determined according to dose intensification, and 5–13% of patients when gauged by drug discontinuation rates. Recent evidence suggests that the mechanisms underlying primary nonresponse and secondary loss of response are multifactorial and include disease characteristics (phenotype, location, severity); drug (pharmacokinetic, pharmacodynamic or immunogenicity) and treatment strategy (dosing regimen) related factors. Clinical algorithms that employ therapeutic drug monitoring (using anti‐TNF tough levels and anti‐drug antibody levels) may be used to determine the underlying cause of primary nonresponse and secondary loss of response respectively and guide clinicians as to which patients are most likely to respond to anti‐TNF therapy and help optimise drug therapy for those who are losing response to anti‐TNF therapy.
Conclusions
Nonresponse or loss of response to anti‐TNF occurs commonly in Crohn's disease. Clinical algorithms utilising therapeutic drug monitoring may establish the mechanisms for treatment failure and help guide the subsequent therapeutic approach.
Summary
Background
Acute severe ulcerative colitis (ASUC) is a life‐threatening condition for which optimal management strategies remain ill‐defined.
Aim
To review the evidence regarding the natural ...history, diagnosis, monitoring and treatment of ASUC to inform an evidence‐based approach to management.
Methods
Relevant articles addressing the management of ASUC were identified from a search of MEDLINE, the Cochrane Library and conference proceedings.
Results
Of ASUC, 31–35% is steroid‐refractory. Infliximab and ciclosporin salvage therapies have improved patient outcomes in randomised controlled trials. Short‐term response rates (within 3 months) have ranged from 40% – 54% for ciclosporin and 46–83% for infliximab. Long‐term clinical response rates (≥1 year) have ranged from 42%–50% for ciclosporin and 50–65% for infliximab. Short‐term and long‐term colectomy rates have been respectively: 26–47% and 36–58% for ciclosporin, and 0–50% and 35–50% for infliximab. Mortality rates for ciclosporin and infliximab‐treated patients have been: 0–5% and 0–2%, respectively. At present, management challenges include the selection, timing and assessment of response to salvage therapy, utilisation of therapeutic drug monitoring and long‐term maintenance of remission.
Conclusions
Optimal management of acute severe ulcerative colitis should be guided by risk stratification using predictive indices of corticosteroid response. Timely commencement and assessment of response to salvage therapy is critical to reducing morbidity and mortality. Emerging pharmacokinetic models and therapeutic drug monitoring may assist clinical decision‐making and facilitate a shift towards individualised acute severe ulcerative colitis therapies.
Summary
Background
Excessive visceral adipose tissue has been associated with poorer outcomes in patients with inflammatory bowel disease.
Aim
To determine whether body composition is associated with ...outcome in a prospective study of post‐operative Crohn's disease patients.
Methods
The POCER study evaluated management strategies for prevention of post‐operative Crohn's disease recurrence; subjects were enrolled after resection of all macroscopic Crohn's disease and were randomised to early endoscopy and possible treatment escalation, or standard care. The primary endpoint was endoscopic recurrence at 18 months. 44 subjects with cross‐sectional abdominal imaging were studied, and body composition analysis performed using established techniques to measure visceral adipose tissue area, subcutaneous adipose tissue area, and skeletal muscle area.
Results
The body composition parameter with the greatest variance was visceral adipose tissue. Regardless of treatment, all subjects with visceral adipose tissue/height2 >1.5 times the gender‐specific mean experienced endoscopic recurrence at 18 months (compared to 47%) relative risk 2.1, 95% CI 1.5–3.0, P = 0.012. Waist circumference correlated strongly with visceral adipose tissue area (ρ = 0.840, P < 0.001). Low skeletal muscle was prevalent (41% of patients), but did not predict endoscopic recurrence; however, appendicular skeletal muscle indices correlated inversely with faecal calprotectin (ρ = 0.560, P = 0.046).
Conclusions
Visceral adiposity is an independent risk factor for endoscopic recurrence of Crohn's disease after surgery. Sarcopenia correlates with inflammatory biomarkers. Measures of visceral adipose tissue may help to stratify risk in post‐operative management strategies.
Linked ContentThis article is linked to Holt et al, and Stidham and Waljee papers. To view these articles visit https://doi.org/10.1111/apt.14102 and https://doi.org/10.1111/apt.14069.
Recent studies report the immunomodulatory lung-protective role of halogenated anaesthetics during lung resection surgery (LRS) but have not investigated differences in clinical postoperative ...pulmonary complications (PPCs). The main goal of the present study was to compare the effect of sevoflurane and propofol on the incidence of PPCs in patients undergoing LRS. The second aim was to compare pulmonary and systemic inflammatory responses to LRS.
Of 180 patients undergoing LRS recruited, data from 174 patients were analysed. Patients were randomized to two groups (propofol or sevoflurane) and were managed otherwise using the same anaesthetic protocol. Bronchoalveolar lavage (BAL) was performed in both lungs before and after one-lung ventilation for analysis of cytokines. Arterial blood was drawn for measurement of the cytokines analysed in the BAL fluid at five time points. Intraoperative haemodynamic and respiratory parameters, PPCs (defined following the ARISCAT study), and mortality during the first month and yr were recorded.
More PPCs were detected in the propofol group (28.4% vs 14%, OR 2.44 95% CI, 1.14–5.26). First-yr mortality was significantly higher in the propofol group (12.5% vs 2.3%, OR 5.37 95% CI, 1.23–23.54). Expression of lung and systemic pro-inflammatory cytokines was greater in the propofol group than in the sevoflurane group. Pulmonary and systemic IL-10 release was less in the propofol group.
Our results suggest that administration of sevoflurane during LRS reduces the frequency of the PPCs recorded in our study and attenuates the pulmonary and systemic inflammatory response.
NCT 02168751; EudraCT 2011-002294-29.
This paper presents an experimental study of the translaminar fracture toughness under tensile and compressive loads of interply hybrid polymer-matrix composite laminates. The studied laminates were ...obtained by combining two of three different reinforcements: woven carbon fabric, woven glass fabric and unidirectional carbon tape, manufactured using the Resin Transfer Molding (RTM) process. The resulting in-plane quasi-isotropic laminates were generated by changing each material location along the thickness.
The incidence and prevalence of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are lower in Asia than in the West. However, across Asia the incidence and ...prevalence of IBD has increased rapidly over the last two to four decades. These changes may relate to increased contact with the West, westernization of diet, increasing antibiotics use, improved hygiene, vaccinations, or changes in the gut microbiota. Genetic factors also differ between Asians and the Caucasians. In Asia, UC is more prevalent than CD, although CD incidence is rapidly increasing in certain areas. There is a male predominance of CD in Asia, but a trend towards equal sex distribution for UC. IBD is diagnosed at a slightly older age than in the West, and there is rarely a second incidence peak as in the West. A positive family history is much less common than in the West, as are extra‐intestinal disease manifestations. There are clear ethnic differences in incidence within countries in Asia, and an increased incidence in IBD in migrants from Asia to the West. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.
Summary
Background
Crohn's disease recurs in the majority of patients after intestinal resection.
Aim
To compare the relative efficacy of thiopurines and anti‐TNF therapy in patients at high risk of ...disease recurrence.
Methods
As part of a larger study comparing post‐operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine‐intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment.
Results
A total of 101 patients 50% male; median (IQR) age 36 (25–46) years were included. There were no differences in disease history between thiopurine‐ and adalimumab‐treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2–i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab‐treated patients intention‐to‐treat (ITT); P = 0.028 or 24 of 62 (39%) vs. 3 of 24 (13%) respectively per‐protocol analysis (PPA); P = 0.020. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab).
Conclusions
In Crohn's disease patients at high risk of post‐operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.
Summary
Background
Inflammatory bowel disease can impact on a patient's ability to maintain normal physical and mental function, and fulfil their social, family and work roles. Aspects of disability ...in IBD have received little attention.
Aim
To develop, validate and apply a questionnaire directed towards evaluating these disease aspects.
Methods
A literature review on disability in IBD was undertaken, and opinion about aspects of disability to measure was sought from six IBD‐specialised gastroenterologists. A questionnaire was developed, and IBD patients completed the new disability questionnaire, the SF‐36 and the short‐IBD (SIBDQ ‐ 10 point). A subgroup of patients completed the questionnaire again 4 weeks later. Healthy volunteers were studied as a control group.
Results
A total of 116 IBD out‐patients were approached, of whom 81 (52 Crohn's disease and 28 ulcerative colitis) participated. Nineteen patients were re‐evaluated at 4 weeks. Twenty‐five controls were studied. All subscales demonstrated good Cronbach's alpha reliability and reproducibility. There was a significant inverse correlation between the disability score and the SIBDQ and between the disability score and the SF36 and a positive correlation with the Crohn's Disease Activity Index (CDAI) (all P < 0.001). Disability differed between ulcerative colitis and controls, but not between active and inactive disease.
Conclusions
The new disability questionnaire is sensitive for detecting disability, is reliable and reproducible, and correlates with disease activity in Crohn's disease, but not ulcerative colitis. Further prospective testing is now needed in the longer term, larger patient populations and in different countries and ethnicities.
Pharmacology has broadened its scope considerably in recent decades. Initially, it was of interest to chemists, doctors and pharmacists. In recent years, however, it has been incorporated into the ...teaching of biologists, molecular biologists, biotechnologists, chemical engineers and many health professionals, among others. Traditional teaching methods, such as lectures or laboratory work, have been superseded by the use of new pedagogical approaches to enable a better conceptualization and understanding of the discipline. In this article, we present several new methods that have been used in Spanish universities. Firstly, we describe a teaching network that has allowed the sharing of pedagogical innovations in Spanish universities. A European experience to improve prescribing safety is described in detail. The use of popular films and medical TV series in biomedical students shows how these audiovisual resources can be helpful in teaching pharmacology. The use of virtual worlds is detailed to introduce this new approach to teaching. The increasingly important area of the social aspects of pharmacology is also considered in two sections, one devoted to social pharmacology and the other to the use of learning based on social services to improve understanding of this important area. Finally, the use of Objective Structured Clinical Evaluation in pharmacology allows to know how this approach can help to better evaluate clinical pharmacology students. In conclusion, this article allows to know new pedagogical methods resources used in some Spanish universities that may help to improve the teaching of pharmacology.
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Inflammatory bowel diseases are thought to develop as a result of dysregulation of the relationship that exists between the gut microbiota, host genetics and the immune system. The advent of ...culture-independent techniques has revolutionised the ability to characterise the role of the gut microbiota in health and disease based on the microbiota's genetic make-up. Inflammatory bowel diseases are characterised by dysbiosis which is an imbalance between pro- and anti-inflammatory bacteria and a reduction in bacterial diversity. Emerging data suggest that it is not only the presence of the gut microbiota but the functional activity of the microbiota that appears to play an important role in health and disease. Current strategies to manipulate therapeutically the gut microbiota using dietary modification, prebiotics, probiotics, antibiotics and faecal microbiota transplantation aim to restore the balance to a state of normobiosis. However, the ability of such strategies to correct dysbiosis and thereby achieve therapeutic benefit is yet to be fully characterised.
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