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Scientific advice to the UK government throughout the COVID-19 pandemic has been informed by ensembles of epidemiological models provided by members of the Scientific Pandemic Influenza group on Modelling. Among other applications, the model ensembles have been used to forecast daily incidence, deaths and hospitalizations. The models differ in approach (e.g. deterministic or agent-based) and in assumptions made about the disease and population. These differences capture genuine uncertainty in the understanding of disease dynamics and in the choice of simplifying assumptions underpinning the model. Although analyses of multi-model ensembles can be logistically challenging when time-frames are short, accounting for structural uncertainty can improve accuracy and reduce the risk of over-confidence in predictions. In this study, we compare the performance of various ensemble methods to combine short-term (14-day) COVID-19 forecasts within the context of the pandemic response. We address practical issues around the availability of model predictions and make some initial proposals to address the shortcomings of standard methods in this challenging situation. [ABSTRACT FROM AUTHOR]

Discusses the active role that practicing managers are expected to take in managing information and using information technology, and reports the results of a survey of middle and senior managers in a business school environment that examined issues of concern relating to information management. The implications of the findings for business administration education are discussed. (CLB)

It is clear that the nutritional state of patients with inflammatory bowel disease is often impaired and that the provision of nutritional support results in an improvement in nutritional state of these patients. Improvement in nutritional status can be achieved as effectively with enteral as with parenteral nutrition. The nutritional support appears to have no primary therapeutic effect in patients with ulcerative colitis. With regard to nutritional support in Crohn's disease, parenteral nutrition should be restricted to use as supportive rather than primary therapy. Available information now seems to suggest that most of the benefits of parenteral nutrition in Crohn's disease are related to improvement in nutritional state rather than as primary therapy, and its use should be restricted to treatments of specific complications of Crohn's disease, such as intestinal obstruction, related to stricture formation or short bowel syndrome following repeated resection. The present available evidence indicates that defined elemental diets may have a primary therapeutic role in the management of first acute attacks of Crohn's disease when there is a need to improve the nutritional status of patients with inflammatory bowel disease as an adjunct to primary drug therapy. Enteral nutrition is as efficacious as parenteral nutrition; moreover, it is safer to administer and more cost-effective. [ABSTRACT FROM AUTHOR]

Background and aims: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a severe motility disorder associated with significant morbidity. Several histopathological (neuropathic and myopathic) phenotypes have been described but only a single adult with jejunal smooth (circular) muscle α-actin deficiency. We present a prospective multinational case series investigating smooth muscle α-actin deficiency as a biomarker of this disease. Methods: A total of 115 fully clinically and physiologically (including prolonged (24 hour) ambulatory jejunal manometry) characterised CIIP patients from three European centres were studied. Immunohistochemical localisation of actins and other cytoskeletal proteins were performed on laparoscopic full thickness jejunal biopsies and compared with adult controls. Distribution of α-actin was also characterised in other gut regions and in the developing human alimentary tract. Results: Twenty eight of 115 (24%) CIIP patient biopsies had absent (n = 22) or partial (n = 6) jejunal smooth muscle α-actin immunostaining in the circular muscle layer. In contrast, smooth muscle α-actin staining was preserved in the longitudinal muscle and in adult jejunal controls (n = 20). Comparative study of other adult alimentary tract regions and fetal small intestine, suggested significant spatial and temporal variations in smooth muscle α-actin expression. Conclusions: The ability to modulate α-smooth muscle actin expression, evident in development, is maintained in adult life and may be influenced by disease, rendering it a valuable biomarker even in the absence of other structural abnormalities. [ABSTRACT FROM AUTHOR]

The rationale for antidepressants in the treatment of functional gastrointestinal disorders (FGDs) has been the subject of much interest. However, because of our incomplete understanding of FGDs, this rationale remains unclear. A key point is whether the high degree of psychiatric co-morbidity associated with FGDs (40-90%) represents a shared pathophysiology or the ascertainment bias of tertiary referral patients. Our aims were four-fold: (i) to review the current rationale for antidepressant therapy in FGDs; (ii) to review the studies comparing the characteristics of FGDs with both organic gastrointestinal disease and psychiatric disorders; (iii) to propose a model of FGDs which explains the high psychiatric co-morbidity; (iv) to compare the treatment regimes and effectiveness of antidepressants in FGDs and psychiatric illnesses. The review highlights two important observations. Firstly, the characteristics of FGDs are similar to those of affective disorders and dissimilar to those of organic disease. Secondly, although antidepressants benefit FGD sufferers, their benefits in psychiatric illnesses are greater. We conclude that, in view of the degree of similarity between FGDs and affective disorders, FGDs could be considered as affective disorders in their own right and, if the prescription of antidepressants conformed to their use in affective disorders, FGD morbidity would be reduced. [ABSTRACT FROM AUTHOR]

Seven infants with mild acute diarrhoeal dehydration were rehydrated with an oral sugar-electrolyte solution containing a glucose polymer mixture. Six of them were rehydrated successfully. The high sodium content of the solution (90 mmol/l) was based on the WHO/UNICEF recommended glucose-electrolyte solution and was implicated as the cause of increases in serum sodium in 4 infants, one of whom developed serious hypernatraemia associated with glucose-positive stools. A solution with a lower sodium and glucose-polymer content may be of nutritional benefit in the oral rehydration of acute infantile diarrhoea. [ABSTRACT FROM AUTHOR]

A case is reported of a patient with dermatitis herpetiformis who has developed an intestinal lymphoma and a bladder carcinoma during the course of his illness. When considered in conjunction with three recently reported cases it is suggested that intestinal lymphoma may complicate the enteropathy of dermatitis herpetiformis. [ABSTRACT FROM AUTHOR]

Diarrhoea complicating enteral feeding is a common clinical problem affecting up to 25% of patients. Its pathogenesis remains unknown. A new technique of human in vivo segmental colonic perfusion was used to investigate colonic water and electrolyte movement in response to enteral feeding. Four groups of studies were performed in which low and high load polymeric enteral diet infusions were undertaken, either intragastrically or intraduodenally (n = 6 each group). Net absorption of sodium, chloride, and water occurred during fasting throughout the colon in all groups. There was a significant net secretion of sodium, chloride, and water in the ascending colon during low load (sodium: -42 mmol/h; 95% confidence limits -52 to -19, Chloride: -18 mmol/h; -50 to +16, water: -174 ml/h; -348 to -30) and high load (sodium: -24 mmol/h; -60 to +8, chloride: -18 mmol/h; -31 to +16, water: -120 ml/h; -246 to +6) gastric feeding, and during high load duodenal feeding (sodium: -12 mmol/h; -22 to -6, chloride; -6 mmol/h; -16 to +3, water: -72 ml/h; -144 to -6). Net secretion persisted in the distal colon only during high load gastric feeding. In the other three groups there was a net absorption in the distal colon. This study identified a significant colonic secretory response to enteral feeding, which is related to the site and load of the diet infusion. This response may play an important part in the pathogenesis of enteral feeding related diarrhoea. [ABSTRACT FROM PUBLISHER]

Thirty two patients (74 (43-93) years; median, (range)) with dysphagia because of inoperable, unresectable or recurrent oesophagogastric carcinoma were treated by ethanol induced tumour necrosis (ETN). Endoscopic injection of absolute alcohol was performed using a variceal injector needle, with 0.5-1 ml aliquots injected retrogradely from distal to proximal tumour margin. Dilatation to 12 mm was used only if the endoscope would not traverse the stricture. In patients with total occlusion, injection into the proximal tumour was followed by a repeat endoscopy 3-7 days later. Dysphagia was graded from 0 = no dysphagia to 4 = total dysphagia. The significance of changes in the dysphagia grade after ETN were assessed using the Wilcoxon rank sum test. Results (median (range)) were as follows: stricture length = 5.0 cm (1-15). Dysphagia grade before treatment was 3 (2-4) improving after first treatment to 1 (0-3), p < 0.003. Best dysphagia grade achieved was 1 (0-3) and interval between treatments was 28.5 days (4-170). The volume of ethanol injected = 10 ml (1.5-29) and survival after first treatment was 93 days (6-660). The number of treatment sessions required to achieve best grade = 1 (1-3). There were no treatment complications. ETN significantly improves dysphagia. Results of palliation are similar to those of laser therapy, but can be achieved quickly and safely on a day case basis in most patients and at a small proportion of the cost. [ABSTRACT FROM PUBLISHER]

Elemental diet is as effective as corticosteroids in the treatment of previously untreated Crohn's disease. It is unclear whether a poor nutritional state is a prerequisite for efficacy of elemental diet, whether previously treated patients respond as well, or how duration of remission using elemental diet compares with corticosteroid induced remission. Forty two patients with active Crohn's disease were stratified for nutritional state and randomised to receive Vivonex TEN 2.1 l/day for four weeks, or 0.75 mg prednisolone/kg/day for two weeks and subsequent reducing doses. Nine of 22 (41%) patients assigned to nutritional treatment were intolerant of the diet. Thirty patients completed four weeks treatment. Disease activity decreased on elemental diet from mean (SEM) 4.8 (0.9) to 1.7 (0.6), p < 0.05, and on prednisolone from 5.3 (0.5) to 1.9 (0.6), p < 0.05. For each treatment, nourished and malnourished patients responded similarly. Patients with longstanding disease responded as well as newly diagnosed patients. The probability of maintaining remission at six months was 0.67 after prednisolone, 0.28 after elemental diet, and at one year was 0.35 after prednisolone and 0.09 after elemental diet, p < 0.05. When tolerated, elemental diet is as effective in the short term as prednisolone in newly and previously diagnosed Crohn's disease, and its benefit is independent of nutritional state. The subsequent relapse rate after elemental diet induced remission, however, is greater than after treatment with prednisolone. [ABSTRACT FROM PUBLISHER]

This prospective double blind randomised seven day crossover controlled clinical trial was carried out to determine whether enterally fed patients with moderately impaired gastrointestinal function require a predigested nitrogen (N) source compared with whole protein. Twelve malnourished patients with varying gastrointestinal abnormalities, who required enteral feeding, received 2.25 l of one of two isocaloric isonitrogenous enteral diets (1 kcal/ml, 4.8 g nitrogen/l) containing either predominantly medium chain peptides (tetra or higher peptides) or whole protein as the nitrogen source. Nitrogen absorption and balance were calculated from dietary intake and analysis of 24 hour total urinary and faecal nitrogen for the last five days of each study period. There was no significant difference in either stool weight (110 (SEM) (49) v 111 (32) g/d), nitrogen absorption (91 (2) v 89 (2)%) or nitrogen balance (+1.0 (1.3) v +0.6 (1.4) g nitrogen/d) between the peptide and whole protein nitrogen sources when all patients are considered. There was, however, evidence to suggest a nutritional advantage from administering an enteral diet whose nitrogen source comprises oligopeptides, rather than whole protein, to a subgroup of patients with small bowel disease. [ABSTRACT FROM PUBLISHER]

Glycine has been regarded as a poor source of nitrogen for total parenteral nutrition. Two prospective randomised cross over controlled clinical trials were undertaken to compare the efficacy of high and low glycine containing amino acid solutions in parenterally fed malnourished hypoalbuminaemic patients with gastrointestinal disease. In the first study (n = 9), amino acid solutions in which glycine accounted for 23% and 4% of total nitrogen were compared. No statistically significant difference was found in urea nitrogen/total urinary nitrogen excretion (mean (SEM) 83.4 (1.4) v 81.6 (1.7)%, p = 0.31), nitrogen balance (-1.9 (2.4) v -0.6 (2.0) g/day, p = 0.31) or plasma protein concentrations and blood urea nitrogen. In the second extended study (n = 5), there was no significant difference in net whole body protein synthesis (+1.3 (4.7) v-0.2 (3.7) mg/kg/hour, p = 0.69) or fractional (0.403 (0.070) v 0.480 (0.41)%/hour, p = 0.68) and absolute albumin synthesis rates (6.0 (0.9) v 7.2 (0.06) mg/kg/hour, p = 0.22), on comparing solutions of 25% and 8% glycine nitrogen. In addition, a significantly higher proportion of total urinary nitrogen comprised urea when patients received the low glycine containing amino acid source (81.4 (2.5) v 83.8 (3.2)%, p = 0.04). It is concluded that there are no apparent short term nutritional or metabolic disadvantages to using amino acid solutions that contain up to 25% of nitrogen as glycine in total parenteral nutrition. [ABSTRACT FROM PUBLISHER]

The effect of sulphasalazine and olsalazine on jejunal and ileal water and electrolyte absorption was investigated in normal subjects by a steady state intestinal perfusion of a physiological glucose bicarbonate electrolyte solution in the absence and presence of increasing concentrations of each drug. (Olsalazine 0.25 g/l, 1.0 g/l, jejunum; 0.5 g/l, 1.0 g/l, ileum; sulphasalazine 0.25 g/l, 0.5 g/l, 2.0 g/l jejunum; 1.0 g/l, 2.0 g/l, ileum.) In the jejunum olsalazine at 1.0 g/l significantly inhibited water, sodium, chloride, and potassium absorption (p less than 0.05). In the ileum olsalazine at 0.5 and 1 g/l significantly inhibited glucose uptake (p less than 0.04) and water absorption (p less than 0.03). In the jejunum sulphasalazine had a dose related and significant inhibitory effect on water, bicarbonate, and sodium absorption and at 2.0 g/l an inhibitory effect on chloride, potassium (p less than 0.005), and glucose (p less than 0.05) absorption. In the ileum sulphasalazine had no significant effect on water and electrolyte absorption. All inhibitory effects were rapidly reversible. These data show that unexplained diarrhoea in patients with ulcerative colitis treated with olsalazine may occur as a consequence of inhibition of water and electrolyte absorption in the small intestine and that the mechanisms of inhibition of sulphasalazine and olsalazine are different. [ABSTRACT FROM PUBLISHER]

The recent launch of a number of fibre enriched polymeric diet in the United States and Europe has stimulated considerable interest in the topic of fibre and enteral nutrition, and several commercial concerns appear to be under considerable pressures from their consumers to produce similar products. As a means of identifying areas of potential application of fibre to enteral nutrition some of the recent knowledge gained about the physical properties of dietary fibre and the processes involved in the intestinal assimilation of fibre has been reviewed. Two areas of interest are identifiable. The first relates to the bulking properties of fibre and the application of this to the regulation of bowel function in enterally fed patients. It is clear from the clinical studies that have been reviewed that there remains a paucity of controlled data, and a great deal more research is needed before widespread use of fibre supplemented diets can be supported. Perhaps of greater interest academically is the potentially beneficial effects that appear to be exerted by the VFA's, liberated as a consequence of colonic bacterial fermentation of fibre, on morphology and function of ileal and colonic mucosa. Although there are a number of potential applications of fibre supplemented enteral diets in this area, more research is required before any firm recommendations can be made about recommending their use. The one exception concerns patients with the nutritionally inadequate short bowel syndrome. There does seem to be sufficient experimental evidence to suggest that clinical studies should be commenced using a pectin supplemented predigested 'elemental' diet in these patients. Overall therefore, one is forced to conclude that the increasing interest and use of fibre supplemented enteral diets is being driven more by market than scientific forces. Nevertheless, the promotion of these diets has already provided a powerful stimulus to the scientific community, and it remains entirely possible that many of the potential applications of these diets will be realised in the near future. [ABSTRACT FROM PUBLISHER]

Results of recent controlled studies show that because of difficulties in administering adequate quantities of enteral diet, positive nitrogen balance is not consistently achieved during enteral feeding. In order to determine whether nitrogen balance can be improved in routine clinical practice by prescribing enteral diets containing higher concentrations of nutrients, 118 patients with normal gastrointestinal function needing enteral nutrition were randomised to receive daily 21 of one of three polymeric diets: Standard diet (1.0 kcal/ml; 6.3 gN/l), Energy Dense diet (1.5 kcal/ml; 7.8 gN/l), and Energy-Nitrogen Dense diet (1.5 kcal/ml; 9.4 gN/l. The three diets, administered by continuous nasogastric infusion, were equally well tolerated. Results were analysed only for patients fed five or more days and who received at least 60% of prescribed enteral diet (n = 42). Positive nitrogen balance was achieved only in the patients receiving the Energy-Nitrogen Dense diet (n = 16; + 1.6 (SE) 0.6 gN/d, compared with the Standard diet (n = 12; -3.8 (1.1) gN/d; p less than 0.001), and the Energy Dense diet (m = 14; -1.9 (0.8) gN/d; p less than 0.005). As the findings of this prospective controlled trial show that positive nitrogen balance was not consistently achieved by administering 21 enteral diet containing up to 15.6 gN, consideration could, therefore, be given to routinely using enteral diets containing up to 9.4 gN/l. [ABSTRACT FROM PUBLISHER]

The fate of orally ingested lactitol, a non-absorbed sugar, was measured in six healthy human subjects by following the three routes of disposal of universally 14C-labelled sugar. Lactitol was given as a 20 g daily dose to six healthy volunteers for 14 days and on the seventh day, 10 muCi of L-[U-14C]-lactitol was given with the unlabelled sugar and excretion of the 14C in breath, urine and faeces was followed. The peak of 14CO2 excretion occurred at six hours and total 14CO2 accounted for 62.9 (5.0)% of isotope given, whilst 6.5 (3.6)% and 2.0 (0.3)% of the label were recovered from faeces and urine respectively. These data suggest that lactitol is extensively metabolised in the human colon and that a significant proportion of the bacterial metabolites are available for colonic absorption. Calculation revealed that 54.5% of the theoretical energy content of this compound was utilised by the subjects. It is suggested that this sugar, and other soluble 'non-absorbed' sugars (lactulose, sorbitol, mannitol), may undergo a similar pattern of colonic metabolism and can be considered as reduced calorie compounds. [ABSTRACT FROM PUBLISHER]