Non-fatal opioid overdose, naloxone access, and naloxone training among people who recently used opioids or received opioid agonist treatment in Australia: The ETHOS Engage study.

BACKGROUND: Overdose is a major cause of morbidity and mortality among people who use opioids. Naloxone can reverse opioid overdoses and can be distributed and administered with minimal training. People with experience of overdose are a key population to target for overdose prevention strategies. This study aims to understand if factors associated with recent non-fatal opioid overdose are the same as factors associated with naloxone access and naloxone training in people who recently used opioids or received opioid agonist treatment (OAT). METHODS: ETHOS Engage is an observational study of people who inject drugs in Australia. Logistic regression models were used to estimate odds ratios for non-fatal opioid overdose, naloxone access and naloxone training. RESULTS: Between May 2018-September 2019, 1280 participants who recently used opioids or received OAT were enrolled (62% aged >40 years; 35% female, 80% receiving OAT, 62% injected drugs in the preceding month). Recent opioid overdose (preceding 12 months) was reported by 7% of participants, lifetime naloxone access by 17%, and lifetime naloxone training by 14%. Compared to people receiving OAT with no additional opioid use, recent opioid, benzodiazepine (preceding six months), and hazardous alcohol use was associated with recent opioid overdose (aOR 3.91; 95%CI: 1.68-9.10) and lifetime naloxone access (aOR 2.12; 95%CI 1.29-3.48). Among 91 people who reported recent overdose, 65% had never received take-home naloxone or naloxone training. CONCLUSIONS: Among people recently using opioids or receiving OAT, benzodiazepine and hazardous alcohol use is associated with non-fatal opioid overdose. Not all factors associated with non-fatal overdose correspond to factors associated with naloxone access. Naloxone access and training is low across all groups. Additional interventions are needed to scale up naloxone provision.

Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study.

OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. METHODS: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. RESULTS: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. CONCLUSIONS: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.

'Idiopathic' intestinal failure--the importance of identifying and treating primary psychopathology.

BACKGROUND: Gastrointestinal neuromuscular disorders (GINMD) are an important cause of intestinal failure (IF). We present six cases of IF in whom a diagnosis of GINMD was initially suspected, but in whom psychopathology was discovered to be the primary etiology. METHODS: (i) Six consecutive cases referred to our unit with IF, initially presumed to be due to GINMD, were selected. Informed consent was obtained from all patients. Case notes were reviewed for salient clinical information. (ii) A literature search was performed to ascertain the epidemiology of psychopathology in IF and the current evidence for the management of severe functional GI disorders with a multidisciplinary psychiatric approach. KEY RESULTS: (i)All six cases required multidisciplinary psychiatric management in a specialized psychiatric unit that included the use of antidepressants, antipsychotics, mood stabilizers, and Electroconvulsive therapy in addition to nutritional support via enteral or parenteral routes. (ii) The evidence base for the treatment of severe FGIDs is sparse. CONCLUSIONS & INFERENCES: There is a need for additional reporting of such cases and further research. Our experience would suggest that a delay in the involvement of a specialist liaison psychiatrist has the potential to be life threatening in such cases. This may be more likely with greater severity, where the apparent predominance of 'physical' symptoms generates reluctance in both patient and physician to consider a psychiatric etiology and also appears to occur due to a lengthier investigative process than existed previously. We therefore propose that the provision of a specialist psychiatric assessment for all patients presenting with IF is indicated at the point of initial clinical contact, based upon the substantial clinical benefit it has the potential to confer upon a significant minority. This process need not delay investigation, which can continue as indicated in parallel, but can be life-saving.

The evolving role of post-ligament of Trietz nasojejunal feeding in enteral nutrition and the need for improved feeding tube design and placement methods.

Nutrition support is an important link in the chain of therapy for intensive care unit patients. The early institution of nutrition support significantly reduces the incidence of septic complications, reduces mortality, and shortens hospital stay. Unfortunately, impaired gastrointestinal function, particularly gastric atony, restricts the use of nasogastric enteral tube feeding, and the use of this route of administration in these patients can lead to regurgitation, aspiration, and the development of pneumonia. Postpyloric enteral feeding was heralded as a means of overcoming many of these problems. Overall, the results of controlled studies do not support a role of postpyloric duodenal feeding in reducing the incidence of aspiration pneumonia. As a consequence, post-ligament of Treitz nasojejunal enteral feeding is proposed as the technique of choice in these patients. Feeding tube design must incorporate a gastric aspiration port to overcome problems of gastroesophageal acid reflux, duodenogastric bile reflux, and increased gastric acid secretion, problems that occur during "downstream" jejunal feeding. Tube placement technique will need to be refined and patients will need to receive a predigested enteral diet. In postoperative surgical patients in the intensive care unit, there is also a need for a newly designed dual-purpose nasogastric tube capable initially of providing a means of undertaking gastric aspiration and decompression and subsequently a means of initiating nasogastric enteral feeding.

Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome.

BACKGROUND: Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). AIM: To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. METHODS: In all, 44 patients with Rome II positive IBS completed a 12-week single centre parallel crossover controlled clinical trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored. RESULTS: The prebiotic significantly enhanced faecal bifidobacteria (3.5 g/d P < 0.005; 7 g/d P < 0.001). Placebo was without effect on the clinical parameters monitored, while the prebiotic at 3.5 g/d significantly changed stool consistency (P < 0.05), improved flatulence (P < 0.05) bloating (P < 0.05), composite score of symptoms (P < 0.05) and SGA (P < 0.05). The prebiotic at 7 g/d significantly improved SGA (P < 0.05) and anxiety scores (P < 0.05). CONCLUSION: The galactooligosaccharide acted as a prebiotic in specifically stimulating gut bifidobacteria in IBS patients and is effective in alleviating symptoms. These findings suggest that the prebiotic has potential as a therapeutic agent in IBS.

Formulation of enteral diets for use in jejunal enteral feeding.

Nasogastric enteral feeding is not tolerated in patients with gastric atony and in many critically-ill patients in whom gastric emptying may be delayed and in whom gastro-oesophageal regurgitation may lead to pulmonary aspiration of enteral feed and the development of pneumonia. Initial attempts to overcome these problems led to the development of post pyloric enteral feeding techniques with the infusion port of the tubes positioned in the duodenum. In many centres this technique is still the most practised post-pyloric enteral feeding technique. Nasoduodenal feeding tubes often retroperistalse into the stomach. The technique of choice, therefore, in these difficult patients is to position the infusion port of the feeding tube well distal to the ligament of trietz (post ligament of trietz nasojejunal enteral tube feeding). While nasogastric and nasoduodenal enteral feeding techniques have been shown to elicit a stimulatory exocrine pancreatic response, distal jejunal enteral feeding does not. During this mode of feeding the ileal brake is activated and pancreatic exocrine pancreatic secretion inhibited by the action of the released peptide YY and glucagon-like peptide-1 hormones, in turn the inhibition of pancreatic secretion being the result of inhibition of trypsin secretion. In the light of the findings showing the absence of a stimulatory pancreatic exocrine response to nasojejunal enteral feeding these patients should receive a predigested rather than a polymeric enteral diet.

Systematic review and meta-analysis: the clinical and physiological effects of fibre-containing enteral formulae.

BACKGROUND: Enteral nutrition can be associated with gastrointestinal side effects and fibre supplementation has been proposed as a means to normalize bowel function. AIM: To evaluate systematically the effects of fibre supplementation of enteral feeds in healthy volunteers and patients both in the hospital and community settings. METHODS: Electronic and manual bibliographic searches were conducted. Controlled studies in adults or children, comparing fibre-supplemented vs. fibre-free formulae given as the sole source of nutrition for at least 3 days, were included. RESULTS: Fifty-one studies (including 43 randomized-controlled trials), enrolling 1762 subjects (1591 patients and 171 healthy volunteers) met the inclusion criteria. Fibre supplementation was generally well tolerated. In the hospital setting, the incidence of diarrhoea was reduced as a result of fibre administration (OR 0.68, 95% CI: 0.48-0.96; 13 randomized-controlled trials). Meta-regression showed a more pronounced effect when the baseline incidence of diarrhoea was high. In both patients and healthy subjects, fibre significantly reduced bowel frequency when baseline frequency was high and increased it when it was low, revealing a significant moderating effect of fibre. CONCLUSIONS: The review indicates that the fibre-supplemented enteral formulae have important physiological effects and clinical benefits. There is a need to use a consistent approach to undertake more studies on this issue in the community setting.

Deranged smooth muscle alpha-actin as a biomarker of intestinal pseudo-obstruction: a controlled multinational case series.

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 alpha-actin deficiency. We present a prospective multinational case series investigating smooth muscle alpha-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 alpha-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 alpha-actin immunostaining in the circular muscle layer. In contrast, smooth muscle alpha-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 alpha-actin expression. CONCLUSIONS: The ability to modulate alpha-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.

Pseudo-pseudo-obstruction: lessons in diagnosis and management.

Chronic intestinal pseudo-obstruction (CIP) has been defined as a rare and severe, disabling disorder, which is characterised by recurring episodes or continuous symptoms and signs of bowel obstruction, including radiological features of obstruction. It is suggested that the diagnosis should be broadened to include patients with severe gastrointestinal symptoms who do not have radiological features of obstruction but who have manometric features of CIP and/or have demonstrable end organ list of pathological features described in CIP. A case of pseudo-pseudo-obstruction is described in this issue of the Journal. Originally the patient was thought to have CIP, and a mechanical cause of obstruction was suspected based on small intestine manometric features, suggesting a distal mechanical obstruction and a worsening of symptoms when treated with a prokinetic agent. As patients with CIP can develop mechanical obstruction and episodes of mechanical obstruction can mimic CIP, small intestine manometry and trials of prokinetic therapy should be undertaken in all difficult cases of obstruction and particularly in patients with documented CIP.

Chronic idiopathic intestinal pseudo-obstruction: the need for a multidisciplinary approach to management.

At the outset of the research programme into irritable bowel syndrome (IBS) it was perceived that there was a need to develop a symptom-based classification for the patients. Four groups of patients were identified, those with spastic colon syndrome, diarrhoea-predominant spastic colon syndrome, functional diarrhoea and midgut dysmotility. While working with outpatients with IBS it was noted how some of them had suffered symptoms for many years; specifically, a group of patients satisfying the criteria for midgut dysmotility had also suffered from particularly severe and intractable intestinal symptoms. These patients underwent 24 h ambulatory studies of small intestinal motility and the majority were found to have manometric features of chronic idiopathic intestinal pseudo-obstruction (CIIP). To characterise the cause, laparoscopic full-thickness small intestine and colonic biopsies have been obtained in forty-five of the latter group of patients. Of these patients 58% have been found to have complete or partial deficiency of alpha-actin epitope staining in the inner circular layer of small intestinal smooth muscle. This deficiency is believed to represent an important biomarker rather than the cause of CIIP, since alpha-actin epitope deficiency has been observed in association with enteric neuropathy and myopathies. In relation to the management of CIIP patients, a multidisciplinary model is proposed incorporating management of co-morbid psychological and psychiatric pathology, abdominal and musculoskeletal pain, fatigue, urological symptoms and nutrition. A six-stage nutritional management plan for these patients is presented.

Randomized clinical trial of the effects of preoperative and postoperative oral nutritional supplements on clinical course and cost of care.

BACKGROUND: Postoperative oral nutritional supplementation has been shown to be of clinical benefit. This study examined the clinical effects and cost of administration of oral supplements both before and after surgery. METHODS: This was a randomized clinical trial conducted in three centres. Patients undergoing lower gastrointestinal tract surgery were randomized to one of four groups: group CC received no nutritional supplements, group SS took supplements both before and after surgery, group CS received postoperative supplements only, and group SC were given supplements only before surgery. Preoperative supplements were given from the time it was decided to operate to 1 day before surgery. Postoperative supplements were started when the patient was able to take free fluids and continued for 4 weeks after discharge from hospital. Data collected included weight change, complications, length of stay, nutritional intake, anthropometrics, quality of life and detailed costings covering all aspects of care. RESULTS: Some 179 patients were randomized, of whom 27 were withdrawn and 152 analysed (CC 44, SS 32, CS 35, SC 41). Dietary intake was similar in all four groups throughout the study. Mean energy intake from preoperative supplements was 536 and 542 kcal/day in the SS and SC groups respectively; that 2 weeks after discharge from hospital was 274 and 361 kcal/day in the SS and CS groups respectively. There was significantly less postoperative weight loss in the SS group than in the CC and CS groups (P < 0.050), and significantly fewer minor complications in the SS and CS groups than the CC group (P < 0.050). There were no differences in the rate of major complications, anthropometrics and quality of life. Mean overall costs were greatest in the CC group, although differences between groups were not significant. CONCLUSION: Perioperative oral nutritional supplementation started before hospital admission for lower gastrointestinal tract surgery significantly diminished the degree of weight loss and incidence of minor complications, and was cost-effective.

Review article: The rationale for antidepressant therapy in functional gastrointestinal disorders.

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.

Clinically significant benign pneumoperitoneum as a complication of percutaneous endoscopic gastrostomy.

Benign pneumoperitoneum is a complication of percutaneous endoscopic gastrostomy (PEG) feeding tube placement. The rate of occurrence is reported as up to 25%. It is usually an incidental finding that arises immediately following the procedure. We report a case of pneumoperitoneum that developed a significant time after the initial procedure. The patient developed intractable vomiting and had to be fed parenterally. The pneumoperitoneum resolved and the gastrostomy tube feed was re-started.

Distal colonic motor activity in four subgroups of patients with irritable bowel syndrome.

With the aim of improving end organ treatment, we describe a new system of classifying irritable bowel syndrome (IBS) according to clinical features into four groups, spastic colon syndrome (SCS), functional diarrhea (FD), diarrhea-predominant spastic colon syndrome (DPSCS), and midgut dysmotility (MGD). The aim of the study was to investigate fasting and postprandial distal colonic motility in the four groups of patients and to compare the results with normal controls. Distal colonic motility studies were performed in the unprepared colon. 2.5-hr recordings were made from four channels with a standard meal administered at 0.5 hr. The intubated colon was treated as a study segment and data analyzed for study segment activity index (SSAI) and number and mean amplitude of pressure peaks over 30-min epochs. Patients with SCS had significantly higher (P < 0.05) mean amplitude of pressure peaks (60 min, 120 min) and SSAI (120 min) than controls and patients with FD, DPSCS, and MGD. In contrast, patients with FD and DPSCS had significantly (P < 0.05) lower postprandial SSAI than controls and patients with SCS (60 min, 120 min). With the exception of raised postprandial mean amplitude of pressure peaks (120 min), MGD patients had normal distal colonic motility. Division of IBS patients into subgroups has highlighted significant differences in distal colonic motility that provide insights into etiopathogenesis and should assist targeting of current and newly developed therapies, particularly receptor active agents.

Impact of irritable bowel syndrome on personal relationships and working practices.

OBJECTIVE: To determine the impact of irritable bowel syndrome on personal relationships and working practices. PATIENTS AND METHODS: A 60-item questionnaire about personal relationships, working practices and treatment was sent to 3090 subscribers of the IBS Bulletin, a quarterly educational publication. A total of 1855 completed questionnaires were returned. Analysis was restricted to 1597 questionnaires (86.1%), returned by respondents in whom the diagnosis of irritable bowel syndrome had been made by a general practitioner or hospital specialist. RESULTS: Of these respondents, 57% were aged 55 or over and the male to female ratio was 1:3.4. On average, respondents had suffered from irritable bowel syndrome for 16.6 years, with 57% reporting their symptoms daily, 25% weekly and 14% monthly. Of the married or cohabiting respondents, 19% stated that their partner experienced difficulties in having a personal relationship with them and 45% stated that irritable bowel syndrome interfered with their sex life. Irritable bowel syndrome had caused 12% of respondents to give up work altogether, while 47% of employed respondents reported having lost time off work, although only 35% of these respondents gave irritable bowel syndrome as the reason. In contrast employers, when informed of the diagnosis of irritable bowel syndrome, accepted these symptoms as a valid reason for absence in 61% of instances. Over half of those employed (53%) suffered embarrassment using toilets at work and 32% stated that irritable bowel syndrome had stopped them from applying for promotion or a new job. At the time of completing the questionnaire, 80% of respondents were actually taking some form of treatment. Smooth-muscle relaxants and fibre supplements remained the commonest treatments prescribed. CONCLUSION: Irritable bowel syndrome impacts significantly on personal relationships and working practices. Items that stimulate responsiveness in the areas of personal relationships and working practices should be included in the construction of disease-specific questionnaires used to assess the impact of new treatments for irritable bowel syndrome on health-related quality of life.