Cost-effectiveness of sigmoid resection with primary anastomosis or end colostomy for perforated diverticulitis: an analysis of the randomized Ladies trial

Background: Several studies have been published favouring sigmoidectomy with primary anastomosis over Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis (Hinchey grade III or IV), but cost-related outcomes were rarely reported. The present study aimed to evaluate costs and cost-effectiveness within the DIVA arm of the Ladies trial. Methods: This was a cost-effectiveness analysis of the DIVA arm of the multicentre randomized Ladies trial, comparing primary anastomosis over Hartmann's procedure for Hinchey grade III or IV diverticulitis. During 12-month follow-up, data on resource use, indirect costs (Short Form Health and Labour Questionnaire) and quality of life (EuroQol Five Dimensions) were collected prospectively, and analysed according to the modified intention-to-treat principle. Main outcomes were incremental cost-effectiveness (ICER) and cost–utility (ICUR) ratios, expressed as the ratio of incremental costs and the incremental probability of being stoma-free or incremental quality-adjusted life-years respectively. Results: Overall, 130 patients were included, of whom 64 were allocated to primary anastomosis (46 and 18 with Hinchey III and IV disease respectively) and 66 to Hartmann's procedure (46 and 20 respectively). Overall mean costs per patient were lower for primary anastomosis (€20 544, 95 per cent c.i. 19 569 to 21 519) than Hartmann's procedure (€28 670, 26 636 to 30 704), with a mean difference of €–8126 (–14 660 to –1592). The ICER was €–39 094 (95 per cent bias-corrected and accelerated (BCa) c.i. –1213 to –116), indicating primary anastomosis to be more cost-effective. The ICUR was €–101 435 (BCa c.i. –1 113 264 to 251 840). Conclusion: Primary anastomosis is more cost-effective than Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis

Cost analysis of laparoscopic lavage compared with sigmoid resection for perforated diverticulitis in the Ladies trial

Background: Laparoscopic peritoneal lavage is an alternative to sigmoid resection in selected patients presenting with purulent peritonitis from perforated diverticulitis. Although recent trials have lacked superiority for lavage in terms of morbidity, mortality was not compromised, and beneficial secondary outcomes were shown. These included shorter duration of surgery, less stoma formation and less surgical reintervention (including stoma reversal) for laparoscopic lavage versus sigmoid resection respectively. The cost analysis of laparoscopic lavage for perforated diverticulitis in the Ladies RCT was assessed in the present study. Methods: This study involved an economic evaluation of the randomized LOLA (LaparOscopic LAvage) arm of the Ladies trial (comparing laparoscopic lavage with sigmoid resection in patients with purulent peritonitis due to perforated diverticulitis). The actual resource use per individual patient was documented prospectively and analysed (according to intention-to-treat) for up to 1 year after randomization. Results: Eighty-eight patients were randomized to either laparoscopic lavage (46) or sigmoid resection (42). The total medical costs for lavage were lower (mean difference € − 3512, 95 per cent bias-corrected and accelerated c.i. −16 020 to 8149). Surgical reintervention increased costs in the lavage group, whereas stoma reversal increased costs in the sigmoid resection group. Differences in favour of laparoscopy were robust when costs were varied by ±20 per cent in a sensitivity analysis (mean cost differ

Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery

Background: The noble gas helium induces pre- and postconditioning in animals and humans. Volatile anesthetics induce cardioprotection in humans undergoing coronary artery bypass graft (CABG) surgery. We hypothesized that helium induces pre-and postconditioning in CABG-patients, affecting signaling molecules protein kinase C-epsilon (PKC-epsilon), p38 mitogen activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK-1/2) and heat shock protein 27 (HSP-27) within cardiac tissue, and reducing postoperative troponin levels. Methods: After ethical approval and informed consent, 125 elective patients undergoing CABG surgery were randomised into this prospective, placebo controlled, investigator blinded, parallel arm single-centre study. Helium preconditioning (3 x 5 min of 70 % helium and 30 % oxygen) was applied before aortic cross clamping; postconditioning (15 min of helium) was applied before release of the aortic cross clamp. Signaling molecules were measured in right atrial appendix specimens. Troponin-T was measured at 4, 12, 24 and 48 h postoperatively. Results: Baseline characteristics of all groups were similar. Helium preconditioning did not significantly alter the primary outcome (molecular levels of kinases PKC-e and HSP-27, ratio of activated p38 MAPK or ERK 1/2). Postoperative troponin T was 11 arbitrary units [5, 31; area-under-the-curve (interquartile range)] for controls, and no statistically significant changes were observed after helium preconditioning [He-pre: 11 (6, 18)], helium postconditioning [He-post: 11 (8, 15)], helium pre-and postconditioning [He-PP: 14 (6, 20)] and after sevoflurane preconditioning [APC: 12 (8, 24), p = 0.13]. No adverse effects related to study treatment were observed in this study. Conclusions: No effect was observed of helium preconditioning, postconditioning or the combination thereof on activation of p38 MAPK, ERK 1/2 or levels of HSP27 and PKC-e in the human heart. Helium pre-and postconditioning did not affect postoperative troponin release in patients undergoing CABG surgery

Randomised Clinical Trial of Supervised Exercise Therapy vs. Endovascular Revascularisation for Intermittent Claudication Caused by Iliac Artery Obstruction:The SUPER study

OBJECTIVE: International guidelines recommend supervised exercise therapy (SET) as primary treatment for all patients with intermittent claudication (IC), yet primary endovascular revascularisation (ER) might be more effective in patients with iliac artery obstruction. METHODS: This was a multicentre RCT including patients with IC caused by iliac artery stenosis or occlusion (NCT01385774). Patients were allocated randomly to SET or ER stratified for maximum walking distance (MWD) and concomitant SFA disease. Primary endpoints were MWD on a treadmill (3.2 km/h, 10% incline) and disease specific quality of life (VascuQol) after one year. Additional interventions during a mean follow up of 5.5 years were recorded. RESULTS: Between November 2010 and May 2015, 114 patients were allocated to SET, and 126 to ER. The trial was terminated prematurely after 240 patients were included. Compliance with SET was 57/114 (50%) after six months. Ten patients allocated to ER (8%) did not receive this intervention. One year follow up was complete for 90/114 (79%) SET patients and for 104/126 (83%) ER patients. The mean MWD improved from 187 to 561 m in SET patients and from 196 to 574 m in ER patients (p = .69). VascuQol sumscore improved from 4.24 to 5.58 in SET patients, and from 4.28 to 5.88 in ER patients (p = .048). Some 33/114 (29%) SET patients had an ER within one year, and 2/114 (2%) surgical revascularisation (SR). Some 10/126 (8%) ER patients had additional ER within one year and 10/126 (8%) SR. After a mean of 5.5 years, 49% of SET patients and 27% of ER patients underwent an additional intervention for IC. CONCLUSION: Taking into account the many limitations of the SUPER study, both a strategy of primary SET and primary ER improve MWD on a treadmill and disease specific Qol of patients with IC caused by an iliac artery obstruction. It seems reasonable to start with SET in these patients and accept a 30% failure rate, which, of course, must be discussed with the patient. Patients continue to have interventions beyond one year

Local immune regulation of mucosal inflammation by tacrolimus

Purpose: Tacrolimus is a potent immunomodulator that is effective in the treatment of inflammatory bowel disease (IBD). However, potential toxicity and systemic effects with oral intake limit its use. Local tacrolimus treatment is effective in a subgrou

¹⁸F-FDG-PET/CT to Detect Pathological Complete Response After Neoadjuvant Treatment in Patients with Cancer of the Esophagus or Gastroesophageal Junction:Accuracy and Long-Term Implications

Purpose : The curative strategy for patients with esophageal cancer without distant metastases consists of esophagectomy with preceding chemo(radio)therapy (CRT). In 10–40% of patients treated with CRT, no viable tumor is detectable in the resection specimen (pathological complete response (pCR)). This study aims to define the clinical outcomes of patients with a pCR and to assess the accuracy of post-CRT FDG-PET/CT in the detection of a pCR. Methods: Four hundred sixty-three patients with cancer of the esophagus or gastroesophageal junction who underwent esophageal resection after CRT between 1994 and 2013 were included. Patients were categorized as pathological complete responders or noncomplete responders. Standardized uptake value (SUV) ratios of 135 post-CRT FDG-PET/CTs were calculated and compared with the pathological findings in the corresponding resection specimens. Results: Of the 463 included patients, 85 (18.4%) patients had a pCR. During follow-up, 25 (29.4%) of these 85 patients developed recurrent disease. Both 5-year disease-free survival (5y-DFS) and 5-year overall survival (5y-OS) were significantly higher in complete responders compared to noncomplete responders (5y-DFS 69.6% vs. 44.2%; P = 0.001 and 5y-OS 66.5% vs. 43.7%; P = 0.001). Not pCR, but only pN0 was identified as an independent predictor of (disease-free) survival. Conclusion: Patients with a pCR have a higher probability of survival compared to noncomplete responders. One third of patients with a pCR do develop recurrent disease, and pCR can therefore not be equated with cure. FDG-PET/CT was inaccurate to predict pCR and therefore cannot be used as a sole diagnostic tool to predict pCR after CRT for esophageal cancer.</p

Designing assisted living technologies 'in the wild' : preliminary experiences with cultural probe methodology

Background There is growing interest in assisted living technologies to support independence at home. Such technologies should ideally be designed ‘in the wild’ i.e. taking account of how real people live in real homes and communities. The ATHENE (Assistive Technologies for Healthy Living in Elders: Needs Assessment by Ethnography) project seeks to illuminate the living needs of older people and facilitate the co-production with older people of technologies and services. This paper describes the development of a cultural probe tool produced as part of the ATHENE project and how it was used to support home visit interviews with elders with a range of ethnic and social backgrounds, family circumstances, health conditions and assisted living needs. Method Thirty one people aged 60 to 98 were visited in their homes on three occasions. Following an initial interview, participants were given a set of cultural probe materials, including a digital camera and the ‘Home and Life Scrapbook’ to complete in their own time for one week. Activities within the Home and Life Scrapbook included maps (indicating their relationships to people, places and objects), lists (e.g. likes, dislikes, things they were concerned about, things they were comfortable with), wishes (things they wanted to change or improve), body outline (indicating symptoms or impairments), home plan (room layouts of their homes to indicate spaces and objects used) and a diary. After one week, the researcher and participant reviewed any digital photos taken and the content of the Home and Life Scrapbook as part of the home visit interview. Findings The cultural probe facilitated collection of visual, narrative and material data by older people, and appeared to generate high levels of engagement from some participants. However, others used the probe minimally or not at all for various reasons including limited literacy, physical problems (e.g. holding a pen), lack of time or energy, limited emotional or psychological resources, life events, and acute illness. Discussions between researchers and participants about the materials collected (and sometimes about what had prevented them completing the tasks) helped elicit further information relevant to assisted living technology design. The probe materials were particularly helpful when having conversations with non-English speaking participants through an interpreter. Conclusions Cultural probe methods can help build a rich picture of the lives and experiences of older people to facilitate the co-production of assisted living technologies. But their application may be constrained by the participant’s physical, mental and emotional capacity. They are most effective when used as a tool to facilitate communication and development of a deeper understanding of older people’s needs

Cost-effectiveness of immediate total-body CT in patients with severe trauma (REACT-2 trial)

Background: The effect of immediate total-body CT (iTBCT) on health economic aspects in patients with severe trauma is an underreported issue. This study determined the cost-effectiveness of iTBCT compared with conventional radiological imaging with selective CT (standard work-up (STWU)) during the initial trauma evaluation. Methods: In this multicentre RCT, adult patients with a high suspicion of severe injury were randomized in-hospital to iTBCT or STWU. Hospital healthcare costs were determined for the first 6 months after the injury. The probability of iTBCT being cost-effective was calculated for various levels of willingness-to-pay per extra patient alive. Results: A total of 928 Dutch patients with complete clinical follow-up were included. Mean costs of hospital care were (sic)25 809 (95 per cent bias-corrected and accelerated (bca) c.i. (sic)22 617 to (sic)29 137) for the iTBCT group and (sic)26 155 ((sic)23 050 to (sic)29 344) for the STWU group, a difference per patient in favour of iTBCT of (sic)346 ((sic)4987 to (sic)4328) (P = 0.876). Proportions of patients alive at 6 months were not different. The proportion of patients alive without serious morbidity was 61.6 per cent in the iTBCT group versus 66.7 per cent in the STWU group (difference -5.1 per cent; P = 0.104). The probability of iTBCT being cost-effective in keeping patients alive remained below 0.56 for the whole group, but was higher in patients with multiple trauma (0.8-0.9) and in those with traumatic brain injury (more than 0.9). Conclusion: Economically, from a hospital healthcare provider perspective, iTBCT should be the diagnostic strategy of first choice in patients with multiple trauma or traumatic brain injury

Immune checkpoint inhibition-related colitis: symptoms, endoscopic features, histology and response to management

Background: Immune checkpoint inhibitors are successfully introduced as anticancer treatment. However, they may induce severe immune-related adverse events (irAEs). One of the most frequent irAEs is diarrhoea. The main objective of this study was to analyse symptoms (ie, grade of diarrhoea), endoscopic and histological features and response to management in immune checkpoint inhibition-related colitis (IRC). Patients and methods: We retrospectively analysed patients who developed diarrhoea on checkpoint inhibition and therefore underwent an endoscopy and/or were treated with corticosteroids. Patients were treated between August 2010 and March 2016 for metastatic melanoma or non-small cell lung cancer. Severity of IRC was scored using the endoscopic Mayo score and the van der Heide score. Results: Out of a cohort of 781 patients, 92 patients were identified who developed diarrhoea and therefore underwent an endoscopy and/or were treated with corticosteroids. Patients were treated with monotherapy anticytotoxic T-lymphocyte antigen-4, antiprogrammed death receptor-1 or a combination of both. All patients had symptoms of diarrhoea (grade 1: 16%; grade 2: 39% and grade 3: 44%). A complete colonoscopy was performed in 62 (67%) patients, of whom 42 (68%) had a pancolitis (>/=3 affected segments). Ulcers were seen in 32% of endoscopies. There was no significant correlation between the grade of diarrhoea at presentation and endoscopic severity scores, the presence of ulcers or histological features. In 54 episodes of diarrhoea (56%), patients received one or more cycles infliximab for steroid-refractory colitis. Patients with higher endoscopic severity scores, ulcers and/or a pancolitis needed infliximab more often. Conclusions: The correlation between grade of diarrhoea and endoscopic or histological features for severity of colitis is poor. Patients with higher endoscopic severity scores, ulcers or a pancolitis needed the addition of infliximab more often. Therefore, endoscopy may have value in the evaluation of the severity of IRC and may help in decision making for optimal management

Extended mobility scale (AMEXO) for assessing mobilization and setting goals after gastrointestinal and oncological surgery: a before-after study

Background: Early structured mobilization has become a key element of Enhanced Recovery After Surgery programs to improve patient outcomes and decrease length of hospital stay. With the intention to assess and improve early mobilization levels, the 8-point ordinal John Hopkins Highest Level of Mobility (JH-HLM) scale was implemented at two gastrointestinal and oncological surgery wards in the Netherlands. After the implementation, however, healthcare professionals perceived a ceiling effect in assessing mobilization after gastrointestinal and oncological surgery. This study aimed to quantify this perceived ceiling effect, and aimed to determine if extending the JH-HLM scale with four additional response categories into the AMsterdam UMC EXtension of the JOhn HOpkins Highest Level of mObility (AMEXO) scale reduced this ceiling effect. Methods: All patients who underwent gastrointestinal and oncological surgery and had a mobility score on the first postoperative day before (July-December 2018) or after (July-December 2019) extending the JH-HLM into the AMEXO scale were included. The primary outcome was the before-after difference in the percentage of ceiling effects on the first three postoperative days. Furthermore, the before-after changes and distributions in mobility scores were evaluated. Univariable and multivariable logistic regression analysis were used to assess these differences. Results: Overall, 373 patients were included (JH-HLM n = 135; AMEXO n = 238). On the first postoperative day, 61 (45.2%) patients scored the highest possible mobility score before extending the JH-HLM into the AMEXO as compared to 4 (1.7%) patients after (OR = 0.021, CI = 0.007-0.059, p Pathophysiology, epidemiology and therapy of agein