Future directions for the concept of salutogenesis: a position article.

Aaron Antonovsky advanced the concept of salutogenesis almost four decades ago (Antonovsky, Health, Stress and Coping. Jossey-Bass, San Francisco, CA, 1979; Unravelling the Mystery of Health. Jossey-Bass, San Francisco, CA, 1987). Salutogenesis posits that life experiences shape the sense of coherence (SOC) that helps to mobilize resources to cope with stressors and manage tension successfully (determining one's movement on the health Ease/Dis-ease continuum). Antonovsky considered the three-dimensional SOC (i.e. comprehensibility, manageability, meaningfulness) as the key answer to his question about the origin of health. The field of health promotion has adopted the concept of salutogenesis as reflected in the international Handbook of Salutogenesis (Mittelmark et al., The Handbook of Salutogenesis. Springer, New York, 2016). However, health promotion mostly builds on the more vague, general salutogenic orientation that implies the need to foster resources and capacities to promote health and wellbeing. To strengthen the knowledge base of salutogenesis, the Global Working Group on Salutogenesis (GWG-Sal) of the International Union of Health Promotion and Education produced the Handbook of Salutogenesis. During the creation of the handbook and the regular meetings of the GWG-Sal, the working group identified four key conceptual issues to be advanced: (i) the overall salutogenic model of health; (ii) the SOC concept; (iii) the design of salutogenic interventions and change processes in complex systems; (iv) the application of salutogenesis beyond health sector. For each of these areas, we first highlight Antonovsky's original contribution and then present suggestions for future development. These ideas will help guide GWG-Sal's work to strengthen salutogenesis as a theory base for health promotion.

Correction to: Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with CT Brody score and lung function in cystic fibrosis patients.

The original version of this article, published on 13 April 2018, unfortunately contained a mistake.

Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with CT Brody score and lung function in cystic fibrosis patients.

OBJECTIVES: To demonstrate, in patients with cystic fibrosis (CF), the correlation between three-dimensional dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements and computed tomography Brody score (CF-CT) and lung function testing (LFT). METHODS: Twenty-one patients (median age, 25 years; female, n = 8) with a range of CF lung disease and five healthy volunteers (median age, 31 years; female, n = 2) underwent OE-MRI performed on a 1.5-T MRI scanner. Coronal volumes were acquired while patients alternately breathed room air and 100% oxygen. Pre-oxygen T1 was measured. Dynamic series of T1-weighted volumes were then obtained while breathing oxygen. T1-parameter maps were generated and the following OE-MRI parameters were measured: oxygen uptake (ΔPO2max), wash-in time and wash-out time. High-resolution CT and LFT were performed. The relationship between CF-CT, LFT and OE-MRI parameters were evaluated using Pearson correlation for the whole lung and regionally. RESULTS: Mean CF-CT was 24.1±17.1. Mean ΔPO2max and mean wash-in as well as skewness of wash-out showed significant correlation with CF-CT (ΔPO2max: r = -0.741, p < 0.001; mean wash-in: r = 0.501, p = 0.017; skewness of wash-out: r = 0.597, p = 0.001). There was significant correlation for the whole lung and regionally between LFT parameters and OE-MR (ΔPO2max: r = 0.718, p < 0.001; wash-in: r = -0.576, p = 0.003; wash-out skewness: r = -0.552, p = 0.004). CONCLUSIONS: Functional lung imaging using OE-MRI has the capability to assess the severity of CF lung disease and shows a significant correlation with LFT and CF-CT. KEY POINTS: • Oxygen-enhanced MRI might play a future role in evaluation and follow-up of cystic fibrosis. • Heterogeneity of parameter maps reflects localised functional impairment in cystic fibrosis. • Avoidance of cumulative radiation burden in CF is feasible using OE-MRI.

Dopamine transporter (DAT1/SLC6A3) polymorphism and the association between being born small for gestational age and symptoms of ADHD.

Being small for gestational age (SGA) has been established as a risk factor for Attention Deficit Hyperactivity Disorder (ADHD). Likewise, several molecular genetic studies have found a link between DAT1 and ADHD. This study investigated whether SGA moderates the effect of dopamine transporter gene variants on the risk of ADHD. A total of 546 children of European descent were genotyped at age 11 for seven DAT1 SNPs (rs6347, rs11564774, rs40184, rs1042098, rs2702, rs8179029 and rs3863145). The Strengths and Difficulties Questionnaire was used to measure symptoms of ADHD at ages 3.5, 7 and 11. We found significant gene-environment interactions between birth weight and DAT1 SNPs (rs6347, rs40184, rs1042098, rs3863145) on ADHD symptoms at 3.5 years only. Results suggest that genotypic variation of DAT1 may confer a relative protective effect against ADHD in SGA individuals. This study supports the idea that being born SGA moderates the effect of the DAT1 gene on ADHD symptoms in the preschool years and may help to explain some of the heterogeneity in ADHD outcomes.

Differential modification of genetic susceptibility to childhood eczema by two probiotics.

BACKGROUND: In a double-blind, randomized, placebo-controlled birth cohort, we have recently shown a beneficial effect of Lactobacillus rhamnosus HN001 (HN001) for the prevention of eczema in children through to 6 years of age but no effect of Bifidobacterium animalis subsp lactis HN019 (HN019). OBJECTIVE: Among this cohort of children, we aim to investigate whether these probiotics could modify the expression of genetic predisposition to eczema conferred by genetic variation in susceptibility genes. METHODS: Thirty-three eczema susceptibility SNPs (in eleven genes) were genotyped in 331 children of European ancestry. RESULTS: Children who carried a genetic variant that put them at a high risk of developing eczema were less likely to develop eczema if they had been randomized to the HN001 intervention group compared to those in the placebo group. HN019 was also able to protect against the effects of some SNPs. As well as modifying genetic susceptibility to childhood eczema, HN001 was also found to modify genetic susceptibility to eczema severity and atopy risk. CONCLUSION AND CLINICAL RELEVANCE: This is the first study to show an effect of a probiotic on reducing eczema risk amongst those with particular eczema-associated genotypes. Our findings suggest that Lactobacillus rhamnosus HN001 may be particularly effective in preventing eczema in children with specific high-risk genotypes.

Mutual information as a measure of image quality for 3D dynamic lung imaging with EIT.

We report on a pilot study of dynamic lung electrical impedance tomography (EIT) at the University of Manchester. Low-noise EIT data at 100 frames per second were obtained from healthy male subjects during controlled breathing, followed by magnetic resonance imaging (MRI) subsequently used for spatial validation of the EIT reconstruction. The torso surface in the MR image and electrode positions obtained using MRI fiducial markers informed the construction of a 3D finite element model extruded along the caudal-distal axis of the subject. Small changes in the boundary that occur during respiration were accounted for by incorporating the sensitivity with respect to boundary shape into a robust temporal difference reconstruction algorithm. EIT and MRI images were co-registered using the open source medical imaging software, 3D Slicer. A quantitative comparison of quality of different EIT reconstructions was achieved through calculation of the mutual information with a lung-segmented MR image. EIT reconstructions using a linear shape correction algorithm reduced boundary image artefacts, yielding better contrast of the lungs, and had 10% greater mutual information compared with a standard linear EIT reconstruction.

Permanent stoma rates: a misleading marker of quality in rectal cancer surgery.

AIM: The latest National Bowel Cancer Audit Programme (NBOCAP) audit identified our colorectal unit as an outlier with regard to the high permanent stoma rate. The aim of this study was to perform an audit of the rationale for stoma formation in patients undergoing rectal cancer resection in our unit. METHOD: A review was conducted of all rectal cancer operations between April 2011 and March 2013. Preoperative staging investigations and operation reports were reviewed to identify the reasons for nonrestorative surgery. Postoperative histology reports were used to identify circumferential resection margin (CRM) involvement and tumour height. RESULTS: One-hundred and twenty-five patients underwent surgery for rectal cancer, of whom 102 underwent elective resection with curative intent. The permanent stoma rate was 63.2% when emergency and palliative procedures were included and 54.9% when only elective curative cases were considered. Tertiary referrals made up 31.4% of elective cases. The main reasons for nonrestorative surgery included multivisceral resection (n = 24) for locally advanced cancer and operations for lesions close to the anal sphincter (n = 21). The median length of stay was 8 days, the 90-day mortality was 2.9% and the rate of CRM involvement was 2.0%. CONCLUSION: Our unit provides multivisceral surgery for locally advanced rectal cancer and receives a substantial number of tertiary referrals. Many of the rectal cancers referred are locally advanced or threaten the anal sphincter. This study demonstrates that the complexity of a unit's case-mix can have a profound effect on the permanent stoma rate. Stoma rates taken at face value do not therefore provide an accurate representation of surgical quality. What does this paper add to the literature? The study reviews the practice of a colorectal surgical unit with an interest in multivisceral surgery with regard to the permanent stoma rate. The reasons for nonrestorative surgery are analysed, and the problems associated with the use of stoma rates as a marker of quality in colorectal surgery are highlighted.

PTPN2 but not PTPN22 is associated with Crohn's disease in a New Zealand population.

Recent genome-wide association studies have provided evidence for the involvement of the genes PTPN2 and PTPN22 in the pathogenesis of Crohn's disease (CD). We investigated whether genetic variants in these genes were associated with CD in a New Zealand population. Single-nucleotide polymorphisms (SNPs) rs2542151 (PTPN2) and rs2476601 (PTPN22) were genotyped in 315 CD cases and 481 controls. In this sample, we were able to confirm an association between CD and PTPN2 (genotypic P = 0.019 and allelic P = 0.011), and phenotypic analysis showed an association of this SNP with late age at first diagnosis, inflammatory and penetrating CD behaviour, requirement of bowel resection and being a smoker at diagnosis. There was no evidence for an association with PTPN22.

Association analysis of dynamin-binding protein (DNMBP) on chromosome 10q with late onset Alzheimer's disease in a large caucasian UK sample.

A recent scan of single nucleotide polymorphisms (SNPs) in the region 40-107 Mb on chromosome 10q in a large Japanese case-control cohort identified six SNPs in or near the dynamin-binding protein gene (DNMBP) that were associated with late onset Alzheimer's disease (LOAD) in individuals lacking the APOE epsilon4 allele [Kuwano et al. (2006); Hum Mol Genet 15:2170-2182]. We genotyped these six SNPs in 1,212 unrelated Caucasian patients of UK origin with LOAD and 1,389 ethnically, gender and age matched control subjects. We did not observe a statistically significant association with the risk of LOAD for any of the six SNPs in the sample as a whole. When stratifying the sample by APOE one SNP (intergenic SNP rs11190302) was associated with LOAD in individuals lacking the epsilon4 allele (genotypic P = 0.027, allelic P = 0.066). However this association was in the opposite direction to that detected in the Japanese population. It remains to be determined whether DNMBP is associated with LOAD.

Local recurrence after abdomino-perineal resection.

OBJECTIVE: Local recurrence of rectal cancer is a major cause of morbidity and mortality following curative resection. The published rates vary after abdomino-perineal resection (APR) from 5% to 47%. The aim of this study was to evaluate local recurrence following curative APR for low rectal cancer in our unit. METHOD: The medical notes of patients treated between 1st January 1996 and 31st December 2000 were retrieved. Local recurrence was defined as the presence of tumour within the pelvis confirmed by clinical findings, pathological specimen or radiological reports. A curative resection was defined as excision of tumour in the absence of macroscopic metastatic disease and whose resection margins were greater than 1 mm circumferentially and 10 mm distally. Outcomes and survival were compared using Fisher's exact test and Kaplan-Meier method. RESULTS: Two hundred consecutive cases with a diagnosis of rectal cancer were identified of which 139 underwent a curative resection (69.5%). Of these 40 patients (28%) underwent APR with curative intent. Two patients (5%) developed local recurrence at 18 and 24 months respectively. The overall local recurrence rate for all curative rectal cancer surgery, in the same period was 2.6%. Eleven patients have died in the follow-up period of which nine were cancer-related deaths. CONCLUSION: The local recurrence rates achieved with APR were not significantly different from those achieved with restorative operations. Tumours at the ano-rectal junction should not be dissected off the pelvic floor, but radically excised en bloc with the surrounding levator ani, as a cylinder, as originally described by Miles.

The surgical management of fistula-in-ano in a specialist colorectal unit.

INTRODUCTION: Fistula-in-ano can be associated with a number of conditions, including Crohn's disease. The majority, however, are classified as idiopathic or cryptoglandular. The aim of this study was to review the outcome of surgical management of fistula-in-ano in a specialist colorectal unit. MATERIALS AND METHODS: One hundred and four consecutive patients underwent surgery for anal fistulae between 1st January 2000 and December 2004. Data was analysed in two main groups, according to the aetiology, cryptoglandular (n = 86) and Crohn's disease (n = 18). Follow-up data was available on 91 patients. RESULTS: In the cryptoglandular group, 62 patients had an inter-sphincteric tract, of which 48 underwent a single-stage fistulotomy. Of those patients with a trans-sphincteric tract, six patients underwent a single-stage fistulotomy, 13 had a seton and staged fistulotomy. Follow-up data revealed that two fistulae recurred. The median number of procedures in this group was 1 (range 1-3). There was a significant difference in the inpatient stay depending of Park's classification (p = 0.001). In the Crohn's group, three patients with an inter-sphincteric tract underwent a single-stage fistulotomy, two patients with a trans-sphincteric tract had single-stage fistulotomy, and five required a loose seton and staged fistulotomy. Eight patients had multiple fistulae which required long-term setons. Four patients from this group eventually required proctectomy. In the Crohn's group, there was a significantly increased complexity of surgery and higher recurrence. This was reflected in an increased inpatient length of stay and a greater reliance on imaging (p = 0.001). The median number of procedures in this group was 3 (range 1-5). DISCUSSION: The majority of cryptoglandular fistula-in-ano were treated by primary fistulotomy or staged fistulotomy with a loose seton. This was associated with a low recurrence rate and low rates of faecal incontinence. There was a low reliance on imaging techniques in this group. However, we would urge caution when dealing with fistula-in-ano related to Crohn's disease. In this group of patients, the fistulae tended to be more complex and require additional imaging and multiple procedures.

Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease.

Late-onset Alzheimer's disease (LOAD) is a genetically complex neurodegenerative disorder. Currently, only the epsilon4 allele of the Apolipoprotein E gene has been identified unequivocally as a genetic susceptibility factor for LOAD. Others remain to be found. In 2002 we observed genome-wide significant evidence of linkage to a region on chromosome 10q11.23-q21.3 [Myers et al. (2002) Am J Med Genet 114:235-244]. Our objective in this study was to test every gene within the maximum LOD-1 linkage region, for association with LOAD. We obtained results for 528 SNPs from 67 genes, with an average density of 1 SNP every 10 kb within the genes. We demonstrated nominally significant association with LOAD for 4 SNPs: rs1881747 near DKK1 (P = 0.011, OR = 1.24), rs2279420 in ANK3 (P = 0.022, OR = 0.79), rs2306402 in CTNNA3 (P = 0.024, OR = 1.18), and rs5030882 in CXXC6 (P = 0.046, OR = 1.29) in 1,160 cases and 1,389 controls. These results would not survive correction for multiple testing but warrant attempts at confirmation in independent samples.

Association studies of 23 positional/functional candidate genes on chromosome 10 in late-onset Alzheimer's disease.

Late-onset Alzheimer's disease (LOAD) is a common neurodegenerative disorder, with a complex etiology. APOE is the only confirmed susceptibility gene for LOAD. Others remain yet to be found. Evidence from linkage studies suggests that a gene (or genes) conferring susceptibility for LOAD resides on chromosome 10. We studied 23 positional/functional candidate genes from our linkage region on chromosome 10 (APBB1IP, ALOX5, AD037, SLC18A3, DKK1, ZWINT, ANK3, UBE2D1, CDC2, SIRT1, JDP1, NET7, SUPV3L1, NEN3, SAR1, SGPL1, SEC24C, CAMK2G, PP3CB, SNCG, CH25H, PLCE1, ANXV111) in the MRC genetic resource for LOAD. These candidates were screened for sequence polymorphisms in a sample of 14 LOAD subjects and detected polymorphisms tested for association with LOAD in a three-stage design involving two stages of genotyping pooled DNA samples followed by a third stage in which markers showing evidence for association in the first stages were subjected to individual genotyping. One hundred and twenty polymorphisms were identified and tested in stage 1 (4 case + 4 control pools totaling 366 case and 366 control individuals). Single nucleotide polymorphisms (SNPs) showing evidence of association with LOAD were then studied in stage 2 (8 case + 4 control pools totaling 1,001 case and 1,001 control individuals). Five SNPs, in four genes, showed evidence for association (P < 0.1) at stage 2 and were individually genotyped in the complete dataset, comprising 1,160 LOAD cases and 1,389 normal controls. Two SNPs in SGPL1 demonstrated marginal evidence of association, with uncorrected P values of 0.042 and 0.056, suggesting that variation in SGPL1 may confer susceptibility to LOAD.

Antegrade continence enema in the treatment of obstructed defaecation with or without faecal incontinence.

BACKGROUND: Obstructed defaecation and faecal incontinence are complex functional disorders that pose management challenges. In recent times, the antegrade continence enema (ACE) has been tried both as a primary procedure and as a final resort to avoid a colostomy in patients with a variety of functional problems. The purpose of this study was to evaluate the role of the ACE procedure as a treatment option for adult patients suffering from obstructed defaecation with or without faecal incontinence, some of whom also had slow transit constipation. METHODS: Twenty female patients underwent ACE as an appendicostomy (65%) or caecostomy (35%). The median age was 44 years (range, 20-65 years). The indications were obstructed defaecation with faecal incontinence (65%) and obstructed defaecation alone (35%). Fifteen of these patients were followed for 3-51 months (median, 6 months). Cleveland continence score, bowel score and quality of life score were recorded pre- and postoperatively along with post-procedure complications. RESULTS: Thirteen (65%) patients were satisfied with the outcome and recorded improvement in their scores while two (10%) remained the same and one (5%) was worse. This latter woman and another patient stopped using their ACE, whilst follow-up data was unavailable for three patients. Minor wound infections were noted in nine patients (45%), of whom one needed drainage of an abscess; the rest settled with antibiotics and dressings. Bowel and Cleveland continence scores improved postoperatively (p<0.001 and p=0.001, respectively) but SF36 scores did not. To date, no patient has had a colostomy following an ACE procedure. CONCLUSIONS: Colostomies can be avoided in patients with obstructed defaecation. There is, however, a need to minimise wound infections which seem to be the most troublesome complication.

The role of rectocele repair in targeted patients with obstructed defaecation.

INTRODUCTION: Obstructed defaecation is a complex disorder that poses serious management challenges. The purpose of this study is to review the functional results of surgery in women undergoing rectocele repair for obstructed defaecation, and in a targeted subgroup in which the rectocele was the only identifiable cause of their symptoms. METHODS: All case notes were reviewed. Demographic details, preoperative symptoms, details of previous pelvic surgery, radiological and anorectal physiology results, operative procedure, post operative symptoms, length of follow-up and details of further pelvic reconstructive surgery were recorded. To enter the targeted group, patients (i) had not undergone previous pelvic surgery, (ii) had presented with obstructive defaecation, (iii) had a proctogram that demonstrated a rectocele with no or partial intrarectal intussusception and (iv) had no other functional abnormality in colonic transit studies, endoanal ultrasound or anorectal physiology. RESULTS: Eighty-two case notes were reviewed. All experienced obstructed defaecation. Forty-two women underwent a per-anal plication of the rectocele, 33 had a transperineal plication and levatorplasty and seven a mesh repair. A total of 63 (77%) women were pleased with the result, though symptoms later returned in 17 (27%) of them. 26 (31%) had further surgery in an attempt to improve their defaecatory difficulties. Sixteen women were eligible for the targeted group. All had a good early result though symptoms returned in three women. Two (12%) had further surgery. CONCLUSION: Careful preoperative patient selection is vital to improve outcomes. Preoperative counselling of all patients undergoing rectocele repair is of extreme importance, in particular explaining the evolving nature of pelvic floor dysfunction and the possible need for further reconstructive surgery.

The rhomboid flap for pilonidal disease.

INTRODUCTION: There have been many surgical techniques described for the treatment of pilonidal sinuses. Recurrent disease causes significant morbidity particularly with time from work. AIM: To assess the rhomboid flap's role in promoting one-stage primary healing in pilonidal disease and to evaluate the morbidity and recurrence. METHODS: Fifty-three patients were prospectively recruited of which 27 had previous multiple abscess formation requiring surgical drainage from their pilonidal disease, although none had acute disease at the time of surgery. By using the transposition flap, we were able to obliterate the natal cleft and therefore the rolling action of the buttocks between the cleft in these patients and thereby remove one of the factors involved in pilonidal disease. Hospital stay, healing time, wound infection, wound breakdown and recurrence were noted. RESULTS: There were 47 males and 6 females with a median age of 28 years (range 16-64 years). Median follow-up was 24 months (range 3-36 months). Post-operative morbidity involved superficial wound infection in 7 (13%) which settled with out-patient dressings. There were four recurrences (7%), two occurred between the flap and the anal canal, and the other two in the flap margin needing intervention. All the patients healed their wounds and the median healing time was 14 days. CONCLUSION: As this condition affects a predominantly young population causing significant time off from work, we feel that the Rhomboid Flap is useful for difficult cases in that it allows early return to full activity and does not necessitate prolonged postoperative care.

A prospective audit of stomas--analysis of risk factors and complications and their management.

AIM: To prospectively audit stomas and to determine the nature and rate of complications and their relationship with various risk factors and their management. MATERIALS AND METHODS: The study was performed prospectively on 97 consecutive patients who had stomas formed between January 2000 to August 2000. Patients were followed up for one year. Risk factors including age, body mass index (BMI), preoperative siting, contour of the abdominal wall, smoking, grade of operating surgeon, emergency or elective procedure, diabetes, type of stoma and suture material used were noted. The type of surgery, and indications for surgery were also recorded. The complications were documented by two qualified stoma nurses and a photographic record taken. Statistical analysis comprising both univariate and multivariate methods, was performed by SPSS 10. RESULTS: The mean age was 65 years (standard deviation 16.01, range 16-99) and mean body mass index was 24.5 (standard deviation 4.66, range 15-37). Forty-nine of 97 (50.5%) stomas developed one or more complications. Twenty-three patients experienced retraction, 18 had stomas sited in a skin crease, 16 had early and 12 had late skin excoriation, 12 had detachments and a further 12 had parastomal hernia. Eleven further stoma complications were noted including prolapse, necrosis, ischaemia and sloughing. None of the risk factors achieved statistical significance when analysed against the overall complication rate. However, when the risk factors were analysed against individual complications using univariate logistic regression, a high body mass index was associated with more retractions (P = 0.003), early skin excoriation (P = 0.036) and poor siting (stoma in crease) occurred more commonly in emergencies (P = 0.022). Diabetes was associated with late skin excoriation (P = 0.02). Multivariate logistic regressions confirmed an independent association of body mass index, diabetes and emergency surgery with complications. Forty-five of 49 patients who had complications needed some conservative management such as a convexity appliance. Four patients needed refashioning. CONCLUSION: Body mass index, diabetes and emergency surgery were the significant risk factors identified in our study. Overall complications compare favourably with other series. We found that preoperative siting by stoma nurses and the grade of operating surgeon did not affect the outcome.

A study on surgical knowledge of house officers and their role in consent.

This study shows a targeted training for house officers relating to surgical procedures and consenting issues was helpful. The authors recommend that advice on obtaining consent should be a part of the induction programme for surgical house officers.