A survey of patient informational preferences when choosing between medical and surgical therapy for ulcerative colitis: a sub-study from the DISCUSS project.

AIM: People living with ulcerative colitis (UC) have two broad treatment avenues, namely medical or surgical therapy. The choice between these can depend on patient preference as well as the receipt of relevant information. The aim of this study was to define the informational needs of patients with UC. METHOD: A postal survey was designed to capture respondent demographics, treatment experienced within the previous 12 months and informational preferences by rating a long list of items. It was delivered through two hospitals that provide tertiary inflammatory bowel disease services. Descriptive analyses were performed to describe demographics and experiences. Principal component analysis was carried out using a varimax rotation to investigate informational needs. RESULTS: A total of 101 responses were returned (20.1% response rate). The median age of respondents was 45 years and the median time since diagnosis was 10 years. Control preferences skewed towards shared (42.6%) or patient-led but clinician-informed (35.6%). Decision regret was low for the population (median 12.5/100, range 0-100). Key informational needs related to medical therapy were benefits and risks of long-term therapy, burden of hospital attendance, reproductive health, need for steroid treatment and impact on personal life. For surgery, these were stoma information, effect on daily life, effect on sexual and reproductive health, risks and benefits and disruption of life due to surgery. CONCLUSION: This study has identified key areas for discussion when counselling patients about treatment decisions around medical therapy and surgery for UC.

A systematic review and meta-analysis of outcomes after elective surgery for ulcerative colitis.

AIM: Approximately 20%-30% of patients with ulcerative colitis (UC) will undergo surgery during their disease course, the vast majority being elective due to chronic refractory disease. The risks of elective surgery are reported variably. The aim of this systematic review and meta-analysis is to summarize the outcomes after elective surgery for UC. METHODS: A systematic review was conducted that analysed studies reporting outcomes for elective surgery in the modern era (>2002). It was prospectively registered on the PROSPERO database (ref: CRD42018115513). Searches were performed of Embase and MEDLINE on 15 January 2019. Outcomes were split by operation performed. Primary outcome was quality of life; secondary outcomes were early, late and functional outcomes after surgery. Outcomes reported in five or more studies underwent a meta-analysis of incidence using random effects. Heterogeneity is reported with I2 , and publication bias was assessed using Doi plots and the Luis Furuya-Kanamori index. RESULTS: A total of 34 studies were included (11 774 patients). Quality of life was reported in 12 studies, with variable and contrasting results. Thirteen outcomes (eight early surgical complications, five functional outcomes) were included in the formal meta-analysis, all of which were outcomes for ileal pouch-anal anastomosis (IPAA). A further 71 outcomes were reported (50 IPAA, 21 end ileostomy). Only 14 of 84 outcomes received formal definitions, with high inter-study variation of definitions. CONCLUSION: Outcomes after elective surgery for UC are variably defined. This systematic review and meta-analysis highlights the range of reported incidences and provides practical information that facilitates shared decision making in clinical practice.

YouTube™ as a source of information for patients undergoing laryngectomy: a thematic analysis.

PURPOSE: Total laryngectomy and end tracheal stoma formation are often required to treat advanced laryngeal cancer. Resources on the internet are commonly accessed by patients as a source of healthcare information. YouTube™, the most popular video-hosting website, is one such resource. The aims of this study were to assess the thematic content of the most viewed YouTube™ videos concerning laryngectomy for laryngeal cancer and to evaluate user response to these videos. METHOD: A search of YouTube™ was performed and data were extracted from videos with > 100 views. Upload source, number of views, likes, dislikes and comments were collected and the content of comments was analysed. User response was compared between upload sources using Kruskal-Wallis testing. Inductive thematic analysis of video content was performed to identify overarching themes and subthemes. RESULTS: A total of 96 videos were identified, 16 uploaded by patients, 24 by individual healthcare professionals and 56 by professional healthcare institutions. There were 1214,503 views and no significant differences in the number of views, likes or dislikes between upload sources. Three overarching themes and 17 subthemes were identified. Comments were most frequently characterised as offering praise. CONCLUSION: YouTube™ has been shown to be a popular platform for sharing information about laryngectomy for laryngeal cancer. There is a lack of data concerning the quality of this information, however, and future work should focus on assessing this. Trusted institutions could make use of this medium to disseminate high-quality information to their patients, and to the wider public.

The assessment of online health videos for surgery in Crohn's disease.

AIM: YouTube™ is an open-access, nonpeer-reviewed video-hosting site and is used as a source of publicly available healthcare information. This study aimed to assess the thematic content of the most viewed videos relating to surgery and Crohn's disease and to explore the viewer interactions with these videos. METHOD: A search of YouTube™ was carried out using one search string. The 50 most viewed videos were identified and categorized by source and content themes and assessed for viewer interactions. Video comments were used to describe the usefulness of the video content to viewers. RESULTS: The majority of videos were uploaded by patients (n = 21).The remainder were uploaded by individual healthcare professionals (n = 9), hospital/speciality associations (n = 18) and industry (n = 2). The median number of likes for patient videos was significantly higher than for hospital/speciality association videos (P < 0.001). Patient videos received more comments praising the video content (n = 27) and more comments asking for further information (n = 14). The median number of likes for 'experience of surgery' (P < 0.001) and 'experience of disease' (P = 0.0015) themed videos were significantly higher than for 'disease management' themed videos. CONCLUSION: Crohn's disease patients use YouTube™ as a surgical information source. The content of patient-sourced videos focused on surgical and disease experience, suggesting that these themes are important to patients. Current patient developed videos provide limited information, as reflected by viewers requesting further information. Storytelling patient-centred videos combined with clinical evidence may be a good model for future videos.

Treatment of primary hyperhidrosis with oral anticholinergic medications: a systematic review.

Primary hyperhidrosis is a condition characterized by excessive sweating. Patients are treated off-license with oral anticholinergic medications and report adverse events associated with systemic anticholinergic interactions. This review assesses clinical evidence of efficacy, impact on quality of life and adverse events associated with oral anticholinergic therapy for primary hyperhidrosis. PRISMA guidelines were implemented to complete a systematic review (PROSPERO:CRD42016036326). MEDLINE, EMBASE and PubMed were searched from 1946 to 2015. Inclusion criteria included observational and experimental studies, anticholinergic medication use in primary hyperhidrosis, oral therapy and clear diagnostic and outcome measures. Twenty-three articles relevant to the inclusion criteria were analysed. Oxybutynin therapy improved symptoms in an average of 76.2% (range 60-97%) patients and improved QOL in 75.6% (range 57.6-100%) of patients. Methantheline bromide therapy was associated with a 41% reduction in axillary sweating, 16.4% reduction in palmar sweating, 25% decrease in HDSS score and 40.9% increase in DLQI score. Outcome measures of glycopyrrolate therapy were too variable to collate. Dry mouth was reported in 73.4% (range 43.3-100%) of participants taking oxybutynin 10 mg/day, 38.6% (range 27.8-63.2%) of patients taking glycopyrrolate and 68.8% of patients taking methantheline bromide. Nine studies reported that patients stopped therapy due to adverse events. In eight of these studies, a mean of 10.9% of total participants ceased treatment due to dry mouth. Evidence of oral anticholinergic therapy for hyperhidrosis is limited. However, its use is associated with improvement in quality of life and clinical symptoms but at the cost of considerable adverse events.

A systematic review of online resources to support patient decision-making for full-thickness rectal prolapse surgery.

BACKGROUND: The internet is becoming an increasingly popular resource to support patient decision-making outside of the clinical encounter. The quality of online health information is variable and largely unregulated. The aim of this study was to assess the quality of online resources to support patient decision-making for full-thickness rectal prolapse surgery. METHODS: This systematic review was registered on the PROSPERO database (CRD42017058319). Searches were performed on Google and specialist decision aid repositories using a pre-defined search strategy. Sources were analysed according to three measures: (1) their readability using the Flesch-Kincaid Reading Ease score, (2) DISCERN score and (3) International Patient Decision Aids Standards (IPDAS) minimum standards criteria score (IPDASi, v4.0). RESULTS: Overall, 95 sources were from Google and the specialist decision aid repositories. There were 53 duplicates removed, and 18 sources did not meet the pre-defined eligibility criteria, leaving 24 sources included in the full-text analysis. The mean Flesch-Kincaid Reading Ease score was higher than recommended for patient education materials (48.8 ± 15.6, range 25.2-85.3). Overall quality of sources supporting patient decision-making for full-thickness rectal prolapse surgery was poor (median DISCERN score 1/5 ± 1.18, range 1-5). No sources met minimum decision-making standards (median IPDASi score 5/12 ± 2.01, range 1-8). CONCLUSIONS: Currently, easily accessible online health information to support patient decision-making for rectal surgery is of poor quality, difficult to read and does not support shared decision-making. It is recommended that professional bodies and medical professionals seek to develop decision aids to support decision-making for full-thickness rectal prolapse surgery.

Assessing internet-based information used to aid patient decision-making about surgery for perianal Crohn's fistula.

BACKGROUND: Decision-making in perianal Crohn's fistula (pCD) is preference sensitive. Patients use the internet to access healthcare information. The aim of this study was to assess the online information and patient decision aids relating to surgery for pCD. METHODS: A search of Google™ and the Decision Aids Library Inventory (DALI) was performed using a predefined search strategy. Patient-focussed sources providing information about pCD surgery were included in the analysis. Written health information was assessed using the International Patient Decision Aids Standards (IPDAS) and DISCERN criteria. The readability of the source content was assessed using the Flesch-Kincaid score. RESULTS: Of the 201 sources found, 187 were excluded, leaving 14 sources for analysis. Three sources were dedicated to pCD, and six sources mentioned pCD-specific outcomes. The most common surgical intervention reported was seton insertion (n = 13). The least common surgical intervention reported was proctectomy (n = 1). The mean IPDAS and DISCERN scores were 4.43 ± 1.65 out of 12 (range = 2-8) and 2.93 ± 0.73 out of 5 (range = 1-5), respectively. The mean reading ease was US college standard. CONCLUSIONS: We found no patient decision aids relating to surgery for pCD. The online sources relating to surgery for pCD are few, and their quality is poor, as seen in the low IPDAS and DISCERN scores. Less than half of the sources mentioned pCD-specific outcomes, and three sources were solely dedicated to providing information on pCD. Healthcare professionals should look to create a patient tool to assist decision-making in pCD.

Topical glycopyrrolate reduces axillary hyperhidrosis.

INTRODUCTION: Oral anti-cholinergic medications reduce generalized hyperhidrosis, but the effectiveness of topical anticholinergic solutions on axillary hyperhidrosis is unclear. This study determines the initial effectiveness of 1% and 2% topical glycopyrrolate spray and compares this with Botulinum toxin type A injections for the management of axillary hyperhidrosis. METHODS: In a non-randomized, consecutive patient, prospective questionnaire, treatment comparison study, 40 patients with axillary hyperhidrosis were allocated to one of four study groups (10 patients to each group): (a) 1% glycopyrrolate spray, (b) 2% glycopyrrolate spray, (c) subcutaneous Botulinum toxin type A injections, (d) no treatment. Clinical outcomes were measured by comparing a prospectively administered questionnaire, completed both pre-treatment and 6 weeks after starting treatment. Forty healthy volunteers without axillary hyperhidrosis completed the same questionnaire. RESULTS: The three treatment groups showed a significant (P < 0.05) improvement in their hyperhidrosis scores following treatment. The degree of improvement was less for the 1% glycopyrrolate group when compared with the Botulinum toxin type A group (P < 0.05), but there was no difference in treatment outcomes between the 2% glycopyrrolate and Botulinum toxin type A groups. No treatment group experienced reduced hyperhidrosis to a level similar to those without hyperhidrosis. Patients in both, the 2% glycopyrrolate and Botulinum toxin type A groups reported a significant improvement in axillary hyperhidrosis symptoms. These included reduction in psychologically precipitating factors (e.g. public speaking) and axillary hyperhidrosis-specific physical effects (e.g. limitation of clothing choice). CONCLUSIONS: Topical glycopyrrolate spray could provide a further treatment modality to manage axillary hyperhidrosis.

HLA-DQ allele-restricted activation of nitroso sulfamethoxazole-specific CD4-positive T lymphocytes from patients with cystic fibrosis.

BACKGROUND: For certain HLA allele-associated drug hypersensitivity reactions, the parent drug has been shown to associate directly with the risk allele. In other forms of hypersensitivity, HLA risk alleles have not been identified and T cells are activated in an allele unrestricted manner. Chemically reactive drug metabolites bind to multiple proteins; thus, it is assumed that the derived peptide antigens interact with a number of HLA molecules to activate T cells; however, HLA restriction of the drug metabolite-specific T-cell response has not been studied. OBJECTIVE: To utilize T cells from sulfamethoxazole (SMX) hypersensitive patients with cystic fibrosis to examine the HLA molecules that interact with nitroso SMX (SMX-NO)-derived antigens. METHODS: T-cell clones were generated from 4 hypersensitive patients. Drug-specific proliferative responses and cytokine secretion were measured. Anti-human class I and class II antibodies were used to analyse HLA restriction. Antigen-presenting cells expressing different HLA molecules were used to determine the alleles involved in the presentation of SMX-NO-derived antigens to T cells. RESULTS: A total of 976 clones were tested for SMX-NO reactivity. Thirty-nine CD4+ clones were activated with SMX-NO and found to proliferate and secrete cytokines. The SMX-NO-specific response was blocked with an antibody against HLA-DQ. SMX-NO-specific responses were detected with antigen-presenting cells expressing HLA-DQB1*05:01 (patient 1) and HLA-DQB1*02:01 (patient 2), but not other HLA-DQB1 alleles. CONCLUSION AND CLINICAL RELEVANCE: HLA-DQ plays an important role in the activation of SMX-NO-specific CD4+ T cells. Detection of HLA-DQ allele-restricted responses suggests that T cells are activated by a limited repertoire of SMX-NO-modified peptides.

LFA-1-deficient mice show normal CTL responses to virus but fail to reject immunogenic tumor.

The leukocyte integrin LFA-1 (CD11a/CD18) plays an important role in lymphocyte recirculation and homotypic interactions. Leukocytes from mice lacking CD11a displayed defects in in vitro homotypic aggregation, in proliferation in mixed lymphocyte reactions, and in response to mitogen. Mutant mice mounted normal cytotoxic T cell (CTL) responses against systemic LCMV and VSV infections and showed normal ex vivo CTL function. However, LFA-1-deficient mice did not reject immunogenic tumors grafted into footpads and did not demonstrate priming response against tumor-specific antigen. Thus CD11a deficiency causes a selective defect in induction of peripheral immune responses whereas responses to systemic infection are normal.

Nitric oxide synthase in critically ischaemic muscle and alterations in isoform expression during revascularization surgery.

BACKGROUND: Dysfunction of the nitric oxide pathway is implicated in peripheral arterial disease. Nitric oxide synthase (NOS) isoforms and NOS activity were studied in muscle from patients with critical leg ischaemia (CLI). Alterations in NOS during revascularization surgery were also assessed. METHODS: Muscle biopsies were taken from patients with CLI undergoing amputation and also from patients undergoing femorodistal bypass at the start of surgery, after arterial clamping and following reperfusion. The presence of NOS within muscle sections was confirmed using reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. NOS isoform distribution was studied by immunohistochemistry. NOS mRNA and protein levels were measured using real-time reverse transcriptase-polymerase chain reaction and western blotting. NOS activity was assessed with the citrulline assay. RESULTS: All three NOS isoforms were found in muscle, associated with muscle fibres and microvessels. NOS I and III protein expression was increased in CLI (P = 0.041). During revascularization, further ischaemia and reperfusion led to a rise in NOS III protein levels (P = 0.008). NOS activity was unchanged. CONCLUSION: Alterations in NOS I and III occurred in muscle from patients with CLI and further changes occurred during bypass surgery.

Cryptic speciation in the cosmopolitan and clonal human pathogenic fungus Aspergillus fumigatus.

Microbes and other organisms smaller than one to a few millimeters in size are hypothesized to have global populations, in contrast to the geographically restricted ranges of larger organisms. However, fungi, which routinely have reproductive propagules no larger than 10 micrometers, challenge the generality of this hypothesis because recent studies have shown that globally distributed morphological species embrace two or more geographically restricted phylogenetic species. We used the concordance of gene genealogies to recognize phylogenetic species in the globally distributed opportunistic human pathogenic fungus, Aspergillus fumigatus. Based on DNA sequence data of five loci for each of 63 individuals collected from five continents, we have delineated two phylogenetic species in this single morphological species. Unlike all other fungi examined to date, both genetically isolated groups showed a global distribution with no evidence of a correlation between genotype and geographic location. Sexual reproduction has never been observed in A. fumigatus, but when the same data were used to explore the association of alleles at the five loci for one of the phylogenetic species, evidence was found to support recombination. The discovery of a cryptic species is medically relevant because different species are likely to differ in virulence or drug resistance. The discovery of a globally distributed A. fumigatus species clade highlights the need for ecological studies of the fungus to either document global dispersal or propose alternative mechanisms by which it persists as single, global phylogenetic population.

Evidence for a decrease in sympathetic control of intestinal function in the aged rat.

The ability of carbachol and isoprenaline to contract and relax respectively the longitudinal layer of ileal smooth muscle has been compared in rats aged six and twenty-four months. The concentration response curve to carbachol did not vary with the age of the animal. In contrast, the ability of isoprenaline to relax longitudinal smooth muscle precontracted with carbachol was significantly (p less than 0.02) reduced in the twenty-four month age group. This reduced response was due to a decrease in the maximal relaxation induced by isoprenaline rather than by a shift to the right of its dose-response curve. These results are discussed in the context of previous histochemical and microscopical studies which have shown a marked reduction in the density of the sympathetic innervation of the rat small intestine in old age.

Morphometric studies on pre- and paravertebral sympathetic neurons in the rat: changes with age.

Morphometric measurements have been made on rat sympathetic neurons at ages between 6 and 24 months. In neurons of the coeliac-superior mesenteric ganglion there is a marked decrease in the neuronal packing density between 12 and 18 months which is accompanied by increases in the size of the neurons and their nuclei. In the superior cervical ganglion, no changes in packing density are seen until 18 months after which a decrease occurs, accompanied by slight increases in the neuronal parameters. These post-maturation changes occurring throughout adult life reveal a continued dynamism of sympathetic neurons into old age as well as revealing further differences between populations of sympathetic neurons.

A quantitative study of the effects of age on the noradrenergic innervation of Auerbach's plexus in the rat.

Noradrenergic nerves were demonstrated in stretch preparations of Auerbach's plexus and longitudinal muscle from the proximal jejunum of Wistar rats using glyoxylic acid-induced fluorescence. The density of the noradrenergic nerve plexus and the number of nerve terminal varicosities/frame area were assessed using a Quantimet 800 image analyser and the number of varicosities/unit length of nerve was measured manually with a calibrated planimeter. With increasing age, especially between 12 and 18 months there occurs a breakdown of plexus regularity and noticeably reduced levels of axonal fluorescence. Image analysis showed a decrease in the total area of the plexus of more than 50% and a decrease of almost 75% in the total number of varicosities. The frequency of varicosities per 100 micron of axon decreased from 18.79 at 12 months to 14.79 at 18 months. Significant changes in these parameters did not occur during the following 6 months. The dramatic decrease in the density of the noradrenergic innervation of Auerbach's plexus and the fall in number of varicosities with age implies a reduction in the potential of the sympathetic nervous system to influence control over motility of the jejunum in the aged rat.

Development of a quantitative histochemical method for determination of succinate dehydrogenase activity in autonomic neurons and its application to the study of aging in the autonomic nervous system.

An accurately validated method was developed for quantitative determination of succinate dehydrogenase (EC 1.3.99.1; SDH) activity in individual sympathetic neuron perikarya by microdensitometric measurement of an SDH-nitroblue tetrazolium-derived formazan final reaction product. Optimal incubation medium and reaction conditions were determined for measurement of reaction product in cryostat sections of rat superior cervical and celiac-superior mesenteric ganglia. The Beer-Lambert laws were verified for the ganglion tissue, and microdensitometric measurements (expressed as mean cell density readings; MCDR/min-1), characteristic of the Michaelis-Menten equation, enabled the results to be used for enzyme kinetic determinations of SDH activity. Km and Vmax values were obtained following Hans linear transformation of the readings. Between the ages of 6-24 months no significant variations in Km values were recorded, indicating an unchanged structure for SDH (overall mean Km = 0.083 +/- 0.055 mM). However, in both ganglia there were significant decreases (ranging from 43-54%) in Vmax values for SDH at 24 months. The overall mean Vmax value at 6 months was 4.01 +/- 0.61 (MCDR) and at 24 months was 2.07 +/- 0.76 (MCDR). This suggests that an overall decrease in metabolic activity takes place with age in sympathetic neurons of the rat superior cervical and celiac-superior mesenteric ganglia.

Dietary lead increases ethanol consumption in the rat.

Rats fed either a diet containing 500 ppm (parts per million) Pb (as lead acetate) or an unadulterated control diet for 50 days were offered a 15% ethanol (ETOH) solution in a nonchoice (one-bottle) test situation. The results from this test indicated that Pb-diet animals consumed greater amounts of the ETOH solution than did controls. In a subsequent choice (three-bottle, two-fluid) test situation offering a nonpreferred ETOH solution or tap water as alternatives, Pb-diet animals once again ingested greater amounts of the ETOH solution. These findings are discussed in terms of possible Pb-induced increases in emotionality and the potential stress-reduction properties of ETOH.

Superiority of conventional culture technique over rapid detection of group A Streptococcus by optical immunoassay.

An optical immunoassay (OIA) has been reported to be more sensitive than conventional culture for the detection of Group A Streptococcus, eliminating the need for culture. We attempted to confirm the sensitivity and specificity through a laboratory quantitation study and a clinical trial. OIA did not detect Group A Streptococcus below 10(5) colony forming units (CFU). Culture detected Streptococcus to 10(2) CFU from the inoculated swab. In the clinical study, throat swabs were obtained from 77 patients in an outpatient clinic. Compared with culture, the sensitivity of OIA was 78% and the specificity was 90%. These results demonstrate that OIA was less sensitive than culture in seeded experiments and missed 22% of positives in clinical practice. Our study, contrary to previous reports, suggests that OIA is not sensitive enough to be used as the sole assay for Group A Streptococcus pharyngitis.

Ethanol consumption and free operant avoidance performance following exposure to dietary lead.

Rats were exposed ad libitum to a diet containing either 500 ppm lead (Group Lead-Diet) or a control diet with no added lead (Group Control-Diet). On Day 60 both groups were presented with a 15% ethanol solution (nonchoice test) in the home cage for five days prior to placement on a choice test that presented animals with a 10% ethanol solution and tap water. Concurrently with the choice test in the home cage, animals were placed in operant chambers for one hr (pre-avoidance) prior to a 30 min free operant avoidance session (avoidance) and remained there for one hr (post-avoidance) after training. Throughout avoidance training, the choice test was conducted in the chamber as well as the home cage. In addition to evidence of greater ethanol consumption by Group Lead-Diet rats, the results showed that these animals lever pressed more frequently, but not more efficiently, than Group Control-Diet animals.

The regional distribution of cadmium in the brains of orally exposed adult rats.

Cadmium (Cd) levels were measured in 13 dissected brain regions of adult male rats from 3 treatment groups. Rats (approximately 200 g each) were each fed 10 g/day of diets containing either 20 or 100 micrograms/g (ppm) Cd or control diet to which no Cd was added but contained approximately 0.35 ppm Cd. After 67 days of treatment, the brain of each rat was removed and each was dissected into 13 anatomical regions including olfactory bulbs, frontal cortex, rest of cortex, corpus callosum, hippocampus, amygdalae, corpus striatum, colliculum, tegmentum, thalamus, hypothalamus, pons-medulla, and cerebellum. Cd residues (dry weight) in each sample were determined by flameless atomic absorption spectrophotometry. With exception of the thalamus and olfactory bulbs, each of the brain regions of the 100 ppm Cd rats had more Cd than did those from either the 20 ppm Cd rats or controls which did not differ. There was evidence of selective accumulation of Cd within the olfactory bulbs of control and treated animals. This selective accumulation may be related to anosmia reported in workers with industrial exposure to Cd.