Habitual dietary fibre and prebiotic intake is inadequate in patients with inflammatory bowel disease: findings from a multicentre cross-sectional study.

BACKGROUND: Recommendations for dietary fibre intake in patients with inflammatory bowel disease are highly variable. Despite the potential benefits of prebiotic fibres on the gut microbiome, many patients with inflammatory bowel disease follow a low fibre diet. The present study comprehensively evaluated intakes of total and prebiotic fibres in patients with inflammatory bowel disease, aiming to determine the adequacy of fibre intake and factors that may influence intake. METHODS: Outpatients with a formal diagnosis of inflammatory bowel disease were recruited to this multicentre cross-sectional study. Habitual dietary fibre intake including prebiotic fibre types was measured using a validated comprehensive nutrition assessment questionnaire. Adequacy of total fibre intake was compared with Australian Nutrient Reference Values. Multiple linear regressions were performed to determine factors influencing fibre intake. RESULTS: Of 92 participants, 52% had Crohn's disease, 51% were male and the mean age was 40 years. Overall, only 38% of the cohort consumed adequate total fibre (median 24 g day-1 , interquartile range 18.5-32.9 g day-1 ). Adequate fibre consumption was significantly less common in males than females (21.3% versus 55.6%, P = 0.002). Resistant starch intake (median 2.9 g day-1 , interquartile range 2.1-4.8 g day-1 ) was significantly less than the proposed recommendations (20 g day-1 ). Disease-related factors such as phenotype and disease activity were not found to influence fibre intake. CONCLUSIONS: Patients with inflammatory bowel disease habitually consume inadequate fibre, particularly prebiotic fibre resistant starch. The potential deleterious effects of low prebiotic intake on the gut microbiome and disease-related outcomes in inflammatory bowel disease are unknown and warrant further research.

Epilepsy in Irish psychiatric inpatient settings

Aims To ascertain epilepsy prevalence in Irish psychiatric inpatient units and compliance with care planning guidelines. Methods Case records were reviewed in seven psychiatric inpatient units. Results The prevalence of epilepsy across seven psychiatric inpatient units (n=9/267) was three times that of general population estimates. Minimal data was recorded pertaining to seizure type (n=1,11.1%), triggers (n=2,22.2%), clinical investigations relating to epilepsy (n=2,22%) and no epilepsy risk assessments were recorded (n=0,0%). Conclusions The introduction of appropriate care plans is needed to optimise physical and mental wellbeing of those with epilepsy in psychiatric units.

Dose tailoring of anti-tumour necrosis factor-alpha therapy delivers useful clinical efficacy in Crohn disease patients experiencing loss of response.

BACKGROUND: 'Dose tailoring' of anti-tumour necrosis factor alpha (TNF-α) therapy in Crohn disease (CD), by dose escalation, or shortening of dosing intervals, has been suggested to regain clinical response following a flare in a proportion of patients. However, reported outcome data are sparse and none exists from Australia. METHOD: In an observational multicentre, retrospective study, the impact of anti-TNF-α dose tailoring on corticosteroid use, the need for surgery and physician perception of clinical efficacy was examined in a real-world setting at six Australian adult teaching hospitals. Demographics, disease characteristics, medications, indication for and duration of dose tailoring were documented. RESULTS: Fifty-five CD patients were identified as requiring dose tailoring and secondary loss of response was the indication in 96%. Either adalimumab (64%) or infliximab (36%) was dose escalated for a median of 5 months (range 1-47), with a median of 20 months follow up (range 3-65). At 3 months, dose tailoring reduced the mean number of days on high-dose corticosteroids (45 vs 23, P = 0.01). Most (78%) patients remained resection free, and 73% of physicians reported good clinical efficacy of dose tailoring. Of those who de-escalated therapy due to induction of remission, long-term (>12 months) follow up and complete data on steroid use were available in 15/28, with 12/15 (80%) remaining steroid free at 1 year. CONCLUSION: Short-term dose tailoring regains disease response in the majority of patients with CD. Of these, most will remain free of corticosteroids at 1 year after de-escalating therapy.

Compassionate access anti-tumour necrosis factor-α therapy for ulcerative colitis in Australia: the benefits to patients.

BACKGROUND: The efficacy of infliximab has been demonstrated in patients with both acute severe and moderate-severe ulcerative colitis (UC). However, there is a need for 'real-life data' to ensure that conclusions from trial settings are applicable in usual care. We therefore examined the national experience of anti-tumour necrosis factor-α (TNF-α) therapy in UC. METHODS: Case notes review of patients with UC who had received compassionate access (CA) anti-TNF-α therapy from prospectively maintained inflammatory bowel disease databases of six Australian adult teaching hospitals. RESULTS: Patients either received drug for acute severe UC (ASUC) failing steroids (n = 29) or for medically refractory UC (MRUC) (n = 35). In ASUC, the treating physicians judged that anti-TNF-α therapy was successful in 20/29 patients (69%); in these cases, anti-TNF-α was able to be discontinued (after 1-3 infusions in 19/20 responders) as clinical remission was achieved. Consistent with this perceived benefit, only 7/29 (24%) subsequently underwent colectomy during a median follow up of 12 months (interquartile range (IQR) 5-16). Eight of the 35 patients with MRUC (23%) required colectomy during a median follow up of 28 months (IQR 11-43). The majority of these patients (20/35 or 57%) had anti-TNF-α therapy for ≥4 months, whereas, 27/29 (93%) of ASUC patients had CA for ≤3 months. CONCLUSIONS: These data show an excellent overall benefit for anti-TNF-α therapy in both ASUC and MRUC. In particular, only short-duration anti-TNF-α was required in ASUC. These real-life data thus support the clinical trial data and should lead to broader use of this therapy in UC.

Possible pro-carcinogenic association of endotoxin on lung cancer among Shanghai women textile workers.

BACKGROUND: Endotoxin (lipopolysaccharide) is a widespread contaminant in many environmental settings. Since the 1970s, there has been generally consistent evidence indicating reduced risks for lung cancer associated with occupational endotoxin exposure. METHODS: We updated a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China. We compared exposure histories of 1456 incident lung cancers cases diagnosed during 1989-2006 with those of a reference subcohort of 3022 workers who were free of lung cancer at the end of follow-up. We applied Cox proportional hazards modelling to estimate exposure-response trends, adjusted for age and smoking, for cumulative exposures lagged by 0, 10, and 20 years, and separately for time windows of ⩽15 and >15 years since first exposure. RESULTS: We observed no associations between cumulative exposure and lung cancer, irrespective of lag interval. In contrast, analyses by exposure time windows revealed modestly elevated, but not statistically significant relative risks (∼1.27) at the highest three exposure quintiles for exposures that occurred >15 years since first exposure. CONCLUSIONS: The findings do not support a protective effect of endotoxin, but are suggestive of possible lung cancer promotion with increasing time since first exposure.

Population densities and tree diameter effects associated with verbenone treatments to reduce mountain pine beetle-caused mortality of lodgepole pine.

Mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae: Scolytinae), is among the primary causes of mature lodgepole pine, Pinus contorta variety latifolia mortality. Verbenone is the only antiaggregant semiochemical commercially available for reducing mountain pine beetle infestation of lodgepole pine. The success of verbenone treatments has varied greatly in previous studies because of differences in study duration, beetle population size, tree size, or other factors. To determine the ability of verbenone to protect lodgepole pine over long-term mountain pine beetle outbreaks, we applied verbenone treatments annually for 3 to 7 yr at five western United States sites. At one site, an outbreak did not develop; at two sites, verbenone reduced lodgepole pine mortality in medium and large diameter at breast height trees, and at the remaining two sites verbenone was ineffective at reducing beetle infestation. Verbenone reduced mountain pine beetle infestation of lodgepole pine trees in treated areas when populations built gradually or when outbreaks in surrounding untreated forests were of moderate severity. Verbenone did not protect trees when mountain pine beetle populations rapidly increase.

Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease.

BACKGROUND AND PURPOSE: In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson's disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association. METHODS: Parkinson's Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS: Two ADORA2A polymorphisms were inversely associated with PD risk - rs71651683, a 5' variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 0.04). CONCLUSION: In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms.

Impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders attending secondary care.

OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic on patients with established anxiety disorders during a period of stringent mandated social restrictions. METHODS: Semi-structured interviews were conducted with 30 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases diagnosis of an anxiety disorder to determine the impact of the COVID-19 restrictions on anxiety and mood symptoms, social and occupational functioning and quality of life. RESULTS: Twelve (40.0%) participants described COVID-19 restrictions as having a deleterious impact on their anxiety symptoms. Likert scale measurements noted that the greatest impact of COVID-19 related to social functioning (mean = 4.5, SD = 2.9), with a modest deleterious effect on anxiety symptoms noted (mean = 3.8, SD = 2.9). Clinician rated data noted that 8 (26.7%) participants had disimproved and 14 (46.7%) participants had improved since their previous clinical review, prior to commencement of COVID-19 restrictions. Conditions associated with no 'trigger', such as generalised anxiety disorder, demonstrated a non-significant increase in anxiety symptoms compared to conditions with a 'trigger', such as obsessive compulsive disorder. Psychiatric or physical comorbidity did not substantially impact on symptomatology secondary to COVID-19 mandated restrictions. CONCLUSIONS: The psychological and social impact of COVID-19 restrictions on individuals with pre-existing anxiety disorders has been modest with only minimal increases in symptomatology or social impairment noted.

A longitudinal evaluation of the impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders.

OBJECTIVES: To examine if the COVID-19 pandemic is associated with a differential effect over time in relation to its psychological and social impact on patients with established anxiety disorders. METHODS: Semi-structured interviews were conducted with 24 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases (ICD)-10 diagnosis of an anxiety disorder at two time points (six months apart) to determine the impact of the COVID-19 restrictions on anxiety and depressive symptoms, social and occupational functioning and quality of life. RESULTS: No statistical difference in symptomatology was noted between the two time points in relation to anxiety symptoms as measured by utilising psychometric rating scales (BAI and HARS) or utilising a Likert scale. The greatest impact of COVID-19 at both time points is related to social functioning and quality of life. Significant variability was noted for individual participants. Qualitative analysis noted social isolation, concern for the participants' future and increased difficulty managing anxiety with ongoing restrictions. CONCLUSIONS: No significant overall change in symptomatology or functioning over time was noted for individuals with pre-existing anxiety disorders. Variability was, however, demonstrated between individuals, with some individuals describing ongoing anxiety, social isolation and concern for their future. Identifying those with ongoing symptoms or distress and providing multidisciplinary support to this cohort is suggested.

Familial associations of Alzheimer disease and essential tremor with Parkinson disease.

BACKGROUND: We constructed a cohort of first-degree relatives of participants in a population-based case-control study of Parkinson disease (PD) and compared the occurrence of Alzheimer disease (AD) and essential tremor (ET) in relatives of PD cases and controls. METHODS: We relied on proband interviews to assess family history in 372 probands with incident PD confirmed by a movement disorder specialist and 404 controls from three rural California counties. RESULTS: Overall, for the 2980 first-degree relatives of PD cases, the risk of AD was not increased compared with the 2981 relatives of controls. But relatives of younger onset PD cases (

Control of heifer mastitis by nutrition.

Nutritional factors that are linked to mastitis in the mature dairy cow can be associated with mastitis in the first lactation cow as well. However, there may also be risk factors unique to the heifer due to differences in feeding management during rearing or pre-calving. Literature was reviewed to summarize current knowledge regarding links between heifer nutrition and mastitis with the potential to identify areas for future research. The preponderance of data relating nutrition and bovine mastitis involves selected micronutrients. Selenium and vitamin E enhance phagocytic activity and have been associated with decreased clinical mastitis risk. Copper has antioxidant functions and can reduce clinical mastitis in heifers. Zinc is implicated in maintaining the epithelial barriers to infection, but reports vary as to its role in udder health. Vitamin A and beta-carotene aid in maintaining the health of mucosal surfaces, and beta-carotene may also have antioxidant properties. Supplementation with vitamin A and beta-carotene has produced inconsistent results. Vitamin and mineral requirements of dairy heifers are generally influenced by growth rate and body weight relative to mature size, though little specific data is available. From a management standpoint, heifer rations should be supplemented where necessary, and a pre-fresh heifer diet is critical to assure that first lactation animals have adequate stores of minerals and vitamins. Adequate stores are necessary for transfer into colostrum by calving. Additional studies using field data and controlled studies are needed to further define the role of nutrition in animal health and in affecting specific mastitis-causing organisms.

Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients.

FMT has gained enormous momentum in the treatment of acute inflammatory and infectious diseases. Despite an encouraging safety profile, FMT has been met with caution in the oncological setting due to perceived infectious risks in immunocompromised patients. Theoretical risks aside, the application of FMT in oncology may stand to benefit patients, via modulation of treatment efficacy and the mitigation of treatment complications. Here, we summarize most recent safety data of FMT in immunocompromised cohorts, including people with cancer, highlighting that FMT may actually provide protection against bacterial translocation via introduction of a diverse microbiome and restoration of epithelial defenses. We also discuss the emerging translational applications of FMT within supportive oncology, including the prevention and treatment of graft vs. host disease and sepsis, treatment of immunotherapy-induced colitis and restoration of the gut microbiome in survivors of childhood cancer.

Association of polymorphisms in the calpain I, calpain II and growth hormone genes with tenderness in bovine M. longissimus dorsi.

The objective of this study was to determine if there is an association between tenderness in bovine M. longisimus dorsi (LD) and polymorphisms in the bovine calpain I (exons 9 & 14), calpain II (regulatory subunit) or growth hormone (intron 3) genes. Genomic DNA was isolated from bovine LD (n=281) on which quality attributes (Warner Bratzler shear force (WBSF), sarcomere length and composition) were also characterised. DNA polymorphisms were analysed using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. Association analyses were performed between genotypes at the four polymorphic loci and day 14 WBSF values. It was found that the calpain 1 exon 9 genotypes had an association with WBSF such that animals with the GA genotype exhibited decreased WBSF and increased tenderness when compared to animals with the GG genotype (P<0.05). This observation concurs with that of earlier studies, suggesting that this polymorphism is a functional marker for beef tenderness.

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.

BACKGROUND: Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. AIM: To determine whether FMT is effective and safe for the induction of remission in active UC. METHODS: Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). RESULTS: There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. CONCLUSIONS: Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent.

Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group.

PURPOSE: To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. PATIENTS AND METHODS: Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated. RESULTS: One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated. CONCLUSION: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.