Effect of Docosahexaenoic Acid (DHA) Supplementation of Preterm Infants on Growth, Body Composition, and Blood Pressure at 7-Years Corrected Age: Follow-Up of a Randomized Controlled Trial.

Aim: To determine if supplementation of infants born <33 weeks' gestation with higher dose docosahexaenoic acid (DHA) affects growth, body composition, and blood pressure at 7 y corrected age (CA) and if treatment effects differed by infant sex at birth and birth weight strata (<1250 and ≥1250 g). Methods: Seven-year follow-up of an Australian multicenter randomized controlled trial in which 657 infants were fed high-DHA (≈1% total fatty acids) enteral feeds or standard-DHA (≈0.3% total fatty acids) from age 2−4 d until term CA. Seven-year CA outcomes were growth (weight, height), body composition (lean body mass, fat mass, waist, and hip circumference), and blood pressure. Results: There was no effect of high-DHA enteral feeds compared with standard-DHA on growth, body composition, and blood pressure at 7-year CA either overall or in subgroup analysis by sex. There was a significant interaction between high-DHA and birthweight strata on height at 7-y CA (p = 0.03). However, the post-hoc analyses by birthweight strata did not reach significance (p > 0.1). High-DHA group infants were more likely to be classified as obese (relative risk 1.6 (95% CI 1.0, 2.6); p = 0.05). Conclusions: DHA supplementation of premature infants did not affect growth, body composition, or blood pressure at 7-year CA overall by sex and birthweight strata. The finding of a higher risk of obesity in children who receive high-DHA needs to be interpreted with caution due to the small number of children classified as obese.

Pre-Antibiotic Treatment Followed by Prolonged Repeated Faecal Microbiota Transplantation Improves Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome: An Observational Australian Clinical Experience.

Background: The use of faecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) has frequently failed to induce long-term symptomatic improvement. The use of multiple FMT infusions is one proposed mechanism through which the efficacy of FMT can be amplified. Aims: To evaluate the safety and efficacy of a novel six-month FMT treatment protocol in IBS. Methods: Patients diagnosed with IBS confirmed by Rome IV Criteria were recruited for single-centre, single-arm, prospective clinical observational study. Participants received one colonoscopically delivered FMT followed by 36 rectal enemas across a six-month period. Validated abdominal symptoms and Short-Form (SF-36) Quality of Life (QOL) questionnaires were collected at baseline, week-12, week-24, and week-56, respectively. Wilcoxon matched-pairs signed-rank tests were conducted to compare differences in abdominal symptom and SF-36 QOL scores over the follow-up timepoints. Statistical significance was set at 5%. Results: Sixty participants diagnosed with IBS [IBS-constipation (n = 27), IBS-diarrhoea (n = 18), and IBS-mixed (n = 15)] received the six-month FMT treatment. IBS symptom severity reduction was achieved in up to 61% of respondents at week-12, 64% of respondents at week-24, and maintained in up to 75% of respondents at week-52. Long-term reduction in symptom severity was associated with an increase in QOL, achieved in up to 64% of respondents at week-52 when compared to baseline. Adverse events were experienced in 28% of participants, though they were both transient and mild in nature. Conclusions: Six-month sustained FMT appears to be both safe and effective in the short- and long-term alleviation of IBS associated symptoms as well as improving participant QOL.

Effectiveness of ivermectin-based multidrug therapy in severely hypoxic, ambulatory COVID-19 patients.

Aims: Ivermectin is a safe, inexpensive and effective early COVID-19 treatment validated in 20+ random, controlled trials. Having developed combination therapies for Helicobacter pylori, the authors present a highly effective COVID-19 therapeutic combination, stemming from clinical observations. Patients & methods: In 24 COVID-19 subjects refusing hospitalization with high-risk features, hypoxia and untreated moderate to severe symptoms averaging 9 days, the authors administered this novel combination of ivermectin, doxycycline, zinc and vitamins D and C. Results & conclusions: All subjects resolved symptoms (in 11 days on average), and oxygen saturation improved in 24 h (87.4% to 93.1%; p = 0.001). There were no hospitalizations or deaths, less than (p < 0.002 or 0.05, respectively) background-matched CDC database controls. Triple combination therapy is safe and effective even when used in outpatients with moderate to severe symptoms. Clinical Trial Registration: NCT04482686 (ClinicalTrial.gov).

Dietary Management for Faecal Microbiota Transplant: An International Survey of Clinical and Research Practice, Knowledge and Attitudes.

Faecal microbiota transplantation (FMT) involves homogenisation and infusion of stool from a healthy, highly screened individual into the bowel of an unwell recipient. Dietary intake is an important modulator of the gut microbiota. Currently there are no clinical practice recommendations available to provide patients or stool donors with dietary advice for FMT. This study aimed to conduct an international survey to examine health professionals and researchers' attitudes, knowledge and current practice recommendations for diet in patients undergoing FMT. An online, cross-sectional, international survey comprising of health professionals and researchers managing patients undergoing treatment with FMT was conducted between July-October 2020. Purposeful and snowball sampling techniques were employed to identify eligible participants who were sent an email invitation and two email reminders with a link to participate in the electronic survey. The survey comprised 21 questions covering demographics, current practice, beliefs and future directions regarding FMT and diet. Closed responses were calculated as proportions of total responses. Open-ended responses were systematically categorised. Common themes were identified from recurring categories. Fifty-eight (M 60%) participants from 14 countries completed the survey. Participants were gastroenterologists (55%), with 1-5 years' experience working in FMT (48%) and treating up to ten patients with FMT per month (74%). Participants agreed that diet was an important consideration for FMT recipients and stool donors (both 71%), and that it would affect the outcomes of FMT. However, they did not feel confident in providing dietary advice to patients, nor that there was sufficient evidence to provide dietary advice and this was reflected in their practice. Future research must collect information on the dietary intake of patients and donors to better understand the relationship between diet and FMT outcomes. In clinical practice, promotion of healthy eating guidelines aligns with current practice and literature.

Combinations of antibiotics and vonoprazan for the treatment of Helicobacter pylori infections-Exploratory study.

BACKGROUND: Vonoprazan fumarate is a novel potassium-competitive acid blocker more effective in suppressing acid production than proton pump inhibitors (PPIs) and when combined with antibiotics has been used to eradicate Helicobacter pylori (H. pylori) infection. However, it has not yet been examined in an Australian setting. This study aimed to report on the efficacy and safety of vonoprazan-containing antibiotic combination therapies in the eradication of H. pylori. METHODS: A single-center, exploratory, clinical review of patients 18 years or over, positive for H. pylori on Urea Breath Test (UBT), and/or histopathology who underwent a 10-day treatment of combination antibiotics plus vonoprazan between January 2017 and September 2019 was conducted. Eleven different combinations of antibiotics that included 2-5 different antibiotics predominantly amoxicillin, rifabutin, levofloxacin, furazolidone, nitazoxanide, and tetracycline were included. The eradication success was based on negative UBT results and/or histopathology results after the treatment. Descriptive statistics were summarized. RESULTS: One hundred and fifty-three patients (Female n = 74, 48%) with a positive for H. pylori were treated with vonoprazan-containing antibiotic combination therapy during the study period. Of the 153 patients, 48 (31%) had previously failed a PPI-based H. pylori treatment. Follow-up was available for 66/153 (43%) patients. In those who completed follow-up, overall eradication was achieved in 97% (64/66) of patients. In the subgroup of patients treated for the first time, eradication was achieved in 100% (44/44). In those who had failed prior, non-vonoprazan-containing treatment, eradication was achieved in 91% (20/22) of patients. CONCLUSIONS: Vonoprazan-containing antibiotic therapy is an effective H. pylori eradication treatment. It is capable of achieving 100% efficacy in patients treated for the first time and even 91% efficacy in patients with previous eradication failure. Subsequent studies utilizing a factorial design will be needed to optimize each regimen as most regimens contained more than two antibiotics.

Dietary Intakes of Recipients of Faecal Microbiota Transplantation: An Observational Pilot Study.

This study reports on the dietary intake of recipients of faecal microbiota transplantation (FMT), comparing this with dietary guidelines, and investigates the relationship between dietary intake and clinical outcomes. Males and females aged ≥ 16 years with irritable bowel syndrome or inflammatory bowel disease undergoing FMT were invited to complete validated symptom and quality of life (QOL) questionnaires and three-day weighed food diaries. Descriptive statistics were calculated for symptom scores, QOL scores, nutrients, and food group servings, and compared to Australian population norms, nutrient reference values, and dietary guidelines. The relationship between dietary intake, symptoms, and QOL was assessed. Participants (n = 18) reported baseline symptoms of urgency, abdominal pain, nausea, and bloating and reduced QOL. Of the participants who completed food diaries, 8/14 met the recommended 30 g of fibre when including supplements. Participants met the recommendations for micronutrients and food groups except calcium, fruit, and dairy/dairy alternatives. There was a non-significant trend towards lower symptom severity scores in participants who met the fibre target. The high degree of variability in participant fibre intakes highlights diet as a key variable that has not been previously controlled for in FMT intervention studies. Future studies examining FMT should include dietary analysis of habitual intake of the recipients and donors.

Two-day enema antibiotic therapy for parasite eradication and resolution of symptoms.

BACKGROUND: Blastocystis hominis (B. hominis) and Dientamoeba fragilis (D. fragilis) are two protozoan parasites of human bowel that are found throughout the world. There is still debate about the pathogenicity of these protozoans, despite them being commonly associated with gastrointestinal symptoms and can cause health issue in both children and adults. These parasites are usually transmitted through faecal-oral contact particularly under poor hygiene conditions or food/water contamination. Once a person is infected, the parasites live in the large intestine and are passed in the faeces. AIM: To investigate the effect of triple antibiotic therapy using enema infusion in the treatment of B. hominis and D. fragilis infections. METHODS: This retrospective longitudinal study was conducted in a single medical centre, which included fifty-four patients (≥ 18 years) who were positive for D. fragilis, B. hominis or both between 2017 and 2018. The treatment consisted of triple antibiotics that were infused over two consecutive days through rectal enema. Faecal samples were collected from participants pre- and post-treatment and were tested for parasites using microscopy and polymerase chain reaction. Patients' symptoms were recorded prior and after the treatment as well as patient demographic data. RESULTS: Patients (n = 54), were either positive for B. hominis (37%), D. fragilis (35%) or both (28%). All patients completed the two-day treatment and no serious adverse effect was reported. The most common side effect experienced by the patients during the treatment was urine discolouration which was cleared by six weeks of follow-up. Common symptoms reported prior to treatment were diarrhoea, abdominal pain, constipation and fatigue. Other symptoms included abdominal discomfort, dizziness and blood in the stool. Eighty-nine percent of patients completed a final stool test post-treatment. At six weeks post-treatment, 79% of patients cleared the parasites from their faeces. Symptoms such as abdominal discomfort, dizziness and blood in the stool decreased significantly at both seven days and six weeks post-treatment (P < 0.040). The enema retention time, bowel preparation, previous antibiotic treatment or previous gastrointestinal problems had no significant effect on parasite eradication. CONCLUSION: Overall, eradication of parasites and improvement of clinical outcomes were observed in treated patients, showing the efficacy of this combination to eradicate the parasites and provide positive clinical outcome.

A Comparative Clinical Study of a Novel Pre-colonoscopy Bowel Capsule Preparation Against Two Commercially Available Liquid Preparations.

Background and Aims: Colonoscopy surveillance depends on effective bowel preparation. Inadequate bowel preparation can lead to inaccurate clinical diagnosis, insufficient visualization of the colon and increased risk of missed diagnosis. This study aimed to compare the efficacy and safety of a novel Capsule Bowel Preparation (RitePrep), high-volume (2L) polyethylene glycol electrolyte solution (MoviPrep®) and low-volume (1L) polyethylene glycol electrolyte solution (Plenvu™). Methods: Patients (n = 120) were divided into three groups and were administered either RitePrep, MoviPrep® or Plenvu™ as a pre-colonoscopy bowel preparation followed by a colonoscopy at a single center. Validated Boston Bowel Preparation Score (BBPS) and bubble score were used to evaluate bowel cleanliness. Blood tests were also evaluated. The scores and the blood results were analyzed using Kruskal-Wallis and Chi-squared tests. Results: A total of 120 patients (median age of 55; 57 males) [RitePrep (n = 40), MoviPrep® (n = 40) and Plenvu™ (n = 40)] were included in the study. RitePrep was the most effective method for cleansing the bowel, with a significantly higher median BBPS compared to MoviPrep® and Plenvu™ (p = 0.006 and 0.024, respectively). Nearly 50% of the patients in Plenvu™ group showed increased serum osmolality disturbance. Nausea and vomiting were higher in Plenvu™ and MoviPrep® groups than RitePrep group. Conclusions: RitePrep was demonstrated to be a more effective and safe preparation than the other two preparations. RitePrep was not only well-tolerated by all patients; the preparation sufficiently cleared the ascending, transverse, and descending colon, enabling optimal visualization for the clinician. RitePrep was also much safer than the comparators, with no alteration in electrolytes measured. For both the clinician and the patient, RitePrep was the preferred preparation.

Docosahexaenoic acid supplementation of preterm infants and parent-reported symptoms of allergic disease at 7 years corrected age: follow-up of a randomized controlled trial.

BACKGROUND: Docosahexaenoic acid (DHA, 22:6n-3) supplementation in the prenatal period is associated with a reduction in the incidence of some symptoms of allergic disease. Infants born preterm are at increased risk of allergic disease, but it is unknown if DHA supplementation reduces the risk of childhood allergies. OBJECTIVES: The aim of this study was to determine if supplementation of infants born at <33 wk gestation with high-DHA compared with standard-DHA enteral feeds decreases the incidence and severity of parent-reported allergic disease symptoms at a corrected age (CA) of 7 y. METHODS: This study was a follow-up of an Australian multicenter randomized controlled trial. Infants were given high-DHA (∼1% total fatty acids) or standard-DHA (∼0.3% total fatty acids) enteral feeds from 2-4 d of postnatal age until 40 wk postmenstrual age. Parent-reported incidence of respiratory allergic disease symptoms including wheeze and rhinitis at 7 y CA were the main outcomes. Other outcomes included the incidence of eczema symptoms; severity of any symptoms; and the incidence of wheeze, rhinitis, rhinoconjunctivitis, and eczema from birth to 7 y CA. RESULTS: Data were available for 569 of 657 (87%) children originally randomized. Symptoms of wheeze or rhinitis at 7 y CA did not differ between high- and standard-DHA groups [wheeze: RR: 1.10; 95% CI: 0.73, 1.65; P = 0.66; rhinitis: RR: 1.09; 95% CI: 0.81, 1.46; P = 0.59]. There was no difference in other allergic disease symptoms at 7 y CA or in the severity of symptoms. Parent-reported symptoms of wheeze, rhinitis, rhinoconjunctivitis, or eczema from birth to 7 y CA did not differ between the groups. CONCLUSIONS: High-dose DHA supplementation of infants born at <33 wk gestation did not alter allergic disease symptoms or severity at 7 y CA, or from birth to 7 y CA compared with standard-dose DHA. This trial was registered with the Australian New Zealand Clinical Trials Registry as ANZCTR 12606000327583 (http://www.anzctr.org.au).

Implementation of a patient blood management program in an Australian private hospital orthopedic unit.

BACKGROUND: Preoperative anemia in surgical patients has been linked to increased rates of allogeneic blood transfusion (ABT) and associated adverse patient outcomes such as prolonged ventilation in intensive care, increased length of hospital stay, and infections. We conducted a multifaceted implementation for orthopedic surgeons to improve preoperative patient assessment of anemia and iron deficiency to reduce perioperative blood transfusions. MATERIALS AND METHODS: Using a before-and-after study design of independent samples, we recruited a convenience sample of surgeons who performed primary total hip arthroplasty at 1 Australian private hospital. Our implementation intervention consisted of: executive support, interactive education, and peer-to-peer support to encourage adherence to the National Blood Authority's Patient Blood Management Program (PBMP) guidelines. We also used monthly reminders, e-learning access, and posters. Pre and post medical record audits evaluated preoperative blood tests, preoperative anemia, and number of blood units transfused between day of surgery until discharge. The primary outcome was an increase in the proportion of patients with preoperative blood tests undertaken prior to total hip arthroplasty surgery as recommended by the PBMP guidelines. RESULTS: Audits from 239 pre- and 263 postimplementation patients from 3 surgeons were conducted. Our primary outcome showed a significantly increased proportion of patients who had all the required preoperative tests postimplementation (0% to 94.6%; P<0.0001). Administration of ABT significantly decreased (pre: 9.2%, n=22; post: 2.3%, n=6; P=0.001) as well as the standard 2 blood units transfused (pre: 73%, n=16; post: 17%, n=1; P=0.022). The time between preoperative tests and day of surgery increased from 16 to 20 days (P<0.0001), allowing more time for physician's review of test results. CONCLUSION: Our results demonstrated successful implementation of a targeted PBMP to improve preoperative assessment to diagnose and treat anemia and/or iron deficiency prior to orthopedic surgery. This avoided unnecessary ABT and therefore mitigated potential risk to the patient.

Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood.

BACKGROUND: Allergies have become more prevalent globally over the last 20 years. Dietary consumption of n-3 (or omega 3) long chain polyunsaturated fatty acids (LCPUFA) has declined over the same period of time. This, together with the known role of n-3 LCPUFA in inhibiting inflammation, has resulted in speculation that n-3 LCPUFA may prevent allergy development. Dietary n-3 fatty acids supplements may change the developing immune system of the newborn before allergic responses are established, particularly for those with a genetic predisposition to the production of the immunoglobulin E (IgE) antibody. Individuals with IgE-mediated allergies have both the signs and symptoms of the allergic disease and a positive skin prick test (SPT) to the allergen. OBJECTIVES: To assess the effect of n-3 LCPUFA supplementation in pregnant and/or breastfeeding women on allergy outcomes (food allergy, atopic dermatitis (eczema), allergic rhinitis (hay fever) and asthma/wheeze) in their children. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 August 2014), PubMed (1966 to 01 August 2014), CINAHL via EBSCOhost (1984 to 01 August 2014), Scopus (1995 to 01 August 2014), Web of Knowledge (1864 to 01 August 2014) and ClinicalTrials.gov (01 August 2014) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the effect of n-3 LCPUFA supplementation of pregnant and/or lactating women (compared with placebo or no treatment) on allergy outcomes of the infants or children. Trials using a cross-over design and trials examining biochemical outcomes only were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and trial quality and performed data extraction. Where the review authors were also investigators on trials selected, an independent reviewer assessed trial quality and performed data extraction. MAIN RESULTS: Eight trials involving 3366 women and their 3175 children were included in the review. In these trials, women were supplemented with n-3 LCPUFA during pregnancy (five trials), lactation (two trials) or both pregnancy and lactation (one trial). All trials randomly allocated women to either a n-3 LCPUFA supplement or a control group. The risk of bias varied across the eight included trials in this review with only two trials with a low risk of selection, performance and attrition bias.N-3 LCPUFA supplementation showed a clear reduction in the primary outcome of any allergy (medically diagnosed IgE mediated) in children aged 12 to 36 months (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.98; two RCTs; 823 children), but not beyond 36 months (RR 0.86, 95% CI 0.61 to 1.20; one RCT, 706 children). For any allergy (medically diagnosed IgE mediated and/or parental report), no clear differences were seen in children either at 12 to 36 months (RR 0.89, 95% CI 0.71 to 1.11; two RCTs, 823 children) or beyond 36 months of age (RR 0.96, 95% CI 0.84 to 1.09; three RCTs, 1765 children).For the secondary outcomes of specific allergies there were no clear differences for food allergies at 12 to 36 months and beyond 36 months, but a clear reduction was seen for children in their first 12 months with n-3 LCPUFA (both for medically diagnosed IgE mediated and medically diagnosed IgE mediated and/or parental report). There was a clear reduction in medically diagnosed IgE-mediated eczema with n-3 LCPUFA for children 12 to 36 months of age, but not at any other time point for both medically diagnosed IgE mediated and medically diagnosed IgE mediated and/or parental report. No clear differences for allergic rhinitis or asthma/wheeze were seen at any time point for both medically diagnosed IgE mediated, and medically diagnosed IgE mediated and/or parental report.There was a clear reduction in children's sensitisation to egg and sensitisation to any allergen between 12 to 36 months of age when mothers were supplemented with n-3 LCPUFA.In terms of safety for the mother and child, n-3 LCPUFA supplementation during pregnancy did not show increased risk of postpartum haemorrhage or early childhood infections. AUTHORS' CONCLUSIONS: Overall, there is limited evidence to support maternal n-3 LCPUFA supplementation during pregnancy and/or lactation for reducing allergic disease in children. Few differences in childhood allergic disease were seen between women who were supplemented with n-3 LCPUFA and those who were not.

Dietary n-3 LC-PUFA during the perinatal period as a strategy to minimize childhood allergic disease.

There has been growing interest in the role of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in the modulation of the immune response during early childhood and whether this may translate to a reduction in childhood allergic disease. Several randomized controlled trials of n-3 LC-PUFA supplementation have been reported, largely involving children who are at high hereditary risk of developing allergies. These studies relatively consistently indicate that supplementation during pregnancy results in fewer children with atopic eczema in early childhood. On the other hand, supplementation studies confined exclusively to the postnatal period have demonstrated mixed results with one trial showing no effect and the other suggesting a transient effect on symptoms of respiratory disease. In summary, supplementation with n-3 LC-PUFA during the perinatal period and before allergic response is established may be a useful strategy to prevent early childhood allergic disease in children at high hereditary risk. Further work is needed to establish the optimal period of supplementation and whether longer term benefits exist.