Factors affecting timing of loop ileostomy closure: a regional centre's experience with 106 patients.

INTRODUCTION: The burden of defunctioning ileostomy is significant with up to two thirds of patients reporting stoma-related morbidity. While timely reversal is safe and cost-effective, the time to reversal in regional Australian hospitals is not well described in professional publications. We aim to assess the current timeliness of ileostomy closure and identify possible reasons for delaying closure. METHODS: A retrospective analysis of loop ileostomies created and reversed in Launceston General Hospital for both rectal cancer surgery and other benign indications was undertaken. Patients with loop ileostomy created between 2010 and 2020 were included. Clinical data of timing of events, complications, readmission and stoma follow-up were recorded; and analysed using multivariate regression analyses to identify clinically relevant risk factors for delayed closure. RESULTS: A total of 123 patients underwent loop-ileostomy formation during the study period, of which 106 patients (86.2%) were reversed. Median time to closure was 8.5 months (IQR 5.2-12.4) for patients with rectal cancers, compared to 5.2 months (IQR 3.6-9.3) for patients who did not have rectal cancer, with a difference of 3.4 months (95% CI 0.9, 5.9; P = 0.008). Adjuvant chemotherapy and unexpected readmission to hospital were associated with delayed reversal (P = 0.0081 and P = 0.0005, respectively). CONCLUSION: Stoma reversal is often scheduled 3-6 months after creation. More than two-thirds of patients experienced delays due to changing clinical concerns and non-clinical factors, such as unexpected delays at each stage of surgical planning. Early placement on the waiting list and better-coordinated follow-ups may expedite reversal surgery and reduce associated morbidities.

Assessing the Variability of the Twelfth Rib as a Landmark for Percutaneous Nephrolithotomy Using Computed Tomography.

Background: The variability in length of the twelfth rib is mentioned in the literature but has never been formally studied. The highly variable rib length provides a challenge for urologists seeking a consistent landmark for Percutaneous Nephrolithotomy (PCNL). We set out to determine whether the twelfth rib is safe to use as a consistent landmark for surgery. Methods: Single centre, cross-sectional retrospective observational study and analysis of CT scans of 100 adults who had imaging between 23rd March and 12th April 2020. The distance from the mid-sagittal line to the twelfth rib tip in the axial plane was measured as was the distance from the twelfth rib tip to the kidney, spleen and liver. Results: Length from the mid-sagittal line to the right twelfth rib tip varied from 46 (percentile 95% CI 40 to 57) to 136mm (percentile 95% CI 133 to 138). On the left, the distances varied from 55 (percentile 95% CI 50 to 64) to 134mm (percentile 95% CI 131 to 135). Twenty-three percent of people had an organ lying between the tip of the twelfth rib and the kidney on the right and 11% on the left. Conclusion: The twelfth rib is highly variable in length. Similar variability was recorded in the distance from the tip to intra-abdominal organs. Due to the frequency of organs lying between the tip of the rib and the kidney it should not be used as a landmark for accessing the kidney without prior knowledge of an individual patient's anatomy as seen on imaging.

Epidemiology, management and outcomes of Cryptococcus gattii infections: A 22-year cohort.

BACKGROUND: Cryptococcus gattii is a globally endemic pathogen causing disease in apparently immune-competent hosts. We describe a 22-year cohort study from Australia's Northern Territory to evaluate trends in epidemiology and management, and outcome predictors. METHODS: A retrospective cohort study of all C. gattii infections at the northern Australian referral hospital 1996-2018 was conducted. Cases were defined as confirmed (culture-positive) or probable. Demographic, clinical and outcome data were extracted from medical records. RESULTS: 45 individuals with C. gattii infection were included: 44 Aboriginal Australians; 35 with confirmed infection; none HIV positive out of 38 tested. Multifocal disease (pulmonary and central nervous system) occurred in 20/45 (44%). Nine people (20%) died within 12 months of diagnosis, five attributed directly to C. gattii. Significant residual disability was evident in 4/36 (11%) survivors. Predictors of mortality included: treatment before the year 2002 (4/11 versus 1/34); interruption to induction therapy (2/8 versus 3/37) and end-stage kidney disease (2/5 versus 3/40). Prolonged antifungal therapy was the standard approach in this cohort, with median treatment duration being 425 days (IQR 166-715). Ten individuals had adjunctive lung resection surgery for large pulmonary cryptococcomas (median diameter 6cm [range 2.2-10cm], versus 2.8cm [1.2-9cm] in those managed non-operatively). One died post-operatively, and 7 had thoracic surgical complications, but ultimately 9/10 (90%) treated surgically were cured compared with 10/15 (67%) who did not have lung surgery. Four patients were diagnosed with immune reconstitution inflammatory syndrome which was associated with age <40 years, brain cryptococcomas, high cerebrospinal fluid pressure, and serum cryptococcal antigen titre >1:512. CONCLUSION: C. gattii infection remains a challenging condition but treatment outcomes have significantly improved over 2 decades, with eradication of infection the norm. Adjunctive surgery for the management of bulky pulmonary C. gattii infection appears to increase the likelihood of durable cure and likely reduces the required duration of antifungal therapy.

An Audit of Pre-Pregnancy Maternal Obesity and Diabetes Screening in Rural Regional Tasmania and Its Impact on Pregnancy and Neonatal Outcomes.

Maternal obesity in pregnancy, a growing health problem in Australia, adversely affects both mothers and their offspring. Gestational diabetes mellitus (GDM) is similarly associated with adverse pregnancy and neonatal complications. A low-risk digital medical record audit of antenatal and postnatal data of 2132 pregnant mothers who gave birth between 2016-2018 residing in rural-regional Tasmania was undertaken. An expert advisory group guided the research and informed data collection. Fifty five percent of pregnant mothers were overweight or obese, 43.6% gained above the recommended standards for gestational weight gain and 35.8% did not have an oral glucose tolerance test. The audit identified a high prevalence of obesity among pregnant women and low screening rates for gestational diabetes mellitus associated with adverse maternal and neonatal pregnancy outcomes. We conclude that there is a high prevalence of overweight and obesity among pregnant women in rural regional Tasmania. Further GDM screening rates are low, which require addressing.

Preoperative physiotherapy is cost-effective for preventing pulmonary complications after major abdominal surgery: a health economic analysis of a multicentre randomised trial.

QUESTION: Is preoperative physiotherapy cost-effective in reducing postoperative pulmonary complications (PPC) and improving quality-adjusted life years (QALYs) after major abdominal surgery? DESIGN: Cost-effectiveness analysis from the hospitals' perspective within a multicentre randomised controlled trial with concealed allocation, blinded assessors and intention-to-treat analysis. PARTICIPANTS: Four hundred and forty-one adults awaiting elective upper abdominal surgery attending pre-anaesthetic clinics at three public hospitals in Australia and New Zealand. INTERVENTIONS: The experimental group received an information booklet and a 30-minute face-to-face session, involving respiratory education and breathing exercise training, with a physiotherapist. The control group received the information booklet only. OUTCOME MEASURES: The probability of cost-effectiveness and incremental net benefits was estimated using bootstrapped incremental PPC and QALY cost-effectiveness ratios plotted on cost-effectiveness planes and associated probability curves through a range of willingness-to-pay amounts. Cost-effectiveness modelling utilised 21-day postoperative hospital cost audit data and QALYs estimated from Short Form-Six Domain health utilities and mortality to 12 months. RESULTS: Preoperative physiotherapy had 95% probability of being cost-effective with an incremental net benefit to participating hospitals of A$4,958 (95% CI 10 to 9,197) for each PPC prevented, given that the hospitals were willing to pay $45,000 to provide the service. Cost-utility for QALY gains was less certain. Sensitivity analyses strengthened cost-effectiveness findings. Improved cost-effectiveness and QALY gains were detected when experienced physiotherapists delivered the intervention. CONCLUSIONS: Preoperative physiotherapy aimed at preventing PPCs was highly likely to be cost-effective from the hospitals' perspective. For each PPC prevented, preoperative physiotherapy is likely to cost the hospitals less than the costs estimated to treat a PPC after surgery. Potential QALY gains require confirmation. TRIAL REGISTRATION: ACTRN12613000664741.

Physiotherapist administered, non-invasive ventilation to reduce postoperative pulmonary complications in high-risk patients following elective upper abdominal surgery; a before-and-after cohort implementation study.

OBJECTIVES: To (1) determine whether short, 30-minute sessions of non-invasive ventilation (NIV) is associated with fewer postoperative pulmonary complications (PPC) following elective high-risk upper abdominal surgery and (2) measure feasibility and safety of this intervention when delivered by physiotherapists. DESIGN: Prospective, pre post cohort, observational, single-centre study. SETTING: Primary referral hospital in Australia. PARTICIPANTS: A total of 182 consecutive high-risk elective upper abdominal surgery patients consisting of 101 pre cohort participants compared to 81 post cohort participants. INTERVENTIONS: Both groups received standardised preoperative physiotherapy and early postoperative mobilisation. The post cohort group received five additional 30-minute NIV sessions in the first two postoperative days. MAIN OUTCOME MEASURE: Primary outcome measure was PPC incidence within the first seven postoperative days. Secondary outcomes included feasibility and safety of physiotherapy-led NIV. RESULTS: Incidence of PPC (7% vs 18%, adjusted relative risk 0.24; 95% CI 0.10 to 0.59, p=0.002) was less in the NIV group compared to those who received no NIV. Mean time to first NIV session was 18.6 (SD 11.0) hours with 74% of participants receiving NIV within 24-hours of surgery. There were no major adverse events. CONCLUSION: These findings suggest PPC reduction may be possible with postoperative NIV following high-risk elective upper abdominal surgery. Results should be seen as hypothesis-generating associations only considering the significant limitations to this study. Physiotherapy-led NIV was delivered safely to ICU and ward patients. However, the planned protocol was not feasible and appropriate physiotherapy staffing and/or a multidisciplinary approach may be required to provide this service successfully. TRIAL REGISTRATION: LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre Operative Physiotherapy) ANZCTR-12613000664741 (for pre cohort group only).

Non-Invasive Positive airway Pressure thErapy to Reduce Postoperative Lung complications following Upper abdominal Surgery (NIPPER PLUS): protocol for a single-centre, pilot, randomised controlled trial.

INTRODUCTION: Postoperative pulmonary complications (PPCs) are a common serious complication following upper abdominal surgery leading to significant consequences including increased mortality, hospital costs and prolonged hospitalisation. The primary objective of this study is to detect whether there is a possible signal towards PPC reduction with the use of additional intermittent non-invasive ventilation (NIV) compared with continuous high-flow nasal oxygen therapy alone following high-risk elective upper abdominal surgery. Secondary objectives are to measure feasibility of: (1) trial conduct and design and (2) physiotherapy-led NIV and a high-flow nasal oxygen therapy protocol, safety of NIV and to provide preliminary costs of care information of NIV and high-flow nasal oxygen therapy. METHODS AND ANALYSIS: This is a single-centre, parallel group, assessor blinded, pilot, randomised trial, with 130 high-risk upper abdominal surgery patients randomly assigned via concealed allocation to either (1) usual care of continuous high-flow nasal oxygen therapy for 48 hours following extubation or (2) usual care plus five additional 30 min physiotherapy-led NIV sessions within the first two postoperative days. Both groups receive standardised preoperative physiotherapy and postoperative early ambulation. No additional respiratory physiotherapy is provided to either group. Outcome measures will assess incidence of PPC within the first 14 postoperative days, recruitment ability, physiotherapy-led NIV and high-flow nasal oxygen therapy protocol adherence, adverse events relating to NIV delivery and costs of providing a physiotherapy-led NIV and a high-flow nasal oxygen therapy service following upper abdominal surgery. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the relevant institution and results will be published to inform future multicentre trials. TRIAL REGISTRATION NUMBER: ACTRN12617000269336; Pre-results.

Does Dexamethasone Reduce Hospital Readiness for Discharge, Pain, Nausea, and Early Patient Satisfaction in Hip and Knee Arthroplasty? A Randomized, Controlled Trial.

BACKGROUND: Reduction in postoperative pain, nausea, and vomiting in patients undergoing total joint arthroplasty may facilitate earlier discharge from hospital and reduce healthcare costs. This study was performed to primarily assess whether perioperative dexamethasone reduced hospital length of stay and to assess the effect on pain, nausea and vomiting, and patient satisfaction. METHODS: One hundred sixty-four patients undergoing total hip arthroplasty or total knee arthroplasty were randomized to receive either 8 mg intravenous dexamethasone (n = 86) or placebo (n = 78) at induction and at 24 hours postsurgery. The primary outcome was length of stay and secondary outcomes were pain and nausea visual analog scale scores, analgesic and antiemetic usage, blood glucose level, and patient satisfaction. RESULTS: Participants in the study group achieved earlier readiness for discharge. There was a 20% reduction in pain scores and morphine usage was 27% lower in the study group. Nausea scores were similar in the 2 groups but there was lower antiemetic usage in the study group. Satisfaction scores at 6 weeks postsurgery in the dexamethasone group were significantly higher than the placebo group. There was no difference in complication rates between the 2 groups. CONCLUSION: The administration of intravenous dexamethasone could lead to earlier readiness for discharge especially in patients undergoing elective total hip arthroplasty, primarily by a reduction in postoperative pain scores and/or morphine requirements.

Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.

OBJECTIVE: To assess the efficacy of a single preoperative physiotherapy session to reduce postoperative pulmonary complications (PPCs) after upper abdominal surgery. DESIGN: Prospective, pragmatic, multicentre, patient and assessor blinded, parallel group, randomised placebo controlled superiority trial. SETTING: Multidisciplinary preadmission clinics at three tertiary public hospitals in Australia and New Zealand. PARTICIPANTS: 441 adults aged 18 years or older who were within six weeks of elective major open upper abdominal surgery were randomly assigned through concealed allocation to receive either an information booklet (n=219; control) or preoperative physiotherapy (n=222; intervention) and followed for 12 months. 432 completed the trial. INTERVENTIONS: Preoperatively, participants received an information booklet (control) or an additional 30 minute physiotherapy education and breathing exercise training session (intervention). Education focused on PPCs and their prevention through early ambulation and self directed breathing exercises to be initiated immediately on regaining consciousness after surgery. Postoperatively, all participants received standardised early ambulation, and no additional respiratory physiotherapy was provided. MAIN OUTCOME MEASURES: The primary outcome was a PPC within 14 postoperative hospital days assessed daily using the Melbourne group score. Secondary outcomes were hospital acquired pneumonia, length of hospital stay, utilisation of intensive care unit services, and hospital costs. Patient reported health related quality of life, physical function, and post-discharge complications were measured at six weeks, and all cause mortality was measured to 12 months. RESULTS: The incidence of PPCs within 14 postoperative hospital days, including hospital acquired pneumonia, was halved (adjusted hazard ratio 0.48, 95% confidence interval 0.30 to 0.75, P=0.001) in the intervention group compared with the control group, with an absolute risk reduction of 15% (95% confidence interval 7% to 22%) and a number needed to treat of 7 (95% confidence interval 5 to 14). No significant differences in other secondary outcomes were detected. CONCLUSION: In a general population of patients listed for elective upper abdominal surgery, a 30 minute preoperative physiotherapy session provided within existing hospital multidisciplinary preadmission clinics halves the incidence of PPCs and specifically hospital acquired pneumonia. Further research is required to investigate benefits to mortality and length of stay. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ANZCTR 12613000664741.

Physiotherapy education and training prior to upper abdominal surgery is memorable and has high treatment fidelity: a nested mixed-methods randomised-controlled study.

OBJECTIVES: To (1) assess memorability and treatment fidelity of pre-operative physiotherapy education prior to elective upper abdominal surgery and, (2) to explore patient opinions on pre-operative education. DESIGN: Mixed-methods analysis of a convenience sample within a larger parallel-group, double-blinded, randomised controlled trial with concealed allocation and intention-to-treat analysis. SETTING: Tertiary Australian hospital. PARTICIPANTS: Twenty-nine patients having upper abdominal surgery attending pre-admission clinic within six-weeks of surgery. INTERVENTION: The control group received an information booklet about preventing pulmonary complications with early ambulation and breathing exercises. The experimental group received an additional face-to-face 30-minute physiotherapy education and training session on pulmonary complications, early ambulation, and breathing exercises. OUTCOME MEASURES: Primary outcome was proportion of participants who remembered the taught breathing exercises following surgery. Secondary outcomes were recall of information sub-items and attainment of early ambulation goals. These were measured using standardised scoring of a semi-scripted digitally-recorded interview on the 5th postoperative day, and the attainment of early ambulation goals over the first two postoperative days. RESULTS: Experimental group participants were six-times more likely to remember the breathing exercises (95%CI 1.7 to 22) and 11-times more likely (95%CI 1.6 to 70) to report physiotherapy as the most memorable part of pre-admission clinic. Participants reported physiotherapy education content to be detailed, interesting, and of high value. Some participants reported not reading the booklet and professed a preference for face-to-face information delivery. CONCLUSION: Face-to-face pre-operative physiotherapy education and training prior to upper abdominal surgery is memorable and has high treatment fidelity. TRIAL REGISTRATION: ACTRN-12613000664741.

Utility of antenatal clinical factors for prediction of postpartum outcomes in women with gestational diabetes mellitus (GDM).

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with life-long increased risk of type 2 diabetes: affected women are advised to undergo oral glucose tolerance testing (OGTT) at 6-12 weeks postpartum, then glucose screening every 1-3 years. AIMS: We investigated whether in women with GDM, antenatal clinical factors predicted postpartum abnormal glucose tolerance and compliance with screening. MATERIALS AND METHODS: In women with GDM delivering 2007 to mid-2009 in a single hospital, antenatal/obstetric data and glucose tests at 6-12 weeks postpartum and during 5.5 years post-pregnancy were retrospectively collected. Predictors of return for testing and abnormal glucose tolerance were identified using multivariate analysis. RESULTS: Of 165 women, 117 (70.9%) returned for 6-12 week postpartum OGTT: 23 (19.6%) were abnormal. Smoking and parity, independent of socioeconomic status, were associated with non-return for testing. Fasting glucose ≥5.4 mmol/L on pregnancy OGTT predicted both non-return for testing and abnormal OGTT. During 5.5 years post-pregnancy, 148 (89.7%) women accessed glucose screening: nine (6.1%) developed diabetes, 33 (22.3%) had impaired fasting glucose / impaired glucose tolerance. Predictors of abnormal glucose tolerance were fasting glucose ≥5.4 mmol/L and 2-h glucose ≥9.3 mmol/L on pregnancy OGTT (~2.5-fold increased risk), and polycystic ovary syndrome (~3.4 fold increased risk). Risk score calculation, based on combined antenatal factors, did not improve predictions. CONCLUSIONS: Antenatal clinical factors were modestly predictive of return for testing and abnormal glucose tolerance post-pregnancy in women with GDM. Risk score calculations were ineffective in predicting outcomes: risk scores developed in other populations require validation. Ongoing glucose screening is indicated for all women with GDM.

Intravenous ferric carboxymaltose versus standard care in the management of postoperative anaemia: a prospective, open-label, randomised controlled trial.

BACKGROUND: Despite increasing efforts in perioperative management, postoperative iron deficiency anaemia persists, and few data are available about the management of this condition. In this study, we aimed to determine whether giving postoperative intravenous iron (in the form of ferric carboxymaltose) improved iron stores, haemoglobin concentrations, and outcomes following surgery. METHODS: We did a prospective, open-label, randomised, controlled study of patients at two centres (a general hospital and a private health-care centre) in Tasmania, Australia, undergoing elective surgery with functional iron deficiency anaemia (haemoglobin 70-120 g/L and ferritin ≤100 µg/L or iron saturation ≤20%), measured at day 1 postoperatively. Consecutive routine elective surgical patients who were having major orthopaedic surgery, abdominal, and genitourinary surgery, and other surgeries were recruited. Via computer-generated randomisation, patients were randomly assigned (1:1) to either a single dose of intravenous 1000 mg ferric carboxymaltose (intervention group) or standard care, consisting of observation (control group). The primary endpoints were changes in haemoglobin concentrations and iron stores at 4 weeks postoperatively, and the number of transfused units of blood required postoperatively until discharge. Analyses were done on an intention-to-treat basis. This trial is registered with the Australian New Zealand Clinical Trials Registry and the WHO International Clinical Trials Registry platform (number ACTRN12614001261606). FINDINGS: Between Dec 17, 2014, and May 7, 2015, we recruited 201 eligible patients, assigning 103 to intravenous ferric carboxymaltose and 98 to standard care only. Baseline mean haemoglobin was 105·5 g/L (SD 13·8) in the standard care group versus 106·2 g/L (11·9) in the ferric carboxymaltose group, improving at 4 weeks to 121·5 g/L (SD 14·5) in the standard group and 130·1 g/L (11·3) in the ferric carboxymaltose group (mean difference of 7·84 g/L, 95% CI 3·79-11·9; p<0·0001 in favour of the ferric carboxymaltose group). Significant improvements in serum iron (5·36 µmol/L, 95% CI 3·62-7·09; p<0·0001), iron saturation (11·40%, 95% CI 8·33-14·50; p<0·0001), and serum ferritin concentrations (468 µg/L, 95% CI 355-582; p<0·0001) were also noted in the ferric carboxymaltose group at 4 weeks compared with standard care, although no differences were noted in transferrin concentrations (0·06 g/L, 95% CI -0·97 to 1·09; p=0·62). Fewer transfused blood units were given in the ferric carboxymaltose group (to one of 103 patients [<1%]) than in the standard care group (to five of 98 patients [5%]; incidence rate ratio 0·10; 95% CI 0·01-0·85; p=0·035). No adverse events were observed with ferric carboxymaltose treatment. INTERPRETATION: Postoperative intravenous ferric carboxymaltose is a feasible and pragmatic management approach in surgical patients with functional iron deficiency anaemia. Our study suggests that patient blood management guidelines should be updated, incorporating the use of postoperative intravenous iron infusion to optimise patient outcomes. Further trials to assess our approach are warranted. FUNDING: Launceston General Hospital, Launceston, TAS, Australia, in affiliation with the University of Tasmania, TAS, Australia.

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

BACKGROUND: Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. METHODS/DESIGN: The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. DISCUSSION: The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.

Effects of atorvastatin on oxidative stress in chronic kidney disease.

AIM: Statins have pleiotropic effects that include attenuation of oxidative stress that may be relevant for chronic kidney disease (CKD) patients. We investigated the effect of long-term atorvastatin therapy on oxidative stress biomarkers in CKD patients. METHODS: This was a pre-specified secondary analysis of data from a randomized, double-blind, placebo-controlled trial (Lipid lowering and Onset of Renal Disease, LORD) in CKD patients. Participants received 10 mg/day atorvastatin (n = 47) or placebo (n = 39) for 3 years. Plasma measures (total F2-isoprostanes, malondialdehyde. protein carbonyls, uric acid, glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC) ) were performed at baseline and at 3 years. Age and sex matched participants (n = 34) with normal kidney function were controls. RESULTS: CKD patients had significantly (P < 0.05) increased F2-isoprostanes and uric acid and decreased GPx activity compared with controls. When comparing the treatment (atorvastatin (A) vs placebo (P) ) change from baseline to 3 years, there were no significant differences (P > 0.05) in the group difference of the change values: (mean (95% CI), F2-isoprostanes = 5.3 (-29.2 to 39.8) pg/mL, protein carbonyls = 0.03 (-0.13 to 0.19) nmol/mg, GPx activity = -0.10 (-4.73 to 4.52) (U/L), uric acid = 8.8 (-33.9 to 51.6) µmol/L or TAC = -0.03 (-0.10 to 0.04) mmol/L. A significant difference (P = 0.04) in the change in malondialdehyde between groups, 1.52(0.09 to 2.96) µmol/L, was due to a large decrease in the placebo group. CONCLUSION: CKD patients had elevated oxidative stress that was not attenuated by atorvastatin 10 mg/day for 3 years.

Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study.

OBJECTIVE: To estimate the efficacy of a probiotic yogurt compared to a pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in children. DESIGN AND SETTING: This was a multisite, randomised, double-blind, placebo-controlled clinical trial conducted between September 2009 and 2012. The study was conducted through general practices and pharmacies in Launceston, Tasmania, Australia. PARTICIPANTS AND INTERVENTIONS: Children (aged 1-12 years) prescribed antibiotics, were randomised to receive 200 g/day of either yogurt (probiotic) containing Lactobacillus rhamnosus GG (LGG), Bifidobacterium lactis (Bb-12) and Lactobacillus acidophilus (La-5) or a pasteurised yogurt (placebo) for the same duration as their antibiotic treatment. OUTCOMES: Stool frequency and consistency were recorded for the duration of treatment plus 1 week. Primary outcome was stool frequency and consistency, classified at different levels of diarrhoea severity. Due to the small number of cases of diarrhoea, comparisons between groups were made using Fisher's exact analysis. RESULTS: 72 children commenced and 70 children (36 placebo and 34 probiotic) completed the trial. There were no incidents of severe diarrhoea (stool consistency ≥6, ≥3 stools/day for ≥2 consecutive days) in the probiotic group and six in the placebo group (Fisher's exact p=0.025). There was also only one episode of minor diarrhoea (stool consistency ≥5, ≥2 stools/day for ≥2 days in the probiotic group compared to 21 in the placebo group (Fisher's exact p<0.001). The probiotic group reported fewer adverse events (1 had abdominal pain, 1 vomited and 1 had headache) than the placebo group (6 had abdominal pain, 4 had loss of appetite and 1 had nausea). CONCLUSIONS: A yogurt combination of LGG, La-5 and Bb-12 is an effective method for reducing the incidence of antibiotic-associated diarrhoea in children. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12609000281291.

Pathways to palliative care for patients with chronic kidney disease.

BACKGROUND: Despite the terminal nature of chronic kidney disease (CKD), end-of-life care planning is often inconsistent and pathways to palliative care are unclear. Health professionals' perceptions of palliative care and the prevailing context may influence their end-of-life decision making. OBJECTIVES: To identify predictors of conservative treatment decisions and their associations with referral to palliative care, and to determine the perceptions that health professionals have about the role of palliative care in management of CKD. METHODS: A retrospective audit of deceased patients' charts, spanning three years, and a survey of renal healthcare professionals, documenting CKD palliative care practices, knowledge and attitudes was carried out. Records of all patients with CKD dying between 1 January 2006 and 31 December 2008 in Australian regional renal service were audited. Renal staff from the service were surveyed. Logistic regression for binomial outcomes and ordinal logistic regression when more than two outcome levels were involved; and thematic analysis using a continual cross comparative approach was undertaken. RESULTS: Loss of function, particularly from stroke, and severe pain are interpreted as representing levels of suffering which would justify the need to withdraw from renal replacement therapy. Family and/or patient indecision complicates and disrupts end-of-life care planning and can establish a cycle of ambiguity. Whilst renal healthcare professionals support early discussion of end-of-life care at predialysis education, congruity with the patient and family when making the final decision is of great importance. CONCLUSION: Healthcare professionals' beliefs, values and knowledge of palliative care influence their end-of-life care decisions. The influence of patient, family and clinicians involves negotiation and equivocation. Health professionals support the early discussion of end-of-life care in CKD at predialysis education to enable clearer decision making.

Effects of atorvastatin on biomarkers of inflammation in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with inflammation. The effects of atorvastatin on biomarkers of inflammation were assessed in CKD patients in the LORD trial. METHODS: 117 patients with serum creatinine >120 µmol/L were randomized to receive atorvastatin 10 mg/day (56) or placebo (61) and followed for a mean of 2.5 years. 33 individuals with normal kidney function were controls. Outcomes included comparison of changes in pentraxin-3 (PTX3), TNF-α, CRP, IL-6, IL-8, and IL-10 between atorvastatin and placebo-treated patients. RESULTS: At baseline, compared with controls, CKD patients had increased PTX3 (mean, 1.08 vs. 0.58 ng/mL; p < 0.001), CRP (4.9 vs. 1.5 mg/L; p < 0.001), IL-8 (6.00 vs. 4.58 pg/mL; p = 0.001), IL-10 (59.0 vs. 17.6 pg/mL; p = 0.007), and TNF-α (18.0 vs. 5.6 ng/mL; p < 0.001). In patients with raised baseline plasma IL-6/8/10 and/or PTX3 the eGFR decline during the trial was significantly less in those treated with atorvastatin compared to placebo (mean change, -3.36; vs. + 1.25 mL/min/1.73 m2/year; difference, 4.61 95% CI 0.98 - 8.25; p = 0.002), whilst those without raised inflammatory biomarkers showed no difference. Placebo treated patients with raised TNF-α levels had no eGFR decline (p > 0.90), whereas in atorvastatin-treated patients eGFR declined (p = 0.05). CONCLUSIONS: CKD patients with inflammation treated with atorvastatin had significantly less eGFR decline. Larger studies using statin therapy, specifically enrolling CKD patients with inflammation, may be worthwhile exploring.

Transcriptionally active human papillomavirus is strongly associated with Barrett's dysplasia and esophageal adenocarcinoma.

OBJECTIVES: The role of human papillomavirus (HPV) in Barrett's esophagus (BE) remains unclear. The few studies that have previously investigated HPV and esophageal adenocarcinoma (EAC) or BE have produced either negative data or positive results of doubtful clinical/etiological significance or have detected only low-risk HPV types. We therefore prospectively determined the prevalence of biologically active HPV in esophageal epithelium of patients representing the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. METHODS: HPV DNA was estimated by nested PCR and viral transcriptional activity detected by E6/7 oncogene mRNA expression and p16INK4A immunohistochemistry in fresh frozen and paraffin-embedded esophageal biopsies of patients with BE, Barrett's dysplasia (BD), and EAC, as well as controls. Biopsies were obtained from the transformation zone (squamocolumnar junction (SCJ)) and the lesion, or corresponding site in controls, i.e., 2 cm above the gastroesophageal junction (GEJ). RESULTS: Of the 261 patients, 81 were positive for HPV DNA. In controls and BE, the virus was mostly detected at the transformation zone. Compared with controls (18.0%), HPV positivity was significantly more common in BD (68.6%, incidence rate ratio (IRR) 2.94, 95% confidence interval (CI) 1.78-4.85, P<0.001) and EAC (66.7%, IRR 2.87, 95% CI 1.69-4.86, P<0.001), but not in BE (22.1%, IRR 1.06, 95% CI 0.60-1.85, P=0.85). Of the patients, 92.6% were high-risk (HR) HPV, i.e., types 16 and 18. Again, p16INK4A positivity was greatest in BD and EAC and much less in BE patients (44.1%, IRR 17.0 (95% CI 4.86-59.6, P<0.001), 44.4%, 17.0 (95% CI 4.87-59.4, P<0.001), and 10.6%, 3.93 (95% CI 1.01-15.3, P=0.048) respectively). In 66 HPV DNA-positive patients tested for E6/E7 mRNA, none of the control (n=16) or BE (n=13) individuals were positive, whereas 9/22 BD and 9/15 EAC patients demonstrated oncogene expression (P<0.001). When HPV DNA, p16INK4A, and E6/E7 mRNA were all positive, there was a very strong association with disease severity (SCJ: odds ratio (OR) 104, 95% CI 20.3-529, P<0.001; lesion: OR 62.2, 95% CI 12.4-311, P<0.001) than when all were negative. CONCLUSIONS: Transcriptionally active HR-HPV was strongly associated with BD and EAC, but was largely biologically irrelevant in BE and controls, suggesting a potential role in esophageal carcinogenesis. These data provide robust justification for further detailed longitudinal, interventional, and molecular studies.