Publications by authors named "Emma Flanagan"

44 Publications

Investigating the utility of COVID-19 antibody testing in end-stage renal disease patients receiving haemodialysis: a cohort study in the United Kingdom.

BMC Nephrol 2021 04 27;22(1):154. Epub 2021 Apr 27.

Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford, M6 8HD, UK.

Background: End-stage renal disease (ESRD) patients receiving haemodialysis (HD) are a vulnerable group of patients with increased mortality from COVID-19. Despite improved understanding, the duration of host immunity following COVID-19 infection and role of serological testing alone or in addition to real-time reverse transcription polymerase chain reaction (rRT-PCR) testing in the HD population is not fully understood, which this study aimed to investigate.

Methods: There were two parts to this study. Between 15th March 2020 to 15th July 2020, patients receiving HD who tested positive on rRT-PCR for SARS-CoV-2 were recruited into the COVID-19 arm, whilst asymptomatic patients without a previous diagnosis of COVID-19 were recruited to the epidemiological arm of the Salford Kidney Study (SKS). All patients underwent monthly testing for anti-SARS-CoV-2 antibodies as per routine clinical practice since August 2020. The aims were twofold: firstly, to determine seroprevalence and COVID-19 exposure in the epidemiological arm; secondly, to assess duration of the antibody response in the COVID-19 arm. Baseline characteristics were reviewed between groups. Statistical analysis was performed using SPSS. Mann-Whitney U and Chi-squared tests were used for testing significance of difference between groups.

Results: In our total HD population of 411 patients, 32 were PCR-positive for COVID-19. Of the remaining patients, 237 were recruited into the SKS study, of whom 12 (5.1%) had detectable anti-SARS-CoV-2 antibodies. Of the 32 PCR-positive patients, 27 (84.4%) were symptomatic and 25 patients admitted to hospital due to their symptoms. Of the 22 patients in COVID-19 arm that underwent testing for anti-SARS-CoV-2 IgG antibodies beyond 7 months, all had detectable antibodies. A higher proportion of the patients with COVID-19 were frail compared to patients without a diagnosis of COVID-19 (64.3% vs 34.1%, p = 0.003). Other characteristics were similar between the groups. Over a median follow up of 7 months, a higher number of deaths were recorded in patients with a diagnosis of COVID-19 compared to those without (18.7% vs 5.9%, p = 0.003).

Conclusions: Serological testing in the HD population is a valuable tool to determine seroprevalence, monitor exposure, and guide improvements for infection prevention and control (IPC) measures to help prevent local outbreaks. This study revealed HD patients mount a humoral response detectable until at least 7 months after COVID-19 infection and provides hope of similar protection with the vaccines recently approved.
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http://dx.doi.org/10.1186/s12882-021-02366-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075608PMC
April 2021

A Single Educational Intervention Improves Pregnancy-Related Knowledge and Emotional Health Among Women With IBD Who Are Pregnant or Wish to Conceive.

Inflamm Bowel Dis 2021 Mar 11. Epub 2021 Mar 11.

Department of Gastroenterology, St. Vincent's Hospital, Melbourne, Australia.

Background: There is considerable interest in improving the education and care of women with inflammatory bowel disease (IBD) to improve pregnancy outcomes. Despite increased awareness, not all women with IBD have access to pregnancy-related education and the quality of counseling is variable. We aimed to assess the effectiveness of a simple educational intervention for improving pregnancy-related knowledge and to evaluate the effect of education on patient outcomes including anxiety, depression, and quality of life in women with IBD.

Methods: This prospective study of women with IBD who were pregnant or planning a pregnancy evaluated the effectiveness of a single gastroenterologist-led educational intervention in improving pregnancy-related knowledge, measured using the Crohn's and Colitis Pregnancy Knowledge score 1 month postintervention. Secondary outcomes included the effect on anxiety and depression, quality of life, medication adherence, and patient satisfaction.

Results: One hundred women with IBD were recruited. Fifty percent were pregnant at the time of the intervention. Baseline knowledge scores were similar independent of the patients' pregnancy status or whether they had previously received counseling from their gastroenterologist. Median Crohn's and Colitis Pregnancy Knowledge scores postintervention (n = 82) were higher than preintervention scores (14/17 vs 10/17; P < 0.001). In addition, 32% of patients had poor knowledge at baseline (score ≤7/17), compared to only 5% after the intervention (P < 0.001). There was a significant improvement in total anxiety and depression and quality of life scores postintervention. Medication adherence and patient satisfaction were excellent.

Conclusions: Uptake of this gastroenterologist-led educational intervention has the potential to improve pregnancy knowledge, promote medication adherence, and enhance quality of life for women with IBD globally.
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http://dx.doi.org/10.1093/ibd/izab021DOI Listing
March 2021

Maternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates.

Aliment Pharmacol Ther 2021 04 19;53(7):810-820. Epub 2021 Feb 19.

Melbourne, Vic., Australia.

Background: Azathioprine and mercaptopurine are considered safe during pregnancy. However, the pharmacokinetic effects of pregnancy on thiopurine metabolism are undefined.

Aims: To characterise thiopurine metabolism in pregnancy and measure infant metabolite levels and outcomes.

Methods: Women with IBD who were taking a thiopurine and pregnant or trying to conceive were recruited. Maternal thiopurine metabolites were measured pre-conception, in each trimester, at delivery and post-partum. Infant metabolite levels, full blood examination and liver function testing were performed at birth, and repeated until levels undetectable and haematological and biochemical abnormalities resolved.

Results: Forty patients were included with measurements on at least two occasions, and two with only mother-baby levels at delivery. The median maternal 6-TGN level dropped in the second trimester compared with post-partum (179.0 vs 323.5 pmol/8 × 10 RBCs, P < 0.001) and the median 6-MMP level increased in the second trimester compared with post-partum (1103.0 vs 329.5 pmol/8 × 10 RBCs, P < 0.01). At delivery, the median 6-TGN level was lower in infants (n = 20) than mothers (78.5 vs 217 pmol/8 × 10 RBCs) (P < 0.001). Metabolites were not detected at 6 weeks in any infants. Anaemia was not seen, but thrombocytosis and abnormal liver biochemistry were detected in 80% of infants from 6 weeks, which gradually improved.

Conclusions: 6-TGN levels decrease and 6-MMP levels increase in the second trimester of pregnancy. Infants are exposed to thiopurine metabolites at low levels with clearance by 6 weeks and no anaemia. The cause of infant thrombocytosis and abnormal liver biochemistry in the absence of metabolites is unclear.
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http://dx.doi.org/10.1111/apt.16294DOI Listing
April 2021

Addressing pregnancy-related concerns in women with inflammatory bowel disease: Insights from the patient's perspective.

JGH Open 2021 Jan 9;5(1):28-33. Epub 2020 Nov 9.

Department of Gastroenterology St Vincent's Hospital Melbourne Victoria Australia.

Background And Aim: Therapeutic options for inflammatory bowel disease (IBD) have expanded, as has the use of IBD medications in women during the reproductive period. However, no qualitative data exist that examine the pregnancy-related concerns of women with IBD in the current era of widespread immunomodulator and biologic use. Hence, we aimed to explore in detail the impact of IBD on pregnancy from the patient's perspective.

Methods: This qualitative study used semistructured interviews to explore participants' experiences regarding IBD and pregnancy until no new themes emerged. Key themes were identified using thematic analysis.

Results: Fifteen women with IBD were interviewed. The majority of participants reported lingering concerns regarding their IBD medications, despite advice from their gastroenterologist that the drugs were considered safe in pregnancy. Participants more often reported medication-related fears, such as potential negative effects on their child's immune system, than concerns regarding the effect of the disease itself on their pregnancy outcomes. A common theme was a perceived lack of knowledge among non-IBD clinicians regarding IBD medications during pregnancy, which augmented pre-existing anxiety.

Conclusions: This study is the first of its kind to provide an in-depth assessment of female patients' perspectives of IBD in relation to conception, pregnancy, and caring for offspring. In particular, this research characterizes the unique fears and persisting anxieties regarding IBD medications in pregnancy. The study has unearthed important insights into the specific concerns and support needs of women with IBD in order to facilitate nonjudgmental counseling designed around patient concerns and beliefs.
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http://dx.doi.org/10.1002/jgh3.12442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812482PMC
January 2021

Safely reducing haemodialysis frequency during the COVID-19 pandemic.

BMC Nephrol 2020 12 7;21(1):532. Epub 2020 Dec 7.

Department of Renal Medicine, Salford Royal NHS Trust, Stott Lane, Salford, M68HD, UK.

Background: Patients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients.

Methods: Dialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice.

Results: There were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project.

Conclusions: Short term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.
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http://dx.doi.org/10.1186/s12882-020-02172-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720264PMC
December 2020

Infliximab, adalimumab and vedolizumab concentrations across pregnancy and vedolizumab concentrations in infants following intrauterine exposure.

Aliment Pharmacol Ther 2020 11 27;52(10):1551-1562. Epub 2020 Sep 27.

Fitzroy, VIC, Australia.

Background: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown.

Aims: To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance METHODS: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable.

Results: We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: -0.33 to -0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing.

Conclusions: During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly.
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http://dx.doi.org/10.1111/apt.16102DOI Listing
November 2020

Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford.

World J Gastroenterol 2020 Aug;26(30):4428-4441

Centre for Inflammatory Bowel Diseases, St John of God Hospital, Subiaco 6008, Western Australia, Australia.

Background: Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients.

Aim: To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission.

Methods: A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded.

Results: Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% 70% = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% 40% < 0.001, 6 mo 73% 46% < 0.001, 12 mo 66% 51% = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% 43% = 0.01). On multi-variate analysis, anti-TNF naïve patients were 1.8 (95%CI: 1.3-2.3) times more likely to achieve remission than anti-TNF exposed ( < 0.001). 32 patients (11%) had colectomy by 12 mo.

Conclusion: VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.
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http://dx.doi.org/10.3748/wjg.v26.i30.4428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438197PMC
August 2020

Nutrition and the ageing brain: Moving towards clinical applications.

Ageing Res Rev 2020 09 24;62:101079. Epub 2020 May 24.

Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address:

The global increases in life expectancy and population have resulted in a growing ageing population and with it a growing number of people living with age-related neurodegenerative conditions and dementia, shifting focus towards methods of prevention, with lifestyle approaches such as nutrition representing a promising avenue for further development. This overview summarises the main themes discussed during the 3 Symposium on "Nutrition for the Ageing Brain: Moving Towards Clinical Applications" held in Madrid in August 2018, enlarged with the current state of knowledge on how nutrition influences healthy ageing and gives recommendations regarding how the critical field of nutrition and neurodegeneration research should move forward into the future. Specific nutrients are discussed as well as the impact of multi-nutrient and whole diet approaches, showing particular promise to combatting the growing burden of age-related cognitive decline. The emergence of new avenues for exploring the role of diet in healthy ageing, such as the impact of the gut microbiome and development of new techniques (imaging measures of brain metabolism, metabolomics, biomarkers) are enabling researchers to approach finding answers to these questions. But the translation of these findings into clinical and public health contexts remains an obstacle due to significant shortcomings in nutrition research or pressure on the scientific community to communicate recommendations to the general public in a convincing and accessible way. Some promising programs exist but further investigation to improve our understanding of the mechanisms by which nutrition can improve brain health across the human lifespan is still required.
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http://dx.doi.org/10.1016/j.arr.2020.101079DOI Listing
September 2020

Mortality risk by peak serum creatinine in hospital episodes complicated by acute kidney injury.

Clin Med (Lond) 2020 03;20(Suppl 2):s109-s110

Salford Royal NHS Foundation Trust, Salford, UK and University of Manchester, Manchester, UK.

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http://dx.doi.org/10.7861/clinmed.20-2-s109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243496PMC
March 2020

Abdominal Imaging in pregnancy (maternal and foetal risks).

Best Pract Res Clin Gastroenterol 2020 Feb - Apr;44-45:101664. Epub 2019 Dec 27.

Faculty of Medicine, Nursing and Health Sciences, Monash University, Director of Gastroenterology, Monash Health, 246 Clayton Rd., Clayton, VIC, 3168, Australia. Electronic address:

Imaging studies are useful in the diagnostic evaluation of inflammatory bowel diseases. However, concern often exists about the safety of imaging for pregnant and lactating women and their infants, leading to unwarranted avoidance of beneficial diagnostic tests or disruption of breastfeeding. Ultrasonography and magnetic resonance imaging (MRI) are not associated with ionizing radiation and are the imaging techniques of choice for pregnant patients. Safety of MRI contrast agent gadolinium in pregnancy is uncertain, therefore MRI without gadolinium should be performed. Intestinal ultrasound where available and MRI without gadolinium can be used to characterise disease complications such as bowel obstruction or intra-abdominal collections. Ionising radiation exposure through computed tomography (CT) is usually at much lower doses than those associated with foetal harm, however CT should be reserved for the rare clinical situations in which ultrasound and MRI are either unavailable or unable to provide the required diagnostic information.
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http://dx.doi.org/10.1016/j.bpg.2019.101664DOI Listing
July 2020

Monitoring Inflammatory Bowel Disease in Pregnancy Using Gastrointestinal Ultrasonography.

J Crohns Colitis 2020 Oct;14(10):1405-1412

Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia.

Background And Aims: Inflammatory bowel disease [IBD] affects women during their childbearing years. Gastrointestinal ultrasonography [GIUS] accurately identifies disease activity in non-pregnant patients with IBD. The utility of GIUS in pregnancy has not been established. We aimed to determine the feasibility and accuracy of GIUS in the assessment of IBD during pregnancy progression.

Methods: A multicentre observational study of women with IBD undergoing GIUS during pregnancy. Clinicians assessed the adequacy of bowel views and disease activity in four colonic segments and the terminal ileum. Location[s] in which views were impeded by the uterus were documented. GIUS disease activity [bowel wall thickness >3 mm] was compared with biochemical disease activity [faecal calprotectin >100 μg/g].

Results: Ninety patients and 127 GIUS examinations were included [median gestation 19 weeks, range 4-33]. Adequate colonic views were obtained in 116/127 [91%] scans. Adequate ileal views were obtained in 62/67 [93%] scans <20 weeks and 30/51 [59%] scans at 20-26 weeks. There was a positive correlation between bowel wall thickness and calprotectin [r = 0.26, p = 0.03]. GIUS delivered a specificity of 83%, sensitivity of 74%, and negative predictive value of 90% compared with calprotectin.

Conclusions: GIUS is a feasible and accurate modality for monitoring IBD in pregnancy. Adequate GIUS views of the colon and terminal ileum can be obtained in the majority of patients up to 20 weeks of gestation. Beyond 20 weeks, GIUS provides good views of the colon but the terminal ileum becomes difficult to assess.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa082DOI Listing
October 2020

Impact of prior stroke on major clinical outcome in chronic kidney disease: the Salford kidney cohort study.

BMC Nephrol 2019 11 27;20(1):432. Epub 2019 Nov 27.

Renal Department, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK.

Background: Chronic kidney disease (CKD) is an independent risk factor for stroke in the general population. The impact of prior stroke on major clinical outcomes in CKD populations is poorly characterised.

Methods: The Salford Kidney Study is a UK prospective cohort of more than 3000 patients recruited since 2002 and followed until March 2018. Multivariable Cox regression examined associations of stroke at two time points; cohort inception, and at dialysis initiation, with risks of death, non-fatal cardiovascular events (NFCVE) and end stage renal disease (ESRD).

Results: 277 (9.1%) of 3060 patients suffered a prior stroke and this was associated with mortality, ESRD and future NFCVE after cardiovascular risk factor adjustments. Median survival for prior stroke patients was 40 months vs 77 months in patients without a stroke. Prior stroke was independently associated with mortality (HR 1.20 95%CI 1.0-1.43, p = 0.05). Of 579 patients who reached ESRD and commenced dialysis, a prior stroke (N = 48) was independently associated with mortality. Median survival for the prior stroke group was 29 months compared with 50 months for the non-stroke group. Only 70 and 75% of patients who had suffered an ischaemic stroke were prescribed antiplatelets or statins respectively.

Conclusions: A diagnosis of stroke is strongly and independently associated with several adverse clinical outcomes for patients with CKD. Prior stroke profoundly alters cardiovascular risk in CKD patients. Greater attention to primary and secondary preventive strategies is warranted which may improve these outcomes.
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http://dx.doi.org/10.1186/s12882-019-1614-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880597PMC
November 2019

Cancer patterns and association with mortality and renal outcomes in non-dialysis dependent chronic kidney disease: a matched cohort study.

BMC Nephrol 2019 10 22;20(1):380. Epub 2019 Oct 22.

Department of Renal Medicine, Salford Royal NHS Foundation Trust, M6 8HD, Salford, UK.

Background: Cancer in patients with chronic kidney disease (CKD) is an added burden to their overall morbidity and mortality. Cancer can be a cause or an effect of CKD. In CKD patients, a better understanding of cancer distribution and associations can aid in the proper planning of renal replacement therapy (RRT) and in the choice of chemotherapeutic agents, many of which are precluded in more advanced CKD. This study aims to investigate the distribution and the association of cancer with mortality, renal progression and RRT assignment in a non-dialysis dependent CKD cohort, few studies have investigated this in the past.

Methods: The study was carried out on 2952 patients registered in the Salford Kidney Study (SKS) between October 2002 and December 2016. A comparative analysis was performed between 339 patients with a history of cancer (previous and current) and 2613 patients without cancer at recruitment. A propensity score matched cohort of 337 patients was derived from each group and used for analysis. Cox-regression models and Kaplan-Meier estimates were used to compare the association of cancer with mortality and end-stage renal disease (ESRD) outcomes. Linear regression analysis was applied to generate the annual rate of decline in estimated glomerular filtration rate (delta eGFR).

Results: Of our cohort, 13.3% had a history of cancer at recruitment and the annual rate of de novo cancers in the non-cancer patients was 1.6%. Urogenital cancers including kidney and bladder, and prostate and testicle in males, ovary and uterus in females, were the most prevalent cancers (46%), as expected from the anatomical or physiological roles of these organs and relationship to nephrology. Over a median follow-up of 48 months, 1084 (36.7%) of patients died. All-cause mortality was higher in the previous and current cancer group (49.6% vs 35%, p < 0.001), primarily because of cancer-specific mortality. Multivariate Cox regression analysis showed a strong association of cancer with all-cause mortality (HR:1.41; 95%CI: 1.12-1.78; p = 0.004). There was no difference between the groups regarding reaching end-stage renal disease (26% in both groups) or the rate of decline in eGFR (- 0.97 for cancer vs - 0.93 mL/min/year for non-cancer, p = 0.93). RRT uptake was similar between the groups (17.2% vs 19.3%, p = 0.49).

Conclusions: Cancer status proved to be an added burden and an independent risk factor for all-cause mortality but not for renal progression. CKD patients with a previous or current history of cancer should be assessed on a case by case basis in planning for renal replacement therapy options, and the presence of cancer should not be a limitation for RRT provision including transplantation.
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http://dx.doi.org/10.1186/s12882-019-1578-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805476PMC
October 2019

Distribution and association of cancer with mortality in end-stage renal disease patients receiving dialysis.

J Nephrol 2019 Dec 25;32(6):1003-1009. Epub 2019 Sep 25.

Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford, M6 8HD, UK.

Background And Aims: Cancer in end-stage renal disease (ESRD) patients is an important comorbidity to be taken into consideration while planning for renal replacement therapy (RRT) options due to its associated increased mortality. This study aims to investigate the natural history and association of cancer with all-cause mortality in an ESRD population receiving dialysis.

Method: The study was conducted on 1271 ESRD patients receiving dialysis between January 2012 and December 2017. A comparative analysis was carried out between 119 patients with and 1152 without cancer history at entry into this study (baseline). A 1:2 (119 cancer: 238 no cancer) propensity score matched sample of 357 patients was also used for analysis. Cox-regression analysis was used to study the strength of the association between cancer and all-cause mortality. Kaplan-Meier (KM) analysis was used to demonstrate the difference in cumulative survival between the groups. A competing risk analysis was also carried out to calculate the probability of competing events (death, transplant and incident cancer).

Results: At baseline, 10.1% of the cohort had a history of cancer (current and past) with the annual incident rate being 1.3%. Urological cancers were the leading site of cancer. The median age of our cohort was 63 years with a predominance of males (63%) and Caucasians (79%). The majority (69%) of the cohort were receiving haemodialysis. 47% had a history of diabetes with 88% being hypertensive. During a median follow-up of 28 months, the proportion of deaths observed was similar between the groups in the matched sample (cancer 49.6 versus no-cancer 52.1%, p value 0.77). In a univariable Cox-regression model, there was no significant association between cancer and all-cause mortality (HR 1.28; 95% CI 0.97-1.67; p = 0.07). The KM estimates showed similar observations in the cumulative survival between the groups (matched sample log-rank, p value 0.85). In competing risk analysis, the cumulative probability of death at 5 years was non-significantly higher in the cancer group (cancer group 64% vs no cancer group 51%, p value 0.16).

Conclusions: In our real-world multi-morbid dialysis cohort of 119 cancer patients, baseline cancer history did not prove to be an independent risk factor for all-cause mortality in the first 5 years of follow-up, suggesting the need for a case-by-case approach in provision of RRT options, including transplantation.
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http://dx.doi.org/10.1007/s40620-019-00649-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821669PMC
December 2019

Comparison of Adalimumab Serum Drug Levels When Delivered by Pen Versus Syringe in Patients With Inflammatory Bowel Disease. An International, Multicentre Cohort Analysis.

J Crohns Colitis 2019 Dec;13(12):1527-1536

Department of Gastroenterology, Alfred Health and Monash University, Melbourne, VIC, Australia.

Background: Adalimumab is administered via a pre-filled syringe or spring-loaded pen. In a previous study in Crohn's disease, higher drug levels were observed in syringe users. The aim of this study was to evaluate the impact of delivery device on adalimumab drug levels in patients with Crohn's disease.

Methods: Consecutive Crohn's disease patients treated with maintenance adalimumab [40 mg fortnightly] were recruited from five centres. The first recorded drug level with matched clinical and biochemical markers of disease activity was compared between pen and syringe users.

Results: Of 218 patients, 64% used pen, with a median faecal calprotectin 110 μg/g and serum C-reactive protein 4 mg/L. In comparison to pen, syringe users had higher albumin [39 vs 42 g/L; p = 0.016], lower Harvey-Bradshaw Index [2 vs 1; p = 0.017], and higher rates of concomitant immunomodulation [54% vs 71%; p = 0.014]. Drug levels were equivalent between pen and syringe users [median 5.3 vs 5.2 μg/ml; p = 0.584], even after controlling for disease activity and immunomodulation. Syringe users at Alfred Health had higher drug levels than pen [6.1 vs 4.5 μg/ml; p = 0.039]; a greater proportion achieved therapeutic levels [75% vs 44%; p = 0.045]. A higher proportion of pen users from Saint-Étienne had therapeutic levels [79% vs 42%; p = 0.027], yet no significant difference in drug levels [7.9 vs 4.5 μg/ml; p = 0.119].

Conclusions: Delivery device does not appear to significantly affect adalimumab drug levels. Given differences between study sites, studies evaluating administration education and technique are warranted.
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http://dx.doi.org/10.1093/ecco-jcc/jjz103DOI Listing
December 2019

The importance of acute kidney injury in suspected community acquired infection.

PLoS One 2019 7;14(5):e0216412. Epub 2019 May 7.

Renal Department, Salford Royal NHS Trust, Salford, United Kingdom.

Background: Most sepsis and acute kidney injury (AKI) cases are community acquired (CA). The aim of this study was to evaluate the characteristics of suspected community acquired infection (sCA-I) and CA-AKI and their impact upon patient outcomes.

Methods: All adult creatinine blood tests from non-elective, non-dialysis attendances to a single centre over a 29-month period were analysed retrospectively. We defined sCA-I and CA-AKI cases as antibiotic prescription and AKI alert within 48 hours of attendance respectively. Binary logistic regression models were created to determine associations with 30-day mortality, intensive care unit (ICU) admission and length of stay (LOS) dichotomised at median.

Results: Of 61,471 attendances 28.1% and 5.7% suffered sCA-I or CA-AKI in isolation respectively, 3.4% suffered both. sCA-I was present in 58.8% of CA-AKI cases and CA-AKI was present in 11.9% of CA-I cases. The combination of sCA-I and CA-AKI was associated with a higher risk for all outcomes compared to sCA-I or CA-AKI in isolation. The 30-day mortality was 8.1%, 11.8% and 26.2% in patients with sCA-I, CA-AKI and when sCA-I and CA-AKI occurred in combination respectively. The adjusted odds ratios (OR) and 95% confidence intervals (CI) for 30-day mortality, ICU admission and LOS for sCA-I combined with CA-AKI stage 1 were OR 6.09:CI: 5.21-7.12, OR 12.52 CI: 10.54-14.88 and OR 8.97 CI: 7.62-10.56, respectively, and for combined sCA-I and CA-AKI stage 3 were OR 9.23 CI: 6.91-12.33, OR 29.26 CI: 22.46-38.18 and OR 9.48 CI: 6.82-13.18 respectively.

Conclusion: The combination of sCA-I and CA-AKI is associated with worse outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216412PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504101PMC
January 2020

Updates in the management of inflammatory bowel disease during pregnancy.

Med J Aust 2019 04 24;210(6):276-280. Epub 2019 Mar 24.

St Vincent's Hospital, Melbourne, VIC.

The best pregnancy outcomes for women with inflammatory bowel disease (IBD) occur when their disease is in remission at conception and remains in remission throughout pregnancy. Active IBD can lead to adverse pregnancy outcomes, including spontaneous abortion, pre-term birth and low birthweight. The majority of women with IBD who are taking maintenance medication will require medication throughout the pregnancy to prevent disease relapse. Most IBD medications are considered safe in pregnancy and breastfeeding, except for methotrexate. Pre-conception counselling should be arranged with the patient's IBD specialist and should include discussions regarding the importance of optimising disease control before and during pregnancy as well as the medication management plan for pregnancy. Patients with IBD should be reassured that their fertility is normal when the disease is quiescent, with the exception of women who have had pelvic surgery. IBD activity should be carefully monitored during pregnancy using non-invasive techniques, and disease flares during pregnancy should be treated promptly with escalation of therapy in consultation with the patient's IBD specialist. Mode of delivery should be determined by obstetric need; however, caesarean delivery is preferred for women with a history of ileal pouch anal anastomosis surgery or active perianal Crohn's disease.
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http://dx.doi.org/10.5694/mja2.50062DOI Listing
April 2019

Coeliac disease in the modern era: Severity of small bowel mucosal injury at diagnosis with analysis of clinical correlates and rate of improvement on a gluten free diet.

World J Gastrointest Pharmacol Ther 2018 Dec;9(6):55-62

Department of Gastroenterology, University Hospital Geelong, Geelong 3220, Australia.

Aim: To analyze the relationships between pre-diagnosis coeliac serology, duodenal histopathology, primary presenting symptoms, coeliac-related comorbidity and response to treatment in a modern cohort with new diagnosis of coeliac disease (CD).

Methods: A retrospective cohort study including 99 participants diagnosed with CD between 1999 and 2013. All patients had the following data recorded: baseline characteristics, coeliac serology, small bowel histopathology. A subset of this cohort underwent a repeat small bowel biopsy. Independent associations were assessed with logistic regression.

Results: The mean age at diagnosis was 43 years (Interquartile range 30-53 years) and 68% of the cohort was female. At diagnosis 49 (49%) patients had total villous blunting (MS 3c), 12 (12%) had subtotal villous blunting (MS 3b), and 29 (29%) had partial villous blunting (MS 3a). The prevalence of symptoms pre diagnosis was not related to the severity of villous blunting ( = 0.490). 87 (88%) of the cohort underwent repeat small bowel biopsy after a median of 7 mo (IQR 6-11 mo). 34 (39%) patients had biopsy results ≥ MS 3a which compared to 90 (90%) at the initial biopsy. 24 (71%) of this group reported adherence to a gluten free diet (GFD). Persistent MS ≥ 3a at repeat biopsy was not associated with symptoms ( = 0.358) or persistent positive coeliac serology ( = 0.485).

Conclusion: Neither symptoms nor serology predict the severity of the small bowel mucosal lesion at CD diagnosis. Whilst a GFD was associated with histological improvement many patients with newly diagnosed CD had persistent mucosal damage despite many months of gluten restriction. Negative CD serology did not exclude ongoing mucosal injury.
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http://dx.doi.org/10.4292/wjgpt.v9.i6.55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288493PMC
December 2018

Reducing acute kidney injury incidence and progression in a large teaching hospital.

BMJ Open Qual 2018 26;7(4):e000308. Epub 2018 Nov 26.

Emergency Admissions Unit, Royal Preston Hospital, Preston, UK.

Acute kidney injury (AKI) is a common syndrome that is associated with significant mortality and cost. The Quality Improvement AKI Collaborative at Salford Royal Foundation Trust was established to review and improve both the recognition and management of AKI. This was a whole-system intervention to tackle AKI implemented as an alternative to employing separate AKI nurses. Our aims were to reduce the overall incidence of AKI by 10%, to reduce hospital-acquired AKI by 25% and to reduce the progression of AKI from stage 1 to stage 2 or 3 by 50%. From 2014 to 2016, several multifaceted changes were introduced. These included system changes, such as inserting an e-alert for AKI into the electronic patient record, an online educational package and face-to-face teaching for AKI, and AKI addition to daily safety huddles. On 10 Collaborative wards, development of an AKI care bundle via multidisciplinary team (MDT) plan, do, study, act testing occurred. Results showed a 15.6% reduction in hospital-wide-acquired AKI, with a 22.3% reduction on the collaborative wards. Trust-wide rates of progression of AKI 1 to AKI 2 or 3 showed normal variation, whereas there was a 48.5% reduction in AKI progression on the Collaborative wards. This implies that e-alerts were ineffective in isolation. The Collaborative wards' results were a product of the educational support, bundle and heightened awareness of AKI. A number of acute hospitals have demonstrated impactful successes in AKI reduction centred on a dedicated AKI nurse model plus e-alerting with supporting changes. This project adds value by highlighting another approach that does not require a new post with attendant rolling costs and risks. We believe that our approach increased our efficacy in acute care in our front-line teams by concentrating on embedding improved recognition and actions across the MDT.
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http://dx.doi.org/10.1136/bmjoq-2017-000308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267307PMC
November 2018

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis A visual rating study.

Dement Neuropsychol 2018 Oct-Dec;12(4):388-393

Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.

Amyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS.

Objective: To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS.

Methods: 21 ALS patients and 17 controls were recruited and underwent an MRI scan. Prefrontal cortex sub-regions of the medial orbitofrontal cortex (MOFC), lateral orbitofrontal cortex (LOFC) and anterior cingulate cortex (ACC), striatal sub-regions of the caudate nucleus (CN) and nucleus accumbens (NAcc) were rated using visual grey matter atrophy 5-point Likert scales.

Results: Significantly higher atrophy ratings in the bilateral MOFC only in ALS patients versus controls was observed (p<.05). Patients with greater MOFC atrophy had significantly higher atrophy of the CN (p<.05) and LOFC (p<.05).

Conclusion: Use of simple visual atrophy rating scales on an individual level reliably detects frontostriatal deficits specific to ALS, showing MOFC atrophy differences with associated CN and LOFC atrophy. This is an applicable method that could be used to support clinical diagnosis and management.
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http://dx.doi.org/10.1590/1980-57642018dn12-040008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289478PMC
December 2018

Letter: vedolizumab drug concentrations in neonates following intrauterine exposure.

Aliment Pharmacol Ther 2018 12;48(11-12):1328-1330

St Vincent's Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/apt.15027DOI Listing
December 2018

Predictors of finance management in dementia: managing bills and taxes matters.

Int Psychogeriatr 2019 02 13;31(2):277-286. Epub 2018 Aug 13.

Personal Social Services Research Unit,The University of Manchester,Manchester,UK.

ABSTRACTObjectives:Finance management skills deteriorate early on in dementia, and can influence the ability to maintain control over personal affairs. The aim of this study was to assess the contributions of different types of cognition and motor functioning to finance management.

Design: Cross-sectional analysis using secondary data.

Setting: Community living.

Participants: Baseline data from the Uniform Data Set from the National Alzheimer's Coordinating Centers were obtained and extracted up until December 2016.

Measurements: Measures on everyday functioning (Functional Assessment Questionnaire) and cognition (memory, executive functioning, and language), the Clinical Dementia Rating scale, and questions on Parkinsonian motor symptoms (gait disturbance, falls, tremors, and slowness) were included. Data were analyzed using bivariate correlation and linear regression analyses.

Results: A total of 9,383 participants were included in the analysis (Alzheimers disease (AD) = 8,201; behavioral variant fronto-temporal dementia (bvFTD) = 796; Dementia with Lewy Bodies (DLB) = 386). Cognition and motor functioning varied significantly across AD, bvFTD, and DLB, with poorer motor functioning and poorer finance management skills in DLB than in AD and bvFTD. In the regression models, slowness, verbal fluency, executive functioning, and language, followed by age, gender, and diagnosis accounted for 13.8% of the variation in managing bills, and for 11.4% of the variation in managing taxes.

Conclusion: Maintaining finance management abilities for as long as possible is important for people with dementia, to avoid potential financial exploitation. Findings from this study highlight avenues to pursue to delay deterioration in managing bills and taxes, and help maintain financial control.
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http://dx.doi.org/10.1017/S1041610218000820DOI Listing
February 2019

Impact of Flavonoids on Cellular and Molecular Mechanisms Underlying Age-Related Cognitive Decline and Neurodegeneration.

Curr Nutr Rep 2018 06;7(2):49-57

Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7UQ, UK.

Purpose Of Review: This review summarises the most recent evidence regarding the effects of dietary flavonoids on age-related cognitive decline and neurodegenerative diseases.

Recent Findings: Recent evidence indicates that plant-derived flavonoids may exert powerful actions on mammalian cognition and protect against the development of age-related cognitive decline and pathological neurodegeneration. The neuroprotective effects of flavonoids have been suggested to be due to interactions with the cellular and molecular architecture of brain regions responsible for memory. Mechanisms for the beneficial effects of flavonoids on age-related cognitive decline and dementia are discussed, including modulating signalling pathways critical in controlling synaptic plasticity, reducing neuroinflammation, promoting vascular effects capable of stimulating new nerve cell growth in the hippocampus, bidirectional interactions with gut microbiota and attenuating the extracellular accumulation of pathological proteins. These processes are known to be important in maintaining optimal neuronal function and preventing age-related cognitive decline and neurodegeneration.
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http://dx.doi.org/10.1007/s13668-018-0226-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960493PMC
June 2018

Executive and social-cognitive determinants of environmental dependency syndrome in behavioral frontotemporal dementia.

Neuropsychology 2018 05;32(4):377-384

Norwich Medical School, University of East Anglia.

Objective: Environmental dependency syndrome (EDS), including utilization (UB) and imitation (IB) behaviors, is often reported in behavioral variant frontotemporal dementia (bvFTD). These behaviors are commonly attributed to executive dysfunction. However, inconsistent associations between EDS and poor executive performance has led to an alternative "social hypothesis," instead implicating patients' misinterpretation of the examiner's intention. We investigated the possible explanatory cognitive mechanisms of EDS in bvFTD by relating UB and IB to performance on tests of executive functioning and theory of mind (ToM).

Method: This study analyzed retrospective data of 32 bvFTD patients. Data included scores of UB and IB, various executive measures, and ToM assessment using the faux pas test, from which we extracted a mental attribution score.

Results: Of the patients, 15.6% and 40.6% exhibited UB and IB, respectively. We conducted an automatic linear modeling analysis with executive and mental attribution measures as predictor variables, and UB and IB sequentially considered as target variables. ToM mental attribution score, visual abstraction and flexibility measures from the Wisconsin Card Sorting Test, and motor sequence performance significantly (corrected ps < .05) predicted IB. No executive or ToM measures significantly predicted UB.

Conclusions: These findings reveal a complex interaction between executive dysfunction and mental attribution deficits influencing the prevalence of EDS in bvFTD. Further investigation is required to improve our understanding of the mechanisms underlying these behaviors. (PsycINFO Database Record
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http://dx.doi.org/10.1037/neu0000433DOI Listing
May 2018

Improved management of acute kidney injury in primary care using e-alerts and an educational outreach programme.

Fam Pract 2018 12;35(6):684-689

Renal Department, Salford Royal NHS Trust, Salford, UK.

Purpose: Acute kidney injury (AKI) detected in primary care is associated with increased morbidity and mortality. AKI electronic alerts (e-alerts) and educational programmes have recently been implemented but their contribution to improve AKI care is unknown. This project aimed to improve response to AKI detected in primary care and used a factorial design to evaluate the impact of the UK National Health Service (NHS) AKI e-alert and AKI educational outreach sessions on time to response to primary care AKI stages 2 and 3 between April and August 2016.

Methods: A total of 46 primary care practices were randomized into four groups. A 2 × 2 factorial design exposed each group to different combinations of two interventions. The primary outcome was 'time to repeat test' or hospitalization following AKI e-alert for stages 2 and 3. Yates algorithm was used to evaluate the impact of each intervention. Time to response and mortality pre- and post-intervention were analysed using Mann-Whitney U test and chi-square test respectively. The factorial design included two interventions: an AKI educational outreach programme and the NHS AKI e-alerts.

Results: 1807 (0.8%) primary care blood tests demonstrated AKI 1-3 (78.3% stage 1, 14.8% stage 2, 6.9% stage 3). There were 391 stage 2 and 3 events from 251 patients. E-alerts demonstrated a reduction in mean response time (-29 hours). Educational outreach had a smaller effect (-3 hours). Median response time to AKI 2 and 3 pre- and post-interventions was 27 hours versus 16 hours respectively (P = 0.037). Stage 2 and 3 event-related 30-day all-cause mortality decreased following the interventions (15.6% versus 3.9% P = 0.036).

Conclusion: AKI e-alerts in primary care hasten response to AKI 2 and 3 and reduce all-cause mortality. Educational outreach sessions further improve response time.
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http://dx.doi.org/10.1093/fampra/cmy030DOI Listing
December 2018

Diagnostic relevance of spatial orientation for vascular dementia: A case study.

Dement Neuropsychol 2018 Jan-Mar;12(1):85-91

Norwich Medical School, University of East Anglia, Norwich, UK.

Spatial orientation is emerging as an early and reliable cognitive biomarker of Alzheimer's disease (AD) pathophysiology. However, no evidence exists as to whether spatial orientation is also affected in vascular dementia (VaD).

Objective: To examine allocentric (map-based) and egocentric (viewpoint-based) spatial orientation in an early stage VaD case.

Methods: A spatial test battery was administered following clinical and neuropsychological cognitive evaluation.

Results: Despite the patient's complaints, little evidence of episodic memory deficits were detected when cueing was provided to overcome executive dysfunction. Similarly, medial temporal lobe-mediated allocentric orientation was intact. By contrast, medial parietal-mediated egocentric orientation was impaired, despite normal performance on standard visuospatial tasks.

Conclusion: To our knowledge, this is the first in-depth investigation of spatial orientation deficits in VaD. Isolated egocentric deficits were observed. This differs from AD orientation deficits which encompass both allocentric and egocentric orientation deficits. A combination of egocentric orientation and executive function tests could serve as a promising cognitive marker for VaD pathophysiology.
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http://dx.doi.org/10.1590/1980-57642018dn12-010013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901255PMC
April 2018

Structural Anatomical Investigation of Long-Term Memory Deficit in Behavioral Frontotemporal Dementia.

J Alzheimers Dis 2018 ;62(4):1887-1900

Norwich Medical School, University of East Anglia, Norwich, UK.

Although a growing body of work has shown that behavioral variant frontotemporal dementia (bvFTD) could present with severe amnesia in approximately half of cases, memory assessment is currently the clinical standard to distinguish bvFTD from Alzheimer's disease (AD). Thus, the concept of "relatively preserved episodic memory" in bvFTD remains the basis of its clinical distinction from AD and a criterion for bvFTD's diagnosis. This view is supported by the idea that bvFTD is not characterized by genuine amnesia and hippocampal degeneration, by contrast to AD. In this multicenter study, we aimed to investigate the neural correlates of memory performance in bvFTD as assessed by the Free and Cued Selective Reminding Test (FCSRT). Imaging explorations followed a two-step procedure, first relying on a visual rating of atrophy of 35 bvFTD and 34 AD patients' MRI, contrasted with 29 controls; and then using voxel-based morphometry (VBM) in a subset of bvFTD patients. Results showed that 43% of bvFTD patients presented with a genuine amnesia. Data-driven analysis on visual rating data showed that, in bvFTD, memory recall & storage performances were significantly predicted by atrophy in rostral prefrontal and hippocampal/perihippocampal regions, similar to mild AD. VBM results in bvFTD (pFWE<0.05) showed similar prefrontal and hippocampal regions in addition to striatal and lateral temporal involvement. Our findings showed the involvement of prefrontal as well as medial/lateral temporal atrophy in memory deficits of bvFTD patients. This contradicts the common view that only frontal deficits explain memory impairment in this disease and plead for an updated view on memory dysfunctions in bvFTD.
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http://dx.doi.org/10.3233/JAD-170771DOI Listing
May 2019

Neuroanatomical Comparison of the "Word" and "Picture" Versions of the Free and Cued Selective Reminding Test in Alzheimer's Disease.

J Alzheimers Dis 2018 ;61(2):589-600

Department of Neurology and Neurosurgery, Clinical Hospital, Universidad de Chile, Santiago, Chile.

Episodic memory tests with cued recall, such as the Free and Cued Selective Reminding Test (FCSRT), allow for the delineation of hippocampal and prefrontal atrophy contributions to memory performance in Alzheimer's disease (AD). Both Word and Picture versions of the test exist but show different profiles, with the Picture version usually scoring higher across different cohorts. One possible explanation for this divergent performance between the different modality versions of the test might be that they rely on different sets of neural correlates. The current study explores this by contrasting the neural correlates of the Word and Picture versions of the FCSRT with voxel-based morphometry (VBM) in AD and healthy subjects. We predicted that the Picture version would be associated with different cortical regions than the Word version, which might be more hippocampal-centric. When comparing 35 AD patients and 34 controls, AD patients exhibited impairments on both versions of the FCSRT and both groups performed higher in the Picture version. A region of interest analysis based on prior work revealed significant correlations between free recall of either version with atrophy of the temporal pole and hippocampal regions. Thus, contrary to expectations, performance on both the Word and the Picture version of the FCSRT is associated with largely overlapping networks. Free recall is associated with hippocampal volume and might be properly considered as an indicator of hippocampal structural integrity.
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http://dx.doi.org/10.3233/JAD-160973DOI Listing
January 2019

Accelerated Long Term Forgetting in patients with focal seizures: Incidence rate and contributing factors.

Epilepsy Behav 2017 07 7;72:108-113. Epub 2017 Jun 7.

Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, and Central Medical School, University of Sydney, Camperdown, NSW, Australia; ARC-Centre of Excellence in Cognition and Its Disorders, University of Sydney, NSW, Australia.

Background: Accelerated Long Term Forgetting (ALF) is usually defined as a memory impairment that is seen only at long delays (e.g., after days or weeks) and not at shorter delays (e.g., 30min) typically used in clinical settings. Research indicates that ALF occurs in some patients with epilepsy, but the incidence rates and underlying causes have not been established. In this study, we considered these issues.

Methods: Forty-four patients with a history of focal seizures were tested at 30min and 7day delays for material from the Rey Auditory Verbal Learning Test (RAVLT) and Aggie Figures Test. Recently published norms from a matched group of 60 control subjects (Miller et al., 2015 ) were used to determine whether patients demonstrated ALF, impairment at 30min or intact memory performance.

Results: The incidence of ALF in the epilepsy patients (18%) was >3 times higher than normal on the RAVLT, but no different (7%) from the incidence in normal subjects on the Aggie Figures. A different, but again significantly high, proportion of patients (36%) showed shorter-term memory deficits on at least one task. ALF was found mainly in patients with temporal-lobe epilepsy, but also occurred in one patient with an extratemporal seizure focus. Presence of a hippocampal lesion was the main predicting factor of ALF.

Conclusions: Many patients with a focal seizure disorder show memory deficits after longer delays that are not evident on standard assessment. The present study explored the factors associated with this ALF memory profile. These new findings will enhance clinical practice, particularly the management of patients with memory complaints.
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http://dx.doi.org/10.1016/j.yebeh.2017.04.039DOI Listing
July 2017