Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.

BACKGROUND: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. METHODS: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. RESULTS: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). CONCLUSIONS: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.).

Vedolizumab and Ustekinumab Levels in Pregnant Women With Inflammatory Bowel Disease and Infants Exposed In Utero.

BACKGROUND & AIMS: Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant after in utero exposure remain incompletely defined. We aim to define the antenatal stability of ustekinumab and vedolizumab levels and the time at which infant drug levels become undetectable. METHODS: This multicenter prospective observational cohort study recruited pregnant or preconception women with inflammatory bowel disease receiving vedolizumab or ustekinumab. Trough drug levels, clinical data, and biochemical data were documented preconception, during each trimester of pregnancy, and postpartum. Maternal and cord blood drug levels were measured at delivery and in infants until undetectable. Infant outcomes were assessed until 2 years of age. RESULTS: A total of 102 participants (vedolizumab, n = 58) were included. The majority of mothers were, and remained, in clinical and biochemical remission. Maternal vedolizumab levels decreased over the course of pregnancy in association with increasing weight, rather than increasing gestation. Maternal ustekinumab levels remained stable. The median time to drug becoming undetectable in the infant was shorter for vedolizumab (11 wk; range, 5-19 wk; n = 32) than ustekinumab (14 wk; range, 9-36 wk; n = 17) and correlated positively with infant delivery level. Thirty-two of 41 (88%) and 17 of 30 (67%) vedolizumab- and ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age, respectively. Pregnancy and infant outcomes were favorable. Twenty infants with undetectable drug levels received the rotavirus vaccine, with no adverse reactions reported. CONCLUSIONS: Maternal vedolizumab levels decreased, whereas ustekinumab levels remained stable over the course of pregnancy. Most vedolizumab- and approximately half of ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age. No concerning maternal or infant safety signals were identified.

Risk factors for malignancy and serious infection in patients with inflammatory bowel disease: a retrospective analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of malignancy and infection compared to the general population. AIMS: We aim to identify risk factors for malignancy or serious infection in our IBD cohort. METHODS: Patients with IBD from a single tertiary referral centre were included. Demographic and clinical details, including immunosuppressant exposure, were collected and medical records retrospectively screened for adverse events, including malignancy or infection requiring hospitalisation. Logistic regression was used to evaluate risk factors for adverse events. RESULTS: Five hundred and forty-nine patients with IBD (340 Crohn disease (CD) and 209 ulcerative colitis (UC)) were studied. Forty-eight malignancies, including 39 (81.3%) non-melanoma skin cancers, 3 (6.3%) haematologic malignancies and 6 (15.4%) solid-organ malignancies, were identified, and 92 cases of serious infection were detected. IBD duration (odds ratio (OR) = 1.08; 95% confidence interval (CI) = 1.03-1.13) and ileocolonic CD (OR = 4.96; 95% CI = 1.13-21.71) were associated with increased odds of overall cancer. Compared with patients not previously exposed to the given class of immunosuppression assessed, the development of overall malignancy was not higher with thiopurine exposure (OR = 1.00; 95% CI = 0.50-2.24) or anti-tumour necrosis factor-alpha (TNF-α) exposure (OR = 0.78; 95% CI = 0.37-1.64). Similarly, compared with patients not exposed, infection risk was not affected by thiopurine (OR = 0.74; 95% CI = 0.46-1.20) or anti-TNF exposure (OR = 0.60; 95% CI = 0.38-0.95). CONCLUSIONS: Factors including ileocolonic CD and increasing IBD duration were associated with higher malignancy risk in this cohort. Compared with non-exposure, patients exposed to thiopurines were not at increased risk of malignancy or serious infection. Similarly, patients exposed to anti-TNF treatment did not experience increased rates of malignancy or serious infection compared to patients not exposed to this treatment.

Australian inflammatory bowel disease consensus statements for preconception, pregnancy and breast feeding.

OBJECTIVE: Because pregnancy outcomes tend to be worse in women with inflammatory bowel disease (IBD) than in those without, we aimed to update consensus statements that guide the clinical management of pregnancy in patients with IBD. DESIGN: A multidisciplinary working group was established to formulate these consensus statements. A modified RAND/UCLA appropriateness method was used, consisting of a literature review, online voting, discussion meeting and a second round of voting. The overall agreement among the delegates and appropriateness of the statement are reported. RESULTS: Agreement was reached for 38/39 statements which provide guidance on management of pregnancy in patients with IBD. Most medications can and should be continued throughout pregnancy, except for methotrexate, allopurinol and new small molecules, such as tofacitinib. Due to limited data, no conclusion was reached on the use of tioguanine during pregnancy. Achieving and maintaining IBD remission before conception and throughout pregnancy is crucial to optimise maternofetal outcomes. This requires a multidisciplinary approach to engage patients, allay anxieties and maximise adherence tomedication. Intestinal ultrasound can be used for disease monitoring during pregnancy, and flexible sigmoidoscopy or MRI where clinically necessary. CONCLUSION: These consensus statements provide up-to-date, comprehensive recommendations for the management of pregnancy in patients with IBD. This will enable a high standard of care for patients with IBD across all clinical settings.

Clinical outcomes amongst elderly patients with inflammatory bowel disease.

BACKGROUNDS AND AIMS: Inflammatory bowel disease (IBD) affects a growing cohort of elderly patients. Our aim was to compare the quality of care received by elderly patients with IBD with a nonelderly adult IBD population using clinical markers including steroid-free clinical remission. METHOD: Retrospective audit of all consecutive patients attending a specialist IBD centre over a 1-year period aged >60 (elderly cohort [EC]) and 50 consecutive patients aged 30-45 years (control cohort [CC]). A follow-up survey was completed assessing current symptoms and perceptions of care. RESULTS: One hundred thirty-nine patients were evaluated (89 EC, 50 CC). Steroid-free clinical remission was observed less commonly in the EC (58, 64%) compared with the CC (40, 80%) (P < 0.05). Biologics such as infliximab (15% EC vs 36% CC; P < 0.01) and adalimumab (14% EC vs 30% CC; P = 0.02) were used less frequently in the EC, whilst vedolizumab (6% EC vs 6% CC; P = 1) and ustekinumab (3% EC vs 2% CC; P = 1) were used at a similar frequency. Patients in the EC were less likely to have specialist IBD nursing contact (P < 0.01), smoking screening (P < 0.011) or influenza vaccinations (P < 0.006). IBD nurse contact was associated with significantly greater provision of the preventative care measures. CONCLUSION: Elderly patients with IBD were less likely to experience steroid-free clinical remission or be prescribed biologics. Elderly patients were less likely to receive education with respect to preventative medicine. The models of care for the elderly need re-evaluation and greater incorporation with the multidisciplinary IBD team.

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

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.

Safely reducing haemodialysis frequency during the COVID-19 pandemic.

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.

Updates in the management of inflammatory bowel disease during pregnancy.

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.

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

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.

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

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.

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

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.

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

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.

Longitudinal Executive Function and Episodic Memory Profiles in Behavioral-Variant Frontotemporal Dementia and Alzheimer's Disease.

OBJECTIVES: With comparable baseline performance on executive functions (EF) and memory between Alzheimer's disease (AD) and behavioral-variant frontotemporal dementia (bvFTD), it is currently unclear if both diseases can be distinguished longitudinally on these measures reliably. METHODS: A total of 111 participants (33 AD, 31 bvFTD, and 47 controls) were followed-up annually over a 4-year period and tested on measures of EF, memory, and orientation. Linear mixed-effect models were constructed using disease severity as a nuisance variable to examine profiles of neuropsychological performance decline. RESULTS: At baseline, overlap in terms of cognitive impairment between bvFTD and AD on multiple EF, memory, and orientation measures was present. Longitudinally, only disinhibition (Hayling total errors) appeared sensitive to discriminating AD from bvFTD; however, only after the first annual follow-up. Subgroup analyses on smaller samples revealed comparable profiles on EF tasks at baseline and over time between bvFTD and AD who presented with impaired EF at presentation, and on memory and orientation tasks between AD and bvFTD who presented with severe amnesia. CONCLUSIONS: Our results replicate previous findings showing only moderate discriminability between AD and bvFTD at clinical presentation on EF and memory measures. More importantly, we also show that longitudinal trajectories strongly overlap for both dementias on these measures. Disinhibition emerged as the sole measure that in the long run was significantly more impaired in bvFTD. Future studies should use tests designed to target cortical regions that are specifically impaired in bvFTD, such as the ventromedial prefrontal cortex, to improve the accurate discrimination of these diseases. (JINS, 2017, 23, 34-43).

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

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.

Detecting clinical change with the CDR-FTLD: differences between FTLD and AD dementia.

OBJECTIVE: To investigate the psychometric properties of the Clinical Dementia Scale-frontotemporal lobar degeneration (CDR-FTLD) psychometric properties using Rasch analysis and its sensitivity distinguishing disease progression between FTLD and Alzheimer's disease (AD). METHODS: Of 603 consecutive patients from the National Alzheimer Coordinating Center dataset (FTLD = 350; AD = 253), 120 FTLDs were included in a Rasch analysis to verify CDR-FTLD psychometric properties; 483 (FTLD = 230; AD = 253) were included to analyse disease progression, with 195 (FTLD = 82; AD = 113) followed-up (24 months). RESULTS: The CDR-FTLD demonstrated good consistency, construct and concurrent validity and correlated well with mini-mental state examination (MMSE) and disease duration (ps < 0.05). At baseline, FTLD showed greater dementia severity than AD after matched for MMSE and disease duration (p < 0.001). Independent Rasch analyses demonstrated different patterns of progression for FTLD and AD in terms of the domains initially and then subsequently affected with disease progression. At follow-up, although MMSE showed significant changes (p < 0.05), these were greater on the CDR-FTLD (p < 0.001). CONCLUSION: The CDR-FTLD satisfactorily measures dementia severity and change in FTLD, distinguishing disease progression between FTLD and AD, with clear implications for care, prognosis and future clinical trials. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.

Liver stiffness plus platelet count can be used to exclude high-risk oesophageal varices.

BACKGROUND/AIMS: Endoscopic screening for high-risk gastro-oesophageal varices (GOV) is recommended for compensated cirrhotic patients with transient elastography identifying increasing numbers of patients with cirrhosis without portal hypertension. Using liver stiffness measurement (LSM) ± platelet count, the aim was to develop a simple clinical rule to exclude the presence of high-risk GOV in patients with Child-Pugh A cirrhosis. METHODS: A retrospective analysis of 71 patients with Child-Pugh A cirrhosis diagnosed by transient elastography (LSM >13.6 kPa) who underwent screening gastroscopy was conducted. A predictive model using LSM ± platelet count was assessed to exclude the presence of high-risk GOV (diameter >5 mm and/or the presence of high-risk stigmata) and validated using a second cohort of 200 patients from two independent centres. RESULTS: High-risk GOV were present in 10 (15%) and 16 (8%) of the training and validation cohorts, respectively, which was associated with LSM and Pl count (P < 0.05). A combined model based on LSM and Pl count was more accurate for excluding the presence of high-risk GOV than either alone (training cohort AUROC: 0.87 [0.77-0.96] vs. 0.78 [0.65-0.92] for LSM and 0.71 [0.52-0.90] for platelets) with the combination of LSM ≤25 kPa and Pl ≥100 having a NPV of 100% in both the training and validation cohorts. A total of 107 (39%) patients meet this criterion. CONCLUSION: The combination of LSM ≤25 kPa and Pl ≥100 can be used in clinical practice to exclude the presence of high-risk GOV in patients with Child-Pugh A cirrhosis.

The Relationship between Behavioural Changes, Cognitive Symptoms, and Functional Disability in Primary Progressive Aphasia: A Longitudinal Study.

BACKGROUND: The contribution of behavioural changes to functional decline is yet to be explored in primary progressive aphasia (PPA). OBJECTIVES: (1) investigate functional changes in two PPA variants [semantic (svPPA) and non-fluent (nfvPPA)], at baseline and after 12 months; (2) investigate baseline differences in behavioural changes between groups, and (3) explore predictors of functional decline after a 12-month period. METHODS: A longitudinal study involving 29 people with PPA (18 svPPA; 11 nfvPPA) seen annually in Sydney/Australia was conducted. A total of 114 functional and behavioural assessments were included for within-group (repeated-measures ANOVA; annual rate of change; multiple regression analyses) and between-group analyses (pairwise comparisons). RESULTS: Functional profiles in svPPA and nfvPPA were similar in people with up to 5 years of disease duration. Behavioural changes were marked in svPPA patients (stereotypical behaviour and apathy) but did not predict annual rate of change of functional abilities; global cognitive scores at baseline did. Despite mild behavioural changes in nfvPPA (disinhibition, apathy), these were significant predictors of annual rate of functional change. CONCLUSIONS: The presentation and interplay of behavioural changes and functional disability differ in svPPA and nfvPPA. These varying factors should be taken into account when considering prognosis, disease management, and selection of outcome measures for interventions.

Old dogs with new tricks: Detecting accelerated long-term forgetting by extending traditional measures.

Accelerated long-term forgetting (ALF) is a condition in which normal memory performance is displayed after short delays, but significant memory loss is detected when memory is tested after several days or weeks. This condition has been reported in patients with epilepsy, but there are few normative scores available for its detection in clinical practice. In the present study, we assessed 60 healthy control subjects 18-60years of age on three memory measures [Rey Auditory Verbal Learning (RAVLT), Logical Memory (LM), and Aggie Figures] at delays of 30min and 7days. With these normative values, we determined cutoff scores to look for ALF and then categorized the performance of 15 patients with focal epilepsy on the same tasks. Seven of the patients showed ALF, and, in four of these, no other memory deficits (i.e., deficits at 30min on at least one task) were detected. Of the several demographic and epilepsy factors examined, only higher estimated IQ and older age predicted ALF (and only on one task: RAVLT). The findings provide a useful set of data to be applied in the clinic and some insight into the factors that influence retention within the first week.

Cut-off scores for mild and moderate dementia on the Addenbrooke's Cognitive Examination-III and the Mini-Addenbrooke's Cognitive Examination compared with the Mini-Mental State Examination.

AIMS AND METHOD: We aimed to establish cut-off scores to stage dementia on the Addenbrooke's Cognitive Examination-III (ACE-III) and the Mini-Addenbrooke's Cognitive Examination (M-ACE) compared with scores traditionally used with the Mini-Mental State Examination (MMSE). Our cross-sectional study recruited 80 patients and carers from secondary care services in the UK. RESULTS: A score ≤76 on the ACE-III and ≤19 on the M-ACE correlated well with MMSE cut-offs for mild dementia, with a good fit on the receiver operating characteristic analysis for both the ACE-III and M-ACE. The cut-off for moderate dementia had lower sensitivity and specificity. There were low to moderate correlations between the cognitive scales and scales for everyday functioning and behaviour. CLINICAL IMPLICATIONS: Our findings allow an objective interpretation of scores on the ACE-III and the M-ACE relative to the MMSE, which may be helpful for clinical services and research trials.

Thrombocytosis and Transaminitis in Infants Born to Women With Inflammatory Bowel Disease Is Associated With Exposure to Maternal Inflammation In Utero.

BACKGROUND: Despite reassuring clinical safety data, thrombocytosis, anemia, lymphopenia, and liver function derangements have been observed in infants born to women with inflammatory bowel disease (IBD) treated with thiopurines and biologics. We aimed to define the prevalence, course, associations, and clinical impact of hematological and biochemical abnormalities in such infants. METHODS: This multicenter prospective cohort study assessed clinical, hematologic, and biochemical outcomes of infants exposed to thiopurines or biologics in utero for management of maternal IBD. Liver transaminases, full blood examination, and infant thiopurine metabolites (where exposed) were taken at delivery and 6 weeks of age. Abnormal results were repeated until normalization. Infants were followed clinically by a pediatric gastroenterologist up to 2 years of age. RESULTS: A total of 130 infants were included. Thrombocytosis and elevated alanine transaminase (ALT) were seen in over half of infants up to 6 months of age with no significant clinical impact. Elevated ALT was associated with increasing maternal C-reactive protein in second trimester, while thrombocytosis was associated with increasing maternal C-reactive protein and fecal calprotectin in third trimester. Preceding infection and vaccination were associated with an increased risk of elevated alkaline phosphatase at 3 months. In those exposed to thiopurines, increasing maternal 6-methylmercaptopurine at delivery was associated with increased ALT to 6 months. CONCLUSIONS: Infants born to women with IBD commonly developed thrombocytosis, elevated alkaline phosphatase, and elevated ALT. These findings were associated with exposure to maternal inflammation, elevated 6-methylmercaptopurine at delivery, and infant vaccinations and infections, and had minimal clinical consequence.

Hematological and biochemical abnormalities have been observed in infants born to women with inflammatory bowel disease. This prospective study shows that thrombocytosis and elevated alanine transaminase are common in infants to 6 months of age and are associated with maternal inflammation, rather than with in utero medication exposures.