Publications by authors named "Raj Shah"

326 Publications

Impact of COVID-19 on gastroenterology fellowship training: a multicenter analysis of endoscopy volumes.

Endosc Int Open 2021 Oct 16;9(10):E1572-E1578. Epub 2021 Sep 16.

Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.

The COVID-19 pandemic has had a profound impact on gastroenterology training programs. We aimed to objectively evaluate procedural training volume and impact of COVID-19 on gastroenterology fellowship programs in the United States. This was a retrospective, multicenter study. Procedure volume data on upper and lower endoscopies performed by gastroenterology fellows was abstracted directly from the electronic medical record. The study period was stratified into 2 time periods: Study Period 1, SP1 (03/15/2020 to 06/30/2020) and Study Period 2, SP2 (07/01/2020 to 12/15/2020). Procedure volumes during SP1 and SP2 were compared to Historic Period 1 (HP1) (03/15/2019 to 06/30/2019) and Historic Period 2 (HP2) (07/01/2019 to 12/15/2019) as historical reference. Data from 23 gastroenterology fellowship programs (total procedures = 127,958) with a median of 284 fellows (range 273-289; representing 17.8 % of all trainees in the United States) were collected. Compared to HP1, fellows performed 53.6 % less procedures in SP1 (total volume: 28,808 vs 13,378; mean 105.52 ± 71.94 vs 47.61 ± 41.43 per fellow;  < 0.0001). This reduction was significant across all three training years and for both lower and upper endoscopies (  < 0.0001). However, the reduction in volume was more pronounced for lower endoscopy compared to upper endoscopy [59.03 % (95 % CI: 58.2-59.86) vs 48.75 % (95 % CI: 47.96-49.54);  < 0.0001]. The procedure volume in SP2 returned to near baseline of HP2 (total volume: 42,497 vs 43,275; mean 147.05 ± 96.36 vs 150.78 ± 99.67;  = 0.65). Although there was a significant reduction in fellows' endoscopy volume in the initial stages of the pandemic, adaptive mechanisms have resulted in a return of procedure volume to near baseline without ongoing impact on endoscopy training.
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http://dx.doi.org/10.1055/a-1526-1419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445682PMC
October 2021

Similar mortality risk in incident cognitive impairment and dementia: Evidence from the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

J Am Geriatr Soc 2021 Sep 17. Epub 2021 Sep 17.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Background: This study examined the risk of mortality in older adults with newly detected cognitive impairment or dementia.

Methods: Data from the Australian cohort of the ASPirin in Reducing Events in the Elderly (ASPREE) trial were examined. The ASPREE clinical trial compared daily low-dose aspirin to a placebo and involved 16,703 individuals aged 70 years and over, who were without major cognitive impairment, physical disability, or cardiovascular disease at recruitment. During the trial, evidence of cognitive impairment, based on cognitive testing and medical record information, triggered dementia adjudication of participants using DSM-IV criteria. Cox proportional hazard models were used to compare mortality rates across the dementia, trigger-only, and no-trigger groups.

Results: Over a median 4.7-year follow-up period, 806 participants triggered dementia adjudication, with 485 (60.2%) judged to have dementia. Following recruitment, mortality risks were 32.9, 33.6, and 10.8 events per 1000 person-years in the dementia, trigger-no-dementia, and no-trigger groups, respectively. In the fully adjusted model, mortality risks remained higher in the dementia and trigger-no-dementia groups, with hazard ratios of 1.7 (95% CI: 1.3-2.1) and 1.9 (95% CI: 1.5-2.6), respectively. There was no discernible difference between the dementia and trigger-no-dementia groups in mortality rates following recruitment, or following a dementia trigger. These two groups were more likely to die from sepsis, respiratory disease, and dementia, but less likely to die from cancer than the no-trigger group, χ  = 161.5, p < 0.001.

Conclusion: ASPREE participants who triggered for a dementia evaluation experienced a substantially higher mortality rate than those who remained cognitively intact. The increase was indistinguishable among persons who met DSM-IV criteria for dementia vs. those who triggered for a dementia evaluation but failed to meet DSM-IV criteria. Future work should investigate whether earlier detection of cognitive decline can be used to identify and prevent early mortality.
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http://dx.doi.org/10.1111/jgs.17435DOI Listing
September 2021

Effect of pancreatic endotherapy on quality of life in chronic pancreatitis patients: A systematic review.

World J Gastrointest Endosc 2021 Aug;13(8):336-355

Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States.

Background: Pancreatic endotherapy provides treatment options for the management of chronic pancreatitis-related structural complications such as pancreatic duct stones, strictures, and pancreatic fluid collections. Most studies detailing endotherapy, however, have focused on technical success outcomes such as stone clearance or stricture resolution.

Aim: To review the effect of pancreatic endotherapy on patient-centered outcomes.

Methods: Systematic review of studies examining pancreatic endotherapy.

Results: A total of 13 studies including 3 randomized clinical trials were included. The majority of studies found an improvement in quality of life with pancreatic endotherapy.

Conclusion: While pancreatic endotherapy does appear to improve quality of life, there are clear gaps in knowledge regarding many pancreatic endotherapy modalities. Furthermore, qualitative analysis is lacking in these studies and further work is needed to elucidate the patient experience with pancreatic endotherapy.
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http://dx.doi.org/10.4253/wjge.v13.i8.336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394180PMC
August 2021

Challenges faced by families of critically ill patients during the first wave of the COVID-19 pandemic.

Patient Educ Couns 2021 Aug 27. Epub 2021 Aug 27.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Psychiatry and Behavioral Sciences, Rush Medical College, Chicago, IL, USA.

Objective: To understand how surrogates of critically ill patients adjusted to challenges that resulted from the COVID-19 pandemic.

Methods: Participants (N = 62) were surrogates of critically ill adults with COVID-19 in the ICU at an urban, academic medical center from March to June 2020. Participants were recruited using convenience sampling and took part in one-time qualitative individual interviews via telephone. Qualitative data were analyzed using thematic content analysis.

Results: Qualitative analyses yielded four types of challenges: Communication with the medical team, communication among family members, understanding and tracking medical information, and distress related to visitor restrictions. To adjust to challenges related to communication, participants developed routines for receiving updates from the medical team and providing updates to other family members. To adjust to the challenge related to comprehension, participants sought information from external sources such as family members in healthcare fields. To adjust to the challenge related to visitation, participants found some comfort in video calls with the patient.

Conclusions: Surrogates of critically ill patients with COVID-19 faced multiple types of challenges yet adjusted to those challenges.

Practical Implications: Future research should focus on ways to support the wellbeing of surrogates during times of restricted hospital visitation. Clinical trial registered at ClinicalTrials.gov (NCT03969810).
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http://dx.doi.org/10.1016/j.pec.2021.08.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393512PMC
August 2021

Correlating wine astringency with physical measures - Current knowledge and future directions.

Adv Colloid Interface Sci 2021 Sep 2;296:102520. Epub 2021 Sep 2.

Department of Fruit Production and Enology, School of Agricultural and Forest Sciences, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.

Oral tribology receives growing attention in the field of food sciences as it offers great opportunities to establish correlations between physical parameters, such as the coefficient of friction, and sensory effects when interacting with components of the human mouth. One important aspect covers the astringency produced by wine, which can be described as the sensation of dryness and puckering in the mouth, specifically occurring between the tongue and the palate after swallowing. Therefore, this article aims at shedding some light on recent trends to correlate physical measures, such as the coefficient of friction derived by oral tribology, with prevailing theories on underlying physiological causes for sensory perception of wines. Some successful cases reported the potential of correlating wine astringency perception with the coefficient of friction in tribological experiments. Our critical assessment demonstrates that the findings are still contradictory, which urgently asks for more systematic studies. Therefore, we summarize the current challenges and hypothesize on future research directions with a particular emphasis on the comparability, reproducibility and transferability of studies using different experimental test-rigs and procedures.
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http://dx.doi.org/10.1016/j.cis.2021.102520DOI Listing
September 2021

Polygenic score modifies risk for Alzheimer's disease in ε4 homozygotes at phenotypic extremes.

Alzheimers Dement (Amst) 2021 5;13(1):e12226. Epub 2021 Aug 5.

Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Australia.

Introduction: Diversity in cognition among apolipoprotein E () ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms.

Methods: We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy ε4 homozygotes aged ≥75 years (n = 213) and early-onset ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity.

Results: The PRS for AD was significantly higher in ε4 homozygote AD cases compared to older cognitively healthy ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0-35.2;  = .003). The difference in the same PRS between ε3/ε3 extremes was not as significant (OR 3.13; CI 0.98-9.92;  = .053) despite similar numbers and power. There was no statistical difference in an educational attainment PRS between these age extreme case-controls.

Discussion: A PRS for AD contributes to modified cognitive expression of the ε4/ε4 genotype at phenotypic extremes of risk.
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http://dx.doi.org/10.1002/dad2.12226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339682PMC
August 2021

Validation of a deficit-accumulation Frailty Index in the ASPREE study and its predictive capacity for disability-free survival.

J Gerontol A Biol Sci Med Sci 2021 Aug 2. Epub 2021 Aug 2.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria Australia.

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterise a 67-item deficit-accumulation frailty index (FI) in 19,110 community-dwelling individuals in the ASPREE clinical trial. Participants aged 65 to 98 years were recruited from the U.S. and Australia, and were without diagnosed dementia and cardiovascular disease, and without major physical disability. The median FI score was 0.10 (IQR: 0.07; 0.14) at baseline, and the prevalence of frailty (FI> 0.21) increased from 8.1% to 17.4% after six years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r =-0.31) and grip strength (r = -0.46), and strongly associated with a modified Fried frailty phenotype (p<0.0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (HR:21.3, 95% CI:15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals, and provides important information about an individual's vulnerability to and risk of disease.
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http://dx.doi.org/10.1093/gerona/glab225DOI Listing
August 2021

Post-Liver Transplant Lymphoproliferative Disorder Presenting as Biliary Stricture.

ACG Case Rep J 2021 Jul 20;8(7):e00628. Epub 2021 Jul 20.

Division of Gastroenterology and Hepatology, University Hospitals Cleveland Medical Center, Cleveland, OH.

A 63-year-old man with nonalcoholic steatohepatitis cirrhosis who underwent orthotopic liver transplant presented 1 year later with obstructive jaundice because of a biliary stricture. This anastomotic stricture was initially believed to be ischemic, but further investigation revealed malignant biliary obstruction because of encasement of the bile duct by a mass arising from liver segment VII, later determined to be post-transplant lymphoproliferative disorder with widespread metastasis. After reduction of immunosuppression and systemic chemotherapy, he experienced complete remission. This case illustrates the need to consider post-transplantation lymphoproliferative disorder-related biliary stricture in any postorthotopic liver transplantation transplant patient presenting with obstructive jaundice.
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http://dx.doi.org/10.14309/crj.0000000000000628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294908PMC
July 2021

Characterization of American teduglutide consumers from 2015 to 2020: A large database study.

JPEN J Parenter Enteral Nutr 2021 Jul 21. Epub 2021 Jul 21.

Gastroenterology and Hepatology, Louis Stokes VA Medical Center, Cleveland, Ohio, USA.

Introduction: Teduglutide, a glucagon-like peptide-2 analog, is a novel therapy for intestinal failure that reduces need for parenteral support, especially in patients without a functional terminal ileum or colon. It can also predispose patients to accelerated progression of gastrointestinal (GI) malignancy and fluid overload. We demographically and clinically characterized American patients prescribed teduglutide.

Methods: The Explorys database is an aggregate of deidentified patient data from dozens of US healthcare systems. We used SNOMED classification to identify patients prescribed teduglutide from 2015 to 2019. Through the browse cohort feature we determined the demographics, postsurgical anatomy, comorbidities, and indication for teduglutide use among these patients.

Results: Of approximately 72 million patients, 170 were prescribed teduglutide. A large majority were female (70.6%). Most common etiologies of short-bowel syndrome were intestinal obstruction (52.9%) and Crohn's disease (41.2%). Common postsurgical anatomy included total colectomy (41.2%) and ileostomy. Common incident symptoms included abdominal pain (41.2%) and nausea (23.5%). Thirty (17.6%) patients were prescribed teduglutide despite comorbid heart failure, and 5.9% despite prior GI malignancy. A total of 11.8% of patients had a history of benign GI neoplasms before starting teduglutide. A total of 5.9% of patients had posttreatment formation of colon polyps.

Conclusion: In a large American database, the teduglutide prescription is rare. Only a minority have postsurgical anatomy associated with the most robust response to teduglutide. Serious adverse events appear rare, but a substantial number of patients are at risk for adverse effects because of the presence of comorbid heart failure or GI neoplasm.
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http://dx.doi.org/10.1002/jpen.2221DOI Listing
July 2021

Written Care Summaries Facilitate Communication Between Families and Providers of ICU Patients: A Pilot Study.

Crit Care Explor 2021 Jul 13;3(7):e0473. Epub 2021 Jul 13.

Division of Pulmonary and Critical Care, Department of Internal Medicine, Rush University Medical Center, Chicago, IL.

ICU providers may invite families to participate in daily rounds to inform them of the patient's condition and to support their emotional well-being. Daily written summaries of care may provide complementary benefits.

Design: Qualitative interviews with surrogates of ICU patients who received daily written summaries of care.

Setting: Single, urban academic medical center.

Patients/subjects: A convenience sample of 30 surrogates of nondecisional, medical ICU patients.

Interventions: Daily written summaries detailed each of the patient's main ICU problems, the presumed causes of each of the problems, and the medical team's plan to address each of the problems for each ICU day.

Measurements And Main Results: There were four ways that written summaries affected the participant's experience: 1) providing clarity to participants regarding the patient's condition, 2) facilitating participant understanding of the patient's clinical course, 3) facilitating communication between participants and medical providers, and 4) facilitating communication between participants and other family members. Overarching themes were that summaries were understandable, had appropriate level of detail, and added value to the ICU experience.

Conclusions: In this pilot study, family members had positive impressions of receiving daily written summaries of care. Further study is needed to determine the extent to which written communication may affect family and patient outcomes.
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http://dx.doi.org/10.1097/CCE.0000000000000473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280084PMC
July 2021

Long-Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults.

J Am Heart Assoc 2021 Jul 26;10(13):e019613. Epub 2021 Jun 26.

Berman Center for Outcomes and Clinical Research Hennepin-Health Research InstituteHennepin Healthcare Minneapolis MN.

Background Blood pressure variability (BPV) in midlife increases risk of late-life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow-up visits. Time-to-event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction =0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19-2.39) but not women (HR, 1.01; 95% CI, 0.72-1.42). For cognitive decline, similar increased risks were observed for men and women (interaction =0.15; men: HR, 1.36; 95% CI, 1.16-1.59; women: HR, 1.14; 95% CI, 0.98-1.32). Conclusions High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583; isrctn.com. Identifier: ISRCTN83772183.
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http://dx.doi.org/10.1161/JAHA.120.019613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403315PMC
July 2021

Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults.

J Am Coll Cardiol 2021 Jun;77(25):3145-3156

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Background: The neurocognitive effect of statins in older adults remain uncertain.

Objectives: The aim of this study was to investigate the associations of statin use with cognitive decline and incident dementia among older adults.

Methods: This analysis included 18,846 participants ≥65 years of age in a randomized trial of aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially and were followed for 4.7 years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer's disease, mixed presentations); mild cognitive impairment (MCI) and its subclassifications (MCI consistent with Alzheimer's disease, other MCI); and changes in domain-specific cognition, including global cognition, memory, language and executive function, psychomotor speed, and the composite of these domains. Associations of baseline statin use versus nonuse with dementia and MCI outcomes were examined using Cox proportional hazards models and with cognitive change using linear mixed-effects models, adjusting for potential confounders. The impact of statin lipophilicity on these associations was further examined, and effect modifiers were identified.

Results: Statin use versus nonuse was not associated with dementia, MCI, or their subclassifications or with changes in cognitive function scores over time (p > 0.05 for all). No differences were found in any outcomes between hydrophilic and lipophilic statin users. Baseline neurocognitive ability was an effect modifier for the associations of statins with dementia (p for interaction < 0.001) and memory change (p for interaction = 0.02).

Conclusions: In adults ≥65 years of age, statin therapy was not associated with incident dementia, MCI, or declines in individual cognition domains. These findings await confirmation from ongoing randomized trials.
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http://dx.doi.org/10.1016/j.jacc.2021.04.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091356PMC
June 2021

Exploring the lubrication mechanisms of synovial fluids for joint longevity - A perspective.

Colloids Surf B Biointerfaces 2021 Oct 16;206:111926. Epub 2021 Jun 16.

Department of Chemical Engineering, Biotechnology and Materials, University of Chile, Santiago, Chile. Electronic address:

Synovial fluids are complex fluids responsible for the exceptional lubrication present in synovial joints. These fluids consist of various constituents, including hyaluronic acid, surface-active proteins (i.e., lubricin), surface-active phospholipids, as well as various other proteins such as human serum albumin and γ -globulin seric proteins, each of them playing an essential role in lubrication. Being the key to the most efficient biotribological systems, this article is intended to review the current understanding of the underlying lubrication mechanisms of the synovial fluids enables prospective usage in numerous applications, especially as a lubricant for hip and knee prosthetics in combatting osteoarthritis. Current research focuses on the determination of the role of proteins in prosthetic lubrication, optimal material combinations for prosthesis, and the effects of relevant physical variables in prosthetic lubrication. The characterization of prosthetic lubrication and wear mechanisms by synovial fluids represents a prominent challenge in tribological research, yet also an important hurdle to overcome towards optimal lubrication of articular prosthetics.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111926DOI Listing
October 2021

Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population.

Aging Cell 2021 06 26;20(6):e13384. Epub 2021 May 26.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia.

Few studies have measured the effect of genetic factors on dementia and cognitive decline in healthy older individuals followed prospectively. We studied cumulative incidence of dementia and cognitive decline, stratified by APOE genotypes and polygenic risk score (PRS) tertiles, in 12,978 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrolment, participants had no history of diagnosed dementia, cardiovascular disease, physical disability or cognitive impairment. Dementia (adjudicated trial endpoint) and cognitive decline, defined as a >1.5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence for all-cause dementia and cognitive decline was calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non-APOE variants. During a median 4.5 years of follow-up, 324 participants developed dementia, 503 died. Cumulative incidence of dementia to age 85 years was 7.4% in all participants, 12.6% in APOE ε3/ε4 and 26.6% in ε4/ε4. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3-fold increased dementia risk and 1.4/1.8-fold cognitive decline risk, versus ε3/ε3 (p < 0.001 for both). High PRS tertile was associated with a 1.4-fold dementia risk versus low (CI 1.04-1.76, p = 0.02), but was not associated with cognitive decline (CI 0.96-1.22, p = 0.18). Incidence of dementia among healthy older individuals is low across all genotypes; however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not.
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http://dx.doi.org/10.1111/acel.13384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208779PMC
June 2021

Hepcidin Signaling in Health and Disease: Ironing Out the Details.

Hepatol Commun 2021 May 26;5(5):723-735. Epub 2021 Mar 26.

Liver Care Network and Organ Care Research Swedish Medical Center Seattle WA USA.

Hepcidin, a peptide hormone produced by hepatocytes, is the central regulator of systemic iron homeostasis through its interaction with ferroportin, the major cellular iron export protein. Hepcidin binding to ferroportin results in reduced iron export from macrophages and intestinal absorptive cells, leading to decreased serum iron levels. Hepcidin expression is influenced by several factors that include serum and liver iron stores, erythropoiesis, hypoxia, inflammation, and infection. Erythropoietic drive and hypoxia suppress hepcidin expression and promote red cell production. In contrast, inflammation and infection are associated with increased hepcidin production to sequester iron intracellularly as a means of depriving microorganisms of iron. Chronic inflammation may up-regulate hepcidin expression through the interleukin-6 (IL-6)-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway. The bone morphogenetic protein (BMP)-mothers against decapentaplegic homolog (SMAD) pathway is a major positive driver of hepcidin expression in response to either increased circulating iron in the form of transferrin or iron loading in organs. Hereditary hemochromatosis (HH) consists of several inherited disorders that cause inappropriately reduced hepcidin expression in response to body iron stores, leading to increased iron absorption from a normal diet. The most common form of HH is due to a mutation in the gene, which causes a failure in the hepatocyte iron-sensing mechanism, leading to reduced hepcidin expression; the clinical manifestations of -HH include increased serum transferrin-iron saturation and progressive iron loading in the liver and other tissues over time among patients who express the disease phenotype. In this article, we review the physiologic mechanisms and cellular pathways by which hepcidin expression is regulated, and the different forms of HH resulting from various mutations that cause hepcidin deficiency. We also review other drivers of hepcidin expression and the associated pathophysiologic consequences.
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http://dx.doi.org/10.1002/hep4.1717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122377PMC
May 2021

Variability in comorbidites and health services use across homeless typologies: multicenter data linkage between healthcare and homeless systems.

BMC Public Health 2021 05 13;21(1):917. Epub 2021 May 13.

Center for Housing and Health, Chicago, IL, USA.

Background: Homelessness is associated with substantial morbidity. Data linkages between homeless and health systems are important to understand unique needs across homeless populations, identify homeless individuals not registered in homeless databases, quantify the impact of housing services on health-system use, and motivate health systems and payers to contribute to housing solutions.

Methods: We performed a cross-sectional survey including six health systems and two Homeless Management Information Systems (HMIS) in Cook County, Illinois. We performed privacy-preserving record linkage to identify homelessness through HMIS or ICD-10 codes captured in electronic medical records. We measured the prevalence of health conditions and health-services use across the following typologies: housing-service utilizers stratified by service provided (stable, stable plus unstable, unstable) and non-utilizers (i.e., homelessness identified through diagnosis codes-without receipt of housing services).

Results: Among 11,447 homeless recipients of healthcare, nearly 1 in 5 were identified by ICD10 code alone without recorded homeless services (n = 2177; 19%). Almost half received homeless services that did not include stable housing (n = 5444; 48%), followed by stable housing (n = 3017; 26%), then receipt of both stable and unstable services (n = 809; 7%). Setting stable housing recipients as the referent group, we found a stepwise increase in behavioral-health conditions from stable housing to those known as homeless solely by health systems. Compared to those in stable housing, prevalence rate ratios (PRR) for those without homeless services were as follows: depression (PRR = 2.2; 95% CI 1.9 to 2.5), anxiety (PRR = 2.5; 95% CI 2.1 to 3.0), schizophrenia (PRR = 3.3; 95% CI 2.7 to 4.0), and alcohol-use disorder (PRR = 4.4; 95% CI 3.6 to 5.3). Homeless individuals who had not received housing services relied on emergency departments for healthcare-nearly 3 of 4 visited at least one and many (24%) visited multiple.

Conclusions: Differences in behavioral-health conditions and health-system use across homeless typologies highlight the particularly high burden among homeless who are disconnected from homeless services. Fragmented and high use of emergency departments for care should motivate health systems and payers to promote housing solutions, especially those that incorporate substance use and mental health treatment.
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http://dx.doi.org/10.1186/s12889-021-10958-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117275PMC
May 2021

Direct Endoscopic Necrosectomy With and Without Hydrogen Peroxide for Walled-off Pancreatic Necrosis: A Multicenter Comparative Study.

Am J Gastroenterol 2021 04;116(4):700-709

1Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA; 2Division Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, Utah, USA; 3Division Gastroenterology and Hepatology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA; 4Borland-Groover Clinic, Jacksonville, Florida, USA; 5Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA; 6Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA; 7Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburg, Pennsylvania, USA; 8Division of Gastroenterology, Hepatology and Nutrition, The Ohio state University Wexner Medical Center, Columbus, Ohio, USA; 9Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA; 10Biostatistics & Bioinformatics Shared Resource, Winship Cancer Institute of Emory University, Atlanta, Georgia, USA; 11Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Introduction: Endoscopic necrosectomy has emerged as the preferred treatment modality for walled-off pancreatic necrosis. This study was designed to evaluate the safety and efficacy of direct endoscopic necrosectomy with and without hydrogen peroxide (H2O2) lavage.

Methods: Retrospective chart reviews were performed for all patients undergoing endoscopic transmural management of walled-off pancreatic necrosis at 9 major medical centers from November 2011 to August 2018. Clinical success was defined as the resolution of the collection by imaging within 6 months, without requiring non-endoscopic procedures or surgery.

Results: Of 293 patients, 204 met the inclusion criteria. Technical and clinical success rates were 100% (204/204) and 81% (166/189), respectively. For patients, 122 (59.8%) patients had at least one H2O2 necrosectomy (H2O2 group) and 82 (40.2%) patients had standard endoscopic necrosectomy. Clinical success was higher in the H2O2 group: 106/113 (93.8%) vs 60/76 (78.9%), P = 0.002. On a multivariate analysis, the use of H2O2 was associated with higher clinical success rate (odds ratio 3.30, P = 0.033) and earlier resolution (odds ratio 2.27, P < 0.001). During a mean follow-up of 274 days, 27 complications occurred. Comparing procedures performed with and without H2O2 (n = 250 vs 183), there was no difference in post-procedure bleeding (7 vs 9, P = 0.25), perforation (2 vs 3, P = 0.66), infection (1 vs 2, P = 0.58), or overall complication rate (n = 13 [5.2%] vs 14 [7.7%], P = 0.30).

Discussion: H2O2-assisted endoscopic necrosectomy had a higher clinical success rate and a shorter time to resolution with equivalent complication rates relative to standard necrosectomy.See the visual abstract at http://links.lww.com/AJG/B714.(Equation is included in full-text article.).
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April 2021

Trajectories of cognitive function in community-dwelling older adults: A longitudinal study of population heterogeneity.

Alzheimers Dement (Amst) 2021 2;13(1):e12180. Epub 2021 May 2.

School of Public Health and Preventive Medicine Monash University Melbourne Australia.

Introduction: This study aimed to investigate cognitive aging trajectories, the associated sociodemographic characteristics, and the association of these trajectories with dementia.

Methods: Generally healthy older adults (n = 19,114) were followed for up to 7 years, with regular cognitive assessments. Group-based trajectory modeling identified distinct cognitive trajectories.

Results: Four to seven trajectories were identified per cognitive domain. Stable trajectories were observed across domains. Improvement in verbal fluency and minor psychomotor slowing were common. Substantial decline in global cognition and episodic memory were observed in a small proportion of individuals. Older, less educated participants and men were more common in lower-functioning trajectories ( < .001). The highest proportions of dementia cases were in trajectories with major decline in global cognition (56.9%) and memory (33.2%).

Discussion: Inter-individual variability in cognitive trajectories was observed across all domains. Some individuals appear resilient to cognitive decline even with advancing age. Further research into factors promoting cognitive resilience is needed.
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http://dx.doi.org/10.1002/dad2.12180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088593PMC
May 2021

Electrocautery-enhanced Lumen-apposing Metal Stents in the Management of Symptomatic Pancreatic Fluid Collections: Results From the Multicenter Prospective Pivotal Trial.

J Clin Gastroenterol 2021 Apr 23. Epub 2021 Apr 23.

Borland-Groover Clinic, Jacksonville, FL Emory University School of Medicine, Atlanta, GA University of Colorado School of Medicine, Aurora, CO Johns Hopkins University School of Medicine, Baltimore, MD Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA University of Chicago Pritzker School of Medicine, Chicago, IL Department of Medicine, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand.

Background And Aims: Endoscopic decompression is considered a first-line treatment for symptomatic pancreatic fluid collections (PFCs). A lumen-apposing metal stent (LAMS) with an electrocautery-enhanced delivery system [electrocautery-enhanced lumen-apposing metal stent (ELAMS)] may facilitate this procedure. This study evaluated the safety and efficacy of ELAMS in the management of symptomatic PFCs.

Patients And Methods: A multicenter, nonblinded, prospective, Food and Drug Administration (FDA)-approved, investigational device exemption clinical trial was conducted. Enrollment criteria included symptomatic PFCs ≥6 cm with ≥70% fluid fraction. Subjects were followed prospectively for safety, efficacy, and resolution of the collections. Primary endpoint success was defined as ≥50% reduction in PFC size. Clinical outcomes were compared with our previously published series of LAMS without the cautery-enhanced delivery system.

Results: The target enrollment of 30 patients was achieved in 7 US tertiary care centers. All patients underwent successful placement of the ELAMS. The mean procedure duration, stent placement time, and fluoroscopy exposures were 28.1±12.5, 5.8±2.6, and 1.8±1.6 minutes, respectively. Eight patients had no fluoroscopy. The primary endpoint was achieved in 83.3% of patients. Two adverse events were attributed to the ELAMS: 1 bleeding upon stent removal and 1 stent migration. Relative to the comparator noncautery LAMS multicenter trial (N=33, 8 tertiary centers), there was a significantly shorter procedure duration [36 min (P<0.001)] with similar technical and clinical outcomes in the ELAMS cohort.

Conclusion: LAMS placed using an electrocautery delivery system significantly reduce procedure duration and were safe and effective in the management of symptomatic PFCs.
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April 2021

Adverse Events Associated With Therapeutic Endoscopic Retrograde Pancreatography.

Pancreas 2021 03;50(3):378-385

From the Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO.

Objectives: Data regarding the safety of endoscopic retrograde pancreatography (ERP) are limited compared with biliary endoscopic retrograde cholangiopancreatography. The aim of this study was to determine adverse events (AEs) associated with therapeutic ERP.

Methods: This single-center retrospective study examined consecutive therapeutic ERPs with the primary intention of cannulating the pancreatic duct. Multivariate logistic regression was performed to identify risk factors for AEs.

Results: A total of 3023 ERPs were performed in 1288 patients (mean age, 50.3 years; 57.8% female) from January 2000 to January 2017. Overall AE rate was 18.9% with abdominal pain requiring admission (9.8%) and post-ERP pancreatitis (5.7%) being most common. On multivariate analysis, female sex (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.9-2.9), acute recurrent pancreatitis (aOR, 5.0; 95% CI, 1.7-15.3), chronic pancreatitis (aOR, 1.8; 95% CI, 1.3-2.6), and pancreatic sphincter of Oddi dysfunction (aOR, 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of overall AEs. Pancreatic sphincterotomy (aOR, 1.9; 95% CI, 1.5-2.4) and therapeutic stenting (aOR, 1.6; 95% CI, 1.2-2.2) also increased the risk of AEs.

Conclusions: Nearly 1 in 5 patients who undergo therapeutic ERP will experience an AE; however, the rates of major AEs, including post-ERP pancreatitis, bleeding, and perforation, are low.
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http://dx.doi.org/10.1097/MPA.0000000000001769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041157PMC
March 2021

CommunityRx: Optimizing a Community Resource Referral Intervention for Minority Dementia Caregivers.

J Appl Gerontol 2021 Apr 9:7334648211005594. Epub 2021 Apr 9.

University of Chicago, IL, USA.

Community resource referral systems have been implemented into care settings that serve persons with dementia but with little input from caregivers. Focus groups were conducted with African American, Hispanic, and Asian caregivers to describe their preferences for community resource referral information. Caregivers discussed the significance of a community resource list for dementia caregiving and self-care and articulated strategies for effective information delivery during a medical visit. Most caregivers acknowledged that resource needs change with progression of dementia, but no patterns emerged with regard to preference for information delivered incrementally based on disease stage or all at once. Hispanic and Asian caregivers felt that resource information should specify service providers' language and cultural capabilities. All caregivers agreed that delivery by a member of the care team with knowledge of dementia-specific resources would be most effective. Optimal delivery of community resource referrals is caregiver-centered and customizable to individual and subgroup preferences.
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http://dx.doi.org/10.1177/07334648211005594DOI Listing
April 2021

AGA Technical Review on Intragastric Balloons in the Management of Obesity.

Gastroenterology 2021 04;160(5):1811-1830

Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.

Several strategies are available to address the obesity epidemic and range from noninvasive lifestyle interventions to medications and bariatric surgical procedures. Endoscopic bariatric techniques, such as intragastric balloons, have become an attractive alternative as a tool for weight loss that can augment the effect of lifestyle interventions. This technical review includes multiple systematic reviews performed to support a clinical practice guideline by the American Gastroenterological Association on the role of intragastric balloons as a tool for weight loss. The systematic reviews targeted a priori selected clinical questions about the effectiveness and periprocedural care of intragastric balloons and concomitant and subsequent weight-loss strategies.
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http://dx.doi.org/10.1053/j.gastro.2021.02.043DOI Listing
April 2021

Spotlight: Intragastric Balloons in the Management of Obesity.

Gastroenterology 2021 04;160(5):1810

Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1053/j.gastro.2021.03.004DOI Listing
April 2021

AGA Clinical Practice Guidelines on Intragastric Balloons in the Management of Obesity.

Gastroenterology 2021 04;160(5):1799-1808

Kern Center for the Science of Health Care Delivery, Rochester, Minnesota.

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http://dx.doi.org/10.1053/j.gastro.2021.03.003DOI Listing
April 2021

Probe-based confocal laser endomicroscopy in the evaluation of dominant strictures in patients with primary sclerosing cholangitis: results of a U.S. multicenter prospective trial.

Gastrointest Endosc 2021 09 30;94(3):569-576.e1. Epub 2021 Mar 30.

Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Background And Aims: Patients with primary sclerosing cholangitis (PSC) and dominant biliary strictures carry increased risk for the development of cholangiocarcinoma. Although ERCP-based techniques including brush cytology and intraductal biopsy sampling represent first-line tissue sampling methods for dominant strictures, sensitivity is low. Probe-based confocal laser endomicroscopy (pCLE) offers microscopic-level imaging of subepithelial biliary mucosa. Because data regarding the use of pCLE in PSC are limited, we aimed to investigate its diagnostic performance in dominant strictures.

Methods: This was a multicenter prospective study involving PSC patients with dominant strictures. ERCP with pCLE was performed with use of the Miami classification (2+ criteria for malignant diagnosis) and Paris classification. Final malignant diagnoses required histopathologic confirmation, and benign diagnoses required a minimum of 1 year of follow-up without development of cancer.

Results: Fifty-nine patients (mean age, 49 years; 59% men) with 63 strictures were included in the study. Stricture locations included the common bile duct (31.7%), bifurcation (22.2%), and common hepatic duct (19%). Seven patients (11.9%) were found to have cholangiocarcinoma. The sensitivity and specificity of pCLE was 85.7% (95% confidence interval [CI], 42.1-99.6) and 73.1% (95% CI, 58.9-84.4), respectively. Within specific stricture locations, the highest sensitivity was seen at the bifurcation (100%; 95% CI, 2.5-100) and the right hepatic duct (100%; 95% CI, 29.2-100). The lowest sensitivities were seen at the common bile duct (25%; 95% CI, 5.5-57.2) and the left hepatic duct (28.6%; 95% CI, 3.7-70.9).

Conclusions: In this prospective multicenter study, pCLE had a high sensitivity in detecting cholangiocarcinoma, but technical aspects of the probe may limit evaluation in the common bile duct and left hepatic duct. Further evaluation is needed to elucidate the role of pCLE in the algorithm of excluding neoplasia in biliary strictures associated with PSC. (Clinical trial registration number: NCT02736708.).
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http://dx.doi.org/10.1016/j.gie.2021.03.027DOI Listing
September 2021

Digital Cholangioscopic Interpretation: When North Meets the South.

Dig Dis Sci 2021 Mar 30. Epub 2021 Mar 30.

Instituto Ecuatoriano De Enfermedades Digestivas (IECED)-University Hospital Omni, Espiritu Santo University, Guayaquil, Ecuador.

Background: Digital single-operator cholangioscopy (DSOC) (SpyGlass DS™, Boston Scientific, MA, USA) allows for high-definition imaging of the biliary tree. The superior visualization has led to the development of two different sets of criteria to evaluate and classify indeterminate biliary strictures: the Monaco criteria and the criteria in Carlos Robles-Medranda's publication (CRM). Our objective was to assess the interrater agreement (IA) of DSOC interpretation for indeterminate biliary strictures using the two newly published criteria.

Methods: Forty de-identified DSOC video recordings were sent to 15 interventional endoscopists with experience in cholangioscopy. They were asked to score the videos based on the presence of Monaco Classification criteria: stricture, lesion, mucosal changes, papillary projections, ulceration, white linear bands or rings, and vessels. Next, they scored the videos using CRM criteria: villous pattern, polypoid pattern, inflammatory pattern, flat pattern, ulcerate pattern and honeycomb pattern. The endoscopists then diagnosed the recordings as neoplastic or non-neoplastic based on the criteria. Intraclass correlation (ICC) analysis was done to evaluate interrater agreement for both criteria set and final diagnosis.

Results: Recordings of 26 malignant lesions and 14 benign lesions were scored. The IA using both the Monaco criteria and CRM criteria ranged from poor to excellent (range 0.1-0.76) and (range 0.1-0.62), respectively. Within the Monaco criteria, IA was excellent for lesion (0.75) and fingerlike papillary projections (0.74); good for tortuous vessels (0.7), mucosal features (0.62), uniform papillary projections (0.53), and ulceration (0.58); and fair for white linear bands (0.4). Within the CRM criteria, the IA was good for villous pattern (0.62), flat pattern (0.62), and honeycomb pattern; fair for ulcerated pattern (0.56), polypoid pattern (0.52) and inflammatory pattern (0.54). The diagnostic IA using Monaco criteria was good (0.65), while the diagnostic IA using CRM was fair (0.58). The overall diagnostic accuracy using the Monaco classification was 61% and CRM criteria were 57%.

Conclusion: The IOA and accuracy rate of DSOC using visual criteria from both Monaco Criteria and CRM are similar. However, some criteria from both sets suffer from poor IA, thus affecting the overall diagnostic accuracy. More formal training and refinements in visual criteria with additional validation are needed to improve diagnostic accuracy.

Trial Registration: ClinicalTrials.gov Identifier: NCT02166099.
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http://dx.doi.org/10.1007/s10620-021-06961-zDOI Listing
March 2021

Impact of Radiation Dose on Postoperative Complications in Esophageal and Gastroesophageal Junction Cancers.

Front Oncol 2021 10;11:614640. Epub 2021 Mar 10.

Icahn School of Medicine at Mount Sinai, New York, NY, United States.

The impact of radiation prescription dose on postoperative complications during standard of care trimodality therapy for operable stage II-III esophageal and gastroesophageal junction cancers has not been established. We retrospectively reviewed 82 patients with esophageal or gastroesophageal junction cancers treated between 2004 and 2016 with neoadjuvant chemoradiation followed by resection at a single institution. Post-operative complications within 30 days were reviewed and scored using the Comprehensive Complication Index (CCI). Results were compared between patients treated with <50 Gy and ≥ 50 Gy, as well as to published CROSS study neoadjuvant chemoradiation group data (41.4 Gy). Twenty-nine patients were treated with <50 Gy (range 39.6-46.8 Gy) and 53 patients were treated with ≥ 50 Gy (range 50.0-52.5 Gy) delivered using IMRT/VMAT (41%), 3D-CRT (46%), or tomotherapy IMRT (12%). Complication rates and CCI scores between our <50 Gy and ≥ 50 Gy groups were not significantly different. Assuming a normal distribution of the CROSS data, there was no significant difference in CCI scores between the CROSS study neoadjuvant chemoradiation, <50 Gy, or ≥ 50 Gy groups. Rates of pulmonary complications were greater in the CROSS group (50%) than our <50 Gy (38%) or ≥ 50 Gy (30%) groups. In selected esophageal and gastroesophageal junction cancer patients, radiation doses ≥ 50 Gy do not appear to increase 30 day post-operative complication rates. These findings suggest that the use of definitive doses of radiotherapy (50-50.4 Gy) in the neoadjuvant setting may not increase post-operative complications.
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http://dx.doi.org/10.3389/fonc.2021.614640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987936PMC
March 2021

A Cohort Study of Anticholinergic Medication Burden and Incident Dementia and Stroke in Older Adults.

J Gen Intern Med 2021 06 22;36(6):1629-1637. Epub 2021 Mar 22.

Department of Pharmacy Practice and Science, College of Pharmacy and Department of Family Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.

Background: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking.

Objective: Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people.

Design: Prospective cohort study.

Setting: Primary care (Australia and USA).

Participants: 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100.

Measurements: Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition.

Results: At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1-2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications.

Limitations: Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible.

Conclusions: High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people.
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http://dx.doi.org/10.1007/s11606-020-06550-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175463PMC
June 2021

Effect of Endoscopic Bariatric and Metabolic Therapies on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Clin Gastroenterol Hepatol 2021 Mar 13. Epub 2021 Mar 13.

Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address:

Background & Aims: Weight loss via lifestyle intervention remains the mainstay of treatment for nonalcoholic fatty liver disease (NAFLD). Endoscopic bariatric and metabolic therapies (EBMTs) have recently been developed as an alternative treatment option for obesity. This study aimed to assess the effect of FDA-approved EBMTs on NAFLD.

Methods: We searched MEDLINE, EMBASE, Web of Science and Cochrane Central through December 2020 for studies that assessed changes in liver outcomes following EBMT. Primary Outcomes: Liver fibrosis.

Secondary Outcomes: Liver biochemistry, steatosis, NAFLD histological changes and insulin sensitivity. The Grading of Recommendations, Assessment, Development, and Evidence (GRADE) approach was conducted to assess quality of evidence.

Results: Of 4,994 potential studies, 18 studies with 863 patients were included. Average weight loss was 14.5% of initial weight at a 6 month follow-up. Primary Outcomes: Following EBMT, liver fibrosis significantly reduced by standardized mean difference (SMD) of 0.7 [95% CI, 0.1,1.3] (p = .02).

Secondary Outcomes: There were significant improvements in other NAFLD surrogates including alanine aminotransferase (-9.0 U/L; 95% CI, -11.6,-6.4; p < .0001), hepatic steatosis (SMD: -1.0; 95% CI, -1.2,-0.8, p < .0001) and histologic NAFLD activity score (-2.50; 95% CI, -3.5,-1.5; p < .0001). Other metabolic parameters including insulin resistance and waist circumference also significantly improved. The overall quality of the evidence for primary outcomes was low to very low.

Conclusions: EBMTs appear effective at treating NAFLD with significant improvement in liver fibrosis. Given the worsening NAFLD pandemic and limitations of currently available therapies, EBMTs should be further investigated as a potential treatment option for this patient population.
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http://dx.doi.org/10.1016/j.cgh.2021.03.017DOI Listing
March 2021
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