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Kumaria A, Kirkman MA, Scott RA, Dow GR, Leggate AJ, Macarthur DC, Ingale HA, Smith SJ, Basu S. A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review. J Neurosurg Anesthesiol 2024; 36:211-217. [PMID: 37188653 DOI: 10.1097/ana.0000000000000918] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 03/21/2023] [Indexed: 05/17/2023]
Abstract
In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration.
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Affiliation(s)
| | | | - Robert A Scott
- NIHR Biomedical Research Centre, Nottingham University Hospitals NHS Trust
- Nottingham Digestive Diseases Centre
| | - Graham R Dow
- Department of Neurosurgery, Queen's Medical Centre
| | | | | | | | - Stuart J Smith
- Department of Neurosurgery, Queen's Medical Centre
- Children's Brain Tumour Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Surajit Basu
- Department of Neurosurgery, Queen's Medical Centre
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Liu S, Wang Y, Gao B, Peng J. A Nomogram for Individualized Prediction of Stress-Related Gastrointestinal Bleeding in Critically Ill Patients with Primary Intracerebral Hemorrhage. Neuropsychiatr Dis Treat 2022; 18:221-229. [PMID: 35177906 PMCID: PMC8843804 DOI: 10.2147/ndt.s342861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 01/18/2022] [Indexed: 11/24/2022] Open
Abstract
PURPOSE To establish and validate a nomogram model for predicting stress-related gastrointestinal bleeding in critically ill patients with primary intracerebral hemorrhage. PATIENTS AND METHODS From January 2018 to March 2021, we conducted a hospital-based study by screening eligible patients with acute intracerebral hemorrhage. Univariate and multivariate logistic regression analyses were performed to determine the predictors for stress-related gastrointestinal bleeding in patients with primary intracerebral hemorrhage. The nomogram was constructed on the basis of multivariate logistic model and was internally validated by bootstrap resampling. The discriminative performance of the nomogram was evaluated using the calibration and concordance index (C-index), which was equal to the area under the curve of receiver-operating characteristics. Hosmer-Lemeshow test was performed to check the model's goodness of fit. A decision curve analysis was used to assess its clinical utility. RESULTS A total of 410 patients were enrolled in this study. Stress-related gastrointestinal bleeding occurred in 115 patients (28.0%). Multivariate analysis demonstrated that gastric pH at admission [odds ratio (OR): 0.52, 95% confidence interval (CI): 0.41-0.66, P < 0.001], ICH volume (OR: 1.03, 95% CI: 1.02-1.05, P < 0.001) and sepsis (OR: 2.56, 95% CI: 1.54-4.25, P < 0.001) were independent predictors for stress-related gastrointestinal bleeding in critically ill patients with ICH. The nomogram including gastric pH at admission, ICH volume and sepsis presented good discrimination with C-index of 0.770 (95% CI: 0.716 to 0.822), which was confirmed to be 0.764 through bootstrapping validation. The calibration plot showed good agreement between the predicted and observed outcomes. The Hosmer-Lemeshow test showed a goodness-of-fit (Chi-Square = 8.085, DF = 8, P = 0.425). Decision curve analysis demonstrated that the nomogram was clinically beneficial. CONCLUSION The proposed nomogram based on gastric pH at admission, ICH volume and sepsis can accurately predict the risk of stress-related gastrointestinal bleeding in critically ill patients with primary intracerebral hemorrhage.
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Affiliation(s)
- Shucheng Liu
- Department of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, People's Republic of China
| | - Yilin Wang
- Department of Neurology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, People's Republic of China
| | - Bin Gao
- Department of Neurology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, People's Republic of China
| | - Jun Peng
- Department of Neurology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, People's Republic of China
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Rachfalska N, Putowski Z, Krzych ŁJ. Distant Organ Damage in Acute Brain Injury. Brain Sci 2020; 10:E1019. [PMID: 33371363 PMCID: PMC7767338 DOI: 10.3390/brainsci10121019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/15/2020] [Accepted: 12/18/2020] [Indexed: 02/07/2023] Open
Abstract
Acute brain injuries pose a great threat to global health, having significant impact on mortality and disability. Patients with acute brain injury may develop distant organ failure, even if no systemic diseases or infection is present. The severity of non-neurologic organs' dysfunction depends on the extremity of the insult to the brain. In this comprehensive review we sought to describe the organ-related consequences of acute brain injuries. The clinician should always be aware of the interplay between central nervous system and non-neurological organs, that is constantly present. Cerebral injury is not only a brain disease, but also affects the body as whole, and thus requires holistic therapeutical approach.
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Affiliation(s)
| | | | - Łukasz J. Krzych
- Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland; (N.R.); (Z.P.)
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Schosheim A, Tobin M, Chawla A. Curling ulcer in the setting of severe sunburn: A case report. World J Gastrointest Endosc 2020; 12:500-503. [PMID: 33269059 PMCID: PMC7677882 DOI: 10.4253/wjge.v12.i11.500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/30/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND While sunburns are very common, especially in pediatrics, curling ulcers secondary to sunburns are a very rare entity that has not been noted in the literature in over fifty years. This case is the first addition to the literature since the originally documented case.
CASE SUMMARY A previously healthy 17 year old male presents to the emergency room with lethargy, shortness of breath on exertion, dark stools and nausea. His fatigue started to become significantly worse four days prior to admission. Approximately two weeks prior to admission, the patient was on a beach vacation with his family at which time he suffered severe sunburns. He had developed crampy epigastric abdominal pain, which was followed by dark, loose stools. On exam, he is non-toxic appearing, but with pallor and peeling skin on his face and chest with epigastric tenderness. Infectious stool studies were all negative including Helicobacter pylori. He denies use of any non-steroidal anti-inflammatory drugs and also denies alcohol or recreational drug use. While admitted he is found to be significantly anemic with his hemoglobin as low as 6.3 requiring two units of packed red blood cells. Endoscopy revealed several severe and deep ulcerations in the antrum and body of the stomach indicative of stress or curling ulcers.
CONCLUSION While the incidence of stress ulcers is not known, it is most common with severe acute illness, most commonly presenting as upper gastrointestinal (GI) bleeding. It is essential to be aware of the risk of curling ulcers secondary to severe sunburns as patients with stress ulcer GI bleeding have increased morbidity and mortality compared to those who do not have GI bleed.
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Affiliation(s)
- Alexander Schosheim
- Department ofPediatric Gastroenterology , Stony Brook University Hospital , Stony Brook, NY 11794, United States
| | - Michelle Tobin
- Department ofPediatric Gastroenterology , Stony Brook University Hospital , Stony Brook, NY 11794, United States
| | - Anupama Chawla
- Department ofPediatric Gastroenterology , Stony Brook University Hospital , Stony Brook, NY 11794, United States
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Investigations to Evaluate Gastric Mucoadhesion of an Organic Product to Ameliorate Gastritis. Pharmaceutics 2020; 12:pharmaceutics12040331. [PMID: 32272788 PMCID: PMC7238041 DOI: 10.3390/pharmaceutics12040331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 04/02/2020] [Accepted: 04/03/2020] [Indexed: 11/16/2022] Open
Abstract
Gastritis is an inflammatory disease leading to abdominal pain, nausea, and diarrhea. While therapy depends on etiology, adhesive agents protecting the gastric tissue represent a promising treatment option. Caricol®-Gastro is an organic product that significantly decreased gastritic abdominal pain in a recent clinical study. To investigate whether this beneficial effect can be attributed to the formation of a protective layer covering the gastric mucosa after oral application, several methods were used to determine adhesion. These include macro-rheological measurements and gastric mucin interactions, which were correlated to network formation, examined by Cryo-scanning electron microscopy technique, wettability via sessile drop method on human gastric adenocarcinoma cell layers, and ex vivo adhesion studies on gastric porcine tissue with the falling liquid film technique considering physiological conditions and Franz diffusion cells for quantification. The results showed that Caricol®-Gastro formed a stable viscoelastic network with shear thinning properties. It exhibited high wettability and spreadability and adhered to the excised gastric mucosa. We found that oat flour, as the main ingredient of Caricol®-Gastro, supports the gel network regarding viscoelasticity and, to a lesser extent, adhesion in a concentration dependent manner. Moreover, our data highlight that a variety of coordinated methods are required to investigate gastric adhesion.
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Abstract
Stress ulcer prophylaxis (SUP) with acid-suppressive drug therapy is widely utilized in critically ill patients following neurologic injury for the prevention of clinically important stress-related gastrointestinal bleeding (CIB). Data supporting SUP, however, largely originates from studies conducted during an era where practices were vastly different than what is considered routine by today's standard. This is particularly true in neurocritical care patients. In fact, the routine provision of SUP has been challenged due to an increasing prevalence of adverse drug events with acid-suppressive therapy and the perception that CIB rates are sparse. This narrative review will discuss current controversies with SUP as they apply to neurocritical care patients. Specifically, the pathophysiology, prevalence, and risk factors for CIB along with the comparative efficacy, safety, and cost-effectiveness of acid-suppressive therapy will be described.
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Affiliation(s)
- Jeffrey F Barletta
- Midwestern University, College of Pharmacy-Glendale, 19555 N 59th Avenue, Glendale, AZ, 85308, USA.
| | | | - Joseph F Sucher
- Honor Health- John C. Lincoln Medical Center, Phoenix, AZ, USA
| | - Victor Zach
- Honor Health, A.T. Still University School of Osteopathic Medicine, Phoenix, AZ, USA
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Pneumonia prevention in intubated patients given sucralfate versus proton-pump inhibitors and/or histamine II receptor blockers. J Surg Res 2016; 206:398-404. [PMID: 27884335 DOI: 10.1016/j.jss.2016.08.028] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Revised: 06/07/2016] [Accepted: 08/04/2016] [Indexed: 11/19/2022]
Abstract
BACKGROUND Ventilator-associated pneumonia (VAP) is a common cause of infectious morbidity and mortality in the intensive care unit (ICU). The type of stress-ulcer prophylaxis (SUP) given to ventilated patients may, in part, be responsible. We observed an increase in VAP as ventilator bundle compliance increased and a decrease in VAP when bundle compliance decreased. We reasoned that SUP which raises gastric pH such as proton-pump inhibitors (PPIs) and histamine II (H2) receptor antagonists as opposed to SUP which does not raise pH such as sucralfate (S) may be responsible and also may alter the causative bacteria. MATERIALS AND METHODS This is a single-center retrospective cohort analysis of all intubated, adult surgical patients admitted to the surgical ICU between January and June during the 3-y period 2012-2014. Demographics, APACHE II, Injury Severity Score, VAP occurrence, culprit bacteria, ventilator days, and ICU days were recorded based on the type of SUP given. RESULTS There were 45 instances of VAP in the 504 study patients, 33 in the PPI/H2 group, and 12 in the S group (P < 0.01). VAP per 1000 ventilator days were 10.2 for PPI/H2 and 3.7 for S (P < 0.01). Culprit bacteria were mostly Pseudomonas, gram-negative bacilli, and methicillin-resistant Staphylococcus aureus in PPI/H2 patients (n = 29) compared with oropharyngeal flora in S patients (n = 6; P < 0.001). CONCLUSIONS There was a substantial difference in VAP occurrence and in the culprit bacteria between S and PPI/H2 treated patients due perhaps to gastric alkalization.
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Abstract
Background: Brain tumors, traumatic head injury, and other intracranial processes including infections, can cause increased intracranial pressure and lead to overstimulation of the vagus nerve. As a result, increased secretion of gastric acid may occur which leads to gastro-duodenal ulcer formation known as Cushing's ulcer. Methods: A review of original records of Dr. Harvey Cushing's patients suffering from gastro-duodenal ulcers was performed followed by a discussion of the available literature. We also reviewed the clinical records of the patients never reported by Cushing to gain his perspective in describing this phenomenon. Dr. Cushing was intrigued to investigate gastro-duodenal ulcers as he lost patients to acute gastrointestinal perforations following successful brain tumor operations. It is indeed ironic that Harvey Cushing developed a gastro-duodenal ulcer in his later years with failing health. Results: Clinically shown by Cushing's Yale Registry, a tumor or lesion can disrupt this circuitry, leading to gastroduodenal ulceration. Cushing said that it was “reasonable to believe that the perforations following posterior fossa cerebellar operations were produced in like fashion by an irritative disturbance either of fiber tracts or vagal centers in the brain stem.” Conclusion: Harvey Cushing's pioneering work depicted in his Yale registry serves as a milestone for continuing research that can further discern this pathway.
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Affiliation(s)
- William J Kemp
- Department of Neurological Surgery, Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Asif Bashir
- Department of Neurosurgery, JFK New Jersey Neuroscience Institute at Seton Hall University, Edison, NJ, USA
| | - Haitham Dababneh
- Department of Neurosurgery, JFK New Jersey Neuroscience Institute at Seton Hall University, Edison, NJ, USA
| | - Aaron A Cohen-Gadol
- Department of Neurological Surgery, Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN, USA
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Uslu E, Aydin S, Carkman S, Uzun H, Altinli E, Apaydin BB, Memisoglu K, Erginoz E. Effects of gender on stress ulcer formation in rats. TOHOKU J EXP MED 2002; 197:17-26. [PMID: 12180789 DOI: 10.1620/tjem.197.17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
In the experimental stress literature, the results of investigations have not shown a specific sex-dependent vulnerability to stress ulceration. The aim of this study was to evaluate the importance of sex differences on stress ulcer development. Related to gender, the contributing factors for stress ulcer production such as luminal acidity, sialic acid as an marker of gastric mucosal protection, oxygen (O2)-derived free radicals and endogenous antioxidant defence mechanisms were also investigated. Fifty Wistar Albino rats weighing about 230 g and aged 7 or 8 months were divided equally into five groups: Group I normal male rats, group II castrated male rats, group III normal female rats in estrus phase, group IV normal female rats in diestrus phase and group V castrated female rats. Cold restraint model was used for 6 hours to produce stress ulcer. No statistically significant difference was found out between groups in view of gross and histopathologic damage. There was no significant difference between groups according to gastric luminal acidity, gastric mucosal sialic acid, gastric malonaldehyde (MDA) and catalase values. Gastric superoxide dismutase (SOD) activity was significantly lower in Group I in comparison to those of Group III and IV. Sex differences do not interfere stress ulcer formation. SOD activity in rat gastric tissue has varied significantly by hormonal milieu.
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Affiliation(s)
- Ezel Uslu
- Department of Biochemistry, Cerrahpaşa Medical Faculty, Istanbul University, Bahcesehir, Turkey.
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O'Keefe GE, Gentilello LM, Maier RV. Incidence of infectious complications associated with the use of histamine2-receptor antagonists in critically ill trauma patients. Ann Surg 1998; 227:120-5. [PMID: 9445119 PMCID: PMC1191181 DOI: 10.1097/00000658-199801000-00017] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To determine the impact of histamine2 (H2)-receptor antagonist use on the occurrence of infectious complications in severely injured patients. SUMMARY BACKGROUND DATA Some previous studies suggest an increased risk of nosocomial pneumonia associated with the use of H2-receptor blockade in critically ill patients, but other investigations suggest an immune-enhancing effect of H2-receptor antagonists. The purpose of this study was to determine whether H2-receptor antagonist use affects the overall incidence of infectious complications. METHODS Patients enrolled in a randomized trial comparing ranitidine with sucralfate for gastritis prophylaxis were examined for all infectious complications during their hospitalization. Data on the occurrence of pneumonia were prospectively collected, and other infectious complications were retrospectively obtained from the medical record. The relative risk of infectious complications associated with ranitidine use and total infectious complications were analyzed. RESULTS Of 98 patients included, the charts of 96 were available for review. Sucralfate was given to 47, and 49 received ranitidine. Demographic factors were similar between the groups. Ranitidine use was associated with a 1.5-fold increased risk of developing any infectious complication (37 of 47 vs. 26 of 47; 95% confidence interval, 1.04 to 2.28). Infectious complications totaled 128 in the ranitidine-treated group and 50 in the sucralfate-treated group (p = 0.0014). These differences remained after excluding catheter-related infections (p = 0.0042) and secondary bacteremia (p = 0.0046). CONCLUSIONS Ranitidine use in severely injured patients is associated with a statistically significant increase in overall infectious complications when compared with sucralfate. These results indicate that ranitidine should be avoided where possible in the prophylaxis of stress gastritis.
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Affiliation(s)
- G E O'Keefe
- Department of Surgery, University of Washington, Harborview Medical Center, Seattle, USA
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Abstract
In current ICU populations, overt bleeding from stress gastritis occurs in 10% to 20% of patients. Bleeding rates may be reduced to about 3% in patients receiving prophylactic therapy. Although patients with bleeding have higher mortality rates than other critically ill patients, it is not clear that the mortality rate is improved with prophylactic therapy, as most patients die from their underlying disease. As new complications of prophylactic therapy are identified, better definitions of the population at risk to develop complications of stress gastritis will be necessary to select those patients who will benefit most from prophylactic therapy.
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Affiliation(s)
- R M Durham
- Trauma Division, St. Louis University School of Medicine, Missouri
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Miller DK, Burton FR, Burton MS, Ireland GA. Acute upper gastrointestinal bleeding in elderly persons. J Am Geriatr Soc 1991; 39:409-22. [PMID: 2010594 DOI: 10.1111/j.1532-5415.1991.tb02911.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
We have seen that UGI bleeding is a serious and apparently growing problem for seniors. Of special concern in the older patient are the frequency with which serious peptic disease presents silently, the limitation frequently imposed on adequate pain relief from NSAIDs, and the higher complication rates from most of the causes of UGI bleeding. Care of the elderly would be enhanced by research focused on defining those older patients most at risk of experiencing NSAID-induced peptic complications, improved methods for preventing or treating NSAID-induced ulceration that are well tolerated and cost-effective, and better regimens for preventing the recurrence of ulcers and UGI bleeding in these patients. In regard to the last, future investigation of the role of H. pylori, methods for successfully eliminating the organism, and the effect of eradication on patients' subsequent course may be particularly helpful.
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Affiliation(s)
- D K Miller
- Division of Geriatric Medicine, St. Louis University Medical Center, Missouri
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