Explore the vast range of titles available.

Fibrillar amyloid-beta (Aβ) is found in the brains of many cognitively normal older people. Whether or not this reflects a predisposition to Alzheimer's disease (AD) is unknown. We used Pittsburgh Compound B (PiB) PET to characterize the relationship between fibrillar Aβ burden and this predisposition in cognitively normal older people at 3 mean levels of genetic risk for AD. Dynamic PiB PET scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest (ROIs) were used to characterize and compare cerebral-to-cerebellar PIB distribution volume ratios, reflecting fibrillar Aβ burden, in 28 cognitively normal persons (mean age, 64 years) with a reported family history of AD and 2 copies, 1 copy, and no copies of the apolipoprotein E (APOE) ε4 allele. The 8 ε4 homozygotes, 8 heterozygotes, and 12 noncarriers did not differ significantly in terms of age, sex, or cognitive scores. Fibrillar Aβ was significantly associated with APOE ε4 carrier status and ε4 gene dose in AD-affected mean cortical, frontal, temporal, posterior cingulate-precuneus, parietal, and basal ganglia ROIs, and was highest in an additional homozygote who had recently developed mild cognitive impairment. These findings suggest that fibrillar Aβ burden in cognitively normal older people is associated with APOE ε4 gene dose, the major genetic risk factor for AD. Additional studies are needed to track fibrillar Aβ accumulation in persons with different kinds and levels of AD risk; to determine the extent to which fibrillar Aβ, alone or in combination with other biomarkers and risk factors, predicts rates of cognitive decline and conversion to clinical AD; and to establish the role of fibrillar Aβ imaging in primary prevention trials.

INTRODUCTION:Spontaneous bacterial peritonitis (SBP) is a fatal complication of cirrhosis. Abdominal paracentesis needs to be performed to collect ascitic fluid for analysis with a good technique. In our hospital, we routinely collected the ascitic fluid in general purpose test tubes. To maximize the yield, we implemented a quality improvement (QI) project to use blood culture bottles for this matter. This is because SBP is a low-colony-count mono-microbial infection similar to bacteremia and the low concentration of bacteria in infected ascites and small volume obtained by conventional methods provides minimal sensitivities and very low yields.METHODS:For baseline, pre-implementation yield rate, the charts for all the patients age 18-85 years old who underwent paracentesis from 2011-2017 in our center were reviewed. All these patients had cirrhosis, abdominal tenderness and identified as having SBP using the ICD diagnostic criteria. Patients with use of antibiotics within the previous week were excluded. Their ascitic fluid was collected in the conventional test tube bottles and results of the fluid analysis were based on these samples. For QI implementation, we created an order set in our electronic medical record to use blood culture bottles for ascitic fluid collection. Appropriate handling of the ascitic fluid was taught to laboratory technicians. For post-implementation yield rate, data from patients who were tested with the new protocol will be evaluated and compared to that of pre-implementation.RESULTS:Data from 60 patients with SBP was tabulated. Baseline positivity rate for the samples collected with regular test tubes was calculated (as determined by PMN >250 cells/mm3). 60% of the samples were positive and 40% negative. Post-implementation data will be determined and final results will be provided during the conference in October.CONCLUSION:SBP can occur through bacteremic seeding, translocation of gut bacteria, or decreased intestinal motility in cirrhotic patients who are presumed to be malnourished and immunocompromised. Ascitic fluid collected with a suboptimal technique with delays and use of standard test tubes leads to falsely negative results and sub-standard treatment of patients. Immediate inoculation of fluid into blood culture bottles will likely increase the yield and direct the treatments.

INTRODUCTION:Levamisole is a widely used cutting agent for cocaine and it also contributes to increased quantity of cocaine. Gastrointestinal (GI) ulcers and bleed is a rare presentation of levamisole intoxication. We report a case of GI ulcers and bleed suspected to be from levamisole contaminated cocaine.CASE DESCRIPTION/METHODS:A 58 year old female presented with sore throat, headache, oral ulcers and multiple necrotic skin lesions following a tooth extraction. On examination, she was noted to have oral ulcers, peri-anal necrotic ulcers, finger eschars and a left lower extremity open blister. Painful violaceous purpuric patches with well-delineated dusky necrotic centers and a bright erythematous rim were also observed peri-anally. Laboratory studies revealed neutropenia, hyponatremia, acute kidney injury, positive antineutrophilic antibody, Hepatitis C, HSV 1 and 2, D-dimers, antidouble-stranded DNA antibodies, anti-neutrophil cytoplasmic antibodies, lupus anticoagulant antibodies and decreased protein S levels. Urine toxicology screen was positive for cocaine and opiates. Patient admitted to cocaine use due to pain from the extracted tooth. Computed Tomography (CT) of abdomen revealed moderate ascites and body wall edema. She was managed with intravenous fluids, pressors, antibiotics, antiviral, antifungal therapy. She also received treatment with filgastrim. Over the course of her hospital stay, she developed lower GI bleed and required multiple units of blood transfused. Endoscopy revealed a clean based gastric ulcer and multiple cecal colon ulcers which was managed with epinephrine injections.DISCUSSION:Levamisole is mostly absorbed from the GI tract and metabolized by the liver. Our patient presented with immune derangements and GI bleed after the use of cocaine to help with her pain from tooth extraction. Laboratory results were compatible with levamisole contamination. CT of the abdomen showed moderate ascites and anasarca similar to MRI characteristics of levamisole-induced leukoencephalopathy which show peripheral ring-type enhancement and edema around lesions. The mechanism of levamisole in the formation of GI ulcers is presumed to be related to ischemia. To our knowledge, this is the first case of levamisole-contaminated cocaine induced gastrointestinal ulceration and bleed. This case illustrates the potential for severe gastrointestinal ulcers and bleed with the use of levamisole and the value of high index of suspicion.

Fibrillar amyloid-β (Aβ) is thought to begin accumulating in the brain many years before the onset of clinical impairment in patients with Alzheimer's disease. By assessing the accumulation of Aβ in people at risk of genetic forms of Alzheimer's disease, we can identify how early preclinical changes start in individuals certain to develop dementia later in life. We sought to characterise the age-related accumulation of Aβ deposition in presenilin 1 (PSEN1) E280A mutation carriers across the spectrum of preclinical disease. Between Aug 1 and Dec 6, 2011, members of the familial Alzheimer's disease Colombian kindred aged 18–60 years were recruited from the Alzheimer's Prevention Initiative's registry at the University of Antioquia, Medellín, Colombia. Cross-sectional assessment using florbetapir PET was done in symptomatic mutation carriers with mild cognitive impairment or mild dementia, asymptomatic carriers, and asymptomatic non-carriers. These assessments were done at the Banner Alzheimer's Institute in Phoenix, AZ, USA. A cortical grey matter mask consisting of six predefined regions.was used to measure mean cortical florbetapir PET binding. Cortical-to-pontine standard-uptake value ratios were used to characterise the cross-sectional accumulation of fibrillar Aβ deposition in carriers and non-carriers with regression analysis and to estimate the trajectories of fibrillar Aβ deposition. We enrolled a cohort of 11 symptomatic individuals, 19 presymptomatic mutation carriers, and 20 asymptomatic non-carriers, ranging in age from 20 to 56 years. There was greater florbetapir binding in asymptomatic PSEN1 E280A mutation carriers than in age matched non-carriers. Fibrillar Aβ began to accumulate in PSEN 1E280A mutation carriers at a mean age of 28·2 years (95% CI 27·3–33·4), about 16 years and 21 years before the predicted median ages at mild cognitive impairment and dementia onset, respectively. 18F florbetapir binding rose steeply over the next 9·4 years and plateaued at a mean age of 37·6 years (95% CI 35·3–40·2), about 6 and 11 years before the expected respective median ages at mild cognitive impairment and dementia onset. Prominent florbetapir binding was seen in the anterior and posterior cingulate, precuneus, and parietotemporal and frontal grey matter, as well as in the basal ganglia. Binding in the basal ganglia was not seen earlier or more prominently than in other regions. These findings contribute to the understanding of preclinical familial Alzheimer's disease and help set the stage for assessment of amyloid-modifying treatments in the prevention of familial Alzheimer's disease. Avid Radiopharmaceuticals, Banner Alzheimer's Foundation, Nomis Foundation, Anonymous Foundation, Forget Me Not Initiative, Colciencias, National Institute on Aging, and the State of Arizona.

The pathological underpinnings of Alzheimer disease (AD) are now known to begin up to two decades before manifestation of clinical disease, and intervention during preclinical AD stages is increasingly recognized as key to therapeutic success. Here, Eric Reiman and colleagues discuss strategies to study changes in the brain and bodily fluids that precede clinical AD, focusing in particular on genetic at-risk individuals, who might be suitable candidates for secondary prevention trials. Researchers have begun to characterize the subtle biological and cognitive processes that precede the clinical onset of Alzheimer disease (AD), and to set the stage for accelerated evaluation of experimental treatments to delay the onset, reduce the risk of, or completely prevent clinical decline. In this Review, we provide an overview of the experimental strategies, and brain imaging and cerebrospinal fluid biomarker measures that are used in early detection and tracking of AD, highlighting at-risk individuals who could be suitable for preclinical monitoring. We discuss how advances in the field have contributed to reconceptualization of AD as a sequence of biological changes that occur during progression from preclinical AD, to mild cognitive impairment and finally dementia, and we review recently proposed research criteria for preclinical AD. Advances in the study of preclinical AD have driven the recognition that efficacy of at least some AD therapies may depend on initiation of treatment before clinical manifestation of disease, leading to a new era of AD prevention research. Key Points The pathogenic cascade of Alzheimer disease (AD) is thought to begin at least one to two decades prior to cognitive impairment Disappointing results of several AD drugs in late-stage trials have suggested the need for early therapeutic intervention, calling for development of biomarkers and sensitive cognitive measures of preclinical disease The best established measurements for detection and tracking of preclinical and clinical AD include MRI, fluorodeoxyglucose PET, amyloid PET, and cerebrospinal fluid measures of amyloid-β 42 , total tau, and phospho-tau Studies of individuals with inherited AD can provide insights into cognitive and biomarker changes that precede clinical manifestation of AD, and are suitable candidates for ongoing monitoring and early-intervention strategies We are entering an era of AD prevention research, with a number of preclinical AD treatment trials in the planning stages or under way for several at-risk, cognitively unimpaired populations

The COVID-19 pandemic transformed the final year of undergraduate medical education for thousands of medical students across the globe. Out of concern for spreading SARS-CoV-2 and conserving personal protective equipment, many students experienced declines in bedside clinical exposures. The perceived competency of this class within the context of the pandemic is unclear. We designed and distributed a survey to measure the degree to which recent medical school graduates from the USA felt clinically prepared on 13 core clinical skills. Of the 1283 graduates who matched at HCA Healthcare facilities, 90% (1156) completed the survey. In this national survey, most participants felt they were competent in their clinical skills. However, approximately one out of four soon-to-be residents felt they were clinically below where they should be with regard to calling consultations, performing procedures, and performing pelvic and rectal exams. One in five felt they were below where they should be with regard to safely transitioning care. These perceived deficits in important skill sets suggest the need for evaluation and revised educational approaches in these areas, especially when traditional in-person practical skills teaching and practice are disrupted.

Methamphetamine abuse is a public health problem across the world, and the cardiovascular system experiences a significant effect on the myocardium over time. Methamphetamine is a common cause of heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). The prevalence and risk factors for HFpEF and HFrEF in this patient population remain unclear. This retrospective case-control study is based on a chart review of patients from 139 Hospital Corporation of America (HCA) community hospitals across the United States from January 2013 to December 2017. Active methamphetamine users were identified based on International Classification of Diseases (ICD) codes and a positive urine drug screen during hospitalization. The total number of patients was then divided into two groups: heart failure (HF) vs. no HF. Then exclusion criteria were applied to remove any possible characteristics that might confound the data. The number of patients left was then analyzed. This study identified 9,518 active methamphetamine users, with 403 patients (4.23%) having HF, 41 having unspecified HF, and 51 having HFpEF only, vs. 311 having HFrEF only, compared to 9,115 in the control group without HF. After exclusion criteria were applied, the HF group had 166 patients, and the control group had 398 patients. Heart failure was significantly higher in men, 65.7% men compared to 34.3% women (adjusted odds ratio (OR): 1.894, p = 0.022). The average ages of HF group patients before exclusion criteria, after exclusion criteria, and in the control group were 52.5 years, 46.5 years, and 42.7 years, respectively. The age difference between the HF group (average 46.5 years old) and the control group (average 42.7 years old) was not statistically significant (adjusted OR: 1.007, p = 0.540). However, the average age of the HFpEF population significantly differs from the HFrEF population, 70.2 years old compared to 47.1 years old, respectively (adjusted OR: 1.053, p = 0.001). Female patients appeared to be more likely to have HFpEF (70.6%) compared to HFrEF (18.9%, adjusted OR: 3.738, p < 0.001). Amongst methamphetamine users who develop HF, men appeared to be affected more compared to women. This difference may stem from the differences in activities between men and women. On the other hand, age appeared to not play a role when viewing the entire HF group as a whole. However, when broken down into reduced and preserved groups, age appeared to play a significant role in the type of HF that methamphetamine users may develop. The HFpEF age in methamphetamine users appeared to follow the trend of the general population age with HFpEF. The HFrEF rate was about six times higher among methamphetamine users, excluding the population with unspecified HF. Higher rates of methamphetamine abuse are prompting further studies and programs to reduce cardiac morbidity and mortality in this group and decrease the burden on health systems.

This article introduces a hypometabolic convergence index (HCI) for the assessment of Alzheimer's disease (AD); compares it to other biological, cognitive and clinical measures; and demonstrates its promise to predict clinical decline in mild cognitive impairment (MCI) patients using data from the AD Neuroimaging Initiative (ADNI). The HCI is intended to reflect in a single measurement the extent to which the pattern and magnitude of cerebral hypometabolism in an individual's fluorodeoxyglucose positron emission tomography (FDG-PET) image correspond to that in probable AD patients, and is generated using a fully automated voxel-based image-analysis algorithm. HCIs, magnetic resonance imaging (MRI) hippocampal volume measurements, cerebrospinal fluid (CSF) assays, memory test scores, and clinical ratings were compared in 47 probable AD patients, 21 MCI patients who converted to probable AD within the next 18 months, 76 MCI patients who did not, and 47 normal controls (NCs) in terms of their ability to characterize clinical disease severity and predict conversion rates from MCI to probable AD. HCIs were significantly different in the probable AD, MCI converter, MCI stable and NC groups ( p = 9e−17) and correlated with clinical disease severity. Using retrospectively characterized threshold criteria, MCI patients with either higher HCIs or smaller hippocampal volumes had the highest hazard ratios (HRs) for 18-month progression to probable AD (7.38 and 6.34, respectively), and those with both had an even higher HR (36.72). In conclusion, the HCI, alone or in combination with certain other biomarker measurements, has the potential to help characterize AD and predict subsequent rates of clinical decline. More generally, our conversion index strategy could be applied to a range of imaging modalities and voxel-based image-analysis algorithms. ► Hypometabolic convergence index (HCI) is a FDG-PET based global single index. ► HCI reflects a person's cerebral hypometabolism pattern similarity to that of AD. ► HCI correlated with cognitive measures. ► HCI distinguished AD, MCI who converted to AD in 18 months, MCI who did not, and NC. ► MCIs with high HCI or small hippocampal volume had higher risk to convert to AD.

Alzheimer's disease (AD) is characterized by specific and progressive reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose (CMRgl), some of which may precede the onset of symptoms. In this report, we describe twelve-month CMRgl declines in 69 probable AD patients, 154 amnestic mild cognitive impairment (MCI) patients, and 79 cognitively normal controls (NCs) from the AD Neuroimaging Initiative (ADNI) using statistical parametric mapping (SPM). We introduce the use of an empirically pre-defined statistical region-of-interest (sROI) to characterize CMRgl declines with optimal power and freedom from multiple comparisons, and we estimate the number of patients needed to characterize AD-slowing treatment effects in multi-center randomized clinical trials (RCTs). The AD and MCI groups each had significant twelve-month CMRgl declines bilaterally in posterior cingulate, medial and lateral parietal, medial and lateral temporal, frontal and occipital cortex, which were significantly greater than those in the NC group and correlated with measures of clinical decline. Using sROIs defined based on training sets of baseline and follow-up images to assess CMRgl declines in independent test sets from each patient group, we estimate the need for 66 AD patients or 217 MCI patients per treatment group to detect a 25% AD-slowing treatment effect in a twelve-month, multi-center RCT with 80% power and two-tailed alpha=0.05, roughly one-tenth the number of the patients needed to study MCI patients using clinical endpoints. Our findings support the use of FDG PET, brain-mapping algorithms and empirically pre-defined sROIs in RCTs of AD-slowing treatments.

The clerkship helps medical students gain clinical experience in psychiatry and is an opportunity to influence students in a positive manner.Methods Medical students rotating in psychiatry at the Maricopa Integrated Health System were given a 13-item questionnaire assessing the overall quality of the rotation, including both clinical and didactic portions.Department of Psychiatry, Mayo Clinic, College of Medicine; Department of Psychiatry, University of Arizona, School of Medicine- Phoenix; Maricopa Integrated Health System and District Medical Group, Phoenix, AZ Devna Rastogi: Department of Psychiatry, Mayo Clinic, College of Medicine; Department of Psychiatry, University of Arizona, School of Medicine- Phoenix; Maricopa Integrated Health System and District Medical Group, Phoenix, AZ Gilbert Ramos: