Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is ...Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.展开更多
Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This...Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.展开更多
In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an imm...In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals.Although avoiding gluten can permit patients to live symptom-free,ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel mucosa.As villous atrophy predisposes patients to life threatening complications,such as osteoporotic fractures or malignancies,therapeutic adjuncts to gluten-free diet become important to improve patients’quality of life and,if these adjuncts can be shown to improve villous atrophy,avoid complications.Oral administration of enzyme preparations,such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflam-mation,is one clinical strategy under investigation.The article is about the utility of one endopeptidase isolated from Aspergillus niger.We critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.展开更多
BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related comorbidities.This can place patients at increased risk of operative and postoperative complications.The intragastri...BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related comorbidities.This can place patients at increased risk of operative and postoperative complications.The intragastric balloon has been shown to aid in minor weight loss,however its weight recidivism in patients requiring short interval weight loss has not been well studied.AIM To evaluate weight loss,ability to undergo successful elective surgery after intragastric balloon placement,and weight management after balloon removal.METHODS This study is a retrospective review of patients in a single academic institution undergoing intragastric balloon placement from 2019-2023 to aid in weight loss prior to undergoing elective surgery.Clinical outcomes including weight loss,duration of balloon placement,successful elective surgery,weight regain postballoon and post-procedure complications were assessed.Exclusion criteria included those with balloon in place at time of study.RESULTS Thirty-three patients completed intragastric balloon therapy from 2019-2023 as a bridge to elective surgery.All patients were required to participate in a 12-month weight management program to be eligible for balloon therapy.Elective surgeries included incisional hernia repair,umbilical hernia repair,inguinal hernia repair,and knee and hip replacements.The average age at placement was 53 years±11 years,majority(91%)were male.The average duration of intragastric balloon therapy was 186 days±41 days.The average weight loss was 14.0 kg±7.4 kg and with an average percent excess body weight loss of 30.0%(7.9%-73.6%).Over half of the patients(52.0%)achieved the goal of 30-50 lbs(14-22 kg)weight loss.Twenty-one patients(64%)underwent their intended elective surgery,2 patients(6%)deferred surgery due to symptom relief with weight loss alone.Twenty-one of the patients(64%)have documented weights in 3 months after balloon removal,in these patients the majority(76%)gained weight after balloon removed.In patients with weight regain at 3 months,they averaged 5.8 kg after balloon removal in the first 3 months,this averaged 58.4%weight regain of the initial weight lost.CONCLUSION Intragastric balloon placement is an option for short-term weight management,as a bridge to elective surgery in patients with body mass index(BMI)>35.Patients lost an average of 14 kg with the balloon,allowing two-thirds of patients to undergo elective surgery at a healthy BMI.However,most patients regained an average of 58%of the original weight lost after balloon removal.The intragastric balloon successfully serves as a tool for rapid weight loss,though patients must be educated on the risks including weight regain.展开更多
BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented...BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.展开更多
Karl Ludwig Kahlbaum(1828-1899)was the first to conceptualize and describe the main clinical features of a novel psychiatric illness,which he termed catatonia in his groundbreaking monograph published 150 years ago.Al...Karl Ludwig Kahlbaum(1828-1899)was the first to conceptualize and describe the main clinical features of a novel psychiatric illness,which he termed catatonia in his groundbreaking monograph published 150 years ago.Although Kahlbaum postulated catatonia as a separate disease entity characterized by psychomotor symptoms and a cyclical course,a close examination of his 26 cases reveals that most of them presented with motor symptom complexes or syndromes associated with various psychiatric and medical conditions.In his classification system,Kraepelin categorized catatonic motor symptoms that occur in combination with psychotic symptoms and typically have a poor prognosis within his dementia praecox(schizophrenia)disease entity.Because of the substantial influence of Kraepelin’s classification,catatonia was predominantly perceived as a component of schizophrenia for most of the 20th century.However,with the advent of the psychopharmacotherapy era starting from the early 1950s,interest in catatonia in both clinical practice and research subsided until the early 2000s.The past two decades have witnessed a resurgence of interest in catatonia.The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition,marked a paradigmatic shift by acknowledging that catatonia can occur secondary to various psychiatric and medical conditions.The introduction of an independent diagnostic category termed“Catatonia Not Otherwise Specified”significantly stimulated research in this field.The authors briefly review the history and findings of recent catatonia research and highlight promising directions for future exploration.展开更多
Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobeha...Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In LASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.展开更多
AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VAR...AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.展开更多
Background:Cardiac troponin assays have improved the ability to detect myocardial damage.However,ascertaining whether troponin elevation is due to myocardial infarction(MI) or secondary to another process can be chall...Background:Cardiac troponin assays have improved the ability to detect myocardial damage.However,ascertaining whether troponin elevation is due to myocardial infarction(MI) or secondary to another process can be challenging.Our aim is to evaluate provider-level variation in the diagnosis of MI and the use of invasive coronary angiography(ICA) among patients with undifferentiated elevations in cardiac troponin.Methods:We analyzed data from all patients with elevated troponin levels in a single Veterans Affairs(VA) Medical Center between 2006 and 2007.One of several cardiologists prospectively evaluated each patient's presentation and course of care.We compared the frequency of MI diagnosis and ICA use between physicians using univariate odds ratios(OR).Results:Among 761 patients,34.0% were diagnosed with MI and 25.9% underwent ICA.The unadjusted rates of MI(23.9% to 56.7%,P=0.02) and ICA(17.3% to 73.3%,P<0.001) differed between physicians.Comparing the patient cohorts for each physician,baseline characteristics were similar except for chest pain.In multivariate regression,factors associated with the use of cardiac ICA included an abnormal electrocardiograph(ECG)(OR=1.89,P=0.014),level of troponin(OR=1.71,P=0.004),chest pain(OR=8.60,P<0.001),and care by non-VA physicians(OR=4.45,P=0.006).One physician had a lower ICA use(OR=0.56,P=0.017).In multivariate regression of MI,no physician-level variation was observed.Conclusion:Among patients with elevated troponin,the likelihood of being diagnosed with MI and undergoing ICA is dependent on their clinical presentation.After adjustment,physician-level variation in care was observed for the use of ICA,but not for the diagnosis of MI.展开更多
AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement.METHODS: We performed a retrospecti...AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement.METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ<sup>2</sup> test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group.RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up.CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes.展开更多
BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bo...BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.展开更多
Background: To evaluate the medium and late term outcomes of coronary artery bypass grafting with pull-through coronary endarterectomy using a saphenous vein patch for bypass distal anastomosis site. Methods: Retrospe...Background: To evaluate the medium and late term outcomes of coronary artery bypass grafting with pull-through coronary endarterectomy using a saphenous vein patch for bypass distal anastomosis site. Methods: Retrospective review of all coronary artery bypass graft (CABG) procedures performed from January 1, 2000 through June 30, 2013 with and without concomitant coronary endarterectomy (CE), was carried out at the Veterans Affairs Medical Center in Washington DC. Patients who underwent concomitant valve operations were excluded. Primary outcome was overall survival, with analyses performed examining CE as well as the use of cardiopulmonary bypass. Secondary outcomes included 30-day mortality and post-operative MI. Results: 1255 CABG operations were performed, 10 of which included CE. All CE procedures were performed with saphenous vein patch. 7 involved left anterior descending artery (LAD) CE with left internal mammary artery (LIMA) conduits. The remaining 3 were diagonal branch artery (D1) CE with saphenous vein bypass conduits. 1-year survival was 70%. 5-year survival was 43% out of 7 patients. Conclusions: Pull-through CE with saphenous vein patch is a safe alternative technique for patients with diffuse coronary artery disease. Perioperative events and intermediate outcomes are favorable, although long-term survival is less than patients without CE.展开更多
Objective: As the veteran population ages, the incidence of clinically significant aortic stenosis (AS) is increasing and aortic stenosis has become a veterans’ health issue. This analysis focused on using serum Brai...Objective: As the veteran population ages, the incidence of clinically significant aortic stenosis (AS) is increasing and aortic stenosis has become a veterans’ health issue. This analysis focused on using serum Brain Natriuretic Peptide (BNP) levels as an adjunct to aid decision making for early aortic valve replacement (AVR) in veterans with severe AS to reduce hospital admission rates. Methods: We retrospectively reviewed the charts of patients referred to the heart valve clinic at the Washington DC, Veterans Affairs Medical Center (VAMC) Heart Center between 2004 and 2015 who were diagnosed with severe AS. We identified veterans who had a BNP drawn in addition to traditional echocardiography during their diagnostic workup. This cohort was then stratified based on their serum BNP levels and whether they received medical therapy or aortic valve replacement. The primary endpoint of interest was admission to a VAMC for valvular heart failure. Results: Univariate analysis of BNP quartile and operative status showed a reduction in number of admissions for veterans who underwent AVR with BNP between 101 and 300 (0.64 vs. 3.71, p = 0.054) and 301 and 1000 (1.36 vs. 4.0, p = 0.003) compared to veterans treated medically. There was no difference in number of admissions for veterans with BNP lower than 100 (p = 0.455) or higher than 1000 (p = 0.659). Conclusion: BNP may be a useful adjunct for selecting patients with AS for earlier AVR leading to lower rates of hospital admissions in the veteran population. Continued analysis in a larger cohort will be needed to further validate the utility of BNP stratification as a diagnostic tool to risk stratify patients with AS in a heart valve clinic.展开更多
The Joint Commission NPSG （National Patient Safety Goals） requires that medication reconciliation be performed upon any transition of care （NPSG 03.06.01）. The hospice clinical pharmacist, in delivering pharmaceut...The Joint Commission NPSG （National Patient Safety Goals） requires that medication reconciliation be performed upon any transition of care （NPSG 03.06.01）. The hospice clinical pharmacist, in delivering pharmaceutical care, performs medication regimen reviews to identify medication-related problems. This project aims to improve the medication reconciliation process upon transition from inpatient units to non-VA （Veterans Affairs） hospice care by identifying and resolving medication discrepancies and medication-related problems. Patients discharged from inpatient to non-VA hospice care from October 2013-March 2014 were included. Medication reconciliation was performed by the pharmacist via telephone with the patient/caretaker and the hospice agency within two weeks of discharge. The patient＇s primary care provider was contacted via telephone when changes were recommended, and upon agreement, medication lists were updated electronically. A total of 18 patients were included. The results found that following medication reconciliation and regimen review, the mean number per patient of VA medications discontinued and non-VA medication documented was 5.7 and 10.8 respectively. The mean number per patient of medication discrepancies and medication-related problems was 14.4 and 8.6 respectively. This quality improvement project demonstrates the vulnerability of patients to medication discrepancies and medication-related problems and highlights the role of pharmacists in resolving these issues during this transition of care.展开更多
To identify risk factors for failure of OPAT （outpatient parenteral antimicrobial therapy） among veterans with SAB （Staphylococcus aureus bacteremia）, a retrospective review was conducted of all patients receiving...To identify risk factors for failure of OPAT （outpatient parenteral antimicrobial therapy） among veterans with SAB （Staphylococcus aureus bacteremia）, a retrospective review was conducted of all patients receiving OPAT for SAB between 01/2011-09/2013 at a large, tertiary-care VA （Veterans＇ Affairs） medical center. Treatment failure was defined as incomplete therapy, therapy extension, infection relapse, or hospital admission or surgical intervention within 60 days of therapy completion. Of 118 SAB patients treated with OPAT, 101 met inclusion criteria. Treatment failure occurred in 36 （35.6%） patients. In multivariate analysis, heart failure （OR 3.67; CI 1.13-12.0）, previous OPAT （OR 14.1; CI 2.02-97.8）, immunosuppression （OR 10.5; CI 1.74-63.3）, and treatment with daptomycin （OR 9.56; CI 1.89-48.4） were independently associated with failure. A trend toward lower failure rates was seen in the community living center, a VA long-term care facility possessing its own infectious diseases consultation service. In veterans with SAB, specific health factors were associated with higher rates of OPAT failure. Given the morbidity and cost of SAB treatment failures, similar analyses may benefit other large OPAT programs to optimize the selection of patients and settings in which successful treatment will most likely occur.展开更多
While the diagnostic and prognostic utility of single photon emission computed tomography(SPECT)myocardial perfusion scan(MPS)has been well established,[1,2]there is a paucity of literature evaluating SPECT MPS in eld...While the diagnostic and prognostic utility of single photon emission computed tomography(SPECT)myocardial perfusion scan(MPS)has been well established,[1,2]there is a paucity of literature evaluating SPECT MPS in elderly populations.Specifically,it is unclear whether the prognostic value of MPS diminishes as patients get older.We conducted this study to evaluate the role of SPECT MPS in risk-stratifying a large sample of elderly patients with or without known coronary artery disease(CAD)and hypothesized that abnormal MPS in patients over 75 years would be associated with a greater risk of all-cause mortality and major adverse cardiac events.展开更多
In the beginning of the 1900s,the prevalence of catatonia in inpatient samples was reported to be between 19.5%and 50%.From the mid-1900s,most clinicians thought that catatonia was disappearing.Advances in medical sci...In the beginning of the 1900s,the prevalence of catatonia in inpatient samples was reported to be between 19.5%and 50%.From the mid-1900s,most clinicians thought that catatonia was disappearing.Advances in medical sciences,particularly in the field of neurology,may have reduced the incidence of neurological diseases that present with catatonic features or mitigated their severity.More active pharmacological and psychosocial treatment methods may have either eliminated or moderated catatonic phenomena.Moreover,the relatively narrow descriptive features in modern classifications compared with classical texts and ascribing catatonic signs and symptoms to antipsychotic-induced motor symptoms may have contributed to an apparent decline in the incidence of catatonia.The application of catatonia rating scales introduced in the 1990s revealed significantly more symptoms than routine clinical interviews,and within a few years,the notion of the disappearance of catatonia gave way to its unexpected resurgence.Several systematic investigations have found that,on average,10%of acute psychotic patients present with catatonic features.In this editorial,the changes in the incidence of catatonia and the possible underlying causes are reviewed.展开更多
BACKGROUND Peptic ulcer disease(PUD)is frequently seen in patients with liver cirrhosis.However,current literature lacks data on PUD in non-alcoholic fatty liver disease(NAFLD)hospitalizations.AIM To identify trends a...BACKGROUND Peptic ulcer disease(PUD)is frequently seen in patients with liver cirrhosis.However,current literature lacks data on PUD in non-alcoholic fatty liver disease(NAFLD)hospitalizations.AIM To identify trends and clinical outcomes of PUD in NAFLD hospitalizations in the United States.METHODS The National Inpatient Sample was utilized to identify all adult(≥18 years old)NAFLD hospitalizations with PUD in the United States from 2009-2019.Hospitalization trends and outcomes were highlighted.Furthermore,a control group of adult PUD hospitalizations without NAFLD was also identified for a comparative analysis to assess the influence of NAFLD on PUD.RESULTS The total number of NAFLD hospitalizations with PUD increased from 3745 in 2009 to 3805 in 2019.We noted an increase in the mean age for the study population from 56 years in 2009 to 63 years in 2019(P<0.001).Racial differences were also prevalent as NAFLD hospitalizations with PUD increased for Whites and Hispanics,while a decline was observed for Blacks and Asians.The all-cause inpatient mortality for NAFLD hospitalizations with PUD increased from 2%in 2009 to 5%in 2019(P<0.001).However,rates of Helicobacter pylori(H.pylori)infection and upper endoscopy decreased from 5%in 2009 to 1%in 2019(P<0.001)and from 60%in 2009 to 19%in 2019(P<0.001),respectively.Interestingly,despite a significantly higher comorbidity burden,we observed lower inpatient mortality(2%vs 3%,P=0.0004),mean length of stay(LOS)(11.6 vs 12.1 d,P<0.001),and mean total healthcare cost(THC)($178598 vs$184727,P<0.001)for NAFLD hospitalizations with PUD compared to non-NAFLD PUD hospitalizations.Perforation of the gastrointestinal tract,coagulopathy,alcohol abuse,malnutrition,and fluid and electrolyte disorders were identified to be independent predictors of inpatient mortality for NAFLD hospitalizations with PUD.CONCLUSION Inpatient mortality for NAFLD hospitalizations with PUD increased for the study period.However,there was a significant decline in the rates of H.pylori infection and upper endoscopy for NAFLD hospitalizations with PUD.After a comparative analysis,NAFLD hospitalizations with PUD had lower inpatient mortality,mean LOS,and mean THC compared to the non-NAFLD cohort.展开更多
基金supported by NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.
基金supported by National Health Institute(NIH)grant NS099596(to LW and SPY),NS114221(to LW and SPY)Veterans Affair(VA)SPiRE grant RX003865(to SPY)+1 种基金supported by the O.Wayne Rollins Endowment Fund(to SPY)John E.Steinhaus Endowment Fund(to LW)。
文摘Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.
基金Supported by the VA Merit Award,2I01BX002906-05.
文摘In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals.Although avoiding gluten can permit patients to live symptom-free,ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel mucosa.As villous atrophy predisposes patients to life threatening complications,such as osteoporotic fractures or malignancies,therapeutic adjuncts to gluten-free diet become important to improve patients’quality of life and,if these adjuncts can be shown to improve villous atrophy,avoid complications.Oral administration of enzyme preparations,such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflam-mation,is one clinical strategy under investigation.The article is about the utility of one endopeptidase isolated from Aspergillus niger.We critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.
文摘BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related comorbidities.This can place patients at increased risk of operative and postoperative complications.The intragastric balloon has been shown to aid in minor weight loss,however its weight recidivism in patients requiring short interval weight loss has not been well studied.AIM To evaluate weight loss,ability to undergo successful elective surgery after intragastric balloon placement,and weight management after balloon removal.METHODS This study is a retrospective review of patients in a single academic institution undergoing intragastric balloon placement from 2019-2023 to aid in weight loss prior to undergoing elective surgery.Clinical outcomes including weight loss,duration of balloon placement,successful elective surgery,weight regain postballoon and post-procedure complications were assessed.Exclusion criteria included those with balloon in place at time of study.RESULTS Thirty-three patients completed intragastric balloon therapy from 2019-2023 as a bridge to elective surgery.All patients were required to participate in a 12-month weight management program to be eligible for balloon therapy.Elective surgeries included incisional hernia repair,umbilical hernia repair,inguinal hernia repair,and knee and hip replacements.The average age at placement was 53 years±11 years,majority(91%)were male.The average duration of intragastric balloon therapy was 186 days±41 days.The average weight loss was 14.0 kg±7.4 kg and with an average percent excess body weight loss of 30.0%(7.9%-73.6%).Over half of the patients(52.0%)achieved the goal of 30-50 lbs(14-22 kg)weight loss.Twenty-one patients(64%)underwent their intended elective surgery,2 patients(6%)deferred surgery due to symptom relief with weight loss alone.Twenty-one of the patients(64%)have documented weights in 3 months after balloon removal,in these patients the majority(76%)gained weight after balloon removed.In patients with weight regain at 3 months,they averaged 5.8 kg after balloon removal in the first 3 months,this averaged 58.4%weight regain of the initial weight lost.CONCLUSION Intragastric balloon placement is an option for short-term weight management,as a bridge to elective surgery in patients with body mass index(BMI)>35.Patients lost an average of 14 kg with the balloon,allowing two-thirds of patients to undergo elective surgery at a healthy BMI.However,most patients regained an average of 58%of the original weight lost after balloon removal.The intragastric balloon successfully serves as a tool for rapid weight loss,though patients must be educated on the risks including weight regain.
基金Supported by Eunice Kennedy Shriver National Institute of Child Health&Human Development of the National Institutes of Health,No.1K08HD079674-01 and 1R41HD092133-01National Institute of Allergy and Infectious Diseases,No.1A21AI169282and VA Research Career Scientist Award,No.1IK6BX004835.
文摘BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.
文摘Karl Ludwig Kahlbaum(1828-1899)was the first to conceptualize and describe the main clinical features of a novel psychiatric illness,which he termed catatonia in his groundbreaking monograph published 150 years ago.Although Kahlbaum postulated catatonia as a separate disease entity characterized by psychomotor symptoms and a cyclical course,a close examination of his 26 cases reveals that most of them presented with motor symptom complexes or syndromes associated with various psychiatric and medical conditions.In his classification system,Kraepelin categorized catatonic motor symptoms that occur in combination with psychotic symptoms and typically have a poor prognosis within his dementia praecox(schizophrenia)disease entity.Because of the substantial influence of Kraepelin’s classification,catatonia was predominantly perceived as a component of schizophrenia for most of the 20th century.However,with the advent of the psychopharmacotherapy era starting from the early 1950s,interest in catatonia in both clinical practice and research subsided until the early 2000s.The past two decades have witnessed a resurgence of interest in catatonia.The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition,marked a paradigmatic shift by acknowledging that catatonia can occur secondary to various psychiatric and medical conditions.The introduction of an independent diagnostic category termed“Catatonia Not Otherwise Specified”significantly stimulated research in this field.The authors briefly review the history and findings of recent catatonia research and highlight promising directions for future exploration.
文摘Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In LASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.
基金Supported by VA HSR&D MERIT Award IIR,No.14-048-3 for Dr Caplansupported by a VA GME Enhancement Award
文摘AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.
基金supported by resources provided by the North Florida/South Georgia Veterans Health System,Gainesville,FL
文摘Background:Cardiac troponin assays have improved the ability to detect myocardial damage.However,ascertaining whether troponin elevation is due to myocardial infarction(MI) or secondary to another process can be challenging.Our aim is to evaluate provider-level variation in the diagnosis of MI and the use of invasive coronary angiography(ICA) among patients with undifferentiated elevations in cardiac troponin.Methods:We analyzed data from all patients with elevated troponin levels in a single Veterans Affairs(VA) Medical Center between 2006 and 2007.One of several cardiologists prospectively evaluated each patient's presentation and course of care.We compared the frequency of MI diagnosis and ICA use between physicians using univariate odds ratios(OR).Results:Among 761 patients,34.0% were diagnosed with MI and 25.9% underwent ICA.The unadjusted rates of MI(23.9% to 56.7%,P=0.02) and ICA(17.3% to 73.3%,P<0.001) differed between physicians.Comparing the patient cohorts for each physician,baseline characteristics were similar except for chest pain.In multivariate regression,factors associated with the use of cardiac ICA included an abnormal electrocardiograph(ECG)(OR=1.89,P=0.014),level of troponin(OR=1.71,P=0.004),chest pain(OR=8.60,P<0.001),and care by non-VA physicians(OR=4.45,P=0.006).One physician had a lower ICA use(OR=0.56,P=0.017).In multivariate regression of MI,no physician-level variation was observed.Conclusion:Among patients with elevated troponin,the likelihood of being diagnosed with MI and undergoing ICA is dependent on their clinical presentation.After adjustment,physician-level variation in care was observed for the use of ICA,but not for the diagnosis of MI.
基金Supported by(in part)by resources from the Veterans Affairs(VA) Cooperative Studies Program Epidemiology Center-Durham,the Puget Sound VA Health Care System,and the VA Office of Public Health and Human Health Pathogens
文摘AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement.METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ<sup>2</sup> test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group.RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up.CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes.
基金results in part from collaboration and network activities promoted under the frame of the international network GENIEUR (Genes in Irritable Bowel Syndrome Research Network Europe),which has been funded by the COST program (BM1106, www.GENIEUR.eu)currently supported by the European Society of Neurogastroenterology and Motility (ESNM, www.ESNM.eu)
文摘BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
文摘Background: To evaluate the medium and late term outcomes of coronary artery bypass grafting with pull-through coronary endarterectomy using a saphenous vein patch for bypass distal anastomosis site. Methods: Retrospective review of all coronary artery bypass graft (CABG) procedures performed from January 1, 2000 through June 30, 2013 with and without concomitant coronary endarterectomy (CE), was carried out at the Veterans Affairs Medical Center in Washington DC. Patients who underwent concomitant valve operations were excluded. Primary outcome was overall survival, with analyses performed examining CE as well as the use of cardiopulmonary bypass. Secondary outcomes included 30-day mortality and post-operative MI. Results: 1255 CABG operations were performed, 10 of which included CE. All CE procedures were performed with saphenous vein patch. 7 involved left anterior descending artery (LAD) CE with left internal mammary artery (LIMA) conduits. The remaining 3 were diagonal branch artery (D1) CE with saphenous vein bypass conduits. 1-year survival was 70%. 5-year survival was 43% out of 7 patients. Conclusions: Pull-through CE with saphenous vein patch is a safe alternative technique for patients with diffuse coronary artery disease. Perioperative events and intermediate outcomes are favorable, although long-term survival is less than patients without CE.
文摘Objective: As the veteran population ages, the incidence of clinically significant aortic stenosis (AS) is increasing and aortic stenosis has become a veterans’ health issue. This analysis focused on using serum Brain Natriuretic Peptide (BNP) levels as an adjunct to aid decision making for early aortic valve replacement (AVR) in veterans with severe AS to reduce hospital admission rates. Methods: We retrospectively reviewed the charts of patients referred to the heart valve clinic at the Washington DC, Veterans Affairs Medical Center (VAMC) Heart Center between 2004 and 2015 who were diagnosed with severe AS. We identified veterans who had a BNP drawn in addition to traditional echocardiography during their diagnostic workup. This cohort was then stratified based on their serum BNP levels and whether they received medical therapy or aortic valve replacement. The primary endpoint of interest was admission to a VAMC for valvular heart failure. Results: Univariate analysis of BNP quartile and operative status showed a reduction in number of admissions for veterans who underwent AVR with BNP between 101 and 300 (0.64 vs. 3.71, p = 0.054) and 301 and 1000 (1.36 vs. 4.0, p = 0.003) compared to veterans treated medically. There was no difference in number of admissions for veterans with BNP lower than 100 (p = 0.455) or higher than 1000 (p = 0.659). Conclusion: BNP may be a useful adjunct for selecting patients with AS for earlier AVR leading to lower rates of hospital admissions in the veteran population. Continued analysis in a larger cohort will be needed to further validate the utility of BNP stratification as a diagnostic tool to risk stratify patients with AS in a heart valve clinic.
文摘The Joint Commission NPSG （National Patient Safety Goals） requires that medication reconciliation be performed upon any transition of care （NPSG 03.06.01）. The hospice clinical pharmacist, in delivering pharmaceutical care, performs medication regimen reviews to identify medication-related problems. This project aims to improve the medication reconciliation process upon transition from inpatient units to non-VA （Veterans Affairs） hospice care by identifying and resolving medication discrepancies and medication-related problems. Patients discharged from inpatient to non-VA hospice care from October 2013-March 2014 were included. Medication reconciliation was performed by the pharmacist via telephone with the patient/caretaker and the hospice agency within two weeks of discharge. The patient＇s primary care provider was contacted via telephone when changes were recommended, and upon agreement, medication lists were updated electronically. A total of 18 patients were included. The results found that following medication reconciliation and regimen review, the mean number per patient of VA medications discontinued and non-VA medication documented was 5.7 and 10.8 respectively. The mean number per patient of medication discrepancies and medication-related problems was 14.4 and 8.6 respectively. This quality improvement project demonstrates the vulnerability of patients to medication discrepancies and medication-related problems and highlights the role of pharmacists in resolving these issues during this transition of care.
文摘To identify risk factors for failure of OPAT （outpatient parenteral antimicrobial therapy） among veterans with SAB （Staphylococcus aureus bacteremia）, a retrospective review was conducted of all patients receiving OPAT for SAB between 01/2011-09/2013 at a large, tertiary-care VA （Veterans＇ Affairs） medical center. Treatment failure was defined as incomplete therapy, therapy extension, infection relapse, or hospital admission or surgical intervention within 60 days of therapy completion. Of 118 SAB patients treated with OPAT, 101 met inclusion criteria. Treatment failure occurred in 36 （35.6%） patients. In multivariate analysis, heart failure （OR 3.67; CI 1.13-12.0）, previous OPAT （OR 14.1; CI 2.02-97.8）, immunosuppression （OR 10.5; CI 1.74-63.3）, and treatment with daptomycin （OR 9.56; CI 1.89-48.4） were independently associated with failure. A trend toward lower failure rates was seen in the community living center, a VA long-term care facility possessing its own infectious diseases consultation service. In veterans with SAB, specific health factors were associated with higher rates of OPAT failure. Given the morbidity and cost of SAB treatment failures, similar analyses may benefit other large OPAT programs to optimize the selection of patients and settings in which successful treatment will most likely occur.
文摘While the diagnostic and prognostic utility of single photon emission computed tomography(SPECT)myocardial perfusion scan(MPS)has been well established,[1,2]there is a paucity of literature evaluating SPECT MPS in elderly populations.Specifically,it is unclear whether the prognostic value of MPS diminishes as patients get older.We conducted this study to evaluate the role of SPECT MPS in risk-stratifying a large sample of elderly patients with or without known coronary artery disease(CAD)and hypothesized that abnormal MPS in patients over 75 years would be associated with a greater risk of all-cause mortality and major adverse cardiac events.
文摘In the beginning of the 1900s,the prevalence of catatonia in inpatient samples was reported to be between 19.5%and 50%.From the mid-1900s,most clinicians thought that catatonia was disappearing.Advances in medical sciences,particularly in the field of neurology,may have reduced the incidence of neurological diseases that present with catatonic features or mitigated their severity.More active pharmacological and psychosocial treatment methods may have either eliminated or moderated catatonic phenomena.Moreover,the relatively narrow descriptive features in modern classifications compared with classical texts and ascribing catatonic signs and symptoms to antipsychotic-induced motor symptoms may have contributed to an apparent decline in the incidence of catatonia.The application of catatonia rating scales introduced in the 1990s revealed significantly more symptoms than routine clinical interviews,and within a few years,the notion of the disappearance of catatonia gave way to its unexpected resurgence.Several systematic investigations have found that,on average,10%of acute psychotic patients present with catatonic features.In this editorial,the changes in the incidence of catatonia and the possible underlying causes are reviewed.
文摘BACKGROUND Peptic ulcer disease(PUD)is frequently seen in patients with liver cirrhosis.However,current literature lacks data on PUD in non-alcoholic fatty liver disease(NAFLD)hospitalizations.AIM To identify trends and clinical outcomes of PUD in NAFLD hospitalizations in the United States.METHODS The National Inpatient Sample was utilized to identify all adult(≥18 years old)NAFLD hospitalizations with PUD in the United States from 2009-2019.Hospitalization trends and outcomes were highlighted.Furthermore,a control group of adult PUD hospitalizations without NAFLD was also identified for a comparative analysis to assess the influence of NAFLD on PUD.RESULTS The total number of NAFLD hospitalizations with PUD increased from 3745 in 2009 to 3805 in 2019.We noted an increase in the mean age for the study population from 56 years in 2009 to 63 years in 2019(P<0.001).Racial differences were also prevalent as NAFLD hospitalizations with PUD increased for Whites and Hispanics,while a decline was observed for Blacks and Asians.The all-cause inpatient mortality for NAFLD hospitalizations with PUD increased from 2%in 2009 to 5%in 2019(P<0.001).However,rates of Helicobacter pylori(H.pylori)infection and upper endoscopy decreased from 5%in 2009 to 1%in 2019(P<0.001)and from 60%in 2009 to 19%in 2019(P<0.001),respectively.Interestingly,despite a significantly higher comorbidity burden,we observed lower inpatient mortality(2%vs 3%,P=0.0004),mean length of stay(LOS)(11.6 vs 12.1 d,P<0.001),and mean total healthcare cost(THC)($178598 vs$184727,P<0.001)for NAFLD hospitalizations with PUD compared to non-NAFLD PUD hospitalizations.Perforation of the gastrointestinal tract,coagulopathy,alcohol abuse,malnutrition,and fluid and electrolyte disorders were identified to be independent predictors of inpatient mortality for NAFLD hospitalizations with PUD.CONCLUSION Inpatient mortality for NAFLD hospitalizations with PUD increased for the study period.However,there was a significant decline in the rates of H.pylori infection and upper endoscopy for NAFLD hospitalizations with PUD.After a comparative analysis,NAFLD hospitalizations with PUD had lower inpatient mortality,mean LOS,and mean THC compared to the non-NAFLD cohort.
