Medical Journey of Patients with Mild Cognitive Impairment and Mild Alzheimer's Disease Dementia: A Cross-sectional Survey of Patients, Care Partners, and Neurologists.

BACKGROUND: Alzheimer's disease (AD) is a progressive, neurodegenerative disease presenting along a continuum ranging from asymptomatic disease to mild cognitive impairment (MCI), followed by dementia characterized as mild, moderate, or severe. OBJECTIVES: To better understand the medical journey of patients with all-cause MCI or mild AD dementia from the perspective of patients, care partners, and physicians. DESIGN: Cross-sectional study. SETTING: Online surveys in the United States between February 4, 2021, and March 1, 2021. PARTICIPANTS: 103 patients with all-cause MCI or mild AD dementia and 150 care partners participated in this survey. 301 physicians (75 of whom were neurologists) completed a survey. MEASUREMENTS: The surveys included questions regarding attitudes, experiences, and behaviors related to diagnosis and management of MCI and mild AD dementia. For the patient and care partner surveys, questions regarding healthcare received for MCI and mild AD dementia were only asked of care partners. RESULTS: Most patients (73%) had a similar medical journey. The majority (64%) initially consulted a primary care physician on average 15 months after symptom onset, with symptoms primarily consisting of forgetfulness and short-term memory loss. About half (51%) of patients in the typical medical journey were diagnosed by a neurologist. Upon diagnosis, most neurologists reported having discussions with patients and care partners about the potential causes of MCI or mild AD dementia (83%); of these physicians, 83% explained the effect other conditions have on the risk of the diagnoses and symptom progression. Neurologists (52%) consider themselves the coordinator of care for patients with MCI or mild AD dementia. Amongst patients and care partners, about one-third (35%) perceive the neurologists to be the coordinating physician. CONCLUSIONS: Neurologists commonly diagnose MCI and mild AD dementia but are typically not the first point of contact in the medical journey, and patients do not consult with a physician for over a year after symptom onset. Neurologists play a key role in the medical journey for patients and care partners, and could help ensure earlier diagnosis and treatment, and improve clinical outcomes by coordinating MCI and mild AD dementia care and collaborating with primary care physicians.

Oxidative removal of stabilized landfill leachate by Fenton's process: process modeling, optimization & analysis of degraded products.

In this study, the stabilized landfill leachate which has a BOD : COD ratio of 0.045 was treated using Fenton's process. The effect of process parameters like reaction time, pH, dose of FeSO4 and dose of H2O2 was estimated using One Factor At a Time (OFAT) and the linear, interactive and quadratic effects between the factors were studied using Face Centered Central Composite Design (CCF). In the OFAT approach, reaction time: 5 minutes, pH: 3.0, dose of FeSO4: 30 mM, and dose of H2O2: 30 mM were optimized. In CCF, the statistically optimized model shows maximum removal of organic substances at an FeSO4 concentration of 14.44 mM, pH 3.0 and 29.12 mM of H2O2. The regression co-efficient R 2 = 0.9079, adj R 2 = 0.854 and adequate precision = 14.676. The degradation of organic substances was assessed by measuring the Chemical Oxygen Demand (COD). Total Organic Carbon (TOC) and Gas Chromatography-Mass Spectroscopy (GC-MS) were investigated for the sample corresponding to the maximum COD reduction.

Selective lactase deficiency is common in pediatric patients undergoing upper endoscopy.

Lactase deficiency can lead to significant symptoms in the pediatric population. To date, few studies have examined the prevalence of enzyme testing-based lactase and other disaccharidase deficiencies (DDs) in pediatric patients undergoing upper endoscopic evaluation. The primary objective of this study was to determine the prevalence of selective lactase and other DDs amongst a large cohort of pediatric patients with and without inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis) via a chart review of 739 patients who underwent esophago-gastro-dudenoscopy EGD between April 2010 and August 2016. We identified 560 pediatric patients (ages 1-18 years) who underwent mucosal enzyme testing at the time of their EGD. The overall rate of lactase deficiency (LD) was 39%. LD positively correlated with age (p=0.00017), but there was no significant difference between age matched IBD and non-IBD patients (45% vs. 42% p=0.68). Four patients (0.17%) were found to have selective maltase deficiency. No selective sucrase or palatinase deficiency was identified. Statistically significant differences occurred in lactase deficiency amongst patients of different races. In conclusion, lactase deficiency is a relatively common finding in children undergoing EGD though at no increased rate amongst the IBD patient population. Disaccharidase testing should be considered in pediatric patients undergoing EGD.

Defining the clinical pathway in cochrane diagnostic test accuracy reviews.

BACKGROUND: The value of a medical test depends on the context in which it might be used. Ideally, questions, results and conclusions of a diagnostic test accuracy (DTA) systematic review should be presented in light of this context. There is increasing acceptance of the value for knowing the impact a test can have on downstream consequences such as costs, implications for further testing and treatment options however there is currently no explicit guidance on how to address this. Authors of a Cochrane diagnostic review have recently been asked to include the clinical pathway in which a test maybe used. We aimed to evaluate how authors were developing their clinical pathways in the light of this. METHODS: We searched the Cochrane Database of Systematic Reviews for all published DTA reviews. We included only those reviews that included a clinical pathway. We developed a checklist, based on the guidance in the Cochrane Handbook for DTA review authors. To this, we added a number of additional descriptors. We checked if the included pathways fulfilled these descriptors as defined by our checklist. RESULTS: We found 47 reviews, of which 33 (73 %) contained aspects pertaining to a clinical pathway. The 33 reviews addressed the clinical pathway differently, both in content and format. Of these, 21 provided a textual description and 12 include visual and textual descriptions. There was considerable variation in how comprehensively review authors adhered to our checklist. Eighteen reviews (51 %) linked the index test results to downstream clinical management actions and patient consequences, but only eight went on to differentially report on the consequences for false negative results and nine on the consequences for false positive results. CONCLUSION: There is substantial variation in the clinical pathway descriptions in Cochrane systematic reviews of test accuracy. Most reviews do not link misclassifications (i.e. false negatives and false positive) to downstream patient consequences. Review authors could benefit from more explicit guidance on how to create such pathways, which in turn can help guide them in their evidence selection and appraisal of the evidence in the context of downstream consequences of testing.

Transcriptional Read-Through Induction Treatment Trial in Intestinal Failure Induced by an EpCAM Nonsense Mutation.

Congenital tufting enteropathy (CTE) is a rare autosomal recessive diarrheal disorder where epithelial tufts can be present from the duodenum to the large intestine. CTE has been linked to mutations in the epithelial cell adhesion molecule gene (EpCAM) Sivagnanam et al. (2008). We recently reported the first case with a nonsense mutation in EpCAM Sivagnanam et al. (2010). Here, we explored the clinical and molecular effects of enterally administered gentamicin in this CTE patient. Altogether, our findings indicate that the therapy employed was insufficient to produce notable read-through induction of the EpCAM premature termination codon. This report highlights the utility of genetic testing not only in respect of diagnostics, prognostics, and family planning, but potential mutation-specific therapeutic considerations as well.

Concomitant gastroparesis negatively affects children with functional gallbladder disease.

OBJECTIVES: The aim of the present study was to determine whether concomitant gastroparesis and biliary dyskinesia (BD) occur in children, and if so, to determine whether concomitant gastroparesis affects clinical outcome in children with BD. METHODS: We conducted a retrospective chart review of children with BD (ejection fraction <35% on cholescintigraphy, with no other metabolic or structural cause) who completed a solid-phase gastric emptying scintigraphy scan within 12 months of abnormal cholescintigraphy. Children were classified into 1 of 4 clinical outcome groups (excellent, good, fair, poor). RESULTS: Thirty-five children with a mean follow-up time of 23.1±17.3 (standard deviation) months were included. Twenty (57%) children were identified as having concomitant gastroparesis (GP) with BD. Children with concomitant GP were more likely to have a poor clinical outcome compared with those with BD alone (P<0.005). In children undergoing cholecystectomy, those with concomitant GP were more likely to have a fair or poor clinical outcome compared with those with BD alone (P<0.01). Factors predicting a more favorable clinical outcome were having BD alone and not having limitations in activity (eg, school absences) at the time of presentation. CONCLUSIONS: Concomitant GP may occur in children with functional gallbladder disorders. Concomitant GP may negatively affect clinical outcome in children with BD.

Hepatic veno-occlusive disease in ataxia-telangiectasia.

Existing descriptions of liver abnormalities in ataxia-telangiectasia have been associated with co-existent hepatitis virus infection. Here we report veno-occlusive disease of the liver in 2 patients with ataxia telangiectasia that is not attributable to bone marrow transplantation or coincidental hepatitis infection.

Immunosuppressive therapy with microemulsion cyclosporine A shortens the hospitalization of pediatric liver transplant recipients.

Intravenous administration of cyclosporine (Sandimmune) to rapidly and effectively achieve therapeutic serum levels in transplant recipients has been the treatment standard in many transplantation centers. With the development of microemulsion cyclosporine (Neoral), that standard is changing. Neoral has greater bioavailability than the oral form of Sandimmune and, consequently, can be more efficacious and cost-effective. To test this hypothesis, we undertook a retrospective study of Sandimmune and Neoral in the treatment of 66 children who underwent uncomplicated orthotopic liver transplantation in the Texas Medical Center between April 1991 and December 1997. Both forms of cyclosporine were evaluated in terms of in-patient treatment cost, recuperative time in the intensive care unit and duration of hospitalization. Twenty-two patients were treated orally with Neoral, and 44 patients were treated intravenously with Sandimmune for a mean time of 14 d. Once the blood concentration of Sandimmune reached a steady state, as confirmed by daily measurements of the trough level, the patients in the Sandimmune group were converted to oral cyclosporine. None of the 22 patients treated with Neoral required intravenous treatment. The mean time spent in the intensive care unit was 4 d for the Neoral group and 5.5 d for the Sandimmune group. The mean duration of hospitalization from the date of transplantation to discharge was 12 d for the Neoral group and 20 d for the Sandimmune group (p < 0.001). Based on these results, we determined that the overall cost per patient in the Neoral group was $3598 less than that per patient in the Sandimmune group.

Epidemiologic features of facial injuries among motorcyclists.

STUDY OBJECTIVE: To describe the extent, nature, and severity of facial injuries among motorcyclists injured in a crash requiring hospital treatment. METHODS: The study population consisted of 5,790 motorcycle riders who sustained a nonfatal crash injury during 1991, 1992, or 1993 in 10 California counties. The injured riders were identified in 28 hospitals during 1991 and 1992 and in 18 of these 28 hospitals in 1993. Information was collected from crash reports and hospital records. All injuries were coded according to the 1990 Abbreviated Injury Scale. RESULTS: Facial injury was present in 24.3% of injured riders, a high proportion of them young men. Among riders wearing helmets, 36.8% had facial injuries, compared with 53.8% of those not wearing helmets. Soft tissue injuries and facial fractures were present in 72% and 22% of the injured, respectively. The maxilla (22%), orbit (16%), and nasal (16%) bones were the most frequently fractured facial bones. The frequency of multiple facial injuries, severity of facial injuries, and incidence of high-severity facial fractures was greater among nonhelmeted riders compared with helmeted riders. Upper facial fractures were more common among riders without helmets compared with those wearing helmets. CONCLUSION: This study provides evidence of the protective value of helmets to reduce risk of facial injury. Information on the positive effect of facial injury sparing provided by helmet use should be incorporated into helmet promotion programs.

Human milk and the rate of small intestinal mucosal recovery in protracted diarrhea.

STUDY OBJECTIVE: To determine whether human milk accelerates the recovery rate of injured small intestinal mucosa. DESIGN: Randomized, controlled trial. SETTING: County and nonprofit, private urban hospitals. PATIENTS: Moderately to severely malnourished infants less than 6 months of age who required parenteral nutrition for treatment of protracted diarrhea. INTERVENTIONS: Either a human milk preparation (n = 7) or sterile water (n = 9) was administered by continuous nasogastric feeding (14 mL/kg/d) over a 2-week study period while the infants received parenteral nutrition. MEASUREMENTS AND MAIN RESULTS: Small intestine perfusion studies and biopsies were performed at the beginning and end of the study. Age, duration of prior illness, severity of malnutrition, glucose and water absorption, disaccharidase activities, atrophy of villi, and nutritional intake were comparable in both groups of infants. At the end of the 2-week study, improvement toward normal sucrase activity and intraepithelial lymphocytes was found in significantly fewer infants in the milk group than in the water group. No differences were noted in glucose and water absorption or in lactase and maltase activities as a function of the milk versus water treatment. CONCLUSIONS: Human milk did not accelerate functional recovery of the small intestinal mucosa.

PIP: Physicians studied 16 moderately to severely malnourished infants 6 months old who had severe diarrhea for 2 weeks and did not gain weight. After admitting the infants, they administered total parenteral nutrition (TPN) to the infants through a central vein. As the infants began receiving TPN, they were randomly assigned to receive either banked human milk or sterile water by continuous nasogastric feeding for 2 weeks. In addition, before beginning nasogastric feedings and at the conclusion of the study, a physician performed a peroral biopsy of the small intestine. Small intestine perfusion studies were also done in the beginning and at the end of the 2 week period. More infants in the human milk group than in the sterile water group had 25% decrease in sucrase activity (p.02). Researchers noted that the villus/crypt ratio was similar in both groups at the beginning of the study and improved only in the sterile water group (p.002), but this was not a function of treatment. Additionally, more infants in the human milk group had an increase in the intraepithelial lymphocyte count than those in the sterile water group (milk, 5/7; water, 1/8; p.03). On the other hand, the data demonstrate that no differences existed in glucose and water absorption or in lactase and maltase activities as a function of the milk versus water treatment. Therefore, the results of this study suggest that human milk does not benefit small intestine mucosa recovery. Research to determine the effect of predigested formulas or specific factors in fresh human milk on the rate of mucosal recovery is needed.

Intestinal strictures presenting with gastrointestinal blood loss.

The typical manifestations of intestinal strictures include abdominal distention, bilious vomiting, hematochezia, diarrhea, disaccharide intolerance, and occasional growth failure. However, chronic gastrointestinal (GI) blood loss from ulcers at the site of the stricture has not been noted as a major feature. We report three patients in whom an intestinal stricture presented with minimal evidence of obstruction, but with GI bleeding and anemia. Our experience indicates that intestinal strictures with ulcers must be considered in the differential diagnosis of blood loss, and that surgical intervention may be required if GI blood loss is chronic and laboratory results are negative.

Comparison of the D-xylose and polyethylene glycol absorption tests as indicators of mucosal damage in infants with chronic diarrhea.

The determination of serum levels of D-xylose and the urinary excretion of an orally administered mixture of low-molecular-weight polyethylene glycol were compared to assess their sensitivity to predict small-bowel mucosal damage. Eighteen infants with severe diarrhea and villus atrophy were observed. Results of the D-xylose and polyethylene glycol tests were compared with the villus-to-crypt ratios that were determined from biopsy specimens. The D-xylose test predicted accurately 12 (67%) of the 18 small-bowel biopsy results, while the polyethylene glycol test predicted 14 (78%). However, the McNemar test indicated that the two tests did not differ significantly in their ability to predict an abnormal small-bowel biopsy. We conclude that neither the D-xylose nor the polyethylene glycol test is a reliable indicator of small intestinal mucosal damage in infants with chronic diarrhea.

Comparison of serum fibronectin, prealbumin, and albumin concentrations during nutritional repletion in protein-calorie malnourished infants.

Anthropometric measurements and serum fibronectin, prealbumin, and albumin concentrations were determined on admission and during the hospitalization of 20 noninfected infants with protein-calorie malnutrition. Serum fibronectin concentrations were significantly decreased on admission but increased to greater than normal serum values in 2 weeks. During this same interval, serum prealbumin values rose from significantly decreased to normal levels. Serum albumin concentrations and anthropometric measurements were not significantly elevated above admission levels until the fourth week of nutritional support. Serum fibronectin and prealbumin concentrations may serve as indices of the short-term efficacy of nutritional support in noninfected infants with protein-calorie malnutrition.

Absorption and tolerance of lactose in infants recovering from severe diarrhea.

Nineteen infants were challenged during their convalescence from severe diarrhea with a lactose-containing meal. Twenty-four hour intake, pre- and post-challenge breath H2 levels, clinical responses, and growth were measured at approximately biweekly intervals for 3 months beginning 1 month after hospital discharge. Ten lactose-tolerant infants were assigned randomly to receive one of two formulas similar in composition except for carbohydrates: lactose (Group L) (n = 6) and sucrose (Group S) (n = 4). Infants in Group L had greater intakes and growth rates during the initial 15 days of the study. No difference in weight for age z-scores was detected between groups at the end of the observation period. Infants in Group L had higher baseline and peak breath H2 levels indicating greater colonic carbohydrate fermentation than infants in Group S: however, breath H2 levels were not predictive of tolerance to lactose-containing meals. Carbohydrate absorption by infants in Group S appeared to exceed that of infants in Group L. Thus, colonic fermentation of malabsorbed carbohydrate may have prevented diarrhea and allowed acceptable rates of catch-up growth.