Anosognosia increases caregiver burden in mild cognitive impairment.

OBJECTIVE: Our aim is to determine the clinical correlates of impaired insight in patients with mild cognitive impairment (MCI) by examining its impact on cognition, functional status, neuropsychiatric symptoms, and caregiver burden. METHODS: The study involved 75 patients with MCI and their caregivers. Patients and caregivers underwent a comprehensive evaluation including the Clinical Dementia Rating, memory tests, and the Functional Assessment Questionnaire. Behavioral symptoms were assessed by the Neuropsychiatric Inventory, caregiver burden by the Zarit Burden Inventory, and insight by comparing self-report on the AD8 dementia screening tool to informant collateral. Patients were asked about their perceptions of their memory, and answers were compared with informants' responses. Patient mood was assessed with the Hospital Anxiety Depression Scale. RESULTS: There was a significant difference in AD8 scores among patients who retained versus lacked insight. Zarit Burden Inventory scores showed a significant rise as patient insight declined; the burden appeared greater on spouse versus non-spouse caregivers. Patients with poor insight had significantly worse ratings in Clinical Dementia Rating domains of personal care and judgment, while patients who retained insight had significantly higher depression and anxiety. Insight impairment was associated with worse caregiver mood. CONCLUSIONS: Decreased patient awareness for cognitive problems was significantly associated with higher caregiver burden, independent of neuropsychiatric symptoms, functional abilities, and cognition. Personal care, judgment, and problem-solving skills could contribute to caregiver burden. Increased awareness seemed a source of patient depression and anxiety. The research highlights the need to focus on the needs of MCI caregivers and to incorporate psychosocial assessments of caregiver-patient dyads into office visits.

George Ryerson Fowler: Brooklyn's surgical pioneer: a biographical sketch based on historical documents.

The Fowler position, widely used in surgery and obstetrics for patient placement, marks a fraction of 19th-century Brooklyn surgeon George Ryerson Fowler's prodigious accomplishments. Fowler was a pioneer who refined the appendectomy, performed the first lung decortication, advocated for sterile techniques, introduced first aid in the US Army, and helped start a precursor to Annals of Surgery. His publications include the first US textbook on appendicitis--ironically, the disease that killed him.

Major differences exist in frequencies of virulence factors and multidrug resistance between community and nosocomial Escherichia coli bloodstream isolates.

Escherichia coli is a major cause of bloodstream infections and death due to sepsis. It is the most frequent Gram-negative bacterial pathogen recovered from cultures of blood from both community-acquired and nosocomial cases. We set out to determine the relationships between E. coli virulence factors (VFs), phylogenetic groups, and antibiotic resistance and whether bacteremia cases had a community, health care-associated. or nosocomial origin. Isolates from consecutive episodes of E. coli bacteremia in 303 patients presenting to a university hospital were screened for their VFs, phylogenetic group, and antibiotic resistance. The majority of VFs present in the collection were equally distributed between antibiotic-susceptible and multiple-drug-resistant (MDR) isolates, but the overall VF score was higher for isolates of community and health care-associated origin than those of nosocomial origin (P = 0.0002 and P = 0.0172, respectively); the papA, papG allele II, hlyA, and hek VFs were more prevalent in this cohort. Most isolates belonged to phylogenetic group B2, which harbored a greater proportion of antibiotic-susceptible isolates than MDR isolates (P = 0.04). The community, health care-associated, or nosocomial origin of E. coli bacteremia determines the virulence capacity of an isolate better than the phylogenetic group does. This study provides new insights into the relationships between the pathogenesis and epidemiology of E. coli bacteremia.

The application of phosphoramidate ProTide technology to the potent anti-HCV compound 4'-azidocytidine (R1479).

We report the design, synthesis and evaluation of a family of ca 50 phosphoramidate ProTides of the potent anti-HCV compound 4'-azidocytidine (R1479), with variation on the ester, amino acid and aryl moiety of the ProTide. Sub-muM inhibitors of HCV emerge. The compounds are all non-cytotoxic in the replicon assay. We herein report detailed SARs for each of the regions of the ProTide.

Application of the phosphoramidate ProTide approach to 4'-azidouridine confers sub-micromolar potency versus hepatitis C virus on an inactive nucleoside.

We report the application of our phosphoramidate ProTide technology to the ribonucleoside analogue 4'-azidouridine to generate novel antiviral agents for the inhibition of hepatitis C virus (HCV). 4'-Azidouridine did not inhibit HCV, although 4'-azidocytidine was a potent inhibitor of HCV replication under similar assay conditions. However 4'-azidouridine triphosphate was a potent inhibitor of RNA synthesis by HCV polymerase, raising the question as to whether our phosphoramidate ProTide approach could effectively deliver 4'-azidouridine monophosphate to HCV replicon cells and unleash the antiviral potential of the triphosphate. Twenty-two phosphoramidates were prepared, including variations in the aryl, ester, and amino acid regions. A number of compounds showed sub-micromolar inhibition of HCV in cell culture without detectable cytotoxicity. These results confirm that phosphoramidate ProTides can deliver monophosphates of ribonucleoside analogues and suggest a potential path to the generation of novel antiviral agents against HCV infection. The generic message is that ProTide synthesis from inactive parent nucleosides may be a warranted drug discovery strategy.

Blood cultures in emergency medical admissions: a key patient cohort.

OBJECTIVES: Blood cultures are performed in the emergency room when sepsis is suspected, and a cohort of patients is thereby identified. The present study investigated the outcomes (mortality and length of hospital stay) in this group following an emergency medical admission. METHODS: Prospective assessment of all emergency medical admissions presenting to the emergency department at St James's Hospital, Dublin, over an 11-year period (2002-2012) was carried out. Outcomes including 30-day in-hospital mortality and length of stay were explored in the context of an admission blood culture. Generalized estimating equations, logistic or zero-truncated Poisson multivariate models were used, with adjustment for confounding variables including illness severity, comorbidity, and chronic disabling disease, to assess the effect of an urgent blood culture on mortality and length of stay. RESULTS: A total of 60 864 episodes were recorded in 35 168 patients admitted over the time period assessed. Patients more likely to undergo blood cultures in the emergency department were male, younger, and had more comorbidity. Univariate and multivariate analyses showed that those who had a blood culture, irrespective of result, had increased mortality and a longer in-hospital stay. This was highest for those with a positive culture, irrespective of the organism isolated. CONCLUSION: A clinical decision to request a blood culture identified a subset of emergency admissions with markedly worse outcomes. This patient cohort warrants close monitoring in the emergency setting.

Feasibility of using a tablet computer survey for parental assessment of resident communication skills.

BACKGROUND: The Accreditation Council for Graduate Medical Education recommends using patient surveys for assessing resident competency in interpersonal and communication skills. Despite the existence of several validated patient surveys for communication assessment, no system has been developed for their sustained use in resident assessment. METHODS: We developed and pilot tested a system to collect surveys from parents of hospitalized children on the day of discharge. We used a 28-item, tablet computer-based survey that measures individual provider and team communication. The computer displays resident photographs to ensure accurate identification and offers the survey in multiple languages. We assessed parental acceptance of the system by analyzing response rate, as well as reasons for response and nonresponse. RESULTS: Of the 98 eligible parents that were approached, 62 (63%) completed the survey. Only 2 (2%) of the eligible families refused to participate, and only 5 (5%) refused participation because of the survey not being available in a language they were familiar with. CONCLUSIONS: Use of a tablet computer parent survey for resident assessment is feasible, with response rates comparable to those of mailed surveys. The low rate of parental refusal indicates our system could be used to attain sufficient numbers of survey responses to help validly measure resident communication skills.