Heterosexually acquired CRF01_AE/B recombinant HIV type 1 found in Thailand

CRF01_AE and subtype B are circulating in Thailand and the strains have become intermixed in some high-risk groups, establishing the possibility of intersubtype recombination. The first such recombinant, mostly B with gp120 from CRF01_AE, was recently identified. Here we report a heterosexually acquired recombinant of different structure, with most of the genome from CRF01_AE but almost the entire envelope from subtype B. Surveillance by V3 serotype and genotype in multiple regions, followed by full-genome sequencing, was used to identify this strain. Pending vaccine trials in Thailand require knowledge of the presence of such strains in the population, and these recombinants provide valuable reagents for the laboratory evaluation of cross-subtype immunity. Studies are underway to determine whether either recombinant is circulating widely.     

Design and synthesis of dipeptide nitriles as reversible and potent Cathepsin S inhibitors

The specificity of the immune response relies on processing of foreign proteins and presentation of antigenic peptides at the cell surface. Inhibition of antigen presentation, and the subsequent activation of T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in a human B cell line. The first X-ray crystal structure of a reversible inhibitor cocrystallized with Cathepsin S is also reported.     

Prism adaptation can improve contralesional tactile perception in neglect

The authors show that prismatic adaptation can reduce tactile inattention in stroke patients with unilateral neglect. Four patients with visuospatial neglect and tactile extinction underwent 10-minute application of 20 degrees right-shifting prismatic lenses during pointing. This improved contralesional tactile perception in all patients, even for a task requiring no exploration or spatial motor responses. This finding suggests a potential role for prismatic adaptation in the rehabilitation of multiple sensory modalities in patients with neglect.     

Antimicrobials in acute exacerbations of chronic obstructive pulmonary disease - An analysis of the time to next exacerbation before and after the implementation of standing orders

OBJECTIVE:

To compare the mean time to next exacerbation in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) before and after the implementation of standing orders.

SETTING:

Tertiary care hospital, Halifax, Nova Scotia, Canada.

POPULATION STUDIED:

The records of 150 patients were analyzed, 76 were in the preimplementation group, 74 in the postimplementation group.

INTERVENTION:

The management and outcomes of patients admitted with an acute exacerbation of COPD before and after the implementation of standing orders were compared.

DESIGN:

A retrospective chart review.

MAIN RESULTS:

There was no difference in the mean time to next exacerbation between treatment groups (preimplementation group: 310 days, postimplementation group: 289 days, P=0.53). Antibiotics were used in 90% of the cases (preimplementation group: 87%, postimplementation group: 93%). The postimplementation group had a 20% increase in the use of first-line agents over the preimplementation group. Overall, first-line agents represented only 37% of the antibiotic courses.

CONCLUSIONS:

The implementation of standing orders encouraged the use of first-line agents but did not influence subsequent symptom resolution, length of hospital stay, or the infection-free interval in patients with acute exacerbations of COPD.Key Words: Antibiotics, Chronic obstructive pulmonary disease, ExacerbationIn Canada, chronic obstructive pulmonary disease (COPD) is a major health issue affecting over 750,000 people and the fourth ranked cause of mortality (1,2). Worldwide, it is the second most common chronic noncommunicable disease and the only leading cause of death that is increasing in prevalence (1,3,(4). The inpatient mortality associated with COPD exacerbations ranges from 3% to 4% (5). Each year, over 52,000 hospital admissions and 16,000 deaths in Canada are attributed to COPD (1,6). At our institution, Queen Elizabeth II Health Sciences Centre, COPD exacerbations are the third leading cause for admissions to the internal medicine service (preceded by pneumonia and congestive heart failure) (7).In patients with COPD, acute infectious exacerbations are the most common precipitating factor leading to hospitalization and the most common cause of death (8-10). Up to 80% of acute exacerbations of COPD are due to respiratory infections, with 50% to 70% of these caused by bacteria and only 10% to 30% caused by viruses (11-13). In September 2000, standing orders for patients with a COPD exacerbation were implemented at our institution (Figures ​(Figures11 and ​and2),2), with the rationale that prompt institution of optimal care, including controlled oxygenation and maximum bronchodilation, anti-inflammatory, and antibiotic therapy, would improve outcomes. The antibiotic choice included as first-line agents were trimethoprim/sulfamethoxazole (TMP/SMX) and doxycycline hyclate. Second-line agents were azithromycin dihydrate, amoxicillin trihydrate/clavulanate pottasium, cefuroxime sodium, and ciprofloxacin. It was our intent to assess the impact of these orders on clinical outcome (time to next exacerbation, clinical symptomatology), antimicrobial outcome (culture eradication), and resource utilization (antimicrobial use) via a quality assurance retrospective chart review.Open in a separate windowFigure 1Physician standing orders for acute exacerbations of chronic obstructive pulmonary disease (COPD) implemented at the Queen Elizabeth II Health Sciences Centre in September 2000-front page, emphasizing use of first-line antibiotics. ABG Arterial blood gas; ac Before meals; BID Twice a day; BP Blood pressure; C&S Culture and sensitivity; CAP Community-acquired pneumonia; CrCl Creatinine clearance; Fi0₂ Fraction of inspired oxygen; Ht Height; HR Heart rate; IV Intravenous; MDI Metered dose inhaler; PRN As requried; RMO Requisition made out; RR Rate of respiration; Wt WeightOpen in a separate windowFigure 2Physician standing orders for acute exacerbations of chronic obstructive pulmonary disease (COPD) implemented at the Queen Elizabeth II Health Sciences Centre in September 2000-back page, with second line antibiotic options. CrCl Creatinine clearance; DS Double Strength; HCNS Home care Nova Scotia; IBW Ideal body weight; po By mouth; Scr Serum creatinine; TMP Sulfa Trimethoprim/sulfamethoxazole     

Post-acute service use following acute myocardial infarction in the elderly

This exploratory study examined the extent to which factors beyond characteristics of the patient, such as discharging hospital attributes and State factors, contributed to variations in post-acute services use (PASU) in a cohort of elderly Medicare patients following acute myocardial infarction (AMI). Thirty-seven percent of this cohort received PAS within 30 days of discharge and home health care was the most common type of service used. Patient severity of illness at hospital discharge, for-profit ownership of the discharging hospital, and discharging hospital provision of home health services were shown to be important predictors of PASU. After adjusting for many patient and hospital characteristics, however, variation in PASU remained across States.     

The selective impairment of arithmetical procedures

The theoretical distinction between arithmetic facts and procedures was first made by Groen and Parkman (1972). This was confirmed with a neuropsychological single case described by Warrington (1982) who had impaired arithmetical facts but well preserved arithmetical procedures. Since this time there have been several patients described who showed a selective impairment of arithmetic facts. There have also been reports of cases with impaired arithmetical procedures. However, there has not yet been a case reported with the selective impairment of procedures in the context of intact arithmetic facts. This paper describes a patient, SR, with probable Alzheimer's dementia who had well preserved addition, multiplication and subtraction facts but who nevertheless had severe difficulties with a range of arithmetical procedures such as multidigit sums, decimals and fractions. The implications of this case for current theoretical models are discussed.     

Epidemiological modelling (including economic modelling) and its role in preventive drug therapy

In contrast to curative therapies, preventive therapies are administered to largely healthy individuals over long periods. The risk-benefit and cost-benefit ratios are more likely to be unfavourable, making treatment decisions difficult. Drug trials provide insufficient information for treatment decisions, as they are conducted on highly selected populations over short durations, estimate only relative benefits of treatment and offer little information on risks and costs. Epidemiological modelling is a method of combining evidence from observational epidemiology and clinical trials to assist in clinical and health policy decision-making. It can estimate absolute benefits, risks and costs of long-term preventive strategies, and thus allow their precise targeting to individuals for whom they are safest and most cost-effective. Epidemiological modelling also allows explicit information about risks and benefits of therapy to be presented to patients, facilitating informed decision-making.     

Alcohol, dementia, and Alzheimer's disease: comparison of neuropsychological profiles

Thirty-nine detoxified elderly alcoholics (mean age = 65.85) completed a comprehensive assessment designed to identify individuals meeting DSM-IV criteria for alcohol-related dementia. Ten subjects meeting criteria (mean age = 69.8; mean Mini-Mental State Examination [MMSE] = 25.1) were compared to the 29 nondemented alcoholics (mean age = 64.5; mean MMSE = 27.8), 9 patients with Alzheimer's disease (mean age = 73.4; mean MMSE = 22.3), and 15 control subjects (mean age = 70.8; mean MMSE = 28). Comparison of neuropsychological test scores revealed several statistically significant differences. Furthermore, the overall pattern of test performance between the two demented groups was different. Alzheimer's patients were more impaired on confrontation naming, recognition memory, animal fluency, and orientation. Alcohol dementia subjects were more impaired than controls on initial letter fluency, fine motor control, and free recall. However, alcohol dementia subjects did not differ from controls on tests of verbal recognition memory. This study suggests that it is possible to clinically differentiate the cognitive deficits of alcohol-related dementia from typical Alzheimer's disease. However, the results are preliminary and are based on small sample sizes so should be interpreted with caution.