Studies on the invasive ability of malarial merozoites (Plasmodium berghei).

Studies were performed to evaluate several methods for the artificial removal of Plasmodium berghei merozoites from infected mouse erythrocytes. These methods, many of which have been reported to yield free parasites capable of establishing a patent infection when injected into a suitable host, included NH4C1-mediated lysis, complement-mediated immune lysis, pressure filtration, and multiple-burst and continuous-flow sonication. Free parasites isolated from infected mouse blood were examined in vitro under conditions known to support merozoite invasion, and were found to be noninvasive, irrespective of the method used for their isolation. Although all methods tested achieved high degrees of lysis, none removed all intact parasitized erythrocytes. Using multiple-burst and continuous-flow sonication, the infective potential of free parasite preparations could be accounted for solely on the basis of the intact parasitized cells contaminating the free parasite preparations.     

The Mycobacterium tuberculosis ino1 gene is essential for growth and virulence

Inositol is utilized by Mycobacterium tuberculosis in the production of its major thiol and of essential cell wall lipoglycans. We have constructed a mutant lacking the gene encoding inositol-1-phosphate synthase (ino1), which catalyses the first committed step in inositol synthesis. This mutant is only viable in the presence of extremely high levels of inositol. Mutant bacteria cultured in inositol-free medium for four weeks showed a reduction in levels of mycothiol, but phosphatidylinositol mannoside, lipomannan and lipoarabinomannan levels were not altered. The ino1 mutant was attenuated in resting macrophages and in SCID mice. We used site-directed mutagenesis to alter four putative active site residues; all four alterations resulted in a loss of activity, and we demonstrated that a D310N mutation caused loss of the active site Zn2+ ion and a conformational change in the NAD+ cofactor.     

Impact of specialist follow-up in outpatients with congestive heart failure

Background

There is uncertainty about whether physician specialty influences the outcomes of outpatients with congestive heart failure after adjustment for differences in case mix. Our objective was to determine the impact of physician specialty on outcomes in outpatients with new-onset congestive heart failure.

Methods

The study was a population-based retrospective cohort study involving patients with new-onset congestive heart failure discharged from 128 acute care hospitals in Alberta between Apr. 1, 1998, and July 1, 2000. Outcomes were resource utilization (clinic visits, emergency department visits and hospital admissions) and survival at 30 days and 1 year.

Results

A total of 3136 patients were discharged from hospital with a new diagnosis of congestive heart failure (median age 76 years, 50% men). Of these, 1062 (34%) received no follow-up visits for cardiovascular care, 738 (24%) were seen by a family physician (FP) alone, 29 (1%) by a specialist (cardiologist or general internist) alone and 1307 (42%) by both a specialist and an FP. Compared with patients who received no follow-up cardiovascular care, patients who received regular cardiovascular follow-up visits with a physician had fewer visits to the emergency department (38% v. 80%), fewer were admitted to hospital (13% v. 94%), and the adjusted 1-year mortality was lower (22% v. 37%) (all p < 0.001). Compared with patients who received combined specialist and FP care, patients cared for exclusively by FPs had fewer outpatient visits (median 9 v. 17 in the first year), fewer of these patients presented to the emergency department (24% v. 45% in the first year), and fewer were readmitted for cardiovascular care (7% v. 16%) (all p < 0.001). However, the adjusted mortality at 1 year was lower among patients treated with combined care (17% v. 28%, p < 0.001) despite a higher burden of comorbidities. In a multivariate model adjusting for comorbidities (with no cardiovascular follow-up visits as the reference category), the mortality was lower among patients followed on an outpatient basis by an FP alone (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.53–0.82) or by an FP and a specialist (OR 0.34, 95% CI 0.28–0.42). In a proportional hazards model with time-dependent covariates (with adjustment for frequency of follow-up visits), the risk of all-cause mortality was reduced significantly (hazard ratio 0.98, 95% CI 0.97– 0.99) with each specialist visit compared with FP care alone.

Interpretation

Patients with congestive heart failure followed by both specialists and FPs had significantly better survival than those followed by FPs alone (or those who received no specific cardiovascular follow-up care). Methods to improve timely and appropriate access to specialists and to improve collaborative care structures are needed.Congestive heart failure (CHF) afflicts up to 2% of North American adults and, despite many advances in diagnosis and therapy, still portends a poor prognosis, with 1-year mortality of 30%–50%.^1,2,3,4,5 Although the prognosis of patients with CHF is poor even with optimal management, suboptimal diagnosis, investigation and treatment of heart failure and comorbidities (e.g., coronary artery disease) in community-dwelling patients contributes to poor survival.^6,7,8,9In previous studies hospital inpatients with CHF who were cared for by specialists received more evidence-based therapies and had better outcomes than those cared for by nonspecialists.^{8,10,11,12,13} However, none of these studies examined the care delivered after discharge from hospital. Although management in specialized multidisciplinary clinics is associated with better outcomes,¹⁴ it is unclear whether similar benefits can be expected when patients are cared for by specialist physicians operating outside the setting of a multidisciplinary clinic. Two recent studies from the United States that reported better outcomes with specialist care^7,15 were flawed, in that neither study adjusted for frequency of outpatient visits or the possibility of time-dependent bias¹⁶ (whereby some variables, including the number of visits, will change over time).To address this important public health issue, we sought to determine whether there is a relation between ambulatory care follow-up and outcomes in patients with new-onset CHF.     

A randomized trial to assess the impact of an antithrombotic decision aid in patients with nonvalvular atrial fibrillation: the DAAFI trial protocol [ISRCTN14429643]

Background

Surprisingly little information on symptoms of paroxysmal atrial fibrillation is available in scientific literature. Using questionnaires, we have analyzed the symptoms associated with arrhythmia attacks.

Methods

One hundred randomly-selected patients with idiopathic paroxysmal atrial fibrillation filled in a structured questionnaire.

Results

Psychic stress was the most common factor triggering arrhythmia (54%), followed by physical exertion (42%), tiredness (41%) coffee (25%) and infections (22%). Thirty-four patients cited alcohol, 26 in the form of red wine, 16 as white wine and 26 as spirits. Among these 34, red wine and spirits produced significantly more episodes of arrhythmia than white wine (p = 0.01 and 0.005 respectively). Symptoms during arrhythmia were palpitations while exerting (88%), reduced physical ability (87%), palpitations at rest (86%), shortage of breath during exertion (70%) and anxiety (59%). Significant differences between sexes were noted regarding swollen legs (women 21%, men 6%, p = 0.027), nausea (women 36%, men 13%, p = 0.012) and anxiety (females 79%, males 51%, p = 0.014).

Conclusion

Psychic stress was the commonest triggering factor in hospitalized patients with paroxysmal atrial fibrillation. Red wine and spirits were more proarrhythmic than white wine. Symptoms in women in connection with attacks of arrhythmia vary somewhat from those in men.     

Heart Failure Re-Admission: Measuring the Ever Shortening Gap between Repeat Heart Failure Hospitalizations

Many quality-of-care and risk prediction metrics rely on time to first rehospitalization even though heart failure (HF) patients may undergo several repeat hospitalizations. The aim of this study is to compare repeat hospitalization models. Using a population-based cohort of 40,667 patients, we examined both HF and all cause re-hospitalizations using up to five years of follow-up. Two models were examined: the gap-time model which estimates the adjusted time between hospitalizations and a multistate model which considered patients to be in one of four states; community-dwelling, in hospital for HF, in hospital for any reason, or dead. The transition probabilities and times were then modeled using patient characteristics and number of repeat hospitalizations. We found that during the five years of follow-up roughly half of the patients returned for a subsequent hospitalization for each repeat hospitalization. Additionally, we noted that the unadjusted time between hospitalizations was reduced ∼40% between each successive hospitalization. After adjustment each additional hospitalization was associated with a 28 day (95% CI: 22-35) reduction in time spent out of hospital. A similar pattern was seen when considering the four state model. A large proportion of patients had multiple repeat hospitalizations. Extending the gap between hospitalizations should be an important goal of treatment evaluation.