An Integrated Coronary Circulation Teaching Model

Objectives: We present in this paper a model of the coronary circulation. This model is integrated with a model of the systemic circulation, and contains models for oxygen supply and demand. Methods: Three compartments are created: one for the right ventricle, one for the epicardial segment of the left ventricle and one for the endo-cardial segment of the left ventricle. The model was implemented in the Java programming language and contains a visual representation of the left and right ventricles which beat in real time. Color shading is used to represent the partial pressure of oxygen in the segments. A multitude of model parameters can be changed to simulate different scenarios. Results: The output of the model was characterized under different conditions and the results verified by clinicians. Conclusions: Educational models of human physiology can be very useful for a more indepth understanding of complete physiologic systems. The models must however have enough complexity, interaction with other systems, and realism to show the concepts being taught.     

A Randomized Trial of Heart Failure Disease Management in Skilled Nursing Facilities: Design and Rationale

BackgroundHeart failure (HF) disease management can improve health outcomes for older community dwelling patients with heart failure. HF disease management has not been studied in skilled nursing facilities, a major site of transitional care for older adults.Methods and anticipated resultsThe objective of this trial is to investigate if a HF- disease management program (HF-DMP) in skilled nursing facilities (SNF)s will decrease all-cause rehospitalizations for the first 60 days post-SNF admission. The trial is a randomized cluster trial to be conducted in 12 for-profit SNF in the greater Cleveland area. The study population is inclusive of patients with HF regardless of ejection fraction but excludes those patients on dialysis and with a life expectancy of 6 months or less. The HF-DMP includes 7 elements considered standard of care for patients with HF documentation of left ventricular function, tracking of weight and symptoms, medication titration, discharge instructions, 7-day follow-up appointment post-SNF discharge, and patient education. The HF-DMP is conducted by a research nurse tasked with adhering to each element of the program and regularly audited to maintain fidelity of the program. Additional outcomes include health status, self-care management, and discharge destination.ConclusionsThe SNF-Connect Trial is the first trial of its kind to assess if a HF-DMP will improve outcomes for patients in SNFs. This trial will provide evidence on the effectiveness of HF-DMP to improve outcomes for older frail HF patients undergoing postacute rehabilitation.     

The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection

Pneumococcal proteins, alone, in combination with each other, or in combination with capsular polysaccharide-protein conjugates may be useful pneumococcal vaccine components. Four proteins with a potential for use in vaccines are PspA, pneumolysin, PsaA, and PspC. In a mouse model of carriage, PsaA and PspC were the most efficacious vaccine proteins. Of these, PsaA was the best at eliciting protection against carriage. However, a combination of PspA and pneumolysin may elicit stronger immunity to pulmonary infection and possibly sepsis than either protein alone. Recently, a phase one trial of a recombinant family 1 PspA was completed in man. PspA was observed to be safe and immunogenic. Injection of 0.1 ml of immune serum diluted to 1/400 was able to protect mice from fatal infection with S. pneumoniae. Under these conditions, pre-immune serum was not protective. The immune human serum protected mice from infections with pneumococci expressing either of the major PspA families (1 and 2) and both of the pneumococcal capsular types tested: 3 and 6.     

Drawing clocks and driving cars

OBJECTIVE: The purpose of the study was to determine whether a new method of scoring the Clock Drawing Test (CDT) is a reliable and valid method for identifying older adults with declining driving competence. DESIGN: Prospective cohort study. SETTING: An outpatient driving evaluation clinic. PARTICIPANTS: One hundred nineteen community-dwelling, active drivers with a valid driver's license, aged 60 and older referred for driving evaluation. MAIN OUTCOME MEASURES: The CDT and a driving test using a STISIM Drive simulator. RESULTS: The CDT showed a high level of accuracy in predicting driving simulation outcome (area under the receiver-operator curve, 0.90; 95% confidence interval, 0.82 to 0.95). CDT scoring scales were comparable and all correlations between CDT scores and driving performance were negative, implying that as the CDT score decreases, the number of errors increases. Interrater reliability of CDT scores was 0.95. Subjects scoring less than 5 out of 7 points on the CDT made significantly more driving errors, hazardous and in total (P<.001). CONCLUSIONS: The CDT can help establish problems with executive function and indicate the need for a formal driving evaluation. Our CDT scoring scale is a reliable, valid, and time-effective screening tool for identifying elderly drivers in need of further evaluation.     

Zanamivir: a review of clinical safety.

Preclinical and clinical studies have clearly demonstrated that zanamivir, a potent and highly selective inhibitor of the influenza A and B virus neuraminidase, has an impressive safety profile. This report describes the safety and tolerability findings from the clinical studies completed up to the 17 July 1998 involving over 6000 adult and adolescent patients from North America, Europe and the Southern Hemisphere. Serious adverse events from an ongoing Japanese clinical programme are also reported. Zanamivir was administered in various dose forms and frequencies and was found to have a comparable safety profile with placebo when given for both the treatment and prophylaxis of influenza-like illness. These findings were independent of age and underlying medical condition. 4152 patients received zanamivir and the most commonly reported adverse events were consistent with the signs and symptoms of influenza-like illness. Most of the adverse events were mild and did not result in patient withdrawal from the studies. Less than 1% of zanamivir and placebo recipients reported a serious adverse event. In addition, 490 healthy volunteers received zanamivir in clinical pharmacology studies. It was well tolerated and the incidence of adverse events was similar in zanamivir and placebo recipients. In addition, no clinically significant laboratory abnormalities were detected. Results from in vitro and in vivo animal studies suggest that zanamivir has low acute toxicity and no significant systemic toxicity or respiratory tract irritancy at plasma exposures more than 100-fold higher than those anticipated following clinical use. Neither genotoxic nor reproductive types of toxicity have been observed in toxicology studies at doses equal to 17 to 197 times the current therapeutic dose (20 mg/day). The characteristics of the molecule and the low systemic exposure indicate a very low potential for drug interactions with the inhaled route. Furthermore, repeated 600mg intravenous doses were well tolerated in healthy volunteers. The observed safety profile of zanamivir compares favourably with currently available agents with anti-influenza virus activity, such as rimantadine and amantadine, as well as GS4104, a neuraminidase inhibitor currently in phase III development. This may be attributed to the low systemic bioavailability of zanamivir, which is given by oral inhalation, direct to the primary site of viral replication. The potential advantages of this include a reduced risk of drug-drug interactions, other nontarget organ toxicities (e.g. brain) and drug clearance issues from both kidney and liver. Therefore, the safety profile of zanamivir supports its use in the management of influenza.     

Growth of Staphylococcus aureus in Diprivan and Intralipid: Implications on the Pathogenesis of Infections

Background: The incidence and severity of infections are increased when Intralipid or Diprivan are administered to patients. Intralipid promotes infection, presumably by inhibiting the reticuloendothelial system, thereby suppressing the host's constitutive immunity, whereas Diprivan supposedly promotes infection by supporting bacterial growth and increasing the inoculating dose. This study considers whether bacterial replication alone in Intralipid and Diprivan adequately explains the increased risk of infection associated with these agents or whether other factors might also be involved.

Methods: Staphylococcus aureus was cultured in 10% Intralipid or Diprivan at clinically relevant conditions or in Intralipid containing 0.005% (w/v) sodium EDTA, a current additive, to measure growth. To determine whether Intralipid affected infection, New Zealand white rabbits were injected intravenously with S. aureus with or without Intralipid. Twenty-four hours later, bacteria in lung, liver, spleen, and kidney tissues were enumerated.

Results: S. aureus failed to grow in Diprivan or Intralipid containing 0.005% EDTA. Whereas S. aureus did replicate in plain Intralipid, growth was delayed until the bacteria conditioned the media. Once initiated, growth was slow at clinically relevant temperatures. The administration of Intralipid to rabbits significantly increased the recovery of staphylococci from the kidneys, P < 0.001, relative to the other tissues 24 h after an intravenous inoculation with S. aureus, compared with rabbits receiving S. aureus with no Intralipid.     

Clinical relevance of long-latency SEPs and VEPs during coma and emergence from coma

Follow-up measurements of long-latency visual (VEP) and somatosensory (SEP) evoked potentials were performed on 30 comatose patients. Twenty-seven of the patients had severe head injury, 2 had encephalitis and 1 was in a posthypoxic state. For the SEP study a mechanical vibration stimulus was used, applied 60 times at intervals of 10 sec. The same rate was used for visual stimulation. The late EP components were classified by a signal-to-noise ratio (SNR), whereby an SNR of less than 2.6 is characteristic of a questionable or unmeasurable EP and an SNR greater than 2.6 is evidence of a clearly existing EP; the clinical state was scored using the Glasgow Coma Scale (GCS); the patient outcome was assessed 6 months after the injury using the Glasgow Outcome Scale. The highest correlation (r = 0.72) was found between the clinical state, represented by the GCS, and the SEP. A similar correlation (r = 0.66) was obtained between the GCS and the vertex VEP. The occipital VEP showed no correlation. Emergence from coma and recovery was accompanied by an increase of the SEP and an increasing spread of the VEP over the whole scalp. Most patients with a clear long-latency SEP in coma had a favourable outcome; a missing or a questionable SEP indicated a poor outcome.