Oseltamivir pharmacokinetics in morbid obesity (OPTIMO trial).

BACKGROUND: Detailed pharmacokinetics to guide oseltamivir (Tamiflu®) dosing in morbidly obese patients is lacking. METHODS: The OPTIMO trial was a single-centre, non-randomized, open-label pharmacokinetic study of single-dose and steady-state oral oseltamivir phosphate and its carboxylate metabolite in healthy, morbidly obese [body mass index (BMI) >  40)] and healthy, non-obese (BMI  <  30) subjects. RESULTS: In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir oral clearance (CL/F) [840 (range 720-1640) L/h versus 580 (470-1800) L/h] was higher, the area under the curve from time zero to infinity (AUC(0-∞)) [89 (46-104) ng·h/mL versus 132 (42-160) ng·h/mL] was lower and the volume of distribution (V/F) [2320 (900-8210) L versus 1670 (700-7290) L] was unchanged. In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir carboxylate CL/F [22 (17-40) L/h versus 23 (12-33) L/h], AUC(0-∞) [3100 (1700-4100) ng·h/mL versus 3000 (2100-5900) ng·h/mL] and V/F [200 (130-370) L versus 260 (150-430) L] were similar. Similar results for oseltamivir and oseltamivir carboxylate CL/F, AUC0₋12 and V/F values were observed in the multiple-dose study. CONCLUSIONS: With single and multiple dosing, the systemic exposure to oseltamivir is decreased but that of oseltamivir carboxylate is largely unchanged. Based on these pharmacokinetic data, an oseltamivir dose adjustment for body weight would not be needed in morbidly obese individuals.

Preventing transmission of bloodborne viruses from infected healthcare workers to patients: Summary of a new Canadian Guideline.

BACKGROUND: Although it is well documented that bloodborne viruses (BBVs), including human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) have been transmitted from patients to healthcare workers (HCWs), there has also been reported transmission from HCWs to patients during the provision of health care. With remarkable progress in infection prevention, diagnosis tools, treatment regimens and major improvements in guideline development methodology, there was a need to develop an evidence-based guideline to replace the 1998 Canadian consensus document for managing HCWs infected with BBVs. PURPOSE: This article summarizes the Canadian Guideline on the Prevention of Transmission of Bloodborne Viruses from Infected Healthcare Workers in Healthcare Settings. METHODS: A Guideline Development Task Group was established and key questions developed to inform the guideline content. Systematic reviews were conducted to evaluate the risk of HCW-to-patient transmission of HIV, HCV and HBV. Environmental scans were used to provide information on Expert Review Panels, disclosure of a HCW's serologic status and lookback investigations. Federal, provincial and territorial partners and key stakeholder organizations were consulted on the Guideline. RESULTS: The risk of HCW-to-patient BBV transmission was found to be negligible, except during exposure-prone procedures, where there is a risk that injury to the HCW may result in exposure of a patient's open tissues to the HCW's blood. Risk of ensuing transmission and the rate of transmission varied by BBV, and were lowest with HIV and highest with HBV. The Guideline provides key content, including recommendations regarding criteria to determine if a procedure is an exposure-prone procedure, management of HCWs infected with a BBV, including considerations for the HCW's fitness for practice, Expert Review Panels, HCW disclosure obligations and right to privacy and lookback investigations. CONCLUSION: This new Guideline provides a pan-Canadian approach for managing HCWs infected with a BBV, with recommendations related to preventing HCW-to-patient transmission of BBVs during the provision of care.

Preventing pneumococcal bacteremia in patients at risk. Results of a matched case-control study.

BACKGROUND: Three randomized controlled trials of the effectiveness of pneumococcal vaccine in elderly and chronically ill adults in the United States have failed to show significant protective efficacy during 44,213 person-years of follow-up. Case-control studies have greater statistical power to detect significant prevention of rare diseases such as pneumococcal bacteremia, but they also have a greater susceptibility to bias, necessitating consistent results from multiple studies. Three case-control studies at two different universities have shown prevention of systemic infection, but another study found no benefit. METHODS: Patients with pneumococcal bacteremia who were at least 2 years old and had chronic illness indicating the need for pneumococcal vaccine, or who were at least 65 years old were compared with matched control subjects for frequency of prior vaccination. Matching variables included date of admission, age, sex, race, type and duration of chronic illness serving as the major vaccine indication, number of vaccine indications and number of medical hospitalizations since licensure of the pneumococcal vaccine in 1978, and type of primary medical care. RESULTS: Pneumococcal vaccination was documented in the records of six (7%) of 85 cases and 26 (17%) of 152 control subjects, suggesting 81% efficacy in conditional logistical regression analysis (95% confidence interval, 34% to 94%, P = .008). CONCLUSIONS: Four case-control studies at three universities have now demonstrated significant protective efficacy of pneumococcal vaccine for preventing pneumococcal bacteremia. The development of antibiotic-resistant Streptococcus pneumoniae indicates an urgent need for an increased rate of vaccination among high-risk patients and for the development of more immunogenic conjugate vaccines that may enhance efficacy among elderly and immunocompromised patients as well as infants.

Intravenous catheter-associated Malassezia furfur fungemia.

Malassezia furfur, a lipophilic yeast that is the etiologic agent of tinea versicolor, has not been considered as a cause of serious illness in adults in the past. Two adults are described in whom Malassezia furfur fungemia developed while receiving total parenteral nutrition supplemented with lipids. The organism was identified in blood cultures from both patients only after isolation media were supplemented with a source of fatty acids. Because M. furfur will grow only in media supplemented with fatty acids, clinicians should alert the laboratory whenever a lipophilic organism is suspected to be present in blood cultures.

Twenty-four-hour continuous electrocardiography during exercise and free activity in 80 apparently healthy runners.

To determine the incidence of arrhythmias and conduction disturbances in trained athletes and the level of physical training at which they occur, 24-hour ambulatory electrocardiographic recordings were obtained in 80 healthy runners during both exercise and free activity. Subjects were grouped according to the number of miles per week (mpw) they had regularly run during the previous 3 months: Group I--0 to less than or equal to 5 mpw (less than or equal to 8 km); Group II--greater than 5 to less than or equal to 15 mpw (greater than 8 to less than or equal to 24 km); Group III--greater than 15 to less than or equal to 30 mpw (greater than 24 to less than or equal to 48 km); and Group IV--greater than 30 mpw (greater than 48 km). Ectopic ventricular complexes occurred in 41 of 80 subjects (50%) and ectopic supraventricular complexes occurred in 33 (41%). There were 2 episodes of paired ventricular ectopic activity and a 5-beat run of ventricular tachycardia with exercise. The study revealed no significant differences in the occurrence of arrhythmias or conduction disturbances in the different groups, although the 2 episodes of paired ventricular ectopic activity and 5-beat run of ventricular tachycardia are of concern.

Telephonically-monitored home exercise early after coronary artery bypass surgery.

To evaluate the usefulness of telephonically-monitored home exercise in patients within two weeks postcoronary bypass surgery, we randomly enrolled 46 male patients in a 12-week home program of either short walks or bicycle ergometry. Home exercise was done five times weekly and monitored both before and immediately after three times weekly. New arrhythmias or conduction disturbances were detected in 18 of 23 (78 percent) of the bicycle group and in 20 of 23 (87 percent) of the short walk patients. New symptoms developed in three patients, two from the short walk group and one from the bicycle group. Two bikers and one walker developed elevated blood pressure; all were referred to physicians and were successfully managed. Electrocardiographic abnormalities led directly to diagnostic and therapeutic intervention in nine of the 46 patients-four bikers and five walkers. There were no complications such as ventricular tachycardia or ventricular fibrillation. Technically clear telephone rhythm strips were obtained from patients calling both locally and long distance.

Cohort study of human immunodeficiency virus (HIV) antibody testing among patients receiving long-term dialysis at a university hospital.

In a longitudinal study to determine the seroprevalence of antibody to the human immunodeficiency virus (HIV) and the natural history of a positive enzyme immunoassay (EIA) result we followed a cohort of 98 patients receiving long-term dialysis. Eight patients (8.2%) in the cohort had a positive EIA and a negative Western blot test result. The EIA-positive results of all patients seroconverted to negative during follow-up. No illness suggestive of HIV infection developed in any of the patients. Significantly associated with a false positive EIA were prior renal transplantation, transfusions during the months just before the positive EIA result, and a greater number of lifetime transfusions before the positive test result. We confirm that routine HIV screening of patients receiving long-term dialysis is associated with a high rate of false positive EIA results and conclude that such testing is unnecessary in the absence of established risk factors for HIV infection.

In vitro activity of novobiocin and rifampin alone and in combination against oxacillin-resistant Staphylococcus aureus.

Rifampin and novobiocin both have excellent activity against oxacillin-resistant Staphylococcus aureus, but their single use may be associated with the development of resistance. To help predict their clinical value in our institution, 60 recent clinical isolates of oxacillin-resistant S. aureus were studied for in vitro susceptibility to the two agents. Ten isolates with increased MICs to both agents or to rifampin alone were also studied by modified checkerboard and kill-curve methods. Indifference was consistently demonstrated by the checkerboard method and generally found in kill-curve studies. Prevention of development of resistance was demonstrated with the antimicrobial combinations for some isolates. Isolates with increased MICs for the two agents fell into two distinctive groups, with prevention of the development of rifampin resistance occurring in one group but not in the other, suggesting that different strains of oxacillin-resistant S. aureus may have different capacities for development of rifampin resistance.

An outbreak of Candida parapsilosis prosthetic valve endocarditis following cardiac surgery.

Five of 34 (15%) patients who received prosthetic cardiac valves between May and August 1982 at the Victoria General Hospital in Halifax, Nova Scotia, developed Candida parapsilosis prosthetic valve endocarditis. The clustering of these cases pointed to a common source outbreak. In a retrospective cohort study, no significant differences were found between infected and uninfected patients in terms of pre-, intra-, and postoperative risk factors. Environmental investigations suggested intraoperative contamination through the cardiac bypass equipment as the source of infection but a causal relationship could not be established. The outcome for the cases was uniformly fatal, emphasizing the need for prevention of such serious nosocomial infections.

Mycobacterium avium-intracellulare endocarditis causing rupture: replacement and repair with aortic homograft.

Aortic valve endocarditis with extension to the tricuspid annulus and ventricular septum in an intravenous drug abuser - with Mycobacterium avium-intracellulare identified as the offending organism - forms the basis of this report. The aortic root and ventricular septal defect were successfully repaired using an aortic cryopreserved homograft. This case is of particular interest because M avium-intracellulare has not been recognized as a cause of endocarditis. The incidence of atypical organisms as a cause of endocarditis may increase in the future because of the rise of drug abuse and the acquired immune deficiency syndrome in North America.

Exercise testing for patients after myocardial infarction and coronary bypass surgery: emphasis on predischarge phase.

Data from the preceding low-level exercise test studies have been compiled and are presented in Table II. The table is arranged according to groups of prognostic indicators for future coronary events or indicators for those patients with multivessel coronary artery disease. In summary, current studies demonstrate safety and predictive value in predischarge low-level exercise testing in patients after myocardial infarction. If the test reveals a positive S-T segment change or angina or both, the predictive value for future cardiac events is significant. In addition, a limited duration on the exercise test, a flat or falling blood pressure response, and the presence or absence of premature ventricular depolarizations add to this predictive value. A more sophisticated technique that employs radionuclide ventriculography may add to the sensitivity and specificity of these various tests but should be used selectively. Post-myocardial infarction patients who perform low-level exercise testing prior to discharge and demonstrate no exercise-induced abnormality from baseline may also harbor multivessel coronary disease, and this group of patients needs to be carefully followed. Testing at 3 weeks and 6 weeks after infarction may be beneficial in revealing additional clinical data. Less data are currently available on predischarge low-level exercise testing in patients with myocardial revascularization. However, these limited data support both feasibility and safety of low-level exercise testing in myocardial revascularization patients before discharge. Prognostic data with regard to low-level exercise testing for this group of patients should be forthcoming. Data from low-level exercise testing need to be incorporated during the in-hospital phase to eliminate unnecessary testing as the patient proceeds home and/or to medically supervised exercise programs. Proper therapeutic modalities based on these data should be included. In accord with this, it is imperative that the cardiac rehabilitation team or exercise testing laboratory correspond directly with the private physician regarding all clinical data and recommendations for discharge activity. Follow-up exercise testing for patients after myocardial infarction and coronary bypass surgery utilizes end points similar to those of predischarge low-level testing and therefore will not be discussed in detail. In general the patient should be able to achieve a higher heart rate or MET level in follow-up testing.(ABSTRACT TRUNCATED AT 400 WORDS)

Eight steps to inpatient cardiac rehabilitation: the team effort-methodology and preliminary results.

The effects of a team approach in cardiac rehabilitation were investigated in 89 postmyocardial infarction patients. Team members followed an eight-step protocol in caring for the patients during the hospitalization phase. Risk factor modification data were collected at a mean time of 13.5 months after hospitalization. The investigated parameters included work, dietary and exercise habits, body weight, high blood pressure and cigarette smoking. Fifty-six per cent (42 of 75) of the survival group were actively working, 66 per cent (49 of 75) were adhering to a fat-controlled diet, 77 per cent (58 of 75) continued an exercise regime, 70 per cent (40 of 57) lost excess body weight, 91 per cent (21 of 23) had their blood pressure controlled and 60 per cent (27 of 45) stopped smoking cigarettes. It is concluded that an in-hospital team approach in rehabilitation of postmyocardial infarction patients is beneficial in long-term risk factor modification.

Sexual activity in exercising patients after myocardial infarction and revascularization.

In order to evaluate the effects of exercise training on coital habits after myocardial infarction and revascularization, questionnaires were mailed to 130 patients enrolled in a gymnasium exercise program. Of 87 (67%) responding, 68 had experienced myocardial infarction and 19 had undergone myocardial revascularization. The postinfarction group significantly decreased their frequency of coitus after infarction by 28%; the revascularization group, however, decreased activity by only 10%. The myocardial infarction group waited 9.4 weeks after infarction to resume sexual intercourse, while the revascularization group waited a mean of only 5.7 weeks. These data suggest that physically trained post-myocardial infarction patients decrease frequency of coitus significantly more than physically trained patients with myocardial revascularization. The overall decrease, however, is notably less than that reported in nontrained post-myocardial infarction patients and suggests a "bedroom benefit" of medically supervised exercise in selected patients after infarction or revascularization.

Seroprevalence of HIV infection in childbearing women in Nova Scotia.

OBJECTIVE: To determine the prevalence of HIV-1 infection in childbearing women in Nova Scotia. DESIGN: An anonymous, unlinked seroprevalence study using "leftover" cord bloods. The study was done in 2 stages: I-Halifax Co. women delivering between February 1, 1992 and December 31, 1993; II-non-Halifax Co. women delivering between November 15, 1993 and December 15, 1994. RESULTS: Of 9,115 deliveries during stage I and 5,515 during stage II, specimens were tested from 8,864 (97.2%) and 5,219 (95%) respectively. Halifax Co. women were older, more often married and more often reported a STD than the non-Halifax Co. participants with 20% under age 20 reporting a history of STD. There was one EIA and WB positive result among Halifax Co. women (seroprevalence 1/10,000; 95% CI 0.03-6.29) and one EIA positive, WB indeterminant result among non-Halifax Co. women (seroprevalence 0/10,000; 95% CI 0-5.7). CONCLUSION: There is a low prevalence of HIV infection among Nova Scotia childbearing women. However, a substantial number, especially those < age 20, reported a history of STD.

Subcutaneous dirofilariasis in Nova Scotia.

A case of dirofilariasis in a 78-year-old woman from Nova Scotia is described along with the histological findings and the basis of identification of the parasite. The patient developed a subcutaneous nodule, which was excised. Dirofilaria ursi and ursi-like nematodes are a rare cause of subcutaneous nodules. This is the first time dirofilariasis has been diagnosed in an adult in Atlantic Canada.

Lyme disease: clinical diagnosis and treatment.

BACKGROUND: Lyme disease is an emerging zoonotic infection in Canada. As the Ixodes tick expands its range, more Canadians will be exposed to Borrelia burgdorferi, the bacterium that causes Lyme disease. OBJECTIVE: To review the clinical diagnosis and treatment of Lyme disease for front-line clinicians. METHODS: A literature search using PubMed and restricted to articles published in English between 1977 and 2014. RESULTS: Individuals in Lyme-endemic areas are at greatest risk, but not all tick bites transmit Lyme disease. The diagnosis is predominantly clinical. Patients with Lyme disease may present with early disease that is characterized by a "bull's eye rash", fever and myalgias or with early disseminated disease that can manifest with arthralgias, cardiac conduction abnormalities or neurologic symptoms. Late Lyme disease in North America typically manifests with oligoarticular arthritis but can present with a subacute encephalopathy. Antibiotic treatment is effective against Lyme disease and works best when given early in the infection. Prophylaxis with doxycyline may be indicated in certain circumstances. While a minority of patients may have persistent symptoms, evidence does not demonstrate that prolonged courses of antibiotics improve outcome. CONCLUSION: Clinicians need to be aware of the signs and symptoms of Lyme disease. Knowing the regions where Borrelia infection is endemic in North America is important for recognizing patients at risk and informing the need for treatment.