Cost effectiveness of ciprofloxacin plus metronidazole versus imipenem-cilastatin in the treatment of intra-abdominal infections.

OBJECTIVE: To compare the cost effectiveness of sequential intravenous (i.v.) to oral ciprofloxacin plus metronidazole (CIP/MTZ i.v./PO) with that of i.v. ciprofloxacin plus i.v. metronidazole (CIP/MTZ i.v.) and i.v. imipenem-cilastatin (IMI i.v.) in patients with intra-abdominal infections. DESIGN AND PARTICIPANTS: Patients enrolled in a double-blind randomised clinical trial were eligible for inclusion into this cost-effectiveness analysis. Decision analysis was used to characterise the economic outcomes between groups and provide a structure upon which to base the sensitivity analyses. 1996 cost values were used throughout. SETTING: The economic perspective of the analysis was that of a hospital provider. MAIN OUTCOME MEASURES AND RESULTS: Among 446 economically evaluable patients, 176 could be switched from i.v. to oral administration. The 51 patients randomised to CIP/MTZ i.v./PO who received active oral therapy had a success rate of 98%, mean duration of therapy of 9.1 days and mean cost of $US7678. There were 125 patients randomized to either CIP/MTZ i.v. or IMI i.v. who received oral placebo while continuing on active i.v. antibacterials; their success rate was 94%, mean duration of therapy was 10.1 days and mean cost was $US8774 (p = 0.029 vs CIP/MTZ i.v./PO). Of the 270 patients who were unable to receive oral administration, 97 received IMI i.v. and had a success rate of 75%, mean duration of therapy of 13.8 days and a mean cost of $US12,418, and 173 received CIP/MTZ i.v. and had a success rate of 77%, mean duration of therapy of 13.4 days and mean cost of $US12,219 (p = 0.26 vs IMI i.v.). CONCLUSIONS: In patients able to receive oral therapy, sequential i.v. to oral treatment with ciprofloxacin plus metronidazole was cost effective compared with full i.v. courses of ciprofloxacin plus metronidazole or imipenem-cilastatin. In patients unable to receive oral therapy, no difference in mean cost was found between i.v. imipenem-cilastatin or i.v. ciprofloxacin plus i.v. metronidazole.

Informed consent: how much information is enough?

BACKGROUND: Recent judicial decisions involving informed consent have led to some medical practitioners altering the way they obtain consent. The aim of this study was to determine the degree to which patients understood the risks associated with a surgical procedure after giving routine consent and whether providing additional detailed verbal and/or written information improved their understanding. It was further determined whether the provision of more extensive information altered patients' anxiety levels. METHODS: Patients undergoing femoral popliteal bypass or carotid surgery were randomized to obtain either routine consent only or routine consent with verbal or written or verbal and written consent. Patients undertook a pre-operative risk and complication questionnaire, a pre- and postoperative anxiety and depression evaluation and a follow-up questionnaire 6 weeks after discharge. RESULTS: Thirty-two patients were included in the trial. The comprehension questionnaire resulted in a correct percentage response of 48% for the routine information only, 59% with added verbal information, 59% with added written information and 55% with added written and verbal information. Twenty-five per cent of patients stated that they had a poor understanding of the risks and complications of the procedure. CONCLUSIONS: Additional written or verbal information did not improve a patient's understanding of risks and complications of the procedure. It also did not improve patients' perceived understanding of the operation or its complications. Patients' anxiety levels were unaltered by the increase in the information they were given. The information provided to patients should be simple, easy to understand and list any possible major complications to enable the patient to determine whether to undergo or decline a procedure.

Insulin resistance in adipocytes after downregulation of Gi subtypes.

To determine whether downregulation of Gi proteins is associated with insulin resistance, we incubated isolated adipocytes with N6-(2-phenylisopropyl)adenosine (PIA; an A1-adenosine receptor agonist; 300 nM), prostaglandin E1 (PGE1; 3 microM), or nicotinic acid (1 mM) for 4 days in primary culture. The cells were washed, and the rate of glucose transport (2-deoxy-[3H]glucose uptake) was measured after incubation with various concentrations of insulin for 45 min. Both PIA and PGE1 (which downregulate Gi) decreased the maximal responsiveness of the cells to insulin by approximately 30% and caused a rightward shift in the dose-response curve. By contrast, nicotinic acid (which does not downregulate Gi) did not alter the insulin sensitivity of the cells. Prolonged treatment of adipocytes with either PIA or PGE1 (but not nicotinic acid) rendered the cells completely resistant to the antilipolytic effect of insulin. The ability of insulin to stimulate autophosphorylation of the beta-subunit of the insulin receptor was decreased by approximately 30% in PIA-treated cells, and the dose-response curve was shifted to the right. Similarly, the ability of the receptor to phosphorylate poly(Glu4-Tyr1) was decreased by approximately 35%. This decrease in tyrosine kinase activity of the receptor may account for the decrease in insulin sensitivity of glucose transport but cannot account for the complete loss of antilipolysis. The findings suggest both a direct and indirect involvement of Gi proteins in insulin action.

Powerful politics at the XI International Conference on AIDS.

The XI International Conference on AIDS, held in Vancouver from July 7 to 12, 1996, produced encouraging signs of significant progress in basic, clinical and preventive science in the field of HIV infection and AIDS. The largest conference ever held on the global AIDS epidemic, it featured political and media highlights that served to focus the attention of participants and the public on controversial issues. Such political activity has become an expected part of international AIDS conferences and serves to remind participants and observers of the urgent need to continue the fight against AIDS.

Qualitative evaluation of the Canadian Medical Association's counselling guidelines for HIV serologic testing.

OBJECTIVE: To evaluate the face and content validity of the CMA's counselling guidelines for HIV serologic testing in order to prepare a revised edition. DESIGN: Qualitative evaluation by structured focus groups in September and October 1994 to assess the relevance, clarity and practicality of the guidelines, followed by content analysis of the discussions. SETTING: Vancouver, Winnipeg, Toronto, Montreal, Quebec City and St. John's. PARTICIPANTS: Primary care physicians randomly selected from the CMA database and nonrandomly selected from the Canadian Medical Directory who had limited experience with HIV testing and counselling and who provided an appropriate mix of characteristics in terms of practice type (solo and group), setting (urban and rural), age and sex. A total of 1247 physicians were approached for the study; a convenience sample of 68 were recruited, of whom 56 participated. The average size of each focus group was eight physicians. OUTCOME MEASURES: Clinical experience and information sources with respect to HIV testing, reactions to the counselling guidelines, and suggestions for revisions and improvements to the guidelines. RESULTS: Most (96% [54/56] of the participants had ordered HIV serologic testing for patients in the 6 months preceding the focus groups, and about half of them (52% [28/54]) had at least one patient with a positive test result. Many (59% [33/56]) of the participants had a copy of the guidelines at the time of recruitment; 19 (58%) of them had used the guidelines in the months before the focus groups. The parts of the guidelines most often read were the checklists and inset boxes. Recommendations for revisions in content were for more information on legal and ethical issues, information on new issues (e.g., rapid testing) and guidelines on how best to tell a patient about a positive test result; recommendations for revisions in format included more tables, algorithms, bulleted points and white space, less text, larger type and plainer language. CONCLUSIONS: The focus groups provided detailed, credible and consistent information about the face and content validity of the HIV counselling guidelines. They are a useful qualitative method for evaluating the relevance, clarity and practicality of clinical practice guidelines at the inception or revision stage.

Yes, minister, Canadians need strong tobacco-control legislation now!

At a meeting with federal health minister Diane Marleau on Nov. 16, 1995, the CMA and other health organizations were told that the minister plans to propose comprehensive measures to limit the manufacture, sale and marketing of tobacco products. On Dec. 11, 1995, the minister announced a "Blueprint on Tobacco Control," which outlined the scope of her plan to introduce tobacco legislation in the spring. On the basis of adamant support for tobacco control from all levels of the organization, the CMA urges the minister to move quickly. It also advocates regulating tobacco as a hazardous product in the meantime. Physicians can take a wide variety of actions to intervene with patients and add their voice to antitobacco lobbying efforts in 1996.

Core and comprehensive health care services: 2. Quality-of-care issues.

Health care services are being evaluated and redefined. Terms such as "medically necessary" and "comprehensive" are being supplanted by "core", "basic" and "optional." Quality-of-care concepts and analysis can assist decision making about which services should be insured, core services. A service is more likely to remain or become insured, and core to the system if it satisfies the key dimensions of high quality: effectiveness, appropriateness, efficiency, patient acceptance and safety. Quality of care, combined with ethical and economic considerations, provides an analytic framework for deciding whether services should be insured.

Tumor necrosis factor increases the rate of lipolysis in primary cultures of adipocytes without altering levels of hormone-sensitive lipase.

To investigate the effects of cytokines on adipocyte lipolysis, a macrophage cell line (RAW 264.7) was treated with Escherichia coli lipopolysaccharide (1 microgram/ml) for 18 h to induce cytokine release. Conditioned medium (5%, vol/vol) from these cells was added to rat epididymal adipocytes isolated and incubated under sterile conditions. After incubation, the adipocytes were washed, and the rate of lipolysis (glycerol release) was determined after a further 1-h incubation. The conditioned medium caused an approximately 2.7-fold increase in lipolysis, detectable after 6-12 h, maximal by 24 h, and reversible by 48 h after washing the cells. The effect of conditioned medium was reversed by a neutralizing antibody to mouse tumor necrosis factor-alpha (TNF alpha), and the direct addition of recombinant human TNF alpha (0.1-50 ng/ml) reproduced the effect, with a half-maximally effective concentration of approximately 3 ng/ml. The effect of TNF on the expression of hormone-sensitive lipase (HSL; the rate-limiting enzyme for lipolysis) was investigated by Western immunoblots using an antibody raised to a bacterially expressed 96-amino acid portion of the HSL enzyme. TNF treatment did not alter the concentration of immunoreactive HSL. From these data we conclude that 1) macrophages release a cytokine(s) in response to lipopolysaccharide that stimulates lipolysis in freshly isolated adipocytes; 2) TNF alpha can account for most, or perhaps all, of this effect; 3) TNF alpha increases the rate of lipolysis by a mechanism that does not involve increased expression of HSL. Based on the time-dependent aspects of TNF alpha stimulation and the lack of change in immunoreactive HSL, the findings suggest a TNF-induced posttranslational modification of the enzyme.

Monocyte chemotactic and activating factor is a potent histamine-releasing factor for basophils.

Monocyte chemotactic and activating factor (MCAF) is a recently cloned cytokine that causes chemotaxis of basophils. In our pursuit of cytokines affecting basophil function, we studied the effect of MCAF on histamine secretion from basophils. Leukocytes from 20 donors, 10 allergic and 10 normal subjects, were studied. MCAF caused dose-dependent release of histamine at concentrations of 10(-8) and 10(-7) M, and the mean release was 31.25 +/- 2.9% at the highest concentration. In the same experiments the mean histamine release by anti-IgE and histamine releasing factor (HRF) was 27.05 +/- 4% and 32.70 +/- 2.7%, respectively. All 20 subjects responded to MCAF with significant histamine release. Allergic subjects released significantly more histamine than normals in response to anti-IgE (P less than 0.01) but not to MCAF (P = 0.2) and HRF (P = 0.1). The histamine release was significantly correlated between MCAF and HRF (P less than 0.01), but not between MCAF and anti-IgE (P greater than 0.05). The histamine release by MCAF was complete within the first 3 min. MCAF-induced degranulation was a calcium-dependent process. Leukocytes depleted of monocytes responded equally well to MCAF. Using an anti-MCAF affinity column we determined that greater than 50% of HRF activity of crude PBMC supernatant could be attributed to MCAF. Thus, we established that MCAF is a potent secretagogue for basophils.

Smoking cessation in family practice: the effects of advice and nicotine chewing gum prescription.

The efficacy of physician anti-smoking intervention with 289 patients in a family practice setting was assessed. The design included two treatment conditions, physician advice and physician advice plus the offer of nicotine chewing gum (NCG) prescription. A no-advice group permitted assessment of the effects of repeated testing. The NCG group had higher rates of abstinence at all follow-up points, but the difference approached statistical significance at 3 months only (p less than .10). Comparison of those who actually used NCG to all other groups revealed significantly more users were abstinent at 1- and 3-month follow-up. A similar pattern occurred for proportion attempting cessation and smoking reduction. A dose-response relationship of gum use to outcome was identified. Long-term users (greater than 20 days) had 86% abstinence at 3 months versus 18% for short-term users. Thus, NCG does appear to have a role in family practice for promoting short-term cessation.

Effects of oral propranolol and exercise protocol on indices of aerobic function in normal man.

The exercise responses to two different progressive, upright cycle ergometer tests were studied in nine healthy, young subjects either with no drug (ND) or following 48 h or oral propranolol (P) (40 mg q.i.d.). The ergometer tests increased work rate by 30 W either every 30 s or every 4 min. Propranolol caused a significant (p less than 0.05) reduction in peak oxygen uptake (VO2) during both the 30-s and 4-min tests (30-s ND, 3949 +/- 718 mL X min-1 (means +/- SD); 30-s P, 3408 +/- 778 mL X min-1; 4-min ND, 4058 +/- 409 mL X min-1; 4-min P, 3725 +/- 573 mL X min-1). There was no difference between 30-s ND and 4-min ND for peak VO2. The ventilatory anaerobic threshold was not significantly different between any test (30-s ND, 2337 +/- 434 mL O2 X min-1; 30-s P, 2174 +/- 406 mL O2 X min-1; ND, 2433 +/- 685 mL O2 X min-1; 4-min P, 2296 +/- 604 mL O2 X min-1). The VO2 at which blood lactate had increased by 0.5 mM above resting levels was significantly lower than the ventilatory anaerobic threshold for the 4-min ND (1917 +/- 489) and the 4-min P (1978 +/- 412) tests, but was not different for the 30-s ND and 30-s P tests. At exhaustion in the progressive tests, the blood PCO2 was higher (p less than 0.05) in both 30-s tests than 4-min tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Practice opportunities for family medicine graduates.

This paper documents the career choices of a graduating class of family medicine residents at Queen's University. In the first post-graduation year, residents were evenly divided between those who undertook a third year of training and those who began practice. For those who began practice, a profile of their first year of experience demonstrates the excellent variety of opportunities awaiting family medicine graduates.