健康儿童作为药物动力学研究受试者的伦理学辩论

儿童是否允许作为健康受试参加药物动力学研究，目前存在较大分歧。本列出截然不同的两种观点，旨在防范这类研究在健康儿童的不适当实施，以保证其符合国际共认的伦理学要求。     

Epidemiology of adverse drug reactions in intensive care units. A multicentre prospective survey

Summary Clinically relevant events possibly attributable to drug exposure have been monitored prospectively over a period of six months in 27 general intensive care units. Fifty-four events attributed to drugs were reported in 51 patients during their stay in hospital, corresponding to an overall incidence of 1.35%. The behaviour of the physicians following attribution of the events to a prescribed drug is analyzed and discussed in detail with respect to its relationship to the quality and severity of the reaction, and the classes of drugs. Twenty-four of the 4537 monitored admissions during the six months were due to life-threatening emergencies linked to the administration of drugs (14) and radio-contrast media (10) (overall incidence 0.5%). While the clinical burden attributable to adverse drug reactions in Intensive Care Units appears to be relatively small, the analysis shows that there is ample room for a greater reduction in their incidence. Coordinators: Drs M. L. Farina and G. Tognoni, Istituto di Ricerche Farmacologiche Mario Negri, Milan; Dr F. Procaccio, Neurosurgical ICU, Ospedale Ca' Granda, Niguarda, Milan.Investigators: Drs G. Barusco, Rovigo; F. Bassi, Milan; L. Bianchetti, Torino; E. Carchietti, Udine; G. Chilloni, Reggio Emilia; G. Costantini, Savigliano (CN); P. Ferrero, Aosta; E. Geat, Trento; F. Gorgerino, Torino; A. Lusini, Empoli (FI); G. Mantovani, Ferrara; S. Marchi, Bologna; P. Marcovigi, Forli; G. Marraro, Merate (CO); F. Merlo, Vicenza; E. Pagni, Bagno a Ripoli (FI); R. Pellegrino, Cuneo; C. Peruselli, Milan; A. Piovesano, Pordenone; R. Rinaldo, Cremona; R. Ruggerini, Piacenza; S. Sammartino, Torino; A. Sartore, Cittadella (PD); A. Scaglioli, Carpi (MO); G. Scopa, Terni; G. Zeffiro, Treviso; P. Zuccoli, Parma     

Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand

BACKGROUND: In Thailand, phase 1/2 trials of monovalent subtype B and bivalent subtype B/E (CRF01_AE) recombinant glycoprotein 120 human immunodeficiency virus type 1 (HIV-1) vaccines were successfully conducted from 1995 to 1998, prompting the first HIV-1 vaccine efficacy trial in Asia. METHODS: This randomized, double-blind, placebo-controlled efficacy trial of AIDSVAX B/E (VaxGen), which included 36-months of follow-up, was conducted among injection drug users (IDUs) in Bangkok, Thailand. The primary end point was HIV-1 infection; secondary end points included plasma HIV-1 load, CD4 cell count, onset of acquired immunodeficiency syndrome-defining conditions, and initiation of antiretroviral therapy. RESULTS: A total of 2546 IDUs were enrolled between March 1999 and August 2000; the median age was 26 years, and 93.4% were men. The overall HIV-1 incidence was 3.4 infections/100 person-years (95% confidence interval [CI], 3.0-3.9 infections/100 person-years), and the cumulative incidence was 8.4%. There were no differences between the vaccine and placebo arms. HIV-1 subtype E (83 vaccine and 81 placebo recipients) accounted for 77% of infections. Vaccine efficacy was estimated at 0.1% (95% CI, -30.8% to 23.8%; P=.99, log-rank test). No statistically significant effects of the vaccine on secondary end points were observed. CONCLUSION: Despite the successful completion of this efficacy trial, the vaccine did not prevent HIV-1 infection or delay HIV-1 disease progression.     

Comparison of the performance of selenite cystine and mannitol selenite enrichment broths in the isolation of Salmonella spp. from faeces

Over a four-month period, 4,658 routine faecal samples were examined in four laboratories and the isolation rates of Salmonella spp. from mannitol selenite (MS) and selenite cystine (SC) broths plated to xylose lysine desoxycholate agar (XLD) compared. The isolation rate by MS was 1.55% and by SC was 1.48%, a small difference which is not statistically significant. Significantly fewer colonies were selected for supplementary testing from SC than MS (p = 0.029), thus reducing confirmatory work. In laboratories where SC is already used for food and environmental work, an opportunity exists to limit stocked salmonella enrichment broths to SC alone.     

Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial

Context  Cardiac resynchronization therapy (CRT) through biventricular pacing is an effective treatment for heart failure (HF) with a wide QRS; however, the outcomes of patients requiring CRT and implantable cardioverter defibrillator (ICD) therapy are unknown. Objective  To examine the efficacy and safety of combined CRT and ICD therapy in patients with New York Heart Association (NYHA) class III or IV congestive HF despite appropriate medical management. Design, Setting, and Participants  Randomized, double-blind, parallel-controlled trial conducted from October 1, 1999, to August 31, 2001, of 369 patients with left ventricular ejection fraction of 35% or less, QRS duration of 130 ms, at high risk of life-threatening ventricular arrhythmias, and in NYHA class III (n = 328) or IV (n = 41) despite optimized medical treatment. Interventions  Of 369 randomized patients who received devices with combined CRT and ICD capabilities, 182 were controls (ICD activated, CRT off) and 187 were in the CRT group (ICD activated, CRT on). Main Outcome Measures  The primary double-blind study end points were changes between baseline and 6 months in quality of life, functional class, and distance covered during a 6-minute walk. Additional outcome measures included changes in exercise capacity, plasma neurohormones, left ventricular function, and overall HF status. Survival, incidence of ventricular arrhythmias, and rates of hospitalization were also compared. Results  At 6 months, patients assigned to CRT had a greater improvement in median (95% confidence interval) quality of life score (–17.5 [–21 to –14] vs –11.0 [–16 to –7], P = .02) and functional class (–1 [–1 to –1] vs 0 [–1 to 0], P = .007) than controls but were no different in the change in distance walked in 6 minutes (55 m [44-79] vs 53 m [43-75], P = .36). Peak oxygen consumption increased by 1.1 mL/kg per minute (0.7-1.6) in the CRT group vs 0.1 mL/kg per minute (–0.1 to 0.8) in controls (P = .04), although treadmill exercise duration increased by 56 seconds (30-79) in the CRT group and decreased by 11 seconds (–55 to 12) in controls (P<.001). No significant differences were observed in changes in left ventricular size or function, overall HF status, survival, and rates of hospitalization. No proarrhythmia was observed and arrhythmia termination capabilities were not impaired. Conclusions  Cardiac resynchronization improved quality of life, functional status, and exercise capacity in patients with moderate to severe HF, a wide QRS interval, and life-threatening arrhythmias. These improvements occurred in the context of underlying appropriate medical management without proarrhythmia or compromised ICD function.      

The Seventh Report of the Joint National Committee on Prevention,Detection, Evaluation,and Treatment of High Blood Pressure: the JNC 7 report

"The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.     

Methodological issues in evaluating workplace interventions to reduce work-related musculoskeletal disorders through mechanical exposure reduction

Researchers of work-related musculoskeletal disorders are increasingly asked about the evidentiary base for mechanical exposure reductions. Mixed messages can arise from the different disciplinary cultures of evidence, and these mixed messages make different sets of findings incommensurate. Interventions also operate at different levels within workplaces and result in different intensities of mechanical exposure reduction. Heterogeneity in reporting intervention processes and in measuring relevant outcomes makes the synthesis of research reports difficult. As a means of synthesizing the current understanding of measures, this paper describes a set of intervention and observation nodes for which relevant workplace indicators prior to, during, and after mechanical exposure reduction can provide useful information. On the basis of this path of impacts from exposure reduction, an approach to the evaluation of multilevel ergonomic interventions is described that can assist fellow researchers in producing evidence relevant to the challenges faced by workplace parties and policy makers.