Hyperbaric oxygen for carbon monoxide poisoning : a systematic review and critical analysis of the evidence

Poisoning with carbon monoxide (CO) is an important cause of unintentional and intentional injury worldwide. Hyperbaric oxygen (HBO) enhances CO elimination and has been postulated to reduce the incidence of neurological sequelae. These observations have led some clinicians to use HBO for selected patients with CO poisoning, although there is considerable variability in clinical practice. This article assesses the effectiveness of HBO compared with normobaric oxygen (NBO) for the prevention of neurological sequelae in patients with acute CO poisoning. The following databases were searched: MEDLINE (1966 to present), EMBASE (1980 to present), and the Controlled Trials Register of the Cochrane Collaboration, supplemented by a manual review of bibliographies of identified articles and discussion with recognised content experts. All randomised controlled trials involving people acutely poisoned with CO, regardless of severity, were examined. The primary analysis included all trials from which data could be extracted. Sensitivity analysis examined trials with better validity (defined using the validated instrument of Jadad) and those enrolling more severely poisoned patients. Two reviewers independently extracted from each trial, including information on the number of randomised patients, types of participants, the dose and duration of the intervention, and the prevalence of neurological sequelae at follow-up. A pooled odds ratio (OR) for the presence of neurological symptoms at 1-month follow-up was calculated using a random effects model. Bayesian models were also investigated to illustrate the degree of certainty about clinical effectiveness. Eight randomised controlled trials were identified. Two had no evaluable data and were excluded. The remaining trials were of varying quality and two have been published only as abstracts. The severity of CO poisoning varied among trials. At 1-month follow-up after treatment, sequelae possibly related to CO poisoning were present in 242 of 761 patients (36.1%) treated with NBO, compared with 259 of 718 patients (31.8%) treated with HBO. Restricting the analysis to the trials with the highest quality scores or those that enrolled all patients regardless of severity did not change the lack of statistical significance in the outcome of the pooled analysis. We found empiric evidence of multiple biases that operated to inflate the benefit of HBO in two positive trials. In contrast, the interpretation of negative trials was hampered by low rates of follow-up, unusual interventions for control patients and inclusion of less severely poisoned patients. Collectively, these limitations may have led negative trials to overlook a real and substantial benefit of HBO (type II error). There is conflicting evidence regarding the efficacy of HBO treatment for patients with CO poisoning. Methodological shortcomings are evident in all published trials, with empiric evidence of bias in some, particularly those that suggest a benefit of HBO. Bayesian analysis further illustrates the uncertainty about a meaningful clinical benefit. Consequently, firm guidelines regarding the use of HBO for patients with CO poisoning cannot be established. Further research is needed to better define the role of HBO, if any, in the treatment of CO poisoning. Such research should not exclude patients with severe poisoning, have a primary outcome that is clinically meaningful and have oversight from an independent data monitoring and ethics committee.     

Olanzapine: a critical review of recent literature

The purpose of this review is to critically review the current literature on olanzapine with an emphasis on emergent themes and key findings in the use of this agent for the treatment of mood disorders and schizophrenia. New information continues to emerge on the impact of olanzapine on schizophrenia and on aspects of the course of mood disorders. There are also continued efforts to understand, predict and manage the side-effect risk with olanzapine.     

Human milk research for answering questions about human health

Concerns regarding human milk in our society are diverse, ranging from the presence of environmental chemicals to the health of breastfed infants and the economic value of breastfeeding to society. The panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States, held at the Hershey Medical Center, Pennsylvania State College of Medicine, on 24--26 September 2004, considered how human milk research may contribute to environmental health initiatives to benefit society. The panel concluded that infant, maternal, and community health can benefit from studies using human milk biomonitoring. Unlike other biological specimens, human milk provides information regarding exposure of the mother and breastfed infant to environmental chemicals. Some of the health topics relevant to this field of research include disorders of growth and development in infants, cancer origins in women, and characterization of the trend of exposure to environmental chemicals in the community. The research focus will determine the design of the study and the need for the collection of alternative biological specimens and the long-term storage of these specimens. In order to strengthen the ability to interpret study results, it is important to identify reference ranges for the chemicals measured and to control for populations with high environmental chemical exposure, because the amount of data on environmental chemical levels in human milk that is available for comparison is extremely limited. In addition, it will be necessary to validate models used to assess infant exposure from breastfeeding because of the variable nature of current models. Information on differences between individual and population risk estimates for toxicity needs to be effectively communicated to the participant. Human milk research designed to answer questions regarding health will require additional resources to meet these objectives.     

Influence of coadministration on the pharmacokinetics of azimilide dihydrochloride and digoxin

The influence of coadministration on digoxin and azimilide pharmacokinetics/pharmacodynamics was assessed in a randomized, 3-way crossover study in 18 healthy men. Serial blood and urine samples were obtained for azimilide and digoxin quantitation. Treatment effects on pharmacokinetics were assessed using analysis of variance. The relationship between azimilide blood concentrations and QT(c) prolongation was characterized by an E(max) model. Effects of coadministration on pharmacodynamics were assessed using a mechanistic-based inhibition model. Azimilide pharmacokinetics was unaffected by digoxin, except for a 36% increase in CL(r) (P = .0325), with no change in CL(o). Digoxin pharmacokinetics was unaffected by azimilide, except for a 21% increase in C(max) (P = .0176) and a 10% increase in AUC(tau) (P = .0121). Digoxin coadministration increased the apparent EC(50) with no effect on E(max), consistent with competitive inhibition (K(i) = 0.899 ng/mL). The pharmacokinetic and pharmacodynamic changes observed upon coadministration were small and are not expected to be clinically important.     

A Phase I trial of protracted oral fixed-dose temozolomide

BACKGROUND: The current Phase I trial was conducted to determine the dose-limiting toxicity (DLT), maximum tolerated dose, and recommended Phase II dose of oral fixed-dose temozolomide when administered for 5 of every 7 days on a continuous basis. METHODS: Patients received a fixed dose of temozolomide daily for 5 of every 7 days continuously. Four weeks of treatment were considered 1 treatment cycle. Patients were accrued at 7 different dose levels ranging from 100 mg/day to 360 mg/day. RESULTS: Forty-six patients received 111 cycles of therapy. DLT consisted of myelosuppression, particularly thrombocytopenia. The primary nonhematologic toxicities were nausea and emesis, which were easily controlled with antiemetics. CONCLUSIONS: Protracted administration of temozolomide at a fixed dose of 300 mg/day for 5 of every 7 days continuously was well tolerated and allowed greater dose intensity compared with various other schedules. This regimen could potentially increase antitumor activity as protracted temozolomide schedules inhibit DNA repair by depletion of the repair protein O6-methylguanine-DNA methyltransferase.     

Physicians' management of filarial lymphoedema and hydrocele in Pondicherry, India

Many countries have implemented mass drug administration programmes to eliminate lymphatic filariasis, but few have also implemented morbidity management programmes to help patients with chronic lymphoedema or hydrocele due to the infection. A study was carried out to assess current morbidity management by physicians in Pondicherry, India. Fifty-two physicians were interviewed, using a semi-structured questionnaire. For the management of hydrocele, all physicians referred hydrocele patients for surgery and 83% prescribed diethylcarbamazine (DEC). For the management of chronic lymphoedema patients, most doctors (75%) prescribed DEC and 56% mentioned the possibility of surgery. Only 10% of the physicians gave advice about limb hygiene, although recent research has shown the importance of hygiene measures to prevent further progression of lymphoedema. For the management of lymphoedema patients presenting with acute attacks, all physicians prescribed DEC and antibiotics and only 15% gave advice about limb hygiene. We conclude that limb hygiene instruction for home care should be more strongly emphasised to optimize management of lymphoedema patients in Pondicherry.     

Socioeconomic and racial disparities in cancer risk from air toxics in Maryland

We linked risk estimates from the U.S. Environmental Protection Agency's National Air Toxics Assessment (NATA) to racial and socioeconomic characteristics of census tracts in Maryland (2000 Census) to evaluate disparities in estimated cancer risk from exposure to air toxics by emission source category. In Maryland, the average estimated cancer risk across census tracts was highest from on-road sources (50% of total risk from nonbackground sources), followed by nonroad (25%), area (23%), and major sources (< 1%). Census tracts in the highest quartile defined by the fraction of African-American residents were three times more likely to be high risk (> 90th percentile of risk) than those in the lowest quartile (95% confidence interval, 2.0-5.0). Conversely, risk decreased as the proportion of whites increased (p < 0.001). Census tracts in the lowest quartile of socioeconomic position, as measured by various indicators, were 10-100 times more likely to be high risk than those in the highest quartile. We observed substantial risk disparities for on-road, area, and nonroad sources by socioeconomic measure and on-road and area sources by race. There was considerably less evidence of risk disparities from major source emissions. We found a statistically significant interaction between race and income, suggesting a stronger relationship between race and risk at lower incomes. This research demonstrates the utility of NATA for assessing regional environmental justice, identifies an environmental justice concern in Maryland, and suggests that on-road sources may be appropriate targets for policies intended to reduce the disproportionate environmental health burden among economically disadvantaged and minority populations.     

Total skin-sparing mastectomy without preservation of the nipple-areola complex

BACKGROUND: We hypothesized that total skin-sparing mastectomy (TSM) including where the skin overlying the nipple and areola is preserved would be oncologically safe and facilitate improved cosmetic reconstruction. METHODS: A review (May 2003 through January 2005) was completed on all procedures that were performed through an inframammary incision or a previous scar with reconstruction using Botox, AlloDerm, and a subpectoral tissue implant. RESULTS: Thirty-one patients had 50 TSMs. Twelve percent (6/50) of TSMs had the skin of the nipple and areola resected: 4 (14% of tumors) because of tumor involvement and 2 (4%) because of skin necrosis. Fourteen percent of patients had other complications: 4% (2/50) had infection and/or flap necrosis and 10% (5/50) had superficial epidermolysis requiring no intervention, for a total complication rate of 18%. Average cosmetic score was 8.5 (range 4 to 10). No recurrences are evident after mean follow-up of 7.9 +/- 5.4 months. CONCLUSION: Our short-term experience suggests that TSM has an acceptable complication rate, is theoretically oncologically safe, and facilitates an improved cosmetic result.