Screening for MRSA and GISA in the intensive care unit.
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Cross Infection↗
Biomedical subjects
M Singer
Publications and source records attributed to M Singer.
Improved survival for HIV infected patients with severe Pneumocystis jirovecii pneumonia is independent of highly active antiretroviral therapy.
BACKGROUND: Despite a decline in incidence of Pneumocystis jirovecii pneumonia (PCP), severe PCP continues to be a common cause of admission to the intensive care unit (ICU) where mortality remains high. A study was undertaken to examine the outcome from intensive care for patients with PCP and to identify prognostic factors. METHODS: A retrospective cohort study was conducted of HIV infected adults admitted to a university affiliated hospital ICU between November 1990 and October 2005. Case note review collected information on demographic variables, use of prophylaxis and highly active antiretroviral therapy (HAART), and hospital course. The main outcome was 1 month mortality, either on the ICU or in hospital. RESULTS: Fifty nine patients were admitted to the ICU on 60 occasions. Thirty four patients (57%) required mechanical ventilation. Overall mortality was 53%. No patient received HAART before or during ICU admission. Multivariate analysis showed that the factors associated with mortality were the year of diagnosis (before mid 1996 (mortality 71%) compared with later (mortality 34%; p = 0.008)), age (p = 0.016), and the need for mechanical ventilation and/or development of pneumothorax (p = 0.031). Mortality was not associated with sex, ethnicity, prior receipt of sulpha prophylaxis, haemoglobin, serum albumin, CD4 count, PaO2, A-aO2 gradient, co-pathology in bronchoscopic lavage fluid, medical co-morbidity, APACHE II score, or duration of mechanical ventilation. CONCLUSIONS: Observed improved outcomes from severe PCP for patients admitted to the ICU occurred in the absence of intervention with HAART and probably reflect general improvements in ICU management of respiratory failure and ARDS rather than improvements in the management of PCP.
AIDS-Related Opportunistic Infections↗
Preconditioning effects of levosimendan in coronary artery bypass grafting--a pilot study.
BACKGROUND: The calcium sensitizer levosimendan protects against myocardial ischaemia and reperfusion injury in animal models. METHODS: The present pilot study investigated whether a short infusion before coronary artery bypass grafting (CABG) would protect the myocardium and improve postoperative haemodynamics. Twenty-four patients with stable angina undergoing elective CABG surgery were randomized to receive either placebo or levosimendan (24 microg kg(-1)) infused i.v. over a 10 min period just before placing the patient on cardiopulmonary bypass. RESULTS: Perioperative haemodynamic variables, concentrations of cardiac troponin I over the 48 h postoperative period, and clinical outcomes were assessed. There were no adverse effects related to levosimendan. Compared with control patients, levosimendan-treated patients had lower postoperative troponin I concentrations (P<0.05) and a higher cardiac index (P<0.05). CONCLUSION: Patients receiving a short infusion of levosimendan before CABG showed evidence of less myocardial damage, suggestive of a preconditioning effect. Larger outcome studies are thus indicated to confirm benefit.
Aged↗
An evaluation of the clinical and cost-effectiveness of pulmonary artery catheters in patient management in intensive care: a systematic review and a randomised controlled trial.
OBJECTIVES: To evaluate the clinical and cost-effectiveness of managing critically ill patients in adult, general intensive care with or without pulmonary artery catheters (PACs). DESIGN: An open, multi-centre, randomised controlled trial with economic evaluation (cost-utility and cost-effectiveness analysis). SETTING: The setting was general (mixed medical/surgical) intensive care units (ICUs) in the UK admitting adults. PARTICIPANTS: Adult patients in participating ICUs deemed by the responsible treating clinician to require management with a PAC. INTERVENTIONS: These were insertion of a PAC and subsequent clinical management, at the discretion of the responsible treating clinicians, using data derived from the PAC. The control group were managed without a PAC but with the option of using alternative cardiac output monitoring devices. MAIN OUTCOME MEASURES: The main outcome measure was hospital mortality. Secondary outcome measures were length of stay in the ICU, length of stay in an acute hospital and organ-days of support in the ICU. For the economic evaluation, the main outcome measure was quality-adjusted life-years (QALYs) and the secondary outcome measure was hospital mortality. RESULTS: Sixty-five ICUs in the UK participated. Of these, 43 (66%) used alternative cardiac output monitoring devices in control group patients. A total of 1263 patients were identified as being eligible for the trial. Of these, 1041 (82.4%) were randomised and allocated to management with (n = 519) or without (n = 522) a PAC. There were no losses to follow-up. However, 27 patients (13 in the PAC group and 14 in the control group) were withdrawn from the trial because either the patient withdrew consent on recovering mental competency or the relatives withdrew agreement following randomisation. Data on 1014 patients were included in the analysis. Participants in the two groups had similar baseline characteristics. There was no difference in hospital mortality for patients managed with (68.4%) or without (65.7%) a PAC. The adjusted hazard ratio (PAC versus no PAC) was 1.09 [95% confidence interval (CI) 0.94 to 1.27]. There was no difference in the median length of stay in ICU, the median length of stay in an acute hospital or mean organ-days of support in ICU between the two groups. The economic evaluation found that the expected cost per QALY gained from the withdrawal of PAC was 2985 pounds. The expected cost per life gained from the withdrawal of PAC was 22,038 pounds. CONCLUSIONS: Clinical management of critically ill patients with a PAC, as currently practised in the UK, neither improves hospital survival for adult, general intensive care patients nor reduces length of stay in hospital. The lack of demonstrable benefit from a device previously believed to be beneficial could be explained by statistical chance, by misinterpretation of PAC-derived data, by ineffective treatment strategies based on data correctly interpreted using the current paradigm or by subsequent inaction following insertion of the device. It is also possible that detailed data on haemodynamics, however used, cannot modify the disease process sufficiently to influence disease outcome. The economic evaluation, using decision analysis techniques rather than conventional hypothesis testing, suggests that the withdrawal of the PAC from routine clinical practice in the NHS would be considered cost-effective in the current decision-making climate, and might result in lives or life-years being saved at modest cost. With the declining use of PACs in the UK and the findings of this report indicating no overall benefit from management with a PAC, it should now be possible to examine protocolised management with a PAC in selected groups of critically ill patients against appropriate controls, something that was difficult while PACs were the considered standard of care.
Adolescent↗
Short-course monotherapy strategy for treating bacteremia in the critically ill.
AIM: Routine practice in the ICU of University College London (UCL) Hospitals is to use short course (5-6 days) monotherapy, unless contraindicated (e.g. endocarditis, osteomyelitis). The aim of this study is to assess our policy by monitoring the clinical response, relapse rate and patient outcome. METHODS: A prospective observational study was carried out from February to July 2000. Clinically significant bacteraemia was identified by daily prospective surveillance of all positive blood cultures. On all the patients we recorded: 1) demographics; 2) antibiotic therapy (type, duration) and ACCP/SCCM sepsis criteria; 3) ICU support techniques (e.g. mechanical ventilation, intravascular catheter changes); 4) development of further bacteraemia or relapses. For all positive results, Gram stain, identification and antibiotic sensitivity patterns were noted. SPSS software was used for statistical analyses. RESULTS: Out of 713 admitted to the ICU over the study period, 84 (8.2%) patients experienced 102 bacteraemic episodes: 14 community-, 28 hospital- and 60 ICU-acquired (occurring in 49 patients). A total of 78 (76.4%) episodes [8 (57%) community-, 22 (79%) hospital- and 48 (80%) ICU-acquired] were treated with short course monotherapy. Moreover a low rate (23.8%) of death directly related to the bacteraemia and a satisfactory (72%) clinical response were recorded. ICU-acquired multidrug resistant Gram-negative bacteraemias (6.5%) and fungaemias (3%) were also uncommon. No patient discharged from the ICU, subsequently developed either bacteraemia relapse, or any long-term related complication. CONCLUSIONS: Short course antibiotic monotherapy strategy appears to provide a satisfactory clinical response, low relapse rate and no long-term infectious complications. Multicentre studies are warranted to confirm the efficacy of our practice.
Aged↗
Computer keyboards and the spread of MRSA.
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Computers↗
Human monoclonal IgG anticardiolipin antibodies induce nitric oxide synthase expression.
OBJECTIVE: Antiphospholipid antibodies are associated with increased risk of thrombosis, particularly as in antiphospholipid syndrome. This study aims to determine the acute effects of anticardiolipin antibodies on nitric oxide production and vascular function. METHODS: Ex vivo aortic rings from male Sprague Dawley rats were incubated with IgG monoclonal anticardiolipin antibody (IS4) or a non-specific IgG control. In organ baths, response to phenylephrine and acetlycholine was determined alone and with nitro-L-arginine methyl ester (L-NAME), 1,400 W, D-arginine, L-arginine, sodium nitroprusside and cardiolipin. In vivo antibodies were injected into anaesthetised, spontaneously breathing male Sprague Dawley rats. Haemodynamic variables and serum nitric oxide were measured. Immunohistochemistry for iNOS and eNOS was performed in kidney vessels. RESULTS: Phenylepherine contraction was decreased in the IS4 group compared to controls (p < 0.001). L-NAME, 1,400 W and cardiolipin, abolished this effect. L-Arginine caused significant relaxation in the IS4 group (p = 0.005). Mean arterial pressure in rats injected with IS4 was reduced compared to IgG and saline controls (p < 0.001). NO in plasma increased significantly after IS4 administration (p < 0.001). Immunohistochemistry showed increased iNOS expression in kidney arteries in the IS4 group, with no change in eNOS. CONCLUSION: Anticardiolipin antibodies induce NO production acutely via increased expression of iNOS in both ex vivo and in vivo models.
Animals↗
Treatment of pulmonary hypertension in the general adult intensive care unit: a role for oral sildenafil?
Use of inhaled nitric oxide for treatment of pulmonary hypertension in adult critical illness is limited by its mode of delivery and high costs, prompting evaluation of alternative therapies. We report the use of oral sildenafil in a patient with severe secondary pulmonary hypertension and right ventricular dysfunction. Following reduction in mean pulmonary artery pressure and pulmonary vascular resistance with inhaled nitric oxide, crossover to sildenafil therapy maintained control of pulmonary hypertension, facilitating discontinuation of respiratory and cardiovascular organ support. The relative pulmonary vascular specificity of oral sildenafil, and its low cost, makes it an attractive therapeutic alternative to inhaled nitric oxide, and warrants further study.
Administration, Oral↗
[Nightmares in patients with Alzheimer's disease caused by donepezil. Therapeutic effect depends on the time of intake].
Dementia of the Alzheimer type (DAT) has been linked to losses of cholinergic function in the brain. The acetylcholinesterase inhibitors donepezil, rivastigmine and galantamine improve cognitive performance in manifest dementia. These substances, however, also influence the quality of sleep, and particularly the quality and amount of dreams. We therefore investigated the influence of the time point of donepezil intake on the occurrence of nightmares. We observed a clear-cut relationship between the occurrence of nightmares and an evening dose of donepezil in eight patients with DAT. None of these patients reported nightmares when donepezil was taken in the morning. We suggest that the activation of the visual association cortex during REM sleep is enhanced by donepezil, a mechanism most likely facilitating the development of nightmares in patients with DAT.
Aged↗
A prospective, randomized, controlled multicenter trial comparing stapled hemorrhoidopexy and Ferguson hemorrhoidectomy: perioperative and one-year results.
PURPOSE: There is a growing body of evidence supporting the lesser degrees of pain with stapled hemorrhoidopexy, also called the procedure for prolapse and hemorrhoids. However, there have been few randomized comparisons assessing both perioperative and long-term outcomes of the procedure for prolapse and hemorrhoids and Ferguson hemorrhoidectomy. Results are presented here from the first prospective, randomized, multicenter trial comparing these hemorrhoid procedures in the United States. METHODS: Patients with prolapsing hemorrhoids (Grade III) were randomized to undergo the procedure for prolapse and hemorrhoids or Ferguson hemorrhoidectomy by colorectal surgeons who had training in using the stapling technique. Primary end points were acute postoperative pain, and hemorrhoid symptom recurrence requiring additional treatment at one-year follow-up from surgery. RESULTS: A total of 156 patients (procedure for prolapse and hemorrhoids, 77; Ferguson, 79) completed randomization and the surgical procedure, 18 (procedure for prolapse and hemorrhoids, 12; Ferguson, 6) had significant protocol violations. One hundred seventeen patients (procedure for prolapse and hemorrhoids, 59; Ferguson, 58) returned for one-year follow-up. Demographic parameters, hemorrhoid symptoms, preoperative pain scores, and bowel habits were similar between groups. There were a similar number of patients with adverse events in each group (procedure for prolapse and hemorrhoids, 28 (36.4 percent) vs. Ferguson, 38 (48.1 percent); P = 0.138). Reoperation for an adverse effect was required in six (7.6 percent) Ferguson patients and in 0 patients having the procedure for prolapse and hemorrhoids (P = 0.028). Postoperative pain during the first 14 days, pain at first bowel movement, and need for postoperative analgesics were significantly less in the procedure for prolapse and hemorrhoids group. Control of hemorrhoid symptoms was similar between groups; however, significantly fewer patients having the procedure for prolapse and hemorrhoids required additional anorectal procedures during one-year follow-up (procedure for prolapse and hemorrhoids, 2 (2.6 percent), vs. Ferguson, 11 (13.9 percent); P = 0.01). Only four of the Ferguson patients (5 interventions) required additional procedures more than 30 days after surgery. CONCLUSIONS: These data demonstrate that stapled hemorrhoidopexy offers the benefits of less postoperative pain, less requirement for analgesics, and less pain at first bowel movement, while providing similar control of symptoms and need for additional hemorrhoid treatment at one-year follow-up from surgery.
Analysis of Variance↗
Extended freeze-dried Mycobacterium bovis Bacillus Calmette-Guérin induces the release of interleukin-12 but not tumour necrosis factor-alpha by alveolar macrophages, both in vitro and in vivo.
BACKGROUND: Airway hyper-responsiveness (AHR), chronic airway inflammation and predominance of the T helper type-2 (Th2; IL-4, IL-5, IL-13) over the Th1 (IL-2, IFN-gamma) immune response are hallmarks of asthma. Alveolar macrophages (AM) are the most numerous cells in the airway lumen, where they represent the first immune cell population encountered by inhaled antigens. AM act as antigen-presenting cells (APC) and they release various soluble mediators and enzymes. AM thus play a prominent role in the modulation of the local immunity in airways. In allergic airways, AM have been implicated in the pathogenesis of inflammation by promoting the Th2 versus the Th1 cytokine patterns. OBJECTIVES: Infections with attenuated bacteria or challenges with bacterial products may involve AM. Such stimuli have been shown to potentially restore the Th1/Th2 balance in asthmatic airways, but they also induce the release of inflammatory mediators. We investigated the response of AM when stimulated by two preparations of non-proliferating Bacillus Calmette-Guérin (BCG). METHODS: We evaluated the cytokine production by AM from BP2 and C57BL/6 mice when cultured with heat-killed (HK) and extended freeze-dried (EFD) BCG. We then investigated in vivo the release of soluble factors in the airway lumen of mice after instillation of these BCG preparations. Finally, we studied the profile of cytokine transcripts in the lung of mice pre-treated with BCG and then challenged with ovalbumin (OVA). RESULTS: HK BCG induced the production of both TNF-alpha and IL-12, and did not prevent high levels of Th2 cytokine transcripts. In contrast, EFD BCG induced a response dominated by the production of IL-12, with no later over-expression of Th2 cytokine transcripts. CONCLUSION: Our results show that EFD BCG induce the release of the Th1-promoting cytokine IL-12 by AM, without the deleterious effects of HK BCG. These data suggest that EFD BCG may be considered as a potential novel treatment to restore the Th1/Th2 imbalance in asthma.
Adjuvants, Immunologic↗
Unintended consequences of using an oral HIV test on HIV knowledge.
This study assessed the effects of oral HIV testing on the belief that HIV can be transmitted in saliva and on overall AIDS knowledge. A sample of current or former street drug users (N = 155) was recruited to complete a survey of HIV risk behaviour at two points in time. The survey included three items that assessed beliefs in the possible transmission of HIV through saliva. Among the 80 participants who received oral HIV testing at baseline, accuracy on the three saliva items decreased at follow-up and, among the 75 participants who did not receive oral HIV testing, accuracy on these items increased at follow-up. This pattern of change was statistically significant. Oral HIV testing has been a significant advance. However, unintended effects may include increased belief in the transmission of HIV through saliva. This problematic outcome suggests the importance of enhanced HIV counselling among participants in oral HIV testing.
Female↗
Linezolid resistance in clinical isolates of Staphylococcus aureus.
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Acetamides↗
Primary repair for penetrating colon injuries.
BACKGROUND: Primary repair of penetrating colon injuries is an appealing management option, however uncertainty about its safety persists. OBJECTIVES: The objective of this review was to compare the morbidity and mortality of primary repair to fecal diversion in the management of penetrating colon injuries using a meta-analysis of randomized controlled trials. SEARCH STRATEGY: We searched MEDLINE (1966 to November 2001), the Cochrane Controlled Trials Register, and EMBASE using the terms colon, penetrating, injury, colostomy, prospective, and randomized. SELECTION CRITERIA: Studies were included if they were randomized controlled trials comparing the outcomes of primary repair versus fecal diversion in the management of penetrating colon injuries. Five studies were included. DATA COLLECTION AND ANALYSIS: Reviewers performed data extraction independently. Outcomes evaluated from each trial included mortality, total complications, infectious complications, intra-abdominal infections, wound complications, penetrating abdominal trauma index (PATI), and length of stay. Peto odds ratios for combined effect were calculated with a 95% confidence interval for each outcome. Heterogeneity was assessed for each outcome using a chi-squared test. MAIN RESULTS: The Penetrating Abdominal Trauma Index (PATI) of included subjects did not significantly differ between studies. Mortality was not significantly different between groups (OR 1.70, 95% CI 0.51,5.66). However, total complications (OR 0.28 95% CI 0.18,0.42), total infectious complications (OR 0.41, 95% CI 0.27, 0.63), abdominal infections including dehiscence (OR 0.59, 95% CI 0.38,0.94), abdominal infections excluding dehiscence (OR 0.52 95% CI 0.31,0.86), wound complications including dehiscence (OR 0.55, 95% CI 0.34,0.89), and wound complications excluding dehiscence (OR 0.43, 95% CI 0.25,0.76) all significantly favored primary repair. REVIEWER'S CONCLUSIONS: Meta-analysis of currently published randomized controlled trials favors primary repair over fecal diversion for penetrating colon injuries.
Colon↗
Design, synthesis, and biological activity of diiminoisoindolines as complement component 3a antagonists.
The failure to fully regulate the inflammation response has been linked to diseases such as rheumatoid arthritis, septic shock syndrome, and asthma. The human complement system initiates and regulates the inflammation response through a cascade of regulatory factors. Complement Component 3a (C3a) is an essential regulatory factor and inhibiting its binding to a C3a receptor will diminish the inflammation response by disrupting the cascade. We report the design, synthesis, in vitro and in vivo activity of diiminoisoindolines as C3a antagonists.
Binding, Competitive↗
Treatment results and prognostic factors of advanced T3--4 laryngeal carcinoma: the University of California, San Francisco (UCSF) and Stanford University Hospital (SUH) experience.
PURPOSE: To review the UCSF-SUH experience in the treatment of advanced T3--4 laryngeal carcinoma and to evaluate the different factors affecting locoregional control and survival. METHODS AND MATERIALS: We reviewed the records of 223 patients treated for T3--4 squamous cell carcinoma of the larynx between October 1, 1957, and December 1, 1999. There were 187 men and 36 women, with a median age of 60 years (range, 28--85 years). The primary site was glottic in 122 and supraglottic in 101 patients. We retrospectively staged the patients according to the 1997 AJCC staging system. One hundred and twenty-seven patients had T3 lesions, and 96 had T4 lesions; 132 had N0, 29 had N1, 45 had N2, and 17 had N3 disease. The overall stage was III in 93 and IV in 130 patients. Seventy-nine patients had cartilage involvement, and 144 did not. Surgery was the primary treatment modality in 161 patients, of which 134 had postoperative radiotherapy (RT), 11 had preoperative RT, 7 had surgery followed by RT and chemotherapy (CT), and 9 had surgery alone. Forty-one patients had RT alone, and 21 had CT with RT. Locoregional control (LRC) and overall survival (OS) were estimated using the Kaplan--Meier method. Log-rank statistics were employed to identify significant prognostic factors for OS and LRC. RESULTS: The median follow-up was 41 months (range, 2--367 months) for all patients and 78 months (range, 6--332 months) for alive patients. The LRC rate was 69% at 5 years and 68% at 10 years. Eighty-four patients relapsed, of which 53 were locoregional failures. Significant prognostic factors for LRC on univariate analysis were primary site, N stage, overall stage, the lowest hemoglobin (Hgb) level during RT, and treatment modality. Favorable prognostic factors for LRC on multivariate analysis were lower N stage and primary surgery. The overall survival rate was 48% at 5 years and 34% at 10 years. Significant prognostic factors for OS on univariate analysis were: primary site, age, overall stage, T stage, N stage, lowest Hgb level during RT, and treatment modality. Favorable prognostic factors for OS on multivariate analysis were lower N stage and higher Hgb level during RT. CONCLUSION: Lower N-stage was a favorable prognostic factor for LRC and OS. Hgb levels > or = 12.5 g/dL during RT was a favorable prognostic factor for OS. Surgery was a favorable prognostic factor for LRC but did not impact on OS. Correcting the Hbg level before and during treatment should be investigated in future clinical trials as a way of improving therapeutic outcome in patients with advanced laryngeal carcinomas.
Adult↗
Computed tomography in the evaluation of penetrating neck trauma: a preliminary study.
HYPOTHESIS: Penetrating neck trauma has traditionally been evaluated by surgical exploration and/or invasive diagnostic studies. We hypothesized that computed tomography (CT), used as an early diagnostic tool to accurately determine trajectory, would direct or eliminate further studies or procedures in stable patients with penetrating neck trauma. DESIGN: Retrospective case series. SETTING: Academic, urban, level I trauma center. PATIENTS: Hemodynamically stable patients without hard signs of vascular injury or aerodigestive violation who had sustained penetrating trauma to the neck. INTERVENTIONS: Patients underwent a spiral CT as an initial diagnostic study after initial evaluation in the trauma bay. Further invasive studies were directed by CT findings. MAIN OUTCOME MEASURES: Number of invasive studies performed. RESULTS: Twenty-three patients were identified during the 30-month period. Nineteen patients sustained gunshot wounds; 3, shotgun wounds; and 1, a stab wound. One patient died of a cranial gunshot wound. Three isolated zone I, 1 isolated zone II, 9 isolated zone III, and 10 multiple neck zone trajectories were evaluated. Thirteen patients were identified by CT to have trajectories remote from vital structures and required no further evaluation. Ten patients underwent angiography. Only 2 underwent bronchoscopy and esophagoscopy. Four patients were discharged from the emergency department; 7 other patients were discharged within 24 hours. No adverse patient events occurred before, during, or after CT scan. CONCLUSIONS: Computed tomography in stable selected patients with penetrating neck trauma appears safe. Invasive studies can often be eliminated from the diagnostic algorithm when CT demonstrates trajectories remote from vital structures. As a result, efficient evaluation and early discharge from the trauma bay or emergency department can be realized. Further prospective study of CT scan after penetrating neck trauma is needed.
Adult↗
Toward a bio-cultural and political economic integration of alcohol, tobacco and drug studies in the coming century.
The 18th and early 20th centuries witnessed the disintegration of a unified approach to understanding the human condition. Political economy, the broad study of human society, fragmented into an array of university-based disciplines, each reductionistically focused on its narrow arena of specialized research. Medicine, which had been concerned with health in social and historic contexts, narrowed its focus to the microscopic level and to encapsulated understandings of the immediate effects of pathogens and of the structures of disintegrated organ systems. Similarly, anthropology, which continued to wave a banner of holism, retreated for much of the 20th century into fine-grained cultural studies of seemingly isolated human communities on the one hand, and highly specialized biological and biobehavioral analyses of only tangential concern to cultural concerns on the other. Consequently, it has appeared at times as if anthropology would fragment into two or more disciplines and the opportunity for an integrated understanding of the human condition would be lost in the process. As we approach ever closer to the 21st century, however, the felt need for interdisciplinary and intradisciplinary reintegration has grown stronger. This trend is manifest increasingly in the field of alcohol, tobacco, and drug studies, and suggests one of the places anthropology may be going in the future. In this light, this paper examines the use of a critical biocultural model employed in the anthropological assessment of the Hartford Syringe Exchange Program. This model integrates the political economy of risk behavior, the ethnographic examination of insider understandings, meaning systems and behaviors, and the biological analysis of health-related issues. Methodologically, the assessment combined methods and concepts from all of the major subfields of anthropology.
Anthropology, Cultural↗