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Biomedical subjects

C French

Publications and source records attributed to C French.

At least 19 recordsLinked to original sources

Relative adrenal insufficiency in etomidate-naïve patients with septic shock.

A recent study reported that 77% of patients with septic shock had relative adrenal insufficiency. However, all patients were mechanically ventilated and received high-dose inotropes. In addition, at least 24% had prior exposure to etomidate, a drug known to suppress adrenal function. We studied the incidence of relative adrenal insufficiency in etomidate-naïve patients with septic shock by analysing the adrenal response to high-dose short synacthen test in 113 consecutive patients from three university-affiliated intensive care units in Australia. Patients were allocated to three groups according to severity of illness and inclusion criteria of the trial of low dose hydrocortisone supplementation using information from patient records. Of the 113 patients, 98 had septic shock (Group A). The incidence of relative adrenal insufficiency in this subpopulation was 24.5%. Eighty-one per cent of patients with septic shock were mechanically ventilated (Group B). In this group, the incidence of relative adrenal insufficiency was 27.8%. Only 38 of the 98 patients with septic shock (39%) fulfilled inclusion criteria for the steroid supplementation trial (Group C). In this group, the incidence of relative adrenal insufficiency was only 34.2%. In all groups its presence was associated with a higher mortality. We conclude that the incidence of relative adrenal insufficiency in etomidate-naive septic shock patients was lower than observed in the steroid supplementation trial. Further, in those who fulfilled inclusion criteria for the trial, the incidence of relative adrenal insufficiency was half that reported by the trial. Our observations raise concerns about the generalizability of the findings of the above trial to etomidate-naïve patients.

APACHE↗

Hyperbaric oxygen therapy for acute ischaemic stroke.

BACKGROUND: Most cases of stroke are caused by impairment of blood flow to the brain (ischaemia) which results in a reduction in oxygen available and subsequent cell death. It has been postulated that hyperbaric oxygen therapy (HBOT) may reduce the volume of brain that will die by greatly increasing the oxygen available, and it may further improve outcome by reducing brain swelling. Some centres are using HBOT routinely to treat stroke. OBJECTIVES: To assess the effectiveness and safety of adjunctive HBOT in the treatment of acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched 9 January 2004), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2004), MEDLINE (1966 to July 2004), EMBASE (1980 to July 2004), CINAHL (1982 to July 2004), and DORCTHIM (Database of Randomised Controlled Trials in Hyperbaric Medicine) (from inception to 2004). We handsearched journals and conference proceedings, searched reference lists of articles, and contacted researchers in an effort to identify additional published and unpublished studies. SELECTION CRITERIA: We included all randomised controlled trials that compared the effect of adjunctive HBOT with no HBOT (no treatment or sham). DATA COLLECTION AND ANALYSIS: Two authors used standardised forms to extract the data independently. Each trial was assessed for internal validity with differences resolved by discussion. Data were extracted and entered into RevMan 4.2. MAIN RESULTS: Three randomised controlled trials (106 participants) satisfied the inclusion criteria. The methodological quality of the trials varied but was generally high. Data could be pooled for a limited number of clinically important outcomes. There were no significant differences in mortality rate at six months in those receiving HBOT compared to the control group (relative risk 0.61, 95% confidence interval (CI) 0.17 to 2.2, P value 0.45). Two of 15 scale measures of disability and functional indicated an improvement following HBOT, both at one year follow up: the mean Trouillas Disability Scale was lower with HBOT (mean difference (MD) 2.2 points reduction with HBOT, 95% CI 0.15 to 4.3, P value 0.04) and the mean Orgogozo Scale was higher (MD 27.9 points, 95% CI 4.0 to 51.8, P value 0.02). These improvements were not reflected in other trials or functional scales. AUTHORS' CONCLUSIONS: This systematic review has not found evidence to show that HBOT improves clinical outcomes when applied during the acute presentation of ischaemic stroke. While evidence from the three randomised controlled trials is insufficient to provide clear guidelines for practice, clinical benefit does not seem likely. Further research is required to better define the role of HBOT in this condition.

Brain Ischemia↗

Commercial low-citrate anticoagulation haemofiltration in high risk patients with frequent filter clotting.

This study assessed the safety and efficacy of a commercial low-citrate concentration-based pre-filter replacement fluid during continuous veno-venous haemofiltration (CVVH) in patients with frequent filter clotting and high risk of bleeding. We used a commercial low-citrate fluid as pre-dilution replacement fluid during CVVH (citrate: 11 mmol/l (33 meq/l), sodium: 140 mmol/l, chloride: 108 mmol/l and potassium: 1 mmol/l). A calcium and magnesium infusion was delivered separately by central line for the maintenance of serum ionized calcium (Cai) and total magnesium (Mg). In this prospective observational study, 30 patients, 124 filters and 1,515 treatment-hours were observed. Median filter life of citrate CVVH was 9.5 hours. Filter life in the 48 hours prior to citrate CVVH was also observed. In the patients on prior non-anticoagulant CVVH (n=14) filter life increased significantly with citrate (9.5 hours vs 5 hours; P<0.0001). In patients on prior heparin CVVH (n = 15), filter life was similar with citrate (10 hours vs 8 hours; P = 0.68). However, in patients with prior early/frequent filter clotting despite heparin (n = 11) filter life increased significantly (10 hours vs 7 hours; P=0.038). Of 411 serum Cai measurements, none showed a Cai < 0.85 mmol/l and, of 84 observations, none showed a serum Mg<0. 6 mmol/l. One patient with sepsis and shock needed to cease citrate CVVH because of progressive ionized hypocalcaemia and increasing anion gap. No other adverse effects were observed. In selected patients, CVVH with a commercial low-citrate concentration solution as pre-filter replacement fluid and a simultaneous calcium and magnesium infusion protocol appears generally safe. Filter life was acceptable and superior to that achieved with previous treatment.

Acute Kidney Injury↗

Low-dose citrate continuous veno-venous hemofiltration (CVVH) and acid-base balance.

OBJECTIVE: To evaluate the acid-base effect of low-dose regional citrate anticoagulation (RCA) during continuous veno-venous hemofiltration (CVVH). DESIGN: Prospective observational study. SETTING: ICUs of tertiary public and private hospitals. SUBJECTS: Thirty critically ill patients with acute renal failure at risk of bleeding or with a major contraindication to heparin-CVVH and/or short filter life. METHODS: We used a commercial citrate-based fluid (11 mmol/L, sodium: 140 mmol/L, chloride: 108 mmol/L and 1 mol/L of potassium) as pre-dilution replacement fluid during CVVH. Further potassium was added according to serum potassium levels. We measured all relevant variables for acid-base analysis according to the Stewart-Figge methodology. RESULTS: Before treatment, study patients had a slight metabolic acidosis, which worsened over 6 hours of RCA-CVVH (pH from 7.39 to 7.38, p < 0.005; bicarbonate from 23.2 to 21.6 mmol/L, p < 0.0001 and base excess from -2.0 to -3.0 mEq/L, p < 0.0001) due to a significant increase in SIG (from 5.8 to 6.6 mEq/L, p < 0.05) and a decrease in SIDa (from 37.5 to 36.6 mEq/L, p < 0.05). These acidifying effects were attenuated by hypoalbuminemia and a decrease in lactate (from 1.48 to 1.34 mmol/L, p < 0.005) and did not lead to progressive acidosis. On cessation of treatment, this acidifying effect rapidly self-corrected within six hours. CONCLUSIONS: Low dose RCA-CVVH induces a mild acidosis secondary to an increased strong ion gap and decreased SIDa which fully self-corrects at cessation of therapy. Clinicians need to be aware of these effects to correctly interpret changes in acid-base status in such patients.

Acid-Base Equilibrium↗

A comparison of two citrate anticoagulation regimens for continuous veno-venous hemofiltration.

AIMS: To assess the safety and efficacy of two different commercial citrate containing pre-filter replacement fluids during continuous veno-venous hemofiltration (CVVH) in patients with frequent filter clotting. SETTING: Four intensive care units. PATIENTS: Sixty-three critically ill patients with acute renal failure (ARF). DESIGN: Prospective observational study. METHODS: We used a commercial citrate fluid (citrate: 11 mmol/L -fluid A) as predilution replacement for CVVH. We then changed to a new commercial citrate fluid (citrate: 14 mmol/L-fluid B) as replacement fluid and performed statistical comparisons. Replacement fluid rate was fixed at 2,000 ml/hour. RESULTS: Filter life was 12.2 hour with fluid A compared with 17.1 hour with fluid B on average (p=0.0001). Mean post filter ionized calcium concentration was 0.52 mmol/L with fluid A compared with 0.40 mmol/L with fluid B (p<0.0001). Citrate intolerance led to cessation of treatment in one patient with fluid A and one patient with fluid B. Overall ionized calcium levels were higher (A: 1.18 vs B: 1.13 mmol/L; p<0.0001) and bicarbonate was lower (A: 22.4 vs B: 24.5 mmol/L; p<0.0001) during treatment with fluid A. Alkalemia was seen in 10 patients treated with fluid A and 16 patients treated with fluid B (NS). CONCLUSIONS: We have developed a simple approach to regional citrate anticoagulation for CVVH using a commercial citrate-containing fluid as replacement fluid. Increasing citrate concentration from 11 to 14 mmol/L increased filter life while maintaining relative safety and simplicity.

Acute Kidney Injury↗

Screening for physical and psychological illness in the British Armed Forces: I: The acceptability of the programme.

OBJECTIVES: To assess the response to a self-administered questionnaire and attendance of a medical centre for physical and psychological health screening. METHODS: 4500 men and women from the three services were randomly selected to receive either a full or abridged screening questionnaire. The full questionnaire included the General Health Questionnaire-12 (GHQ-12) and Post-traumatic Stress Disorder (PTSD) checklist, 15 symptoms, a self-assessed health status question and three questions on alcohol behaviour (WHO Audit). The abridged questionnaire included GHQ-4, a slightly shortened PTSD checklist and five symptoms, but excluded questions on alcohol behaviour. All 'screen-positive' and a random 'screen-negative' sample were invited to attend a medical centre. RESULTS: 67.1% of the servicemen completed a questionnaire; slightly but significantly more the abridged than the full questionnaire (4.9%, 95% confidence interval 2.3-7.4%). Of those receiving a full or abridged questionnaire, 32% and 22.5% respectively were 'screen-positives', most of the difference (7.5%) attributable to alcohol behaviour. Less than 30% of the servicemen invited to attend a medical centre accepted the invitation, even fewer during the preparation for deployment to Iraq. Those who fulfilled the criteria for PTSD, alcohol behaviour or multi-criteria 'screen-positive' were more reluctant than controls to attend. CONCLUSIONS: Screening for psychological illness has little support among servicemen, perhaps because they may not wish to share concerns with a military doctor. Avoidance behaviour among those with a psychological condition may also selectively reduce willingness to attend a medical centre. Screening during pre-deployment periods has even less support than at other times.

Adult↗

Screening for physical and psychological illness in the British Armed Forces: III: The value of a questionnaire to assist a Medical Officer to decide who needs help.

OBJECTIVES: To estimate the positive and negative predictive values (PPVT and NPVT), sensitivity and specificity of a full and abridged screening questionnaire of physical and psychological health, using primary care doctors' (medical officers [MOs]) assessments as to whether the servicemen needed medical help as a gold standard. METHODS: From a tri-service random sample of those who completed a questionnaire, all 'screen-positive' and an equal random sample of 'screen-negative' were selected to attend their medical centre. MOs were aware that the screening was aimed at detecting psychological illness, but were blind as to the 'screen-positivity' of any serviceman. The MO completed a questionnaire that asked whether the patient needed medical help and whether s/he was previously aware of this need. RESULTS: 314 subjects were available for analysis. The PPVT was 47% (95% confidence interval [CI] 36-59%) for the full questionnaire and 48% (95% CI 36-60%) for the abridged questionnaire. Of those 'screen-positive' subjects whom the MO rated as needing help, one third had problems already known to the MO, regardless of the length of the questionnaire. The sensitivity and specificity of the full and abridged questionnaires were 43% and 74%, and 36% and 83% respectively. The PPVT did not vary greatly between health dimensions nor did selection of servicemen with very high scores. CONCLUSIONS: The use of MOs as a gold standard is important because of their central role in initiating the management of any condition uncovered by a screening programme. Using MOs as a gold standard, the validity of the screening questionnaires for physical and psychological health in the military was mediocre.

Adult↗

Screening for physical and psychological illness in the British Armed Forces: II: Barriers to screening--learning from the opinions of Service personnel.

OBJECTIVE: To identify any potential barriers to the effectiveness of a military health screening programme based on the beliefs of British Service personnel. METHODS: As part of a pilot evaluation of the suitability of a new health screening questionnaire for the British Armed Forces, 73 men and women from the three Services, of various ranks and age, underwent a semi-structured interview after completing a screening questionnaire. Participants were asked about the veracity of their answers and their views regarding a screening questionnaire. Afterwards questionnaires were sent to 4496 randomly selected personnel from the three Services, which validated the main emerging themes. A constant comparative method of analysis was used to identify and categorise all ideas presented. RESULTS: The main barriers to health screening were lack of trust, perceived low quality of healthcare, and perceived lack of concern within the institution about work environments and home life. The central issue was 'confidence' in military health care provision. Screening was considered worthwhile, but many confided that they would not honestly answer some items in the questionnaire. Lack of trust in medical confidentiality, stigmatisation and fears that the process would jeopardise career prospects were stressed. Many Service personnel admitted to seeking medical help outside the Armed Forces. CONCLUSIONS: Concerns raised by Service personnel may endanger the value of a screening programme and the provision of health services. Greater emphasis needs to be placed upon gaining the confidence of those targeted for health screening.

Adult↗

A rapid intravenous phosphate replacement protocol for critically ill patients.

OBJECTIVE: There is a high incidence of hypophosphataemia in the critically ill. It is known that even moderate hypophosphataemia can produce a variety of adverse consequences. Many phosphate replacement regimens have been suggested, most are conservative and few validated in the critical care environment. We designed a study to determine the apparent volume of distribution of phosphate and quantify phosphate loss in critically ill patients following rapid phosphate infusion. With these data we sought to design a phosphate replacement protocol. METHODS: A prospective clinical study of an infusion of 14.5 mmol of phosphate ions over 1 hour in seven patients with mild, moderate or severe hypophosphataemia was performed. Serum phosphate, total calcium, ionised calcium, urea, creatinine, urinary phosphate excretion and creatinine clearance were measured prior to phosphate administration. Urinary phosphate excretion and creatinine clearance and serum phosphate levels were followed for 24 hours. RESULTS: The median phosphate increment was 0.65 mmol/L (0.17 - 0.85). The median initial volume of distribution was 0.45 L/kg (0.21 - 0.87). There was no reduction in ionised calcium or creatinine clearance. The renal phosphate threshold was reduced in all patients. CONCLUSIONS: The apparent volume of distribution of phosphate in this group of critically ill patients is large. Urinary phosphate losses contributed to the development of hypophosphataemia in these patients. In this patient cohort, there were no adverse effects from phosphate infusion of 14.5 mmol/hr. A rational protocol based on the estimated volume of distribution and estimated urinary losses can be developed to achieve the rapid and sustained correction of hypophosphataemia in such patients.

Journal Article↗

Propofol infusion syndrome--report of an adult fatality.

This report describes a fatal case of the propofol infusion syndrome in an adult patient being sedated for a closed head injury using high doses of propofol. The features of circulatory collapse, metabolic acidosis, mild rhabdomyolysis and renal impairment are consistent with the syndrome and not readily attributable to alternative aetiologies. Potential mechanisms for the syndrome may relate to antagonism of beta-receptors, impaired myocardial oxygen utilization and a specific disruption to fatty-acid oxidation. This is the first published Australian case of the propofol infusion syndrome in an adult and should serve as an additional case report to the existing literature highlighting this potentially fatal syndrome in adults.

Adult↗

Preoperative cardiopulmonary risk assessment by cardiopulmonary exercise testing.

OBJECTIVE: To review the strategies for identification and subsequent management of high-risk patients that have been proposed to reduce perioperative morbidity and mortality. DATA SOURCES: Articles and published reviews of studies on evaluation and management of patients to reduce perioperative morbidity and mortality. SUMMARY OF REVIEW: Many strategies have been devised to evaluate the perioperative risk in elderly patients, particularly those who are about to undergo major intra-abdominal surgery. An assessment of cardiac and pulmonary responses to exercise-induced stress (i.e. cardiopulmonary exercise testing) using a bicycle ergometer, metabolic cart (to measure oxygen uptake and carbon dioxide excretion) and a 12 lead electrocardiograph has been found to be a non.invasive test that is quick, cheap, easy to perform and requires no special preparation. It has advantages over any other preoperative test by defining operative risk and allowing logical triage according to objective risk assessment. It is able to objectively evaluate the extent of any cardiac failure (by assessing the anaerobic threshold), myocardial ischaemia, provides insight into stroke index, the presence of pulmonary artery hypertension and defines obstructive and restrictive lung disease and ventilation perfusion inequality better than conventional preoperative respiratory function tests. CONCLUSIONS: In patients who are about to undergo major intra-abdominal surgery, preoperative cardiopulmonary exercise testing is an excellent predictor of risk in the postoperative period. No other test is able to offer such a comprehensive preoperative risk evaluation for an operative patient.

Journal Article↗

Pneumonia in HIV-infected patients: a case-control survey of factors involved in risk and prevention.

OBJECTIVE: To assess the factors that increase or decrease the risk of pneumonia with particular attention to immunization with pneumococcal and influenza vaccines in a group of HIV-infected persons. DESIGN: A retrospective, case-control study based on information entered into a standard database and the medical record. SETTING: Patients attending a referral clinic specializing in AIDS/HIV care at a public hospital. PATIENTS: Among over 2000 subjects entered into a database in 8 years, 127 incidents of pneumonia were identified from the record. These cases were matched with 127 CD4 cell count matched, concurrent controls. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The principal hypothesis was that chart review would find a decreased frequency of pneumococcal immunization in the pneumonia cases compared with matched controls. RESULTS: Pneumococcal immunization was associated with a reduction of the risk of pneumonia by nearly 70%. The effect was seen even when immunization was given with a CD4 cell count of less than 100/mm3. Injection drug users and African-Americans had a twofold increased risk of pneumonia. CONCLUSION: The study provides data to support the current recommendation for pneumococcal immunization of all HIV-infected persons. Although this conclusion could lead to renewed enthusiasm for increasing pneumococcal immunization rates in HIV-infected persons, it must be recognized that the study is observational and ascertainment bias cannot be excluded.

AIDS-Related Opportunistic Infections↗

Novel, nonconsensus cellular splicing regulates expression of a gene encoding a chemokine-like protein that shows high variation and is specific for human herpesvirus 6.

There are few genes that are specific and diagnostic for human herpesvirus-6. U83 and U22 are two of them. U22 is unique, whereas U83 encodes distant similarity with some cellular chemokines. Reverse transcription-polymerase chain reaction, cDNA cloning, and sequence analyses show polyadenylated RNA transcripts corresponding to minor full-length and abundant spliced forms of U83 in human herpesvirus 6-infected cells. The splice donor and acceptor sites do not fit consensus sequences for either major GT-AG or minor AT-AC introns. However, the spliced form can also be detected in a U83 transfected cell line; thus the novel sites are used by cellular mechanisms. This intron may represent a new minor CT-AC splicing class. The novel splicing regulates gene expression by introducing a central stop codon that abrogates production of the chemokine-like molecule, resulting in an encoded truncated peptide. The use of metabolic inhibitors and an infection time course showed expression of the two RNA transcripts with immediate early kinetics. However, the full-length product accumulated later, dependent on virus DNA replication, similar to U22. Sequence analyses of 16 strains showed high variation (13%) in U83, with conservation of the novel splice sites. Representative strain variants had similar kinetics of expression and spliced products.

3' Untranslated Regions↗

Sequence analyses of human herpesvirus-8 strains from both African human immunodeficiency virus-negative and -positive childhood endemic Kaposi's sarcoma show a close relationship with strains identified in febrile children and high variation in the K1 glycoprotein.

Human herpesvirus-8 (HHV-8) DNA sequences have been identified in all forms of Kaposi's sarcoma (KS), a cancer found primarily in adult AIDS patients. We have identified HHV-8 strains in a rare human immunodeficiency virus (HIV)-negative form of KS, which is endemic in children in parts of sub-Saharan Africa. This was shown in Zambia, where we also had identified HHV-8 sequences in blood from HIV-negative febrile children without KS. In order to investigate the relationship of these Zambian strains to each other and to those from other forms of KS, we compared them to strains we have characterized from European AIDS KS (Denmark) and all published sequences from all forms of KS. Four distinct genomic regions were examined by PCR and sequencing: ORF26, ORF75, gH and K1. The results showed a distinct grouping of strains from both sets of Zambian children in all genomic regions studied, but which was most pronounced in the K1 glycoprotein gene. This gene was highly variable, encoding up to 25% amino acid sequence variation. In contrast, the Zambian groups were closely related to each other, with only 2% variation. Similar results were found in comparisons to the K1 sequences from HIV-positive febrile infants or KS children. The data raise the possibility that in areas where rare childhood endemic KS occurs, geographical variation in HHV-8 may relate to differences in virulence or transmission.

AIDS-Related Opportunistic Infections↗

Telemedicine in neonatology: lessons from North Queensland.

Using videoconferencing technology, educational programs in neonatology were provided for staff at rural hospitals. The technology was also used to reunite babies with their families and its usefulness in long-distance diagnosis was assessed. Eighty-two educational sessions were delivered over a 9 month period and, despite problems with technology, operation and presentation, were considered worthwhile by the audiences. Family reunions were very successful. Neonatal diagnosis was impossible at the narrow bandwidth used (128 kilobits/s). Valuable lessons were learned regarding optimum use of this medium.

Education, Medical, Continuing↗

Assessment of health risks due to hazardous air pollutant emissions from electric utilities.

Hazardous air pollutant (HAP) emissions from electric utilities were evaluated. Cancer risks, as well as noncancer effects, due to inhalation exposure were assessed for 67 HAPs. Also, cancer risks due to multipathway exposure to radionuclide emissions were assessed. In addition, an assessment of the fate of mercury (Hg) through various environmental media was included. Results suggest arsenic, chromium, and nickel are the HAPs that present the highest cancer risk due to inhalation exposure. For noncancer effects due to inhalation exposure, hydrogen chloride appears to present the greatest potential concern. The risks due to multipathway exposure to radionuclides are estimated to be of similar magnitude to the risks posed by inhalation of arsenic and nickel. Mercury is of potential concern for multipathway exposures because it persists in the environmental and bioaccumulates in the aquatic food web. The study suggests there is a plausible link between Hg emissions from utilities and the Hg found in soil, water, and freshwater fish.

Air Pollutants↗