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1.
Anaesthesia ; 75(7): 896-903, 2020 07.
Article in English | MEDLINE | ID: mdl-32363573

ABSTRACT

Critical care survivors suffer persistent morbidity and increased risk of mortality as compared with the general population. Nevertheless, there are no standardised tools to identify at-risk patients. Our aim was to establish whether the Sabadell score, a simple tool applied by the treating clinician upon critical care discharge, was independently associated with 5-year mortality through a prospective observational cohort study of adults admitted to a general critical care unit. The Sabadell score, which is a measure of clinician-assigned survival perception, was applied to all patients from September 2011 to December 2017. The primary outcome was 5-year mortality, assessed using a multivariable flexible parametric survival analysis adjusted for baseline characteristics and clinically relevant covariates. We studied 5954 patients with a minimum of 18 months follow-up. Mean (SD) age was 59.5 (17.0) years and 3397 (57.1%) patients were men. We categorised 2287 (38.4%) patients as Sadabell 0; 2854 (47.9%) as Sadabell 1; 629 (10.5%) as Sadabell 2; and 183 (3.1%) as Sadabell 3. Adjusted hazard ratios for mortality were 2.1 (95%CI 1.9-2.4); 4.0 (95%CI 3.4-4.6); and 21.0 (95%CI 17.2-25.7), respectively. Sabadell 3 patients had 99.9%, 99.5%, 98.5% and 87.4% mortality at 5 years for patients in the age brackets ≥ 80, 60-79, 40-59 and 16-39 years, respectively. Sabadell 2 patients had 71.0%, 52.7%, 44.8% and 23.7% 5-year mortality for these same age categories. The Sabadell score was independently associated with 5-year survival after critical care discharge. These findings can be used to guide provision of increased support for patients after critical care discharge and/or informed discussions with patients and relatives about dying to ascertain their future wishes.


Subject(s)
Attitude of Health Personnel , Critical Care , Critical Illness/mortality , Health Status Indicators , Patient Discharge , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Critical Illness/rehabilitation , England/epidemiology , Female , Follow-Up Studies , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Postoperative Period , Prognosis , Prospective Studies , Risk Assessment/methods , Survival Analysis , Young Adult
3.
Br J Anaesth ; 111(4): 594-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23690528

ABSTRACT

BACKGROUND: Retrosternal goitre (RSG) is an uncommon problem encountered rarely by anaesthetists working outside specialized head and neck (H&N) surgical units. Traditional anaesthetic teaching warns of difficult airway management in these patients. The incidence and extent of these problems is unclear. METHODS: We have performed a retrospective review of the anaesthetic management all patients with massive RSG (extending to the aortic arch or beyond) presenting for thyroidectomy at University Hospital Aintree from January 2007 to May 2012. RESULTS: Five hundred and seventy-three patients underwent a thyroidectomy procedure at Aintree University Hospitals NHS Foundation Trust (AUH) between January 2007 and May 2012. Of these, 34 cases were documented as having a RSG. Review of each patient's preoperative computerized tomography imaging identified 19 patients with massive RSG. There was one case of failed intubation. All other patients underwent uneventful tracheal intubation via direct laryngoscopy. All glands were removed through the neck with no requirement to proceed to sternotomy. There were no instances of postoperative respiratory problems or tracheomalacia. Three patients suffered recurrent laryngeal nerve (RLN) injuries. CONCLUSION: When managed within a dedicated H&N operating theatre we have found a low incidence of difficult tracheal intubation, difficult mechanical ventilation nor postoperative respiratory difficulties in patients with massive RSG and mid-tracheal compression because of benign multi-nodular goitre. Surgical complications, however, are more frequent than those associated with cervical thyroidectomy with RLN injury and postoperative bleeding more likely.


Subject(s)
Anesthesia, General/methods , Goiter, Substernal/surgery , Thyroidectomy/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Intubation, Intratracheal/methods , Laryngeal Nerve Injuries/etiology , Laryngoscopy , Male , Middle Aged , Referral and Consultation , Retrospective Studies , Tertiary Care Centers , Thyroidectomy/adverse effects
5.
Br J Anaesth ; 105(6): 782-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20813838

ABSTRACT

BACKGROUND: The single tapered dilator (STD) percutaneous dilatational tracheostomy (PDT) technique now appears to be the single most common method of performing a tracheostomy in the critical care unit (CCU). METHODS: A single-centre, prospective evaluation of all PDTs performed in an adult mixed surgical and medical CCU between November 2003 and October 2009 was done. All procedures were undertaken by critical care physicians. A proforma recorded intraoperative complications and technical difficulties encountered during the procedure; all patients were followed up for a minimum of 3 months for delayed complications. RESULTS: A tracheostomy was performed on 589 patients during the study period. PDT was attempted in 576 patients and successfully completed in 572. PDT was abandoned in four patients due to bleeding, with three of these subsequently undergoing surgical tracheostomy (ST). ST was performed in 17 patients. Intraoperative technical difficulties were encountered in 149 (26%) cases. Sixteen (3%) procedures were deemed as having early complications. A further four (0.7%) cases had significant late complications including two tracheo-innominate fistulae (TIF). Both TIF patients died as a result of their complications giving a mortality directly attributable to PDT of 0.35%. There were no differences with respect to the occurrence of complications according to grade of operator. CONCLUSIONS: PDT performed by the STD technique is a relatively safe procedure with more than 96% of procedures performed without any early or late complications. Using this technique, more than 97% of tracheostomies undertaken during the study period were performed percutaneously. Further audit at a national level is warranted to fully evaluate long-term complications after PDT.


Subject(s)
Tracheostomy/methods , Adolescent , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical , Clinical Competence , Dilatation/adverse effects , Dilatation/methods , Female , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Minimally Invasive Surgical Procedures/methods , Prospective Studies , Tracheostomy/adverse effects , Treatment Failure , Young Adult
6.
J Hosp Infect ; 74(4): 337-43, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20202717

ABSTRACT

Hospital-acquired pneumonia (HAP) is a common cause of morbidity and mortality in the critically ill, yet the optimal duration of antibiotic therapy is unknown. Too short a course may lead to treatment failure, whereas too long a course may lead to increased antibiotic resistance, antibiotic-related morbidity and increased costs. Standard duration of antibiotic therapy for Gram-negative (GN-)HAP at our institution is 5 days, significantly shorter than advocated in many current guidelines. We performed a retrospective review of all cases of GN-HAP on our critical care unit fulfilling clinical and microbiological criteria to investigate recurrence rate and mortality following short course antibiotic therapy. Seventy-nine eligible patients with GN-HAP were identified. Of these, 79% were receiving mechanical respiratory support at diagnosis; 42% had GN-HAP due to non-fermenting Gram-negative bacilli (NF-GNB) and 72% were treated with the recommended 5 day course of antibiotics. Two patients had clear evidence of non-resolution of pneumonia after 5 days of therapy. Overall recurrence rate was 14%, with relapse rates significantly higher among patients with NF-GNB when compared to patients with other Gram-negative organisms (17% vs 2%; P=0.03). The overall recurrence rate was no higher than rates reported in earlier studies (17-41%). Critical care mortality (34.2%) was also not in excess of previously reported values (18-57%). In this limited study, use of a 5 day course of appropriate antibiotics for GN-HAP does not appear to increase risk of recurrence or mortality when pneumonia resolution has been achieved prior to the cessation of therapy.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Gram-Positive Bacteria/drug effects , Gram-Positive Bacterial Infections/drug therapy , Pneumonia, Bacterial/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Critical Illness , Drug Therapy/methods , Female , Gram-Positive Bacteria/isolation & purification , Hospitals , Humans , Male , Middle Aged , Time Factors , Young Adult
7.
J Hosp Infect ; 71(4): 348-52, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19157643

ABSTRACT

Pneumonia caused by Pseudomonas spp. has been associated with an increase in mortality in critical care patients. Previous assessments, however, have failed to compare outcome solely with other pathogens associated with hospital-acquired pneumonia (HAP). We have performed a retrospective review of all critical care patients with late-onset HAP (hospital inpatient stay >72 h at time of diagnosis) due to pure respiratory cultures of Pseudomonas spp., meticillin-resistant Staphylococcus aureus (MRSA) or non-pseudomonal Gram-negative (NPGN) organisms from 1998 to 2007. Casenote review involved assessments of illness severity, clinical pulmonary infection scoring (CPIS), critical care and hospital survival, and critical care length of stay. Out of 252 casenotes, 204 were reviewed. There were 186 treated cases of pneumonia. Ten patients had both pseudomonal and NPGN pneumonias during the same admission and two patients presented with community-acquired infections due to these organisms. These 12 patients were excluded from further analysis. Of the remaining 174 patients, 80 were infected with pseudomonas, 40 with MRSA and 54 had NPGN organisms. The three groups of patients were well-matched, with similar age, sex, CPIS scores, incidence of bacteraemia and Acute Physiology and Chronic Health Evaluation II scores at diagnosis. There were no outcome differences between the groups with respect to hospital and critical care survival and critical care length of stay. In this series, there appears to be no survival disadvantage associated with pseudomonal pneumonia when compared with other hospital-acquired organisms associated with HAP, where disease severity between the groups is similar.


Subject(s)
Cross Infection/drug therapy , Gram-Negative Bacterial Infections/drug therapy , Pneumonia, Bacterial/drug therapy , Pseudomonas Infections/drug therapy , Staphylococcal Infections/drug therapy , Aged , Aged, 80 and over , Critical Illness , Cross Infection/microbiology , Cross Infection/mortality , Female , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/mortality , Humans , Length of Stay , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/mortality , Pseudomonas/isolation & purification , Pseudomonas Infections/microbiology , Pseudomonas Infections/mortality , Retrospective Studies , Severity of Illness Index , Staphylococcal Infections/microbiology , Staphylococcal Infections/mortality , Treatment Outcome
8.
Br J Anaesth ; 100(5): 663-6, 2008 May.
Article in English | MEDLINE | ID: mdl-18369239

ABSTRACT

BACKGROUND: The role of routine chest radiography (CXR) after percutaneous dilatational tracheostomy (PDT) has been questioned. METHODS: We performed a prospective observational study, on a mixed medical/surgical critical care unit in a university teaching hospital. We studied all patients undergoing PDT as part of their critical care management from November 1, 2003 until July 31, 2007. All PDTs were performed under bronchoscopic guidance. After PDT, we reviewed the immediate post-procedural films to assess the utility of routine postoperative CXR. For the purposes of CXR review, we considered a procedure to be either uncomplicated or technically difficult. Clinically relevant CXR findings were new barotrauma (pneumothorax, pneumomediastinum) or a significant change in consolidation from the pre-procedure film. RESULTS: A total of 384 patients underwent PDT during the study period. Of these, 345 had immediate post-procedural CXRs available for review. There were 252 PDTs (73%) documented as uncomplicated. There were 93 (27%) technically difficult procedures, with 107 adverse events recorded. In 82 (24%) procedures, these difficulties were described as minor procedural complications [multiple attempts at needle insertion (> or = 3), minor bleeding or tracheal ring fracture]. Significant complications (mal-placement in the anterior mediastinum and major bleeding) were documented in 12 (3.5%) patients. New abnormalities were noted on 8 (2.3%) immediate post-procedural CXRs. In only one patient was there a new CXR change in an uncomplicated PDT. CONCLUSIONS: Immediate CXR after uncomplicated PDT performed under bronchoscopic guidance rarely reveals unexpected radiological abnormalities. The role of CXR after PDT appears to be restricted to those patients undergoing technically difficult and complicated procedures. A change in practice to this effect will lead to reductions in both medical costs and exposure of staff and patients to ionizing radiation.


Subject(s)
Postoperative Care/methods , Radiography, Thoracic , Tracheostomy/adverse effects , Adult , Aged , Barotrauma/diagnostic imaging , Barotrauma/etiology , Bronchoscopy , Female , Humans , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Prospective Studies , Tracheostomy/methods , Unnecessary Procedures
9.
Br J Cancer ; 94(5): 647-53, 2006 Mar 13.
Article in English | MEDLINE | ID: mdl-16523195

ABSTRACT

The influence of perioperative blood transfusion in oral and oropharyngeal squamous cell carcinoma remains uncertain. It is believed that blood transfusion downregulates the immune system and may have an influence on cancer recurrence and survival. In all, 559 consecutive patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma between 1992 and 2002 were included in this study. Known prognostic variables along with transfusion details were obtained from head and neck cancer and blood transfusion service databases, respectively. Adjusting for relevant prognostic factors in Cox regression, the hazard ratio for patients having 3 or more transfused units relative to those not transfused was 1.52 (95% confidence interval (CI) 0.93-2.47) for disease-specific and 1.52 (95% CI 1.05-2.22) for overall mortality. Blood transfusion of 3 or more units might confer a worse prognosis in patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma. Therefore, every effort should be made to limit the amount of blood transfused to the minimum requirement.


Subject(s)
Carcinoma, Squamous Cell/surgery , Mouth Neoplasms/surgery , Oropharyngeal Neoplasms/surgery , Transfusion Reaction , Adult , Aged , Carcinoma, Squamous Cell/pathology , Female , Humans , Immune System , Male , Middle Aged , Mouth Neoplasms/pathology , Oropharyngeal Neoplasms/pathology , Prognosis , Retrospective Studies , Surgical Flaps , Survival Analysis , Transplantation, Homologous , Treatment Outcome
10.
Br J Anaesth ; 96(1): 127-31, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16299043

ABSTRACT

Tracheo-innominate artery fistula (TIF) is an uncommon yet life threatening complication after a tracheostomy. Rates of 0.1-1% after surgical tracheostomy have been reported, with a peak incidence at 7-14 days post procedure. It is usually fatal unless treatment is instituted immediately. Initial case reports of TIF resulted from surgically performed tracheostomies. We present three fatalities attributable to TIF, confirmed by histopathology, after percutaneous dilatational tracheostomy (PDT). The use of PDT has resulted in tracheostomies being performed by specialists from different backgrounds and the incidence of this complication may be increasing. Pressure necrosis from high cuff pressure, mucosal trauma from malpositioned cannula tip, low tracheal incision, radiotherapy and prolonged intubation are all implicated in TIF formation. Massive haemorrhage occurring 3 days to 6 weeks after tracheostomy is a result of TIF until proven otherwise. We present a simple algorithm for management of this situation. The manoeuvres outlined will control bleeding in more than 80% of patients by a direct tamponade effect. Surgical stasis is obtained by debriding the innominate artery proximally, then transecting and closing the lumen. Neurological sequelae are few. Post-mortem diagnosis of TIF may be difficult, but specific pathology request should be made to assess innominate artery abnormalities.


Subject(s)
Brachiocephalic Trunk/injuries , Respiratory Tract Fistula/etiology , Tracheal Diseases/etiology , Tracheostomy/adverse effects , Vascular Fistula/etiology , Adult , Aged , Fatal Outcome , Female , Humans , Male , Middle Aged , Respiratory Tract Fistula/diagnosis , Respiratory Tract Fistula/therapy , Tracheal Diseases/diagnosis , Tracheal Diseases/therapy , Vascular Fistula/diagnosis , Vascular Fistula/therapy
11.
Crit Care Med ; 28(6): 1803-7, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10890623

ABSTRACT

OBJECTIVE: To report four cases of pyroglutamic acidemia in adults causing clinically significant acidosis. DATA SOURCES: Patients admitted to the intensive care units of the Alfred Hospital (a quaternary referral center) and Geelong Hospital (a major regional center) with an unexplained high anion gap acidosis. CONCLUSIONS: Pyroglutamic acidemia (5-oxoprolinemia) is a rare cause of high anion gap metabolic acidosis that should be suspected in patients presenting with sepsis, hepatic, and/or renal dysfunction who are receiving drugs such as acetaminophen, flucloxacillin, and vigabatrin after the more common causes of a high anion gap acidosis have been excluded. Should pyroglutamic aciduria be present, known precipitants should be ceased, infection should be managed aggressively, and supportive management should be instituted.


Subject(s)
Acidosis/etiology , Acidosis/metabolism , Pyrrolidonecarboxylic Acid/blood , Aged , Aged, 80 and over , Female , Humans , Middle Aged
12.
Anesthesiology ; 93(6): 1384-91, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11149430

ABSTRACT

BACKGROUND: Recent trials indicate that rapacuronium's pharmacokinetic characteristics are influenced by both renal failure and cirrhosis but the time course of a single bolus dose of 1.5 mg/kg is affected minimally. The authors reassessed these pharmacokinetic findings and examined the time course of the same bolus dose followed by a 30-min infusion. METHODS: During nitrous oxide-isoflurane anesthesia, patients with normal renal and hepatic function (n = 25), those with renal failure (n = 28), and those with cirrhosis (n = 6) received a bolus dose of rapacuronium (1.5 mg/kg) followed by a 30-min infusion adjusted to maintain 90-95% twitch depression. At 25% recovery, neostigmine was administered. Blood was sampled until 8 h after the infusion to determine concentrations of rapacuronium and its active metabolite ORG9488. Rapacuronium's pharmacokinetic parameters were determined using mixed-effects modeling. RESULTS: Onset and facilitated recovery of twitch depression were similar in the three groups. Patients with renal failure required 22% less rapacuronium to maintain target twitch depression during the infusion. Rapacuronium's plasma clearance was 24% smaller in renal failure and decreased 0.5%/yr of age; rapid distribution clearance was 51% smaller in men than in women. After the infusion, ORG9488 concentrations decreased markedly more slowly in patients with renal failure. Cirrhosis did not alter the pharmacokinetics of rapacuronium. CONCLUSION: Rapacuronium's plasma clearance and infusion requirement were decreased by renal failure. By dosing to maintain target twitch depression, recovery was not prolonged. Cirrhosis does not affect the pharmacokinetics or neuromuscular effects of rapacuronium. Persistence of ORG9488 in patients with renal failure might prolong recovery after rapacuronium if target twitch depression is not maintained or with administration of rapacuronium for more than 30 min.


Subject(s)
Kidney Failure, Chronic/metabolism , Liver Cirrhosis/metabolism , Neuromuscular Nondepolarizing Agents/pharmacokinetics , Vecuronium Bromide/analogs & derivatives , Vecuronium Bromide/pharmacokinetics , Adolescent , Adult , Age Factors , Aged , Anesthetics, Inhalation , Female , Humans , Male , Middle Aged , Neuromuscular Junction/drug effects , Neuromuscular Nondepolarizing Agents/administration & dosage , Neuromuscular Nondepolarizing Agents/pharmacology , Nitrous Oxide , Time Factors , Vecuronium Bromide/administration & dosage , Vecuronium Bromide/pharmacology
13.
Clin Biochem ; 32(4): 275-82, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10463820

ABSTRACT

OBJECTIVE: Apolipoprotein E (APOE) E4, apolipoprotein B-100 (APOB) Q3611 allele, the angiotensin converting enzyme (ACE) deletion (D) allele and glycoprotein IIIa (GP3A) P33 mutant allele are reported to predispose to early-onset coronary heart disease (CHD). These associations were not all confirmed in more recent studies. To determine the impact of these alleles on CHD, we examined the prevalence of these mutations in patients presenting with early-onset CHD and compared them to those manifesting CHD later in life. The delayed-onset was considered a sign of longevity and would serve as a comparative group to assess prevalence of the biochemical and genetic risk factors. METHODS: 300 patients with a history of myocardial infarction or angina pectoris and angiographically documented CHD were studied. Patients were divided into two groups: group 1 (G1 = 150 patients) presenting with these findings under the age of 50 years; while group 2 (G2 = 150 patients) were patients presenting for the first time over the age of 65 years. Prevalence of the alleles of APOE, APOB, ACE and GP3A was assessed by molecular analysis. An association of any of these genotypes with early onset CHD could lead to a higher prevalence in the younger age group. RESULTS AND CONCLUSIONS: None of the suspected alleles namely APOB Q3611 [G1: 10.7% vs. G2: 9.0%, p = 0.57], ACE D (G1: 52.0% vs. G2: 49.7%, p = 0.57), or the GP3A P33 (G1: 17.3% vs. G2: 15.7%; p = 0.58) showed any significant difference between the two groups. Subjects with APOE E4 were more frequent in the younger age group (G1: 18.3% vs. G2: 13.7%; p = 0.047), while APOE E2 was more frequent in G2 (G2: 10.0% vs. G1: 2.7%; p = 0.0002). Multivariate analysis showed an odds ratio of APOE E2 allele in G1 of 0.27 with a confidence interval of 0.10-0.73.


Subject(s)
Apolipoproteins B/genetics , Apolipoproteins E/genetics , Coronary Disease/genetics , Peptidyl-Dipeptidase A/genetics , Platelet Glycoprotein GPIIb-IIIa Complex/genetics , Polymorphism, Genetic , Adult , Age of Onset , Aged , Analysis of Variance , Apolipoprotein B-100 , Coronary Disease/mortality , Female , Genetic Predisposition to Disease , Humans , Longevity , Male , Middle Aged , Risk Factors , Survival Rate
14.
Int J Geriatr Psychiatry ; 13(7): 445-53, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9695032

ABSTRACT

This article combines data from a clinical trial of donepezil with costing figures to evaluate expected direct costs of care over 5 years after diagnosis of Alzheimer's disease (AD) for patients aged 75 years and over at diagnosis. A Markov model simulates the progression of elderly persons through changing levels of severity. The model compares three treatment regimes for each of two patient groups; mild AD at start of treatment; moderate AD at start of treatment. Patients are followed until 5 years after the start of the treatment. Despite the acquisition costs, use of donepezil is approximately cost-neutral for both 5 mg and 10 mg treatment groups and for patients initially at either mild or moderate states of illness. Expected costs are slightly higher than for the placebo group, but higher expenditure on drugs is partly offset by lower costs of care consequent on treated patients not declining as rapidly as those untreated. The model showed that donepezil patients spent less time in the state of severe dementia, where costs of care are higher. Sensitivity analysis on key assumptions demonstrated that expected costs were highly dependent on discount rate and, more significantly, on the mortality rate.


Subject(s)
Alzheimer Disease/drug therapy , Indans/economics , Nootropic Agents/economics , Piperidines/economics , Aged , Alzheimer Disease/economics , Cognition Disorders/drug therapy , Cognition Disorders/economics , Cost-Benefit Analysis/statistics & numerical data , Disease Progression , Donepezil , Dose-Response Relationship, Drug , Humans , Indans/therapeutic use , Markov Chains , Models, Economic , Models, Neurological , Models, Psychological , Nootropic Agents/therapeutic use , Piperidines/therapeutic use , Severity of Illness Index , Treatment Outcome , United Kingdom/epidemiology
15.
Clin Biochem ; 31(2): 95-100, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9622772

ABSTRACT

OBJECTIVE: In the presence of low serum folate, mutant 5,20-methylenetetrahydrofolate reductase (MTHFR + [A223V/C677T]) in the homozygous state (+/+), may predispose to higher plasma homocysteine (tHct) levels and coronary artery disease (CAD). To determine the impact of this relationship on predisposition to early-onset CAD, we examined the prevalence of the mutation and plasma tHct in patients with early-onset CAD and compared them to patients manifesting CAD later in life. METHODS: Three hundred patients with history of acute myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients) presenting with these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation was assessed by molecular analysis, and plasma tHct and folate were measured. An association of the +/+ genotype with early onset CAD could lead to its higher prevalence in the younger age group. RESULTS: There was no significant difference in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2: 11.3%). However, patients with the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01). CONCLUSION: The mutant MTHFR genotype was not found to be a determining factor in early-onset CAD. Higher tHct values were obtained in the older age group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTHFR genotype and low folate status yielding high tHct levels in those with the (+/+) genotype. As this relation was seen in both groups, although to a lesser extent in the older G2, it does not explain the underlying cause of early-onset CAD.


Subject(s)
Coronary Disease/blood , Coronary Disease/genetics , Homocysteine/blood , Oxidoreductases Acting on CH-NH Group Donors/genetics , Point Mutation , Age of Onset , Aged , Autoanalysis , Chromatography, High Pressure Liquid , Disease Susceptibility , Genetic Variation , Genotype , Heterozygote , Homozygote , Humans , Methylenetetrahydrofolate Reductase (NADPH2) , Middle Aged
16.
Can J Cardiol ; 14(2): 215-20, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9520858

ABSTRACT

OBJECTIVE: To determine the impact of mutations in the HFE gene (human leukocyte antigen H) on predisposition to coronary artery disease (CAD) in patients not diagnosed with hereditary hemochromatosis. BACKGROUND: Elevated iron stores can predispose to acute myocardial infarction. Two mutations (C282Y and H63D) in the novel major histocompatibility complex (MHC) class 1 gene HFE were found in most patients with hereditary hemochromatosis causing high iron stores. The effect of these mutations on predisposition to CAD has not been investigated previously. METHODS: Three hundred patients with a history of myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients were divided into two groups: group 1 (150 patients), manifesting early onset CAD and presenting with these findings under age 50 years; and group 2 (150 patients), presenting for the first time over age 65 years. Prevalence of the C282Y and H63D mutations was assessed by molecular analysis, and plasma ferritin was measured immunochemically. RESULTS: There was no difference in the prevalence of homozygous, heterozygous or compound heterozygous (C282Y/H63D) states between the groups. Males in group 1 had higher plasma ferritin than those in group 2 (234 +/- 174 micrograms/L versus 136 +/- 103 micrograms/L, P < 0.0001), but this was not significantly different in females (75 +/- 54 micrograms/L versus 92 +/- 73 micrograms/L, P = 0.26). Ferritin remained higher in group 1 than in group 2 males after exclusion of mutation carriers (195 +/- 121 micrograms/L versus 109 +/- 76 micrograms/L, respectively, P < 0.0001), but did not change in females. CONCLUSIONS: Higher iron stores were found in males with early onset CAD. This association was not related to the C282Y or H63D mutation in HFE. It is suggested that association of the MHC locus with delayed onset CAD is probably unrelated to HFE in these patients, and that HFE mutations are not a major risk factor in the development of high iron stores in early onset CAD.


Subject(s)
Coronary Disease/genetics , HLA Antigens/genetics , Iron/blood , Mutation , Coronary Disease/blood , Female , Ferritins/blood , Hemosiderosis/genetics , Humans , Immunohistochemistry , Male , Sex Factors
17.
J Affect Disord ; 47(1-3): 183-90, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9476759

ABSTRACT

The purpose of the present study was to detect any problems among anxious patients in switching from alprazolam to extended release alprazolam. Fifty-four patients with an anxiety disorder, stabilized on alprazolam, entered the study. During the first 2 weeks, all patients took alprazolam as usual. During the second 2 weeks, they all took the same dosage of the extended release formulation. They were evaluated weekly with standard clinical measures and were asked to report any adverse medical events. The clinical measures showed modest, steady improvement over the course of the study. Patients reporting adverse medical events increased from 26% of the sample to 60% after the switch of dosage forms. Most of these events were anxiety-like (48%) or sedative (37%). Patients who developed sedative events took slightly higher mean doses of alprazolam. Patients who developed anxiety-like events had higher baseline scores on the Somatization, Anxiety and Phobia clusters of the SCL-90. The results suggest that more anxious patients confronted with a change of regimen commonly generate anxiety symptoms that they attribute to the medication, i.e., negative placebo responses, perhaps especially if they have a tendency toward somatization. A study designed to sort out pharmacological and psychological effects and further explore the mechanisms at work is indicated.


Subject(s)
Alprazolam/adverse effects , Anxiety Disorders/drug therapy , Acute Disease , Adult , Alprazolam/administration & dosage , Alprazolam/therapeutic use , Anxiety Disorders/chemically induced , Delayed-Action Preparations , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Placebo Effect , Psychiatric Status Rating Scales , Sleep , Somatoform Disorders/chemically induced , Somatoform Disorders/diagnosis , Somatoform Disorders/psychology , Treatment Outcome
18.
Eur Heart J ; 19(12): 1879-88, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9886732

ABSTRACT

AIMS: The American Heart Association has endorsed the concept of Public Access Defibrillation. However, there have been reports of inappropriate direct current shocks from automatic external defibrillators. The specificity of automatic external defibrillators for shockable rhythms may be improved by the incorporation of a haemodynamic sensor. METHODS AND RESULTS: This study examined the use of four parameters extracted from the impedance cardiogram i.e. Peak dz/dt (the peak of the impedance cardiogram measured from the line dz/dt=0 ohms(-1)), Peak-trough (the peak-to-trough measurement of the impedance cardiogram ohms(-1)), Area 1 (the area under the C wave of the impedance cardiogram above the line dz/dt=0 mohm) and Area 2 (the area under the impedance cardiogram 50 ms on either side of the Peak and above the line dz/dt=0 mohm) as predictors of cardiac output. At 116 cardiac arrest calls the ECG and impedance cardiogram were recorded through two ECG/defibrillator pads placed in an antero-apical position. Nine recordings were rejected for artefact. The rhythm recorded in the remaining 107 calls was asystole (19), ventricular fibrillation (14), agonal rhythm (20), electromechanical dissociation (22), ventricular tachycardia (27) and sinus rhythm (5). These rhythms were divided into those associated with haemodynamic collapse i.e. no pulse -- asystole, ventricular fibrillation, agonal rhythm, electromechanical dissociation and shockable ventricular tachycardia (associated with loss of consciousness, pulselessness or a systolic blood pressure of <80 mmHg) (Group 1) and those associated with a satisfactory cardiac output i.e. non-shockable ventricular tachycardia (conscious with a pulse) and sinus rhythm (Group 2). On univariate analysis each of the four impedance cardiogram parameters were significantly greater in Group 2 than Group 1 (P<0.001). On multivariate analysis the parameters which best differentiated the two groups were Area 1 and Peak-trough. CONCLUSION: Thus the impedance cardiogram is a potential haemodynamic sensor for an automatic external defibrillator.


Subject(s)
Cardiography, Impedance , Electric Countershock , Adult , Aged , Case-Control Studies , Electric Countershock/instrumentation , Female , Heart Arrest/therapy , Hemodynamics/physiology , Humans , Male , Multivariate Analysis , Signal Processing, Computer-Assisted
19.
Br J Anaesth ; 78(6): 671-4, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9215017

ABSTRACT

We have assessed the effect of two concentrations of hyaluronidase on the quality of peribulbar block, using a low volume, single injection technique. We studied 200 patients undergoing elective intraocular surgery, allocated randomly to one of three groups. Group 1 (n = 50) received peribulbar block with 5 ml of a 1:1 mixture of 0.5% plain bupivacaine and 2% plain lignocaine. Group 2 (n = 75) received this solution supplemented with hyaluronidase 50 iu ml-1. Group 3 (n = 75) received the same solution supplemented with hyaluronidase 300 iu ml-1. Lack of ocular motility was considered to be the only objective sign of successful block and movement of each rectus muscle was scored at 1-, 5- and 10-min intervals. If the block was successful at 5 min, the 10-min score was omitted. If the block was unsuccessful at 5 min, a second injection of 2% lignocaine 3 ml was given and additional assessments performed at 5-min intervals. At 1 min, ocular motility scores were significantly lower in group 3 compared with the control group (P < 0.05). The incidence of satisfactory block at 5 min was increased in both groups given hyaluronidase (group 2, P < 0.05; group 3, P < 0.001). There were no significant differences between groups 2 and 3 with respect to quality of block at 5 min. Hyaluronidase in both concentrations improved the quality of peribulbar block at 5 min, and when used in a concentration of 300 iu ml-1, also improved the speed of onset of block.


Subject(s)
Adjuvants, Anesthesia/administration & dosage , Anesthesia, Local/methods , Hyaluronoglucosaminidase/administration & dosage , Ophthalmologic Surgical Procedures , Aged , Aged, 80 and over , Anesthetics, Combined , Bupivacaine , Dose-Response Relationship, Drug , Eye Movements/drug effects , Female , Humans , Lidocaine , Male , Middle Aged
20.
Pacing Clin Electrophysiol ; 20(1 Pt 2): 226-9, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9121995

ABSTRACT

We postulated that reducing peak leading edge shock voltage and its rate of rise (waveform rounding) would reduce energy requirements for cardioversion of AF and AFl, and may therefore reduce patient discomfort. Transvenous defibrillating catheters (In-Control Inc.) were placed in the RAA (active fixation) and the CS of six anesthetized sheep. AF or AFl was induced by electrical stimulation (100 Hz, 2 V; Grass stimulator). A standard trapezoidal biphasic (S) waveform (3-ms duration each phase) was compared with a similar waveform that had the first phase rounded (R). Cardioversion was attempted after 30 seconds of arrhythmia, using a Ventritex HVS-O2 defibrillator modified to allow waveform rounding. Each waveform was randomly tested several times at 100-, 150-, and 200-V leading edges, and percentage cardioversion success calculated. Shock energy was calculated from delivered current and voltage using Flukeview (Fluke, Inc.) software. At 100-V leading edge R (64% success) and S (59%), shocks were similarly efficacious (P = 0.37). However, R delivered less current, voltage, and energy than the comparable S shock (means 1.30 A, 65.0 V, 0.33 J R vs 1.92 A, 94.2 V, 0.47 J S; P = 0.0001). Both waveforms were equally successful at 150 V (88% vs 100%; P = NS) and 200 V (100% vs 100%), but again R delivered less current, voltage, and energy (2.05 A, 102.5 V, 0.82 J R vs 2.78 A, 142.3 V, 1.11 J S at 150 V; 2.76 A, 141.2 V, 1.58 J R vs 3.77 A, 189.4 V, 2.03 J S at 200 V; both P = 0.0001). No arrhythmic or other complications occurred in the 174 shocks delivered. Waveform rounding reduces delivered peak voltage, current, and energy without reducing defibrillation efficacy. To determine if these changes are associated with a reduction in discomfort, patients with AF are currently being cardioverted with these waveforms during electrophysiological studies.


Subject(s)
Atrial Fibrillation/therapy , Atrial Flutter/therapy , Electric Countershock/methods , Animals , Arrhythmias, Cardiac/prevention & control , Catheterization/instrumentation , Coronary Vessels , Electric Conductivity , Electric Countershock/instrumentation , Electric Stimulation , Electrophysiology , Heart Atria , Sheep , Software , Time Factors , Treatment Outcome
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