A retrospective analysis of mycophenolic acid and cyclosporin concentrations with acute rejection in renal transplant recipients

Objectives: Although monitoring of cyclosporin (CsA) is standard clinical practice postrenal transplantation. mycophenolic acid (MPA) concentrations are not routinely measured. There is evidence that a relationship exists between MPA area under the concentration-time curve (AUC) and rejection. In this study, a retrospective analysis was undertaken of 27 adult renal transplant recipients. Methods: Patients received CsA and MPA therapy and had a four-point MPA AUC investigation. The relationship between MPA AUC performed in the first week after transplantation, as well as median trough cyclosporin concentrations, and clinical outcomes in the first month posttransplant were evaluated. Results: A total of 12 patients experienced biopsy proven rejection (44.4%) and 4 patients had gastrointestinal adverse events (14.8%). A statistically significant relationship was observed between the incidence of biopsy proven rejection and both MPA AUC (p = 0.02) and median trough CsA concentration (p = 0.008). No relationship between trough MPA concentration and rejection was observed (p = 0.21). Only 3 of 11 (27%) patients with an MPA AUC > 30 mg.h/L and a median trough CsA > 175 mug/L experienced acute rejection, compared with a 56% incidence of rejection for the remaining 16 patients. Patients who experienced adverse gastrointestinal events had significantly lower MPA AUC (p = 0.04), but median trough CsA concentrations were not significantly different (p = 0.24). Further, 3 of these 4 patients had rejection episodes. Conclusions: in addition to standard CsA monitoring, we propose further investigation of the use of a 4-point sampling strategy to predict MPA AUC in the first week posttransplant, which may facilitate optimization of mycophenolate mofetil dose at a rime when patients are most vulnerable to acute rejection. (C) 2001 The Canadian Society of Clinical Chemists. All rights reserved.

A retrospective analysis of leadership development through sport

The purpose of this study was to examine the development of six leader-athletes. In-depth qualitative interviews were used to explore the various activities that leader athletes engaged in from an early age as well as the roles and influences that peers, coaches, and parents played within these activities. Results indicated that leadership development in sport focused on developing four central components: high skill, strong work ethic, enriched cognitive sport knowledge, and good rapport with people. The types of activities engaged in throughout development as well as receiving feedback, acknowledgement, support, cognitive engagement, mature conversations with adults, and physical encounters with older peers are important social influences that can play an instrumental role in the formation of these four central tenets.

Is mortality from heart failure increasing in Australia? An analysis of official data on mortality for 1997-2003

Objective To assess whether trends in mortality from heart failure(HF) in Australia are due to a change in awareness of the condition or real changes in its epidemiology. Methods We carried out a retrospective analysis of official data on national mortality data between 1997 and 2003. A death was attributed to HF if the death certificate mentioned HF as either the underlying cause of death (UCD) or among the contributory factors. Findings From a total of 907 242 deaths, heart failure was coded as the UCD for 29 341 (3.2%) and was mentioned anywhere on the death certificate in 135 268 (14.9%). Between 1997 and 2003, there were decreases in the absolute numbers of deaths and in the age-specific and age-standardized mortality rates for HF either as UCD or mentioned anywhere for both sexes. HF was mentioned for 24.6% and 17.8% of deaths attributed to ischaemic heart disease and circulatory disease, respectively, and these proportions remained unchanged over the period of study. In addition, HF as UCD accounted for 8.3% of deaths attributed to circulatory disease and this did not change materially from 1997 to 2003. Conclusion The decline in mortality from HF measured as either number of deaths or rate probably reflects a real change in the epidemiology of HF. Population-based studies are required to determine accurately the contributions of changes in incidence, survival and demographic factors to the evolving epidemiology of HF.

Arrhythmias and mortality after myocardial infarction in diabetic patients - Relationship to diabetes treatment

OBJECTIVE- To assess the relationship between clinical course after acute myocardial infarction (AMI) and diabetes treatment. RESEARCH DESIGN AND METHODS- Retrospective analysis of data from all patients aged 25-64 years admitted to hospitals in Perth, Australia, between 1985 and 1993 with AMI diagnosed according to the International Classification of Diseases (9th revision) criteria was conducted. Short- (28-day) and long-term survival and complications in diabetic and nondiabetic patients were compared. For diabetic patients, 28-day survival, dysrhythmias, heart block, and pulmonary edema were treated as outcomes, and factors related to each were assessed using multiple logistic regression. Diabetes treatment was added to the model to assess its significance. Long-term survival was compared by means of a Cox proportional hazards model. RESULTS- Of 5,715 patients, 745 (12.9%) were diabetic. Mortality at 28 days was 12.0 and 28.1% for nondiabetic and diabetic patients, respectively (P < 0.001); there were no significant drug effects in the diabetic group. Ventricular fibrillation in diabetic patients taking glibenclamide (11.8%) was similar to that of nondiabetic patients (11.0%) but was lower than that for those patients taking either gliclazide (18.0%; 0.1 > P > 0.05) or insulin (22.8%; P < 0.05). There were no other treatment-related differences in acute complications. Long-term survival in diabetic patients was reduced in those taking digitalis and/or diuretics but type of diabetes treatment at discharge had no significant association with outcome. CONCLUSlONS- These results do not suggest that ischemic heart disease should influence the choice of diabetes treatment regimen in general or of sulfonylurea drug in particular.

Interval breast cancers in an Australian mammographic screening program

Objective: To determine the incidence of interval cancers which occurred in the first 12 months after mammographic screening at a mammographic screening service. Design: Retrospective analysis of data obtained by crossmatching the screening Service and the New South Wales Central Cancer Registry databases. Setting: The Central & Eastern Sydney Service of BreastScreen NSW. Participants: Women aged 40-69 years at first screen, who attended for their first or second screen between 1 March 1988 and 31 December 1992. Main outcome measures: Interval-cancer rates per 10 000 screens and as a proportion of the underlying incidence of breast cancer (as estimated by the underlying rate in the total NSW population). Results: The 12-month interval-cancer incidence per 10 000 screens was 4.17 for the 40-49 years age group (95% confidence interval [CI], 1.35-9.73) and 4.64 for the 50-69 years age group (95% CI, 2.47-7.94). Proportional incidence rates were 30.1% for the 40-49 years age group (95% CI, 9.8-70.3) and 22% for the 50-69 years age group (95% CI, 11.7-37.7). There was no significant difference between the proportional incidence rate for the 50-69 years age group for the Central & Eastern Sydney Service and those of major successful overseas screening trials. Conclusion: Screening quality was acceptable and should result in a significant mortality reduction in the screened population. Given the small number of cancers involved, comparison of interval-cancer statistics of mammographic screening programs with trials requires age-specific or age-adjusted data, and consideration of confidence intervals of both program and trial data.

An evaluation of the time dependence of the anisotropy of the water diffusion tensor in acute human ischemia

We have performed MRI examinations to determine the water diffusion tensor in the brain of six patients who were admitted to the hospital within 12 h after the onset of cerebral ischemic symptoms. The examinations have been carried out immediately after admission, and thereafter at varying intervals up to 90 days post admission. Maps of the trace of the diffusion tensor, the fractional anisotropy and the lattice index, as well as maps of cerebral blood perfusion parameters, were generated to quantitatively assess the character of the water diffusion tensor in the infarcted area. In patients with significant perfusion deficits and substantial lesion volume changes, four of six cases, our measurements show a monotonic and significant decrease in the diffusion anisotropy within the ischemic lesion as a function of time. We propose that retrospective analysis of this quantity, in combination with brain tissue segmentation and cerebral perfusion maps, may be used in future studies to assess the severity of the ischemic event. (C) 1999 Elsevier Science Inc.

Overseas visitors admitted to Queensland hospitals for water-related injuries

Objective: To determine the number of overseas visitors admitted to Queensland hospitals for water-related injuries over three years, the causes of their injuries, the resulting conditions treated, and the type of hospitals to which they were admitted. Design: Retrospective analysis of admissions of overseas visitors to Queensland hospitals over the three financial years 1995/96, 1996/97 and 1997/98. Patients: 296 overseas visitors admitted for water-related injuries, identified from hospital records by their usual place of residence. Main outcome measures: Number of admissions, causes of injuries, conditions treated. and bed days occupied by these patients at different types of hospitals (metropolitan, regional and rural public hospitals, and private hospitals). Results: The 296 overseas visitors accounted for a total of 596 separate admissions, many of these the result of patients with decompression illness being admitted several times to a regional hospital hyperbaric chamber for treatment as day patients. The largest number of injuries involved the use of diving equipment. The main conditions treated were decompression illness (54.7%), fractures and dislocations (15.5%), and drowning and non-fatal submersion (14.9%). Overall, overseas visitors admitted to hospital following a water-related incident occupied 1215 bed days; 90% of these admissions were to regional hospitals. Conclusions: The main reason for admission of overseas visitors is for decompression illness, suggesting that the prevention of injuries among scuba divers requires further coordinated efforts by health and tourism authorities.

Referral to post-acute care following traumatic brain injury (TBI) in the Australian context

The study aimed to describe the types of care allocated at the end of acute care to people diagnosed with TBI and to identify the factors associated with variations in referral to care. A retrospective analysis of medical records of 61 patients was conducted based on a sample from two hospitals. While 60.7% of the study sample were referred to formal rehabilitation care, this was primarily non-inpatient rehabilitation care (32.8%). Discriminant analysis was used to determine medical and non-medical predictors of referral. Results indicated that place of treatment and age contribute to group differences and were significant in separating the inpatient rehabilitation group from the non-inpatient and no rehabilitation groups. Review by a rehabilitation physician was associated with referral to inpatient rehabilitation but was not adequate to explain referral to non-inpatient rehabilitation. An in-depth exploration of post-acute referral is warranted to improve policy and practice in relation to continuity of care following TBI.

Low tacrolimus concentrations and increased risk of early acute rejection in adult renal transplantation

Background. A retrospective analysis was performed on adult renal transplant recipients to evaluate the relationship between tacrolimus trough concentrations and the development of rejection in the first month after transplant. Methods. A total of 349 concentrations from 29 patients, measured by enzyme-linked immunosorbent assay (ELISA), were recorded. Based on an increased serum creatinine, 12 patients were considered to have organ rejection. Rejection was confirmed by biopsy in five of these. The median trough concentration of tacrolimus over the first month of therapy, or until the time of first rejection was compared in rejecters vs non-rejecters. Results. Median trough concentrations of tacrolimus were found to be lower in biopsy-proven rejecters vs non-rejecters (P=0.03) and all rejecters vs nonrejecters (P = 0.04). The average median concentration (+/- SD) in the biopsy-proven rejecter group was 5.09 +/-1.16 ng/ml, compared to 9.20 +/-3.52 ng/ml in the non-rejecter group. After exclusion of an outlier, the average median concentration in all rejecters was 5.57 +/-1.47 ng/rnl, compared with 9.20 +/-3.52 ng/ml in non-rejecters. A rejection rate of 55% was found for patients with a median trough concentration between 0 and 10 ng/ml. This compared with no observed rejection in patients with a median concentration between 10 and 15 ng/ml. Conclusion. A significant relationship exists between organ rejection and median tacrolimus trough concentrations in the first month post-transplant, with patients displaying low concentrations more likely to reject. In order to minimize rejection in the first month after renal transplantation, trough concentrations greater than 10 ng/ml must be achieved.

Single institution outcomes of treatment of severe aplastic anaemia

Background: In severe aplastic anaemia, the treatment of choice for young patients with a human leucocyte antigen-matched sibling is now established as allogeneic bone marrow transplantation (BMT). In older patients and in those without a matched sibling donor, immunosuppressive therapy is the usual first option. 'Alternative' marrow donors are emerging as an option for those without a matched sibling donor. Aims: To review 10 years of local experience in treating severe aplastic anaemia with BMT and immunosuppressive therapy with emphasis on long-term outcomes. Methods: A retrospective analysis was performed of all patients with severe aplastic anaemia presenting to the Royal Brisbane and Royal Children's Hos- pitals between 1989 and 1999. Data were abstracted regarding patient demographics, pretreatment characteristics and outcome measures, including response rates, overall survival and long-term complications. Results: Twenty-seven consecutive patients were identified, 12 treated with immunosuppression alone and 15 with BMT. In these two groups, transfusion independence was attained in 25% and 100%, respectively, with overall survival being 36% and 100%, respectively. Those treated with immunosuppression were significantly older (median 41.5 versus 22 years, P = 0.008). Long-term survivors of either treatment had extremely low morbidity. Three patients carried pregnancies to term post-transplant. Three patients received alternative donor BMT with correspondingly excellent survival. Conclusions: Patients treated with allogeneic BMT for severe aplastic anaemia enjoyed extremely good long-term survival and minimal morbidity. Patients treated with immunosuppressive therapy had a poorer outcome reflecting their older age and different usage of therapies over the past decade. Optimal treatment strategies for severe aplastic anaemia remain to be determined.

Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment of steroid-resistant acute graft-versus-host disease developing during cyclosporine prophylaxis

We report our experience with the combination of anti-thymocyte globulin (ATGAM) and tacrolimus in the treatment of 20 patients with steroid refractory and dependent acute graft-versus-host disease (GVHD) transplanted between August 1996 and February 2000. All patients received cyclosporine-based GVHD prophylaxis. Thirteen patients developed a maximum of grade TV, five grade III and two grade II acute GVHD, with 15 patients being refractory to steroids and five dependent on steroids. Patients were treated with ATGAM (15 mg/kg for 5 d) and tacrolimus (0.025-0.1 mg/kg/d) in addition to continuation of their high-dose steroids and cessation of their cyclosporine. Within 28 d of treatment, we observed eight complete responses (CR), six partial responses (PR) and six with no response. Overall response (CR + PR) was predicted by GVHD severity. Infectious complications occurred in 80% of patients. The median survival was 86.5 d (range, 21-1081 d) with 35% of patients remaining alive, Survival following combination therapy was significantly more likely in men (P < 0.001), skin-only GVHD (P = 0.027), less severe GVHD (P = 0.048), and in responders to tacrolimus and ATGAM (P< 0.001). In conclusion, concurrent introduction of ATGAM and tacrolimus is a promising therapeutic combination for GVHD refractory to steroids and cyclosporine.

The use of ACE-inhibitors after myocardial infarction

Background: There is good evidence that angiotensin-converting enzyme (ACE) inhibitors are beneficial after myocardial infarction (MI). However, it is not known how widely this evidence is used in practice and whether all eligible patients receive this therapy. Aim: To assess the usage of ACE inhibitors in patients after MI in a large teaching hospital. Method: A one month prospective analysis, combined with a three month retrospective analysis, was conducted at the Royal Brisbane Hospital (RBH) in February-March 2000. Patients admitted with an MI or who had been diagnosed with an MI during admission from November 1999 to March 2000 were identified from the coronary care unit (CCU) records. Inpatient medication charts and outpatient records were then reviewed. Information collected included: ACE inhibitor use, doses, reasons for prescribing/not prescribing ACE inhibitors, and ACE inhibitor prescribers (cardiologists or general physicians). Results: Forty four patients with an MI were included in the study, 28 of whom were prescribed ACE-inhibitors (64%). Twenty four of the 28 patients on ACE inhibitors were prescribed perindopril. The major reason given for prescribing ACE inhibitors was signs of congestive cardiac failure. All ACE inhibitors initiated in patients after MI at RBH were ordered by cardiologists. Conclusion: ACE inhibitors were prescribed appropriately in 88% of patients who met criteria for their use. This high percentage of appropriate prescribing was encouraging. Reevaluation as part of an ongoing quality assurance activity could be used to ensure this is maintained.

Iatrogenic bile duct injury: The scourge of laparoscopic cholecystectomy

Background: Laparoscopic cholecystectomy (LC) has become the first-line surgical treatment of calculous gall-bladder disease and the benefits over open cholecystectomy are well known. In the early years of LC, the higher rate of bile duct injuries compared with open cholecystectomy was believed to be due to the 'learning curve' and would dissipate with increased experience. The purpose of the present paper was to review a tertiary referral unit's experience of bile duct injuries induced by LC. Methods: A retrospective analysis was performed on all patients referred for management of an iatrogenic bile duct injury from 1981 to 2000. For injuries sustained at LC, details of time between LC and recognition of the injury, time from injury to definitive repair, type of injury, use of intraoperative cholangiography (IOC), definitive repair and postoperative outcome were recorded. The type of injury sustained at open cholecystectomy was similarly classified to allow the severity of injury to be compared. Results: There were 131 patients referred for management of an iatrogenic bile duct injury that occurred at open cholecystectomy (n = 62), liver resection (n = 5) and at LC (n = 64). Only 39% of bile duct injuries were recognized at the time of LC. Following conversion to open operation, half the subsequent procedures were considered inappropriate. When the injury was not recognized during LC, 70% of patients developed bile leak/peritonitis, almost half of whom were referred, whereas the rest underwent a variety of operative procedures by the referring surgeon. The remainder developed jaundice or abnormal liver function tests and cholangitis. An IOC was performed in 43% of cases, but failed to identify an injury in two-thirds of patients. The bile duct injuries that occurred at LC were of greater severity than with open cholecystectomy. Following definitive repair, there was one death (1.6%). Ninety-two per cent of patients had an uncomplicated recovery and there was one late stricture requiring surgical revision. Conclusions: The early prediction that the rate of injury during LC would decline substantially with increased experience has not been fulfilled. Bile duct injury that occurs at LC is of greater severity than with open cholecystectomy. Bile duct injury is recognized during LC in less than half the cases. Evidence is accruing that the use of cholangiography reduces the risk and severity of injury and, when correctly interpreted, increases the chance of recognition of bile duct injury during the procedure. Prevention is the key but, should an injury occur, referral to a specialist in biliary reconstructive surgery is indicated.

Assault-related admissions to hospital in Central Australia

Objective: To determine the number of assault-related admissions to hospital in the Central Australia region of the Northern Territory over a six-year period. Design and setting: Retrospective analysis of all patients admitted to Alice Springs Hospital (ASH) and Tennant Creek Hospital (TCH) from July 1995 to June 2001, where the primary cause of injury was assault. Main outcome measures: Frequency of assault-related admission to hospital; demographic characteristics of the victims. Results: in the six years, there were 2449 assault-related admissions to ASH and 545 to TCH. Adults aged 25-34 years were most frequently hospitalised for assault, in a proportion greater than their proportion in the NT population, Females represented 59.7% of people admitted to ASH and 54.7% to TCH, greater than their proportion in the NT population. Aboriginals comprised 95.2% of ASH and 89.0% of TCH admissions, and were admitted in a significantly greater proportion than their proportion in the NT population (P < 0.001). The age-adjusted hospital admission rate resulting from assault has increased (P = 0.002) at an average rate of 1.6 (SE, 0.2) per 10 000 people per year. The proportion of assault-related admissions associated with alcohol has also increased significantly (P < 0.001). Conclusion: The frequency of assault-related admissions to hospital, especially among the Aboriginal population, suggests that this major public health issue is escalating.