Low INSL3 in Klinefelter syndrome is related to osteocalcin, testosterone treatment and body composition, as well as measures of the hypothalamic-pituitary-gonadal axis.

Klinefelter syndrome (KS) is characterized by infertility and hypogonadism associated with increased prevalence of osteoporosis, diabetes and metabolic syndrome. Insulin-like factor 3 (INSL3) is produced in the Leydig cells. INSL3 has been suggested to play a role in bone health. Here, we studied INSL3 in relation to bone markers, body composition, the metabolic syndrome and diabetes. This was a case-control study. Sex hormones, anthropometric measures, vitamin D metabolites, parathyroid hormone, growth factors, muscle strength, maximal oxygen consumption and BMD were measured. We included 70 adult KS patients and 71 age-matched controls. INSL3 was lower in testosterone-treated KS compared with untreated KS. Correlation analyses showed a positive correlation between INSL3 and osteocalcin among KS, but not in controls; a significant positive correlation between INSL3 and testosterone in controls and in untreated KS, but not in treated KS men. Among controls a negative correlation was found between INSL3 and lipids, and glucose, but not in KS. HOMA2-B and impaired fasting glycaemia was positively correlated with INSL3 in controls. Among KS males we found a negative correlation between INSL3 and BMI, weight and waist/hip ratio, as well as positive correlations between INSL3 and FSH, LH, SHBG and testis volume. Multivariate analyses showed that age, testosterone and HDL cholesterol were the principal independent variables among healthy controls, whereas the determinants of INSL3 concentration among KS were age, LH, current testosterone treatment and testicular volume. INSL3 in KS is influenced by testosterone treatment and INSL3 is correlated with measures of bone metabolism, body composition and the metabolic syndrome. This may suggest that low INSL3 concentration is related to the pathogenesis behind an unfavourable change in body composition and bone metabolism among KS patients.

Human testicular insulin-like factor 3: in relation to development, reproductive hormones and andrological disorders.

Knockout of the gene encoding insulin-like factor 3 (INSL3) results in cryptorchidism in mice due to disruption of the transabdominal phase of testicular descent. This finding was essential for understanding the complete course of testis descensus, and wound up years of speculations regarding the endocrine regulation of this process. INSL3 is, along with testosterone, a major secretory product of testicular Leydig cells. In addition to its crucial function in testicular descent, INSL3 is suggested to play a paracrine role in germ cell survival and an endocrine role in bone metabolism. INSL3 is produced in human prenatal and neonatal, and in adult Leydig cells to various extents, and is in a developmental context regulated like testosterone, with production during second trimester, an early postnatal peak and increasing secretion during puberty, resulting in high adult serum levels. INSL3 production is entirely dependent on the state of Leydig cell differentiation, and is stimulated by the long-term trophic effects mediated by luteinizing hormone (LH). Once differentiated, Leydig cells apparently express INSL3 in a constitutive manner, and the hormone is thereby insensitive to the acute, steroidogenic effects of LH, which for example is an important factor in the regulation of testosterone. Clinically, serum INSL3 levels can turn out to be a usable tool to monitor basal Leydig cell function in patients with various disorders affecting Leydig cell function. According to animal studies, foetal INSL3 production is, directly or indirectly, sensitive to oestrogenic or anti-androgenic compounds. This provides important insight into the mechanism by which maternal exposure to endocrine disrupters can result in cryptorchidism in the next generation. Conclusively, INSL3 is an interesting testicular hormone with potential clinical value as a marker for Leydig cell function. It should be considered on a par with testosterone in the evaluation of testicular function and the consequences of Leydig cell dysfunction.

Optimising ankle sprain prevention: a critical review and practical appraisal of the literature.

OBJECTIVES: To establish the effect of preventive measures and assert the optimal prevention strategy for acute lateral ligament injury to the ankle. METHODS: An electronic literature search was employed to look for published randomised controlled trials, a controlled trials or time interventions containing research questions regarding the prevention of lateral ankle ligament injuries. Two reviewers reviewed relevant studies for strengths and weaknesses in design and methodology, according to a standardised set of predefined criteria. A total of 24 relevant studies met the criteria for inclusion and were analysed. RESULTS: Overall taping, bracing and neuromuscular training were all effective for the prevention of ankle-sprain recurrences. The RRs of these prophylactic measures are of similar magnitude, ranging from 0.2 to 0.5 when compared with control groups. Although preventive effects have been reported in a general athletic population, evidence suggests this overall effect is due to a strong preventive effect in previously injured athletes and that any effect on fresh ankle sprains is either non-existent or very low. CONCLUSIONS: Based on these outcomes, a combination of an external prophylactic measure (tape or brace) with neuromuscular training will achieve the best preventive outcomes with minimal burden for the athlete.

Alpha-2 adrenergic regulation of pedunculopontine nucleus neurons during development.

Rapid eye movement sleep decreases between 10 and 30 days postnatally in the rat. The pedunculopontine nucleus is known to modulate waking and rapid eye movement sleep, and pedunculopontine nucleus neurons are thought to be hyperpolarized by noradrenergic input from the locus coeruleus. The goal of the study was to investigate the possibility that a change in alpha-2 adrenergic inhibition of pedunculopontine nucleus cells during this period could explain at least part of the developmental decrease in rapid eye movement sleep. We, therefore, recorded intracellularly in 12-21 day rat brainstem slices maintained in oxygenated artificial cerebrospinal fluid. Putative cholinergic vs. non-cholinergic pedunculopontine nucleus neurons were identified using nicotinamide adenine dinucleotide phosphate diaphorase histochemistry and intracellular injection of neurobiotin (Texas Red immunocytochemistry). Pedunculopontine nucleus neurons also were identified by intrinsic membrane properties, type I (low threshold spike), type II (A) and type III (A+low threshold spike), as previously described. Clonidine (20 microM) hyperpolarized most cholinergic and non-cholinergic pedunculopontine nucleus cells. This hyperpolarization decreased significantly in amplitude (mean+/-S.E.) from -6.8+/-1.0 mV at 12-13 days, to -3.0+/-0.7 mV at 20-21 days. However, much of these early effects (12-15 days) were indirect such that direct effects (tested following sodium channel blockade with tetrodotoxin (0.3 microM)) resulted in hyperpolarization averaging -3.4+/-0.5 mV, similar to that evident at 16-21 days. Non-cholinergic cells were less hyperpolarized than cholinergic cells at 12-13 days (-1.6+/-0.3 mV), but equally hyperpolarized at 20-21 days (-3.3+/-1.3 mV). In those cells tested, hyperpolarization was blocked by yohimbine, an alpha-2 adrenergic receptor antagonist (1.5 microM). These results suggest that the alpha-2 adrenergic receptor on cholinergic pedunculopontine nucleus neurons activated by clonidine may play only a modest role, if any, in the developmental decrease in rapid eye movement sleep. Clonidine blocked or reduced the hyperpolarization-activated inward cation conductance, so that its effects on the firing rate of a specific population of pedunculopontine nucleus neurons could be significant. In conclusion, the alpha-2 adrenergic input to pedunculopontine nucleus neurons appears to consistently modulate the firing rate of cholinergic and non-cholinergic pedunculopontine nucleus neurons, with important effects on the regulation of sleep-wake states.

Prenatal exposure to cigarette smoke affects the physiology of pedunculopontine nucleus (PPN) neurons in development.

Prenatal exposure to cigarette smoke is known to produce lasting arousal, attentional and cognitive deficits in humans. The pedunculopontine nucleus (PPN), as the cholinergic arm of the reticular activating system (RAS), is known to modulate arousal, waking and rapid eye movement (REM) sleep. REM sleep decreases between 10 and 30 days postnatally in the rat, especially at 12-21 days. Pregnant dams were exposed to 350 ml of cigarette smoke for 15 min, 3 times per day, from day E14 until birth, and the pups allowed to mature. Intracellularly recorded PPN neurons in 12-21 day rat brainstem slices were tested for intrinsic membrane properties, including the hyperpolarization-activated cation current Ih, which is known to drive oscillatory activity. Type II (A-current) PPN cells from 12-16 day old offspring of treated animals had a 1/2max Ih amplitude of (mean +/- SE) 4.1 +/- 0.9 mV, while 17-21 day cells had a higher 1/2max Ih of 9.9 +/- 1.1 mV (p < 0.0001). Cells from 12-16 day old control brainstems had a 1/2max Ih of 1.3 +/- 0.1 mV, which was lower (p < 0.05) than in cells from prenatally treated offspring; while 17-21 day old cells from controls had a 1/2max Ih of 3.3 +/- 0.3 mV, which was also lower (p < 0.01) than in cells from prenatally treated offspring. In addition, changes in resting membrane potential [control -65. +/- 0.9 mV (n=32); exposed -55.0 +/- 1.4 mV (n = 27) (p < 0.0001)], and action potential (AP) threshold [control -56.5 +/- 0.7 mV (n = 32), exposed -47.0 +/- 1.4 mV (n = 27) (p < 0.0001)], suggest that prenatal exposure to cigarette smoke induced marked changes in cells in the cholinergic arm of the RAS, rendering them more excitable. Such data could partially explain the differences seen in individuals whose parents smoked during pregnancy, especially in terms of their hypervigilance and increased propensity for attentional deficits and cognitive/behavioral disorders.

Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis.

Insulin-like factor 3 (INSL3) serum levels were measured in 135 andrologically well-characterized normal men and 85 patients with testicular disorders to investigate how the hormone, which is a major secretory product of human Leydig cells, is related to testosterone (T), LH, and semen quality. INSL3 was measured by using a newly developed fluorescence immunoassay. Median (2.5-97.5 percentiles) INSL3 serum levels were as follows: normal men (n = 135), 0.99 (0.55-1.73) ng/ml; infertile men (n = 23), 1.11 (0.60-2.07) ng/ml; anorchid men (n = 21), nondetectable (ND); patients with 47, XXY, Klinefelter syndrome (n = 21), 0.12 (ND-0.78) ng/ml; men with hypogonadotropic hypogonadism and T substitution (n = 11), ND; and men with hypogonadotropic hypogonadism and human chorionic gonadotropin (hCG) treatment (n = 5), 0.36 (0.13-0.73) ng/ml. Before testicular biopsy, two infertile men had blood samples drawn directly from vena spermatica. Here, the serum INSL3 levels were 15-fold higher than in serum from peripheral blood samples (13.84 and 14.00 ng/ml, respectively). In two unilaterally orchiectomized former testis cancer patients, who underwent hCG stimulation test, INSL3 serum levels were unchanged 72 and 96 h after hCG stimulation. In conclusion, we provide a normal range for INSL3 serum levels in adult men and show that the majority, if not all, circulating INSL3 derives from the testes. Furthermore, our data strongly indicate that INSL3 secretion is dependent on the differentiating effect of LH on Leydig cells but independent of the steroidogenic LH-mediated action. Thus, even though T and INSL3 are both dependent on LH, these two Leydig cell hormones are regulated differently.

Total hip and knee replacement surgeries in Alberta utilization and associated outcomes.

OBJECTIVE: Between 1994/95 and 1996/7, the healthcare system in Alberta underwent a radical transformation that saw the regionalization of service delivery and a reduction in overall healthcare funding. The aim of this study is to examine trends in utilization and associated post-operative complications and readmissions for two procedures, total hip arthroplasty (THA) and total knee arthroplasty (TKA) during this period of restructuring. METHODS: This is a six-year retrospective analysis using hospital separation and healthcare insurance plan registry databases. During the study period, we looked at trends in inpatient procedure volumes, average lengths of stay, post-operative complications during the index hospital stay and readmissions within one year. RESULTS: Over a six-year period, the age-sex standardized provincial rate of THAs increased by 18% while the rate of TKAs increased by 73%. Average lengths of stay decreased for both procedures by over 50%. The rate of procedures with at least one post-operative complication within the index episode of care decreased over the study period by 19% for THA and 21% for TKA. Readmissions due to complications of surgery increased overall by 32% for THA and 2% for TKA. Regional and sex differences were observed throughout the period. CONCLUSIONS: While the overall rate of hospitalizations has decreased in Alberta, the rates of THA and TKA procedures have increased. The lengths of stay following these procedures have, at the same time, reduced dramatically. Adverse outcomes as measured by complication rates associated with these procedures have decreased, though readmissions due to complications after surgery have increased.

Socioeconomic risk factors and population-based regional allocation of healthcare funds.

Using the notion of professional uncertainty a population-based proxy need measure for hospital services was developed. Its relationship with socioeconomic variables and Standardized Mortality Ratios (SMR) was investigated in an attempt to develop an adjustment factor for socioeconomic risk factors beyond age-sex adjustment to be used for a population-based healthcare funding formula for Alberta. The data used are 1990, 1991, 1992 vital statistics and hospital separation abstracts, 1991 census data and Refined Diagnosis Related Group (RDRG) case weights. Geographic units studied were the 26 federal electoral districts in Alberta using postal codes as a linkage geo-code between census and hospital utilization and death data. SMRs, age-sex standardized per capita hospital utilization and proxy need rates were derived and correlated with socioeconomic variables derived from the census files. It appears that the poor, the less educated and aboriginals need more hospital services than the affluent, employed and educated, confirming previous findings. The unemployed tend to need more but use fewer services while immigrants and non-white ethnics tend to need and use fewer services. The unemployed, less educated and non-white ethnics are associated with positive correlation with premature mortality (SMR based on deaths under age 75 years), while the employed, highly educated tend to live longer. In general SMRs have positive but very low correlations with utilization and need rates suggesting that SMRs should not be used for resource allocation. Stepwise multiple regression analyses showed that the percentages of unemployed, immigrants, non-whites, aboriginals and those with education less than grade 9 explain about 90% of the variation in age-sex standardized hospital utilization rates. Percentages of unemployed, non-white ethnics, residents with education less than grade 9 and aboriginals explained 71% of variations in age-sex standardized per capita proxy hospital service need measures. Based on the results of regression analyses, a SEAM (Socio-Economic Adjustment Multiplier) scale was developed for utilization (SEAM-U) and proxy needs (SEAM-N). In essence a SEAM is a set of relative value (RV) multipliers applicable to a provincial common per age-sex adjusted capita allocation value to account for the impact of socioeconomic risk factors on hospital service needs or utilization. Finally, the resulting regression equations derived from the 26 Federal electoral district data were applied to Alberta's health regions, regional SEAMs were derived, and the impact of such adjustment was assessed.

Regionalization and hospital utilization: Alberta 1991/2-1996/7.

BACKGROUND: In February 1994 Alberta Health announced a three-year business plan for the radical restructuring of the health care system in Alberta. The business plan outlined large reductions in funding for acute hospital care spending and the establishment of 17 Regional Health Authorities (RHAs). OBJECTIVES: The objectives of this study are to describe for the period 1991/2 to 1996/7: 1) Trends in overall acute hospital utilization by Alberta residents and residents of each of the 17 RHAs. 2) Trends in the provision of acute hospital services by each of the 17 RHAs and the Alberta Cancer Board. 3) Trends in the transfer of patients between RHAs. RESULTS: Between 1991/2 and 1996/7, the age-sex standardized separation rate, the age-sex standardized average length of stay, and age-sex standardized hospital days rate for Alberta residents fell by 25.6%, 18.7%, and 39.5% respectively. The age-standardized hospital days rate fell in all 17 RHAs. The total number of separations (Alberta residents and non-residents) from Alberta acute care facilities fell by 19.6% while the average care intensity for all separations from Alberta acute care facilities rose by 8.7%. The ratio of the highest to lowest average RHA care intensity remained between 1.7 and 1.9 during the study period. RHA self-sufficiency indices increased dramatically in one RHA and remained largely unchanged in the remaining RHAs. RHA import indices decreased for most RHAs. CONCLUSIONS: Large reductions in the use of acute hospital services have occurred in Alberta during the period of major health care restructuring. Further research is needed to examine shifts in services to other sectors and to assess the impact of these reductions on patient outcomes.

Utilization of hospital services by the elderly: geriatric crisis in one Canadian single payer system.

As the number and proportion of elderly persons in the Canadian population increase, utilization of health services by the elderly becomes a growing concern for health service insurers, financial managers and policy makers, as well as for care providers. The purpose of this paper is to present the results of a study to analyse the use of hospital services by the elderly in Alberta since the introduction of a universal single payer health care insurance system in 1970. The study period coincides with the implementation of publicly-financed comprehensive medical and hospital insurance programmes for all Alberta residents, making it possible to perform historical and population-based utilization analyses. Thus the data used for the study included all hospital discharge abstracts generated by all Alberta hospitals from 1971 to 1991. Trends in hospital service utilization by the elderly in terms of total number of separations, patient-days, and per case measures such as average length of stay as well as per capita utilization rates were reviewed to identify utilization patterns over the study period. Further, relative per capita utilization measures, in comparison with the base year (1971), age group 15-44, male, metropolitan residents, were derived and historical trends identified. A series of regression analyses were carried out to estimate the effects of age, sex and origin on utilization rates. In addition, for the period of 1984-1991, Diagnosis Related Groups (DRG) case weights were used to measure per capita and per case rates and to analyse historical relative utilization rates over the 8-year period. In general, there has been a significant decline in hospital utilization by Albertans under the publicly-financed single payer system, but utilization rates for elderly have remained high, resulting in high relative utilization rates in comparison with other age groups. It was also noted that per capita utilization rates for rural residents were substantially higher than urban residents. It appears that these higher utilization rates by the elderly and rural residents in combination with tight bed and financial control by the government have been causing significant bed shortage problems for non-elderly elective patients in urban areas.

Emergency care episodes: an economic profile.

A new "episode of care" definition of emergency care was developed, consisting of the emergency department encounter and all subsequent, related care delivered within 48 hrs from the initial contact. Data were analyzed by ICD-9-CM Major Diagnostic Category (MDC) and surgical intervention using 1.6 million episodes generated by 809,145 separate patients from a national claims database. Secondary/adjunct services were a major component of episode charges. For several MDCs, hospitalization and/or surgical procedures were also major determinants of overall episodic charges. Results support the premise that economic analysis and reimbursement of emergency care benefits from the use of episodic data.

Mortality risk and patterns of practice in 2,070 patients with acute myocardial infarction, 1987-92. Relative importance of age, sex, and medical therapy.

OBJECTIVE: To define contemporary age- and sex-related mortality risks and patterns of medical practice in acute myocardial infarction (AMI). DESIGN: Retrospective comparison of demographic and clinical variables, including the use of proven effective AMI medical therapy, among AMI patients cohorts from 1987 to 1992. PATIENTS/SETTING: Of a total of 2,070 AMI patients, 629 were women and 1,441, men; 951 patients were managed in university hospitals, 641 in a regional hospital, and 478 in community hospitals. INTERVENTIONS: No direct study interventions; results of practice patterns and risk analyses of the earlier (1987-90) AMI cohorts, however, were published concurrently with the actual practices of the more recent (1991-92) cohorts and may have had some indirect effect on the recent practice patterns. RESULTS: Univariate analysis showed that mortality was higher (p < 0.0001) and use of thrombolysis, beta blockers, and acetylsalicylic acid was lower (p < 0.0001) in patients 70 years of age and older, compared with younger patients, and in women, compared with men. Multivariate analysis of the entire patient sample revealed age of 75 years or older (154 percent) and age 70 to 74 years (141 percent) to be associated with the highest relative risk of death in hospital. The increased relative risk associated with previous AMI was 45 percent. Acetylsalicylic acid use was associated with the greatest decrease in relative risk of death (-69 percent), followed by beta blockers (-36 percent) and thrombolysis (-31 percent). These patterns of relative risk were the same for men and women. CONCLUSIONS: Among contemporary AMI patients, advanced age and female sex are associated with relative under-utilization of proven effective medical therapy and increased risk of dying in the hospital. Although the contribution of age to AMI risk appears greater than that of gender, survival in any high risk group would likely be improved by increased use of proven medical therapy.

The changing clinical profile of coronary artery bypass graft patients, 1970-89.

OBJECTIVE: To review the changing clinical profile of isolated coronary artery bypass graft (CABG) surgery patients at the University of Alberta Hospitals during the past two decades. DESIGN: Data were obtained retrospectively by review of patients' hospital charts and cardiologists' charts. The three patient cohorts consisted of the first 411 consecutive patients who underwent isolated CABG surgery between 1970 and 1974, 302 consecutive patients who had CABG surgery in 1984 and 346 consecutive patients who had the operation in 1989. RESULTS: Patients who underwent CABG surgery in 1984 and 1989 were older than patients undergoing the same operation in the 1970s. Emergency and/or urgent operations and the number of patients with prior myocardial infarct were increased significantly in 1984 and 1989. The incidence of patients with multiple vessel disease and left main stem stenosis increased significantly over the two decades. The number of bypass grafts per patient and the use of internal mammary grafts have increased since 1970. The endarterectomy procedure was performed less frequently in 1984 and 1989. The use of radial artery grafts has been discontinued. Perioperative mortality remained stable throughout the study period despite an increasing incidence of high risk patients. The major cause of death was pump failure. The incidence of peripostoperative myocardial infarct was higher in the 1970s. A multivariate analysis of the 1984 and 1989 cohorts was performed to identify temporal trends in risk factors. Emergency surgery, preoperative heart failure, age (older than 65 years), prior CABG surgery and preoperative renal failure are significant predictors of operative motility. CONCLUSIONS: The clinical profile of patients for isolated CABG surgery has changed over the years. The mortality rate has been stable over two decades despite the advancement of medical and surgical practices, representing a balance of increasingly high risk patients presenting for CABG surgery.

Some computer-based decision support tools for the rehabilitation manager.

The recent introduction of the Management Information System (MIS) guidelines has sparked much interest among health care institutions across Canada regarding proper approaches to the recording and interpretation of various financial and workload indicators. While the benefits of the MIS guidelines are widely acknowledged, much less attention has been directed to how departmental managers can analyze and make use of the vast amount of information generated. In this paper we attempt to review some of the computer-based decision-support tools that may be useful to the manager of the rehabilitation services department in analyzing the various MIS data that are collected. The data are assumed to be available through a computerized rehabilitation information system which includes workload measures. The quantitative models reviewed in this paper include basic descriptive statistics, deviation, trend and what-if-analysis and graph-plotting. Although the use of such tools can assist the rehabilitation manager in the routine decision-making process, it is very important that we ask the right questions and employ the proper model to make the most rational and best decision. In this respect, ongoing training in general problem-solving skills, decision-making processes, and use of computer-based decision-support tools may be very beneficial.

Long term clinical outcomes following isolated mitral valve replacement.

OBJECTIVE: This study reviews the short and long term outcomes of patients who underwent isolated mitral valve replacement at the University of Alberta Hospitals during the past decade. DESIGN: Data were obtained retrospectively by review of patients' hospital charts, cardiologists' follow-up charts, contact with patients' physicians, and direct telephone or mail contact with patients and/or their surviving relatives. RESULTS: The clinical outcomes of 198 consecutive patients (124 women and 74 men) who underwent isolated mitral valve replacement from January 1981 to December 1990 at the University of Alberta Hospital were reviewed. Overall early operative mortality was 11%. Deaths were mainly related to pump failure and previous mitral valve replacement. Late mortality was 17%. Follow-up data were available except in five patients. Average follow-up was 6.3 years. Overall cumulative survival was 72.9 +/- 3.4% at five years and 63.1 +/- 4.8% at 10 years. The cumulative freedom from complications was 64.3 +/- 3.9% and 36.4 +/- 4.9% at five and 10 years, respectively. Long term survival rates obtained after isolated mitral valve replacement are higher than those reported in series of medically treated patients with mitral valve disease. CONCLUSIONS: Mitral valve replacement can prolong survival as well as improve symptoms in patients with symptomatic mitral valve disease.

Survey of nursing quality assurance programs in selected hospitals in Alberta, Canada.

This study represents a survey of the nursing quality assurance programs in 12 hospitals in Alberta. The objectives of the study were: to identify the nature, content and costs of the programs, to determine the extent of nurse involvement in the design and operation of the programs, and the value and importance nurses place on their programs. The major findings of the study tend to support the view that the principles of organizational change theory have not been adequately addressed in terms of nursing quality assurance programs. Generally, nurses reported that they were insufficiently informed concerning their programs. Among the study recommendations is a call for improvements in the audit tools used, with greater emphasis being placed on the patient and the nurse providing the care and more decentralization of programs to the unit level to improve staff involvement and program relevancy.

Changes in acute myocardial infarction risk and patterns of practice for patients older and younger than 70 years, 1987-90.

OBJECTIVE: To evaluate temporal changes in risk and patterns of hospital practice for acute myocardial infarction (AMI). DESIGN/PATIENTS: Retrospective analysis of age-related medical therapy and outcome of 342 consecutive patients (132 at least 70 years old and 210 younger than 70) with AMI between July 1, 1989, and June 30, 1990, and comparison with data from two previous analyses of AMI practice in 1987 (n = 207) and 1988-89 (n = 402). SETTING: Tertiary care medical centre. INTERVENTIONS: No direct interventions; results of the two previous AMI practice pattern analyses, however, were propagated during the practice time of the most recent analysis. RESULTS: In 1989-90, hospital mortality was higher (19%) among patients at least 70 years old compared with patients younger than 70 (8%) (P less than 0.01). Therapies proven by repeated clinical trials to be effective in reducing AMI risk were all used less frequently in patients aged at least 70 years: thrombolysis (20 versus 43%); beta-blockers (41 versus 62%); acetylsalicylic acid (71 versus 87%); and nitrates (86 versus 97%). Qualitatively, these age-specific patterns of AMI mortality and therapy were similar to previous studies. Quantitatively, however, comparing 1987 with 1989-90 demonstrated parallel and marked increases in the use of all proven medications in both age groups, ranging from 42 to 230% (P less than 0.01). There was also a significant overall decrease in mortality from the 1987 patient cohort (20%) to the 1989-90 cohort (13%) (P less than 0.05). The decrease in mortality was entirely due to decreased mortality within the group 70 years or older; 35% in 1987 versus 19% in 1989-90 (P less than 0.05). Mortality in the AMI patients younger than 70 years old remained unchanged from 1987 to 1989-90. CONCLUSIONS: Pattern of practice analyses were associated with, and may have contributed to, improved patient care and outcomes in AMI. Increased use of effective AMI medical therapy had a greater benefit in elderly higher risk AMI patients than lower risk younger patients. Persisting age-specific differences in AMI therapy may respond to more direct quality improvement measures, such as critical path management.

Comparison of risk and patterns of practice in patients older and younger than 70 years with acute myocardial infarction in a two-year period (1987-1989)

To further evaluate contemporary risk and practice patterns in acute myocardial infarction (AMI), 402 consecutive patients with AMI between July 1, 1988, and June 30, 1989 were studied. The clinical investigations, medical therapy and outcome of patients aged greater than or equal to 70 years (n = 132; group 1) were compared with patients aged less than 70 years (n = 270; group 2). In group 1, 20% of patients had no typical cardiac pain versus 6% in group 2 (p less than 0.01). History of previous AMI, Q-wave AMI and peak creatine kinase were not different in the 2 groups. In-hospital mortality was markedly higher in group 1 (27%) than in group 2 (8%), p less than 0.01. Multivariate analysis revealed previous AMI, presentation without typical pain and age greater than or equal to 70 years to be independently associated with the greatest relative risk. Post-AMI exercise testing, ejection fraction calculations and coronary angiography were all performed less often (p less than 0.01); proven effective medical therapies, including thrombolysis, beta blockers, acetylsalicylic acid and nitrates were all used less frequently (p less than 0.01). The very high mortality and less aggressive management of elderly patients with AMI confirm similar data from our 1987 AMI patient cohort and other recently reported AMI patient outcome analyses. However, it remains uncertain why older patients with AMI are investigated and treated differently from younger patients. Further studies are warranted.

Mortality risk factors associated with mitral valve replacement: a survival analysis of 10 year follow-up data.

The primary purpose of this study was to evaluate the long term performance of several prosthetic cardiac valves and the influence on outcome of different surgeons by following 328 patients for up to 10 years after mitral valve replacement surgery in a tertiary care centre. This type of follow-up study is faced with severe methodological difficulties, as mortality and complications after surgery can be influenced not only by preoperative clinical status but also by the competence of the operating surgeons, the type of prosthesis used, and system-related variables such as the overall quality of nursing care. The primary statistical models used were life-table analysis, logistic regression and Cox's proportional hazard regression, employing prosthesis type, surgeon and other patient- or system-specific variable as covariates. The relative performance of valve prostheses and surgeons were assessed for short and long term survival. Biologic and Omniscience valves outperformed others for short and long term survival, while Lillehei-Kaster valves performed well for short term but not long term survival. The results also suggest that the performance levels of surgeons do vary, and the choice of surgeon could be a significant risk factor in a given medical centre.