Do medical courses adequately prepare interns for safe and effective prescribing in New South Wales public hospitals?

AIMS: To assess ability of interns immediately before starting clinical practice in New South Wales (NSW) teaching hospitals to prescribe medications safely and appropriately and to describe their impressions of the adequacy of their clinical pharmacology training in medical school. METHODS: A cross-sectional study was performed on all interns (n= 191) who attended intern orientation programmes at four NSW hospitals in January 2008. A clinical case scenario that tested prescribing ability and a survey investigating impressions of clinical pharmacology training in medical school were administered to the interns in exam format. Outcome measures were: (i) ability to prescribe medications safely and appropriately for the clinical case scenario and (ii) interns' impressions of their training in clinical pharmacology at medical school. RESULTS: No intern completed all prescribing tasks correctly. No intern charted the patient's usual medications on admission completely correctly, only six wrote an accurate discharge medication list, and none wrote both an accurate discharge medication list and a legal Schedule 8 discharge script. None of the respondents strongly agreed that they felt adequately trained to prescribe medications in their intern year and 84% would have liked to have more training in pharmacology as medical students. CONCLUSIONS: Interns about to commence clinical practice in NSW teaching hospitals demonstrated significant deficits in prescribing of regular medications, initiation of new therapies, prescribing of discharge medications, and particularly prescribing of Schedule 8 medications. Most interns recognized these deficits and would have liked more clinical pharmacology training at medical school.

The relationship between admission blood glucose levels and hospital mortality.

AIMS/HYPOTHESIS: The purpose of this study was to examine the relationship between blood glucose level (BGL) on admission with mortality rates among patients admitted to hospital through the Emergency Department. METHODS: In a prospective observational study, BGLs were routinely measured on 6,187 consecutive patients requiring blood testing and admitted through the Emergency Department of a tertiary referral hospital. These measurements were matched against demographic data and hospital mortality rates. RESULTS: Overall in-hospital mortality was 4.8%. Admission BGL was an independent predictor of mortality (HR 1.04 per 1 mmol/l increase, 95% CI 1.02-1.06, p=0.02). There was a significant interaction between diabetes status and increasing BGL on mortality (p<0.001), with higher BGLs being associated with greater mortality among non-diabetic than among diabetic patients. Among non-diabetic patients, the lowest mortality rate (3.0%) was in people with a BGL of 4.0-5.9 mmol/l. Compared with this group, patients with a BGL of 8.0-9.9 mmol/l had increased mortality rate (7.6%, HR 1.56, 95% CI 1.03-2.35, p=0.04, after adjustment for age and sex). The risk increased further at higher glucose levels. In the cohort with diagnosed diabetes, the increase in mortality rates at higher BGL bands was not significant. CONCLUSIONS/INTERPRETATION: Among people who do not have diabetes, even modest degrees of hyperglycaemia on hospital admission are associated with increased mortality.

Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome.

BACKGROUND: beta-blockers are routinely prescribed in congenital long-QT syndrome (LQTS), but the effectiveness and limitations of beta-blockers in this disorder have not been evaluated. METHODS AND RESULTS: The study population comprised 869 LQTS patients treated with beta-blockers. Effectiveness of beta-blockers was analyzed during matched periods before and after starting beta-blocker therapy, and by survivorship methods to determine factors associated with cardiac events while on prescribed beta-blockers. After initiation of beta-blockers, there was a significant (P<0.001) reduction in the rate of cardiac events in probands (0.97+/-1.42 to 0.31+/-0.86 events per year) and in affected family members (0. 26+/-0.84 to 0.15+/-0.69 events per year) during 5-year matched periods. On-therapy survivorship analyses revealed that patients with cardiac symptoms before beta-blockers (n=598) had a hazard ratio of 5.8 (95% CI, 3.7 to 9.1) for recurrent cardiac events (syncope, aborted cardiac arrest, or death) during beta-blocker therapy compared with asymptomatic patients; 32% of these symptomatic patients will have another cardiac event within 5 years while on prescribed beta-blockers. Patients with a history of aborted cardiac arrest before starting beta-blockers (n=113) had a hazard ratio of 12.9 (95% CI, 4.7 to 35.5) for aborted cardiac arrest or death while on prescribed beta-blockers compared with asymptomatic patients; 14% of these patients will have another arrest (aborted or fatal) within 5 years on beta-blockers. CONCLUSIONS: beta-blockers are associated with a significant reduction in cardiac events in LQTS patients. However, syncope, aborted cardiac arrest, and LQTS-related death continue to occur while patients are on prescribed beta-blockers, particularly in those who were symptomatic before starting this therapy.

The long QT syndrome. Prospective longitudinal study of 328 families.

BACKGROUND: The Long QT Syndrome (LQTS) is an infrequently occurring familial disorder in which affected individuals have electrocardiographic QT interval prolongation and a propensity to ventricular tachyarrhythmic syncope and sudden death. We prospectively investigated the clinical characteristics and the long-term course of 3,343 individuals from 328 families in which one or more members were identified as affected with LQTS (QTc greater than 0.44 sec1/2). METHODS AND RESULTS: The first member of a family to be identified with LQTS, the proband, was usually brought to medical attention because of a syncopal episode during childhood or teenage years. Probands (n = 328) were younger at first contact (age 21 +/- 15 years), more likely to be female (69%), and had a higher frequency of preenrollment syncope or cardiac arrest with resuscitation (80%), congenital deafness (7%), a resting heart rate less than 60 beats/min (31%), QTc greater than or equal to 0.50 sec1/2 (52%), and a history of ventricular tachyarrhythmia (47%) than other affected (n = 688) and unaffected (n = 1,004) family members. Arrhythmogenic syncope often occurred in association with acute physical, emotional, or auditory arousal. The syncopal episodes were frequently misinterpreted as a seizure disorder. By age 12 years, 50% of the probands had experienced at least one syncopal episode or death. The rates of postenrollment syncope (one or more episodes) and probable LQTS-related death (before age 50 years) for probands (n = 235; average follow-up 54 months per patient) were 5.0% per year and 0.9% per year, respectively; these event rates were considerably higher than those observed among affected and unaffected family members. CONCLUSIONS: Among 232 probands and 1,264 family members with prospective follow-up, three factors made significant independent contributions to the risk of subsequent syncope or probable LQTS-related death before age 50 years, whichever occurred first (Cox hazard ratio; 95% confidence limits): 1) QTc (1.052; 1.017, 1.088), 2) history of cardiac event (3.1; 1.3, 7.2), and 3) heart rate (1.017; 1.004, 1.031). The findings from this prospective longitudinal study highlight the clinical features, risk factors, and course of LQTS.

Left cardiac sympathetic denervation in the therapy of congenital long QT syndrome. A worldwide report.

BACKGROUND: Long QT syndrome (LQTS) is a congenital disorder accompanied by a high incidence of sudden cardiac death. beta-Adrenergic blockade is the therapy of choice, and it is successful in 75-80% of patients. For those in whom cardiac events (syncope or cardiac arrest) are not prevented by beta-blockade, experimental studies suggest that left cardiac sympathetic denervation (LCSD) may be useful. METHODS AND RESULTS: We identified 85 LQTS patients worldwide who underwent LCSD, and we provide here the first large-scale evaluation of its efficacy. The time interval between the first cardiac event and LCSD and the follow-up period after LCSD were similar (5.6 +/- 6.1 versus 5.9 +/- 5.7 years). The mean age of the patients at surgery was 20 +/- 13 years. LCSD was followed by highly significant (p less than 0.0001) decreases in the number of patients with cardiac events (from 99% to 45%), in the number of cardiac events per patient (from 22 +/- 32 to 1 +/- 3), and in the number of patients with five or more cardiac events (from 71% to 10%). There were seven sudden deaths (8%), and the 5-year survival rate was 94%. The marked reduction in the incidence of tachyarrhythmic syncope suggests that LCSD has also reduced the risk for sudden death in this high-risk population. CONCLUSIONS: The present findings demonstrate that for LQTS patients who continue with syncope or cardiac arrest despite the use of beta-blockers, LCSD is a very effective therapy.

Acute myocardial infarction associated with single vessel coronary artery disease: an analysis of clinical outcome and the prognostic importance of vessel patency and residual ischemic myocardium.

The long-term outcome and the significance of residual ischemic myocardium, as assessed by predischarge exercise thallium scintigraphy and vessel patency, were studied in 97 patients with single vessel coronary artery disease by angiography 12 +/- 4 days after uncomplicated myocardial infarction. During a mean follow-up period of 39 +/- 17 months, no patients died, 6 (6%) had a recurrent nonfatal infarction and 25 (26%) experienced rapidly progressive angina requiring hospitalization. Although neither exercise-induced angina nor ST segment depression was predictive of a recurrent cardiac event, the mean number of infarct zone scan segments showing thallium redistribution (1.0 +/- 1.0 versus 0.5 +/- 0.8, p = 0.01) and the percent of patients with infarct zone redistribution (61 versus 39%, p = 0.05) were greater in those patients who experienced a late ischemic event. Kaplan-Meier analysis demonstrated a lower event-free survival rate in patients with redistribution (n = 45) than in those without redistribution (n = 52) (p = 0.019). Although no patient received immediate thrombolytic therapy, the infarct-related vessel was angiographically patent in 40 patients (41%). Vessel patency did not influence event-free survival, although a patent vessel, as compared with an occluded vessel, was associated with a greater prevalence of non-Q wave infarction (58 versus 21%, p less than 0.001), fewer persistent infarct zone thallium defects (1.2 +/- 1.1 versus 2.0 +/- 1.2, p = 0.001), more reversible infarct zone thallium defects (1.0 +/- 1.0 versus 0.5 +/- 0.9, p = 0.02) and a trend toward a higher left ventricular ejection fraction (53 +/- 10% versus 49 +/- 12%, p = 0.07). In summary, uncomplicated myocardial infarction in patients with single vessel coronary artery disease is associated with a very low incidence of subsequent death and reinfarction. The presence of infarct zone thallium redistribution, compared with its absence, is predictive of a higher cardiac event rate. These data should be considered when recommending prophylactic percutaneous transluminal angioplasty after uncomplicated myocardial infarction in asymptomatic patients with single vessel coronary disease. On the basis of these results, future randomized trials designed to evaluate the therapeutic efficacy of revascularization in asymptomatic postinfarction patients with single vessel disease should limit enrollment to those patients with residual ischemia located within the infarct zone.

Acute non-Q wave myocardial infarction associated with early ST segment elevation: evidence for spontaneous coronary reperfusion and implications for thrombolytic trials.

The clinical significance of early ST segment elevation in patients with non-Q wave infarction is unknown. Therefore, 150 consecutive patients with creatine kinase isoenzyme-confirmed acute uncomplicated myocardial infarction who had ST segment elevation of 1 mm or more in at least two contiguous leads on the admission electrocardiogram were analyzed. None received thrombolytic therapy or acute coronary angioplasty. Predischarge angiography, radionuclide ventriculography and exercise thallium-201 scintigraphy were performed 10 +/- 3 days after myocardial infarction. Based on serial electrocardiograms (on days 1, 2, 3 and 10), all 150 infarcts were classified as Q wave (n = 115 [77%]) or non-Q wave (n = 35 [23%]). Although patients with Q wave infarction exhibited greater ST elevation, the amount observed in the non-Q wave group was appreciable, as reflected by the number of leads with ST elevation (3.8 +/- 1.8 versus 3.1 +/- 1.2, p = 0.007) and the sum of the ST elevation (9.6 +/- 7.4 versus 6.2 +/- 6.2 mm, p = 0.016). When compared with the Q wave group, patients with non-Q wave infarction had a shorter time to peak creatine kinase (23.0 +/- 9.1 versus 15.8 +/- 7.9 hours, p = 0.0001), a higher infarct vessel patency rate (24 versus 57%, p = 0.001), lower peak creatine kinase values based on 4 hour sampling (1,372 +/- 964 versus 664 +/- 924 IU/liter, p = 0.0002) and a higher left ventricular ejection fraction (46 +/- 12% versus 54 +/- 9%, p = 0.0003).(ABSTRACT TRUNCATED AT 250 WORDS)

Lidocaine enhances intraoperative ventricular defibrillation.

The efficacy of lidocaine during myocardial reperfusion in coronary artery bypass surgery was evaluated in 20 patients randomly assigned to a control group (n = 10) or to receive lidocaine, 1 mg/kg intravenously 5 min before aortic unclamping and cardiac reperfusion, followed by infusion at 40 micrograms X kg-1 X min-1 (n = 10). We recorded ECG leads II and V5 continuously, and number, energy, and current of direct current (DC) shocks starting at 1 joule. The number of low energy DC shocks to sustained defibrillation (5.5 +/- 2.0 vs 3.5 +/- 2.0, mean +/- SD, P less than 0.05) decreased significantly with lidocaine infusion. The energy (11.0 +/- 6.3 vs 5.6 +/- 3.9 joules, P less than 0.05) and current (12.7 +/- 4.2 vs 8.9 +/- 4.7 amperes, not significant) likewise decreased with lidocaine infusion. Energy and current for the first successful shock, although lower in the lidocaine group, were not statistically significantly lower than in the control group. Initial reperfusion rhythm was not influenced by lidocaine. Plasma electrolyte levels, arterial blood gas tensions, myocardial temperature, and surgical technique--factors known to influence defibrillation--were similar in all patients. Administration of lidocaine during myocardial reperfusion allows defibrillation with fewer DC shocks of lower energy and current.

Effects of coronary grafting technique upon reperfusion cardiac rhythm, ventricular function, and other variables.

The effects of different techniques of aortocoronary bypass grafting on reperfusion cardiac rhythm and ventricular function have not been systematically evaluated for possible advantages or disadvantages. The placement of proximal anastomoses before cardiopulmonary bypass and sequential coronary grafting with reperfusion via both the grafts and the native circulation were prospectively compared to traditional grafting and reperfusion via native arteries. More than 40 biochemical, thermal, temporal, hemodynamic, and other variables, including arrhythmias and myocardial failure, were measured intraoperatively and postoperatively. Spontaneous resumption of a cardiac rhythm occurred more frequently with traditional grafting technique in association with a larger cardioplegia volume and a higher serum potassium. However, the disadvantage of the traditional technique was a higher incidence of cardiac failure postoperatively and greater use of isoproterenol after discontinuation of bypass. While cardiac rhythm resumed spontaneously more often with the traditional technique, the increased incidence of cardiac failure postoperatively has serious implications. Thus, placement of proximal anastomoses before cardiopulmonary bypass seems warranted.

Low-energy defibrillation: safe and effective.

During cardiopulmonary bypass, 150 cardiac surgical patients were prospectively evaluated for the number, energy, current, and success rates of direct current (DC) shocks required to terminate reperfusion ventricular fibrillation (1 degree) or ventricular fibrillation occurring subsequent to a nonfibrillatory reperfusion rhythm (2 degrees). Thirty-one percent of 1-J shocks and 58% of 2.5-J shocks defibrillated. Above 2.5 J, the defibrillation success rate reached a plateau of 50-60%. Myocardial resistance decreased significantly after the first shock but remained stable during subsequent shocks. Lower defibrillating currents and myocardial resistances than had been previously reported were observed. The feasibility of low-energy defibrillation during cardiopulmonary bypass was therefore documented.

The long QT syndrome: a prospective international study.

During the past 4 years 196 patients with the idiopathic long QT syndrome were enrolled in a prospective international study conducted to obtain a better understanding of the clinical course of this unusual repolarization disorder. The mean patient age was 24 years, 64% were female, and 88% had family members with QT prolongation. During an average follow-up of 26 months per patient, four patients died suddenly (1.3% per year) and 27 patients had one or more syncopal episodes (8.6% per year). Multivariate analysis identified congenital deafness, history of syncope, female gender, and a documented episode of torsades de pointes or ventricular fibrillation as independent risk factors for postenrollment syncope or sudden death. Two types of treatment (left stellate ganglionectomy and beta-blocker therapy) were associated with a significant reduction in the occurrence of cardiac events during follow-up.

Influence of magnesium ion on human ventricular defibrillation after aortocoronary bypass surgery.

The administration of magnesium ion (Mg++) has been reported to defibrillate the ventricles and to decrease the incidence of arrhythmias after cardiopulmonary bypass. In a prospective study of 76 randomly selected patients undergoing coronary artery bypass grafting, patients received either no Mg++, 0.25 mEq/kg of Mg++ during cardiopulmonary bypass with the aorta clamped, or 0.375 mEq/kg of Mg++ before cardiopulmonary bypass. Spontaneous resumption of a cardiac rhythm or spontaneous defibrillation during reperfusion was not significantly affected by Mg++ administration. However, the number of shocks to initial and to sustained defibrillation and the energy required for the last direct-current shock was greatest in patients who received Mg++ before bypass and in those whose plasma Mg++ was greater than 2.26 mg/dl. Thus, the administration of Mg++ may have adverse effects on the heart if intraoperative plasma Mg++ exceeds 2.26 mg/dl.

Determinants of reperfusion cardiac electrical activity after cold cardioplegic arrest during coronary bypass surgery.

In a prospective study of 99 patients with coronary artery disease, reperfusion of the heart after a period of ischemia (protected by contemporary techniques of myocardial preservation) resulted in spontaneous resumption of cardiac electrical activity in 53%, spontaneous defibrillation in 10%, reperfusion ventricular fibrillation (VF) in 32% and indeterminate rhythm in 5%. In hearts spontaneously developing rhythms excluding VF (as opposed to hearts requiring direct-current shock), factors significantly associated were a higher plasma potassium concentration (5.2 vs 4.8 mEq/liter), shorter reperfusion time (1 vs 4 minutes), higher plasma magnesium concentration (1.36 vs 1.25 mg/dl) and a lower myocardial temperature (27 vs 32 degrees C). The duration of ischemia, arterial blood gas levels, plasma catecholamine levels, plasma ionized calcium levels, volume of cardioplegia and mean arterial pressure did not relate to occurrence of spontaneous episodes. However, VF developed in 39 of 52 patients (75%) with spontaneous resumption of electrical activity. This event was associated with lower myocardial temperature. Thus, direct-current shocks were ultimately required in 77 of the 99 patients (78%). Although certain thermal, biochemical and hemodynamic variables facilitate spontaneous resumption of cardiac rhythm, the development of VF may negate the potential benefit of this event in the prevention of myocardial damage from direct-current defibrillation.

Energy dose and other variables possibly affecting ventricular defibrillation during cardiac surgery.

Previous studies have suggested that shocks of 5-10 J are required for direct ventricular defibrillation during open heart surgery. However, the efficacy of shocks of less than 5 J, the effects of thermal, biochemical, and temporal factors, and the influence of disease process on defibrillation have not been fully investigated, particularly with modern techniques of myocardial preservation. The purpose of this prospective study in 150 adult cardiac surgical patients was to evaluate the energy, current, and myocardial resistance with low energy DC shocks of 1, 2.5, and 5 J and to relate which biochemical, temporal, thermal, or other factors influence the outcome of a DC shock. Twenty-eight percent of shocks of 1 J and 55% of shocks of 2.5 J produced defibrillation. Above 2.5 J, the success rate reached a plateau at 55%. Other factors associated with the success of DC shocks were high normal serum potassium levels, high PaO2, high ionized calcium levels, and longer reperfusion times at mean arterial and coronary perfusion pressures above 50 mm Hg. Disease process may also play a role because patients with valvular heart disease were more difficult to defibrillate. Heart weight and thickness of ventricular myocardium, measured angiographically, appeared less important in direct defibrillation, except with 1 J shocks when thinner-walled ventricles defibrillated more easily.

The problem of cardiac arrest in the community.

Out-of-hospital cardiac arrests constitute 350,000 cases yearly in the United States and 60,000 in the United Kingdom. Prompt resuscitation (CPR) by lay persons and fast defibrillation by paramedics have had epidemiologic consequences on both sides of the Atlantic. In Seattle there are 20.6 and in Brighton 10.0 long-term life-saves yearly per 100,000 persons. In Piedmont Virginia, coronary deaths fell 16% for persons 30-69 years old and 25% for those of all ages; prehospital life-saves accounted for 23% and 8% of each respective reduction. Since CPR by lay persons now triples the long-term survival rate when coupled with prehospital defibrillation, favorable benefit-to-cost ratios can be effected by adding advanced life support and citizen CPR to an extant ambulance system. Meticulous direct and indirect medical control by the physician assures the highest quality of CPR and early cardiac care (ECC). Diagnostic procedures like electro-provocation identify high-risk patients. Changes of behavior and diet, new drugs, new operations, and external and implantable automated devices reduce sudden deaths. In the future, automated defibrillation by first responders and trained lay persons (including members of families of high-risk patients) should increase the number of early survivors who become candidates for long-term therapy with drugs, operations, and devices.