Substance misuse in patients with schizophrenia: epidemiology and management

Substance misuse in individuals with schizophrenia is very common, especially in young men, in communities where use is frequent and in people receiving inpatient treatment. Problematic use occurs at very low intake levels, so that most affected people are not physically dependent (with the exception of nicotine). People with schizophrenia and substance misuse have poorer symptomatic and functional outcomes than those with schizophrenia alone. Unless there is routine screening, substance misuse is often missed in assessments. Service systems tend to be separated, with poor inter-communication, and affected patients are often excluded from services because of their comorbidity. However, effective management of these disorders requires a fully integrated approach because of the close inter-relationship of the disorders. Use of atypical antipsychotics may be especially important in this population because of growing evidence (especially on clozapine and risperidone) that nicotine smoking, alcohol misuse and possibly some other substance misuse is reduced. Several pharmacotherapies for substance misuse can be used safely in people with schizophrenia, but the evidence base is small and guidelines for their use are necessarily derived from experience in the general population.

Complex language functions and subcortical mechanisms: evidence from Huntington's disease and patients with non-thalamic subcortical lesions

The neuropathological changes associated with Huntington's disease (HD) are most marked in the head of the caudate nucleus and, to a lesser extent, in the putamen and globus pallidus, suggesting that at least part of the language impairments found in patients with HD may result from non-thalamic subcortical (NTS) pathology. The present study aimed to test the hypothesis that a signature profile of impaired language functions is found in patients who have sustained damage to the non-thalamic subcortex, either focally induced or resulting from neurodegenerative pathology. The language abilities of a group of patients with Huntington's disease (n=13) were compared with those of an age- and education-matched group of patients with chronic NTS lesions following stroke (n=13) and a non-neurologically impaired control group (n=13). The three groups were compared on language tasks that assessed both primary and more complex language abilities. The primary language battery consisted of The Western Aphasia Battery and The Boston Naming Test, whilst the more complex cognitive-linguistic battery employed selected subtests from The Test of Language Competence-Expanded, The Test of Word Knowledge and The Word Test-Revised. On many of the tests of primary language function from the Western Aphasia Battery, both the HD and NTS participants performed in a similar manner to the control participants. The language performances of the HD participants were significantly more impaired (p<0.05 using modified Bonferroni adjustments) than the control group, however, on various lexico-semantic tasks (e. g. the Boston Naming Test and providing definitions), on both single-word and sentence-level generative tasks (e. g. category fluency and formulating sentences), and on tasks which required interpretation of ambiguous, figurative and inferential meaning. The difficulties that patients with HD experienced with tasks assessing complex language abilities were strikingly similar, both qualitatively and quantitatively, to the language profile produced by NTS participants. The results provide evidence to suggest that a signature language profile is associated with damage to the non-thalamic subcortex resulting from either focal neurological insult or a degenerative disease.

Germline BRCA1 promoter deletions in UK and Australian familial breast cancer patients: Identification of a novel deletion consistent with BRCA1 :psi VBRCA1 recombination

Inherited susceptibility to breast cancer results from germline mutations in one of a number of genes including BRCA1. A significant number of BRCA1-linked familial breast cancer patients, however, have no detectable BRCA1 mutation. This could be due in part to the inability of commonly used mutation-detection techniques to identify mutations outside the BRCA1 coding region. This paper addresses the hypothesis that non coding region mutations, specifically in the BRCA1 promoter, account for some of these cases. We describe a new and detailed restriction map of the 5' region of the BRCA1 gene including the nearby NBR2, psiBRCA1, and NBR1 genes and the isolation of a number of new informative hybridization probes suitable for Southern analysis. Using this information we screened DNA from lymphoblastoid cell-lines made from 114 UK familial breast cancer patients and detected one large deletion in the 5' region of BRCA1. We show that the breakpoints for this deletion are in BRCA1 intron 2 and between NBR2 and exon 2 of psiBRCA1, raising the possibility that this deletion arose via a novel mechanism involving BRCA1:psiBRCA1 recombination. We have also screened 60 familial breast cancer patients from the Australian population, using an amplification refractory mutation system (ARMS) technique described previously by our group, and found one patient with a genotype consistent with a BRCA1 promoter deletion. These findings indicate that germline BRCA1 promoter deletions are a rare and yet significant mutation event and that they could arise via a novel genetic mechanism. Hum Mutat 19:435-442, 2002. (C) 2002 Wiley-Liss, Inc.

Patients' interactions with health providers - A linguistic category model approach

Two studies investigated interactions between health providers and patients, using Semin and Fiedler's linguistic category model. In Study 1 the linguistic category model was used to examine perceptions of the levels of linguistic intergroup bias in descriptions of conversations with health professionals in hospitals. Results indicated a favourable linguistic bias toward health professionals in satisfactory conversations but low levels of linguistic intergroup bias in unsatisfactory conversations. In Study 2, the language of patients and health professionals in videotaped interactions was examined for levels of linguistic intergroup bias. Interpersonally salient interactions showed less linguistic intergroup bias than did intergroup ones. Results also indicate that health professionals have high levels of control in all types of medical encounters with patients. Nevertheless, the extent to which patients are able to interact with health professionals as individuals, rather than only as professionals is a key determinant of satisfaction with the interaction.

Urine D-arabinitol/L-arabinitol ratio in diagnosing Candida infection in patients with haematological malignancy and HIV infection

Adult patients with hematologic malignancies along with HIV infected patients were prospectively studied to determine the performance of urine D-arabinitol/L-arabinitol (DA/LA) ratio in diagnosing invasive candidiasis. Ten evaluable febrile neutropenic patients had proven invasive candidiasis and elevated DA/LA ratios were found in 5. Invasive candidiasis with normal DA/LA ratios was most frequently due to Candida krusei infection. This Candida species is a non-producer of arabinitol. Only 4 of 81 febrile neutropenic patients given either antifungal prophylaxis or empiric antifungal treatment had elevated DA/LA ratios. Only 1 of 15 HIV positive patients with either oropharyngeal or esophageal candidiasis had elevated DA/LA ratios. Widespread use of fluconazole prophylaxis in bone marrow transplantation patients at the study hospital has led to an increased prevalence of C. krusei infection. This is the likely reason for the low sensitivity of the test in proven and suspected invasive Candida infections reported here. (C) 2002 Elsevier Science Inc. All rights reserved.

Fatigue-related changes in torque output and electromyographic parameters of trunk muscles during isometric axial rotation exertion - An investigation in patients with back pain and in healthy subjects

Study Design. A cross-sectional case-control study. Objectives. To examine the effect of fatigue on torque output as well as electromyographic frequency and amplitude values of trunk muscles during isometric axial rotation exertion in back pain patients and to compare the results with a matched control group. Summary of Background Data. Back pain patients exhibited different activation strategies in trunk muscles during the axial rotation exertions. Fatigue changes of abdominal and back muscles during axial rotation exertion have not been examined in patients with back pain. Methods. Twelve back pain patients and 12 matched controls performed isometric fatiguing axial rotation to both sides at 80% maximum voluntary contraction in a standing position. During the fatiguing exertion, electromyographic changes of rectus abdominis, external oblique, internal oblique, latissimus dorsi, iliocostalis lumborum, and multifidus were recorded bilaterally. The primary torque in the transverse plane and the coupling torques in sagittal and coronal planes were also measured. Results. No difference in the endurance capacity was found between back pain and control groups. At the initial period of the exertion, back pain patients demonstrated a statistical trend (P = 0.058) of greater sagittal coupling torque as well as lower activity of rectus abdominis and multifidus and higher activity in external oblique. During the fatigue process similar changes of coupling torque were demonstrated in both sagittal and coronal planes, but a smaller fatigue rate for right external oblique, increase in median frequency for latissimus dorsi, and lesser increase in activity for back muscles were found in the back pain group compared with the control group. Conclusions. Alterations in electromyographic activation and fatigue rates of abdominal and back muscles demonstrated during the fatigue process provide insights into the muscle dysfunctions in back pain and may help clinicians to devise more rational treatment strategies.

Use of stress echocardiography to predict mortality in patients with diabetes and known or suspected coronary artery disease

OBJECTIVE - This study sought to determine whether stress echocardiography using exercise (when feasible) or dobutamine echo could be used to predict mortality in patients with diabetes. RESEARCH DESIGN AND METHODS - Stress echo was performed in 937 patients with diabetes (aged 59 +/- 13 years, 529 men) for symptom evaluation (42%) and follow-up of known coronary artery disease (CAD) (58%). Stress echocardiography using exercise was performed in 333 patients able to exercise maximally, and dobutamine echo using a standard dobutamine stress was used in 604 patients. Patients were followed for less than or equal to9 years (mean 3.9 +/- 2.3) for all-cause mortality. RESULTS - Normal studies were obtained in 567 (60%) patients; 29% had resting left ventricular (LV) dysfunction, and 25% had ischemia. Abnormalities were confined to one territory in 183 (20%) patients and to multiple territories in 187 (20%) patients. Death (in 275 [29%] patients) was predicted by referral for pharmacologic stress (hazard ratio [HR] 3.94, P < 0.0001), ischemia (1.77, P <0.0001), age (1.02, P = 0.002), and heart failure (1.54, P = 0.01). The risk of death in patients With a normal scan was 4% per year, and this was associated with age and selection for pharmacologic stress testing. In stepwise models replicating the sequence of clinical evaluation, the predictive power of independent clinical predictors (age, selection for pharmacologic stress, previous infarction, and heart failure; model chi(2) = 104.8) was significantly enhanced by addition of stress echo data (model chi(2) = 122.9). CONCLUSIONS - The results of stress echo are independent predictors of death in diabetic patients with known or suspected CAD.. Ischemia adds risk that is incremental to clinical risks and LV dysfunction.

Prediction of outcomes in hypertensive patients with suspected coronary disease

Stress echocardiography has been shown to improve the diagnosis of coronary artery disease in the presence of hypertension, but its value in prognostic evaluation is unclear. We sought to determine whether stress echocardiography could be used to predict mortality in 2363 patients with hypertension, who were followed for up to 10 years (mean 4.0+/-1.8) for death and revascularization. Stress echocardiograms were normal in 1483 patients (63%), 16% had resting left ventricular (LV) dysfunction alone, and 21% had ischemia. Abnormalities were confined to one territory in 489 patients (21%) and to multiple territories in 365 patients (15%). Cardiac death was less frequent among the patients able to exercise than among those undergoing dobutamine echocardiography (4% versus 7%, P<0.001). The risk of death in patients with a negative stress echocardiogram was <1% per year. Ischemia identified by stress echocardiography was an independent predictor of mortality in those able to exercise (hazard ratio 2.21, 95% confidence intervals 1.10 to 4.43, P=0.0001) as well as those undergoing dobutamine echo (hazard ratio 2.39, 95% confidence intervals 1.53 to 3.75, P=0.0001); other predictors were age, heart failure, resting LV dysfunction, and the Duke treadmill score. In stepwise models replicating the sequence of clinical evaluation, the results of stress echocardiography added prognostic power to models based on clinical and stress-testing variables. Thus, the results of stress echocardiography are an independent predictor of cardiac death in hypertensive patients with known or suspected coronary artery disease, incremental to clinical risks and exercise results.

The Cys282Tyr polymorphism in the HFE gene in Australian Parkinson's disease patients

Iron homeostasis is altered in Parkinson's disease (PD). The HFE protein is an important regulator of cellular iron homeostasis and variations within this gene can result in iron overload and the disorder known as hereditary haemochromatosis. We studied the Cys282Tyr single nucleotide polymorphism as a genetic risk factor for PD in two distinct and separately collected cohorts of Australian PD patients and controls. In the combined cohort comprising 438 PD patients and 485 control subjects, we revealed an odds ratio for possession of the 282Tyr allele of 0.61 (95% confidence interval, Cl = 0.42-0.90, P = 0.011) from univariate chi-squared and 0.59 (95% Cl = 0.39-0.90, P = 0.014) after logistic regression analyses (correcting for potential confounding factors). These results suggest that possession of the 282Tyr allele may offer some protection against the development of PD. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Barriers to effective cancer pain management: A survey of hospitalized cancer patients in Australia

The purpose of this study was to examine attitudinal barriers to effective pain management in a consecutively recruited cohort of 114 cancer patients from four Australian hospitals. When surveyed, 48% of this sample reported experiencing pain within the previous 24 hours. Of these, 56% reported this pain to be distressing, horrible or excruciating, with large proportions indicating that this pain had affected their movement, sleep and emotional well-being. Three factors were identified as potentially impacting on patients responses to pain-poor levels of patient knowledge about pain, low perceived control over pain, and a deficit in communication about pain. A trend for older patients to experience more severe pain was also identified. These older patients reported being more willing to tolerate pain and perceive less control over their pain. Suggestions are made for developing patient education programs and farther research using concepts drawn from broader social and behavioral models. J Pain Symptom Manage 2002:23:393-405. (C) U.S. Cancer Pain Relief Committee, 2002.

Myocardial abnormalities in hypertensive patients with normal and abnormal left ventricular filling: a study of ultrasound tissue characterization and strain

Abnormal left ventricular (LV) filling is common, but not universal, in hypertensive LV hypertrophy (LVH). We sought to elucidate the relative contributions of myocardial structural changes, loading and hypertrophy to LV dysfunction in 113 patients: 85 with hypertensive LVH and 28 controls without LVH and with normal filling. Patients with normal dobutamine stress echocardiography and no history of coronary artery disease were selected, in order to exclude a contribution from ischaemia or scar. Abnormal LV filling was identified in 65 LVH patients, based on Doppler measurement of transmitral filling and annular velocities. All patients underwent grey-scale and colour tissue Doppler imaging from three apical views, which were stored and analysed off line. Integrated backscatter (113) and strain rate imaging were used to detect changes in structure and function; average cyclic variation of 113, strain rate and peak systolic strain were calculated by averaging each segment. Calibrated 113 intensity, corrected for pericardial 113 intensity, was measured in the septum and posterior wall from the parasternal long-axis view. Patients with LVH differed significantly from controls with respect to all backscatter and strain parameters, irrespective of the presence or absence of abnormal LV filling. LVH patients with and without abnormal LV filling differed with regard to age, LV mass and incidence of diabetes mellitus, but also showed significant differences in cyclic variation (P < 0.01), calibrated 113 in the posterior wall (P < 0.05) and strain rate (P < 0.01), although blood pressure, heart rate and LV systolic function were similar. Multivariate logistic regression analysis demonstrated that age, LV mass index and calibrated IB in the posterior wall were independent determinants of abnormal LV filling in patients with LVH. Thus structural and functional abnormalities can be detected in hypertensive patients with LVH with and without abnormal LV filling. In addition to age and LVH, structural (not functional) abnormalities are likely to contribute to abnormal LV filling, and may be an early sign of LV damage. 113 is useful for the detection of myocardial abnormalities in patients with hypertensive LVH.

Usefulness of clinical risk markers and ischemic threshold to stratify risk in patients undergoing major noncardiac surgery

The risk of cardiac events in patients undergoing major noncardiac surgery is dependent on their clinical characteristics and the results of stress testing. The purpose of this study was to develop a composite approach to defining levels of risk and to examine whether different approaches to prophylaxis influenced this prediction of outcome. One hundred forty-five consecutive patients (aged 68 +/- 9 years, 79 men) with >1 clinical risk variable were studied with standard dobutamine-atropine stress echo before major noncardiac surgery. Risk levels were stratified according to the presence of ischemia (new or worsening wall motion abnormality), ischemic threshold (heart rate at development of ischemia), and number of clinical risk variables. Patients were followed for perioperative events (during hospital admission) and death or infarction over the subsequent 16 10 months. Ten perioperative events occurred in 105 patients who proceeded to surgery (10%, 95% confidence interval [CI] 5% to 17%), 40 being cancelled because of cardiac or other risk. No ischemia was identified in 56 patients, 1 of whom (1.8%) had a perioperative infarction. Of the 49 patients with ischemia, 22 (45%) had 1 or 2 clinical risk factors; 2 (9%, 95% CI 1% to 29%) had events. Another 15 patients had a high ischemic threshold and 3 or 4 risk factors; 3 (20%, 95% Cl 4% to 48%) had events. Twelve patients had a low ischemic threshold and 3 or 4 risk factors; 4 (33%, 95% CI 10% to 65%) had events. Preoperative myocardial revascularization was performed in only 3 patients, none of whom had events. Perioperative and long-term events occurred despite the use of beta blockers; 7 of 41 eta blocker-treated patients had a perioperative event (17%, 95% CI 7% to 32%); these treated patients were at higher anticipated risk than untreated patients (20 +/- 24% vs 10 +/- 19%, p = 0.02). The total event rate over late follow-up was 13%, and was predicted by dobutamine-atropine stress echo results and heart rate response. (C) 2002 by Excerpta Medica, Inc.

Quality of care of patients hospitalized with acute coronary syndromes

Background: Measurement and improvement of quality of care is a priority issue in health care. Patients hospitalized with acute coronary syndromes (ACS) constitute a high-risk population whose care, if shown to be suboptimal on the basis of available research evidence, may benefit from quality improvement interventions. Aim: To evaluate the quality of in-hospital care for patients with ACS, using explicit quality indicators. Methods: Retrospective case note review was undertaken of 397 patients admitted to three teaching hospitals in Brisbane, Queensland, Australia, between 1 October 2000 and 17 April 2001. The main out-come measures were 12 process-of-care quality indicators, calculated as either: (i) the proportion of all patients who received specific interventions or (ii) the proportion of ideal patients who received -specific interventions (i.e. patients with clear indi-cations and lacking contraindications). Results: Quality indicators with values above 80% included: (i) patient selection for thrombolysis (100%) and discharge prescription of beta-blockers (84%), (ii) antiplatelet agents (94%) and (iii) lipid-lowering agents (82%). Indicators with values between 50% and 80% included: (i) timely per-formance of electrocardiogram (ECG) on admission (61%), (ii) early coronary angiography (75%), (iii) measurement of serum lipids (71%) and (iv) discharge prescription of angiotensin-converting-enzyme (ACE) inhibitors (73%). Indicators with values <50% included: (i) timely administration of thrombolysis (35%), (ii) non-invasive risk assessment (23%) and (ii) formal in-hospital and post-hospital cardiac rehabilitation (47% and 7%, respectively). Conclusion: There were delays in performing ECG and administering thrombolysis to patients who presented to emergency departments with ACS. Improvement is warranted in use of non-invasive procedures for identifying high-risk patients who may benefit from coronary revascularization as well as use of serum lipid measurements, ACE inhibitors and cardiac rehabilitation.