The prevalence of co-prescription of clinically relevant CYP enzyme inhibitor and substrate drugs in community-dwelling elderly Australians.

WHAT IS KNOWN AND OBJECTIVE: The elderly are at increased risk of adverse effects resulting from drug interactions due to decreased drug clearance and polypharmacy. This study examines the prevalence of the co-administration of clinically relevant cytochrome P450 (CYP) enzyme inhibitors with drugs that are substrates for these enzymes, in the community-dwelling elderly in Australia. METHODS: Participants aged 75 years or older (n = 1045) were recruited via their general practitioners at four Australian sites (Newcastle, Sydney, Melbourne and Adelaide). A research nurse visited the home of each patient to compile a list of all prescription medications (including doses) currently used by the patient, and to complete assessments for depression, quality of life and cognitive status. The medication data were searched for the co-prescription of clinically relevant CYP inhibitor and corresponding substrate drugs. RESULTS AND DISCUSSION: Potentially inappropriate CYP inhibitor-substrate combinations were found in 6·2% (65/1045) of patients. These patients were on significantly more medications (6·1 ± 3·0 vs. 3·9 ± 2·5; P = 0·001) and had a significantly lower physical quality of life (P = 0·047) than those who were not on any CYP inhibitor-substrate combinations. The most commonly prescribed inhibitor-substrate combinations involved the CYP 3A4 inhibitors, diltiazem and verapamil, with the substrates simvastatin or atorvastatin. Only 1 of 41 patients on a CYP3A4 inhibitor and a statin was prescribed a non-CYP 3A4 metabolized statin. Metoprolol was another substrate commonly co-prescribed with a CYP2D6 inhibitor. In many cases, the risks and benefits of potential interactions may have been considered by the GP as the prescribed doses of both the inhibitor and substrate were relatively low. There were, however, some notable exceptions, also involving the substrates simvastatin, atorvastatin and metoprolol. There were no GP factors that were associated with co-prescription of CYP inhibitors and substrates. WHAT IS NEW AND CONCLUSION: There is not a particular GP demographic that should be targeted for education regarding CYP interactions, but a focus on particular medications such as the statins may reduce the potential for clinically significant drug-drug interactions. As CYP drug-drug interactions are more common in patients on higher number of medications, particular vigilance is required at the time of prescribing and dispensing medications for elderly patients with multiple conditions.

Rural Organization of Australian Stroke Teams: Emergency Department project.

BACKGROUND: Many junior doctors have poor stroke assessment skills. Although major efforts have gone in to changing the attitudes of clinicians to stroke through the development of guidelines and implementation strategies, the most important step may be to make sure that medical schools include appropriate teaching of this important topic in their curricula. The Rural Organization of Australian Stroke Teams Emergency Department (ROASTED) project sought to determine the effectiveness of a practical intervention to improve the assessment and education of stroke knowledge among our junior emergency department doctors. METHODS: We used a prospective before and after study of two separate cohorts (intervention vs no intervention) to assess the stroke knowledge of our junior emergency department doctors and to test the effectiveness of an educational intervention. The project took place at five sites in rural Victoria in November 2006. Both cohorts undertook the same two validated quizzes 1 month apart. At the intervention sites two 1-h tutorials were conducted between the quizzes and participants were encouraged to use a web-based educational tool. RESULTS: Pre-project stroke knowledge was shown to be poor at all of the participating sites. At the sites where no intervention took place no improvement in knowledge was shown (z = 0.83, P = 0.41, two-sided Mann-Whitney U-test). The median score for quiz 1 was 8.1 (41%, interquartile range (IQR) 6.5-9.4) and for quiz 2, 7.2 (36%, IQR 5.1-9.3). At the intervention sites, participants significantly improved their stroke knowledge between quiz 1 and quiz 2 (z = 4.75, P < 0.001). The median score for quiz 1 in this cohort was 8.3 (42%, IQR 6.5-10.0) and for quiz 2, 12.8 (64%, IQR 12.0-14.8). CONCLUSION: This project showed that junior doctors have an inadequate knowledge of stroke and that among our junior emergency department doctors there is a need for the ROASTED intervention and other innovative educational measures.

Rural Organisation of Acute Stroke Teams project.

BACKGROUND: Improving the care of stroke patients is a national priority for the health system in Australia. In rural areas the challenges may be greater. Although best-practice guidelines for acute and subacute stroke care are well established, their general uptake appears to be limited and implementation strategies are required to promote the use of this evidence-based care. The Rural Organisation of Australian Stroke Teams (ROAST) project sought to promote the evidence-based stroke practice in rural hospitals. METHODS: This was a prospective observational project designed to improve the services provided to rural stroke patients, primarily through better organisation of care on general medical wards and emergency departments. Using recognized support strategies, we encouraged the use of nationally recognized key performance indicators and provided audit and feedback of adherence to these indicators to participating hospitals. RESULTS: Six Victorian hospitals participated in this initial phase of the ROAST project. Information was collected on 348 patients. Ten of the 11 indicators showed greater than 10% improvement in adherence levels and by the end of the project period compared favourably to levels of adherence described in metropolitan hospitals. CONCLUSION: The ROAST projected supported a network of clinicians to implement evidence-based guidelines in acute stroke care in the setting of general medical wards. In doing so, this project has shown that it is quite feasible to deliver best-practice care to stroke patients in rural Australia.

Rehabilitation interventions for foot drop in neuromuscular disease.

BACKGROUND: "Foot drop" or "Floppy foot drop" is the term commonly used to describe weakness or contracture of the muscles around the ankle joint. It may arise from many neuromuscular diseases. OBJECTIVES: To conduct a systematic review of randomised trials of treatment for footdrop resulting from neuromuscular disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (July 2005), MEDLINE (January 1966 to July 2005), EMBASE (January 1980 to July 2005), AMED (January 1985 to July 2005) and CINAHL databases (January 1982 to July 2005). SELECTION CRITERIA: Randomised and quasi-randomised trials of physical, orthotic and surgical treatments for footdrop resulting from lower motor neuron or muscle disease and related contractures were included. People with primary joint disease were excluded. Interventions included a 'wait and see' approach, physiotherapy, orthotics, surgery and pharmacological therapy. The primary outcome measure was ability to walk whilst secondary outcome measures included dorsiflexor torque and strength, measures of 'activity' and 'participation' and adverse effects. DATA COLLECTION AND ANALYSIS: Methodological quality was evaluated by two authors using the van Tulder criteria. Three studies with altogether 139 participants were included in the review. Heterogeneity of the studies precluded pooling the data. MAIN RESULTS: Early surgery did not significantly affect walking speed in a trial including 20 children with Duchenne muscular dystrophy. After one year, the mean difference (MD) of the 28 feet walking time was 0.00 seconds (95% confidence interval (CI) -0.83 to 0.83) and the MD of the 150 feet walking time was -2.88 seconds, (95% CI -8.18 to 2.42). In a trial with altogether 26 participants with Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy), long-term strength training significantly increased walking speed on a 6 metre timed walk (MD -0.70 seconds, 95% CI -1.17 to -0.23) but not on a 50 metre timed walk (MD -1.9 seconds, 95% CI -4.09 to 0.29). In a trial of a 24-week strength training programme in 28 participants with myotonic dystrophy, there was no significant change in walking speed on either a 6 or 50 metre walk. AUTHORS' CONCLUSIONS: Using the primary outcome of ability to walk, only one study demonstrated a positive effect and that was an exercise programme for people with Charcot-Marie-Tooth disease. Surgery was not significantly effective in children with Duchenne Muscular Dystrophy. More evidence generated by methodologically sound trials is required.

Multi-disciplinary rehabilitation for acquired brain injury in adults of working age.

BACKGROUND: Evidence from systematic reviews demonstrates that multi-disciplinary rehabilitation is effective in the stroke population, where older adults predominate. However, the evidence base for the effectiveness of rehabilitation following acquired brain injury (ABI) in younger adults is not yet established, perhaps because there are different methodological challenges. OBJECTIVES: To assess the effects of multi-disciplinary rehabilitation following ABI in adults, 16 to 65 years. To explore approaches that are effective in different settings and the outcomes that are affected. SEARCH STRATEGY: We used a wide range of sources including: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966-2004), EMBASE (1988-2004), CINAHL (1983-2004), PsycLIT (1967-2004), AMED, the National Research Register 2004 and ISI Science Citation Index (1981-2004). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing multi-disciplinary rehabilitation with either routinely available local services or lower levels of intervention; or trials comparing intervention in different settings or at different levels of intensity. Quasi-randomised and quasi-experimental designs were also included, providing they met pre-defined methodological criteria. DATA COLLECTION AND ANALYSIS: Trials were selected by two authors independently, and their methodological quality rated, again by two independent authors. A third reviewer arbitrated when disagreements could not be resolved by discussion. A 'best evidence' synthesis was performed by attributing levels of evidence, based on methodological quality. Trials were sub-divided in terms of severity of ABI and the setting and type of rehabilitation offered. MAIN RESULTS: Ten trials were identified of good methodological quality and four of lower quality. Within the subgroup of predominantly mild brain injury, 'strong evidence' suggested that most patients make a good recovery with provision of appropriate information, without additional specific intervention. For moderate to severe injury, there is 'strong evidence' of benefit from formal intervention. For patients with moderate to severe ABI already in rehabilitation, there is strong evidence that more intensive programmes are associated with earlier functional gains, and 'moderate evidence' that continued outpatient therapy can help to sustain gains made in early post-acute rehabilitation. There is 'limited evidence' that specialist in-patient rehabilitation and specialist multi-disciplinary community rehabilitation may provide additional functional gains, but the studies serve to highlight the particular practical and ethical restraints on randomisation of severely affected individuals for whom there are no realistic alternatives to specialist intervention. AUTHORS' CONCLUSIONS: Problems following ABI vary; different services are required to suit the needs of patients with different problems. Patients presenting acutely to hospital with moderate to severe brain injury should be routinely followed up to assess their need for rehabilitation. Intensive intervention appears to lead to earlier gains. The balance between intensity and cost-effectiveness has yet to be determined. Patients discharged from in-patient rehabilitation should have access to out-patient or community-based services appropriate to their needs. Those with milder brain injury benefit from follow-up, and appropriate information and advice. Not all questions in rehabilitation can be addressed by traditional research methodologies. There are important questions still to be answered and future research should employ the most appropriate methodology.

Chronic granulocytic leukemia in a patient with a renal allograft.

A man received a cadaver renal allograft for end-stage renal failure. After 35 months of immunosuppressive therapy with azathioprine and prednisone, he developed septicemia and a high leukocyte count. In spite of successful treatment of the infection, the leukocyte count continued to rise and a diagnosis of Philadelphia chromosome positive chronic granulocytic leukemia was made. An increased incidence of malignant disease, especially lymphoreticular malignancy, is well described in immunosuppressed patients with allografts. However, the association of chronic granulocytic leukemia and immunosuppressive therapy previously has not been reported. An additional etiological factor in this patient may have been the extensive diagnostic radiological investigations undertaken in childhood. The recent addition of allopurinol to the immunosuppressive therapy has normalized the platelet and leukocyte counts, probably by potentiating mercaptopurine.

Treatment of hemodialysis-related porphyria cutanea tarda with plasma exchange.

A patient with hemodialysis-related porphyria cutanea tarda was treated with plasma exchange. A rapid clinical response occurred coincidentally with a significant fall in the plasma porphyrin level. The level fell further over the following few months without additional therapeutic intervention, whereafter a slow rise occurred without recurrence of skin disease. We suggest that this form of treatment may be ideal for the patient with porphyria cutanea tarda and chronic renal failure in whom no alternative therapy is available for the cutaneous problem.

The role of diet in the pathogenesis and control of hyperlipidemia after renal transplantation.

Twenty-one Caucasian renal transplant recipients with hyperlipidemia and normal renal function were assessed with regard to their diet. Their average daily intake of energy and cholesterol was lower and the ratio of polyunsaturated to saturated fat higher in their diet than in that of a comparable urban Caucasian South African population. Nevertheless modification of their diets in one year produced a significant lowering of their body weight and a statistically significant drop in the mean plasma cholesterol (9.2 +/- 0.5 mmoles/l to 7.6 +/- 0.5 mmoles/l, P less than 0.05). Although the fall in plasma triglyceride in the group as a whole was not statistically significant (3.8 +/- 0.6 mmoles/l to 3.2 +/- 0.5 mmoles/l) the level did decrease substantially in 13 of the 21 patients (4.2 +/- 0.9 mmoles/l to 2.5 +/- 0.5 mmoles/l, P less than 0.01). It is suggested that diet has a definite role in the control of post-transplant hyperlipidemia but should probably be introduced immediately after immunosuppression is started and be coupled with a suitable exercise program for optimal effect.

Reliability of the American Medical Association guides' model for measuring spinal range of motion. Its implication for whole-person impairment rating.

STUDY DESIGN: Repeated measures design for intra- and interrater reliability. OBJECTIVES: To determine the intra- and interrater reliability of the lumbar spine range of motion measured with a dual inclinometer, and the thoracolumbar spine range of motion measured with a long-arm goniometer, as recommended in the American Medical Association Guides. SUMMARY OF BACKGROUND DATA: The American Medical Association Guides (2nd and 4th editions) recommend using measurements of thoracolumbar and lumbar range of movement, respectively, to estimate the percentage of permanent impairment in patients with chronic low back pain. However, the reliability of this method of estimating impairment has not been determined. METHODS: In all, 34 subjects participated in the study, 21 women with a mean age of 40.1 years (SD, +/- 11.1) and 13 men with a mean age of 47.7 years (SD, +/- 12.1). Measures of thoracolumbar flexion, extension, lateral flexion, and rotation were obtained with a long-arm goniometer. Lumbar flexion, extension, and lateral flexion were measured with a dual inclinometer. Measurements were taken by two examiners on one occasion and by one examiner on two occasions approximately 1 week apart. RESULTS: The results showed poor intra- and interrater reliability for all measurements taken with both instruments. Measurement error expressed in degrees showed that measurements taken by different raters exhibited systematic as well as random differences. As a result, subjects measured by two different examiners on the same day, with either instrument, could give impairment ratings ranging between 0% and 18% of the whole person (excluding rotation), in which percentage impairment is calculated using the average range of motion and the average systematic and random error in degrees for the group for each movement (flexion, extension, and lateral flexion). CONCLUSIONS: The poor reliability of the American Medical Association Guides' spinal range of motion model can result in marked variation in the percentage of whole-body impairment. These findings have implications for compensation bodies in Australia and other countries that use the American Medical Association Guides' procedure to estimate impairment in chronic low back pain patients.

Applications of functional assessment to musculoskeletal disability evaluation.

A review of the history of the disability determination for LBP suggests that the early focus upon disability as a direct "effect" of impairment has given way to an updated approach acknowledging the multitude of factors, many of which are subjective, that contribute to an individual's future return to work and disability status. In addition to the evaluation of the underlying impairment and pathology, physicians performing disability evaluations for LBP will be best served when they can assess the individual's functional status, and incorporate that information into their decision regarding the individual's current limitations and prognosis. As discussed above, many of the factors contributing to the evaluation of functional status, including pain, physical functioning, and affective status, are necessarily subjective. Nonetheless, the rehabilitation literature suggests that inclusion of this information into the disability determination using a patient-centered approach may provide the factors that are most potent with respect to patient prognosis and eventual return to work.

Caregivers of people with multiple sclerosis: a survey in New Zealand.

A survey carried out in the Manawatu and Wanganui area of New Zealand was designed to locate all those known to have multiple sclerosis; as part of the research, 31 primary caregivers (20 males, 11 females) of MS patients in the study were interviewed to gain information about their roles, self-defined tasks, and life situations.

The acute attack of porphyria.

The acute neurological crisis is the most significant complication of variegate and acute intermittent porphyria and hereditary coproporphyria. If it is managed correctly, the mortality rate should be negligible. An outline is given of the major symptoms and signs encountered in the acute attack, and the therapy which should be used for their relief is discussed. Mention is made of forms of treatment which may decrease the activity of the haem biosynthetic pathway and thus specifically influence the clinical problems.

The UCT class of '32--50 years on.

In 1982 several members of the 1932 final-year M.B. Ch.B. class of the University of Cape Town met for a golden anniversary dinner. Apart from its nostalgic significance, it provided an opportunity to compare the career choices of that era with those of today. Unlike present graduates, 50 years ago graduating doctors tended not to specialize and tended to enter rural areas to practise. The significance of these changes for local medical manpower needs is discussed.

Breast-feeding in a socio-economically disadvantaged area of Cape Town. Part I. Analysis of breast-feeding patterns among clinic attenders.

A survey of infant-feeding practices in a socio-economically disadvantaged community in the Cape Peninsula was undertaken. By the age of 6 weeks 47,3% of the infants were receiving bottle feeds, and this had increased to 76,3% by the age of 7-12 weeks. Analysis of factors which might have influenced this pattern indicated that subjective dissatisfaction with the quantity and quality of milk dominated the mothers' reasons for stopping breast-feeding. Since contact between the local authority and mothers often took place only after breast-feeding had been discontinued, it is suggested that concentrating on education and support during the perinatal period may have a positive influence on this disturbing trend.