Management of Parkinson's disease in the acute hospital environment.

There have been a number of exciting developments in the management of Parkinson's disease (PD) in the past decade. However the objective for the vast majority of patients remains the maintenance of quality of life through the achievement of steady levels of dopaminergic stimulation within the target neurones of the basal ganglia. While there is a great deal of guidance available for the PD specialist, it remains a challenge for the generalist to know which patients require specialist input, how urgently that input should be obtained and what steps should be taken while awaiting review. Diagnosis can be difficult in the acute setting. While a high index of suspicion is important, it is not a diagnosis that should be made lightly and all cases should be reviewed by a specialist who will then advise on initial treatment. Management of PD medication during intercurrent illness is a challenge, particularly when the gastrointestinal tract is dysfunctional. Some guidance on dealing with this situation is available and has been summarised in this article. Problems that may present to the general physician include aspiration pneumonia, uncontrolled dyskinesias, psychosis, dopamine agonist withdrawal syndrome and rarely, neuroleptic malignant-like syndrome. These conditions will be reviewed, along with general guidance for managing patients on more sophisticated regimes such as continuous intrajejunal levodopa infusion (Duodopa) and patients with a deep brain stimulator in situ.

A new low-dose formulation of selegiline: clinical efficacy, patient preference and selectivity for MAO-B inhibition.

Three studies were performed using a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption "Zydis Selegiline". The aim of the first study was to compare the therapeutic efficacy of Zydis Selegiline (1.25 mg or 10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg) in patients with Parkinson's disease (PD) who were previously treated with conventional selegiline tablets as an adjunct to levodopa/dopamine agonist therapy. Patients were observed for 4 weeks to ensure that they were stable. Stable patients (n=197) were then randomised to continue with conventional selegiline tablets 10 mg (n=68), or to treatment with Zydis Selegiline 1.25 mg (n=64) or Zydis Selegiline 10 mg (n=62) for 12 weeks in this randomised, parallel group study. A further aim was to establish the acceptability of Zydis Selegiline compared with conventional selegiline tablets. Patient preference for Zydis Selegiline was also evaluated in a second study, a single-dose, randomised, two-way crossover study conducted in patients with PD (n=148). Patients were stratified by the presence or absence of swallowing and salivation problems and were randomised to either Zydis Selegiline 5 mg or a placebo fast-dissolving formulation. In a third study, the degree of potentiation of the tyramine pressor effect following Zydis Selegiline was compared with that following conventional selegiline tablets in healthy volunteers. A total of 24 healthy volunteers were randomised to receive Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg for 14-16 days in an open-label, randomised parallel group study. Both Zydis Selegiline (1.25 mg and 10 mg) treatments were shown to be therapeutically equivalent to conventional selegiline tablets 10 mg based on comparison of mean total Unified Parkinson's Disease Rating Scale (UPDRS) scores. Therapeutic equivalence was defined a priori as the 90% confidence interval (CI) for the difference in total UPDRS scores between groups to lie entirely within the range +/-5. The difference (90% CI) in mean adjusted total UPDRS between Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg was -2.50 (-4.84, -0.17), and for Zydis Selegiline 10 mg and conventional selegiline tablets 10 mg, 0.04 (-2.30, 2.38). For the motor subscores of the UPDRS, differences between adjusted means (90% CI) compared with the conventional selegiline tablets group were: Zydis Selegiline 1.25 mg, -2.14 (-3.94, -0.33) and Zydis Selegiline 10 mg, -0.90 (-2.70, +0.91). Patients who switched from conventional selegiline tablets to Zydis Selegiline 1.25 mg showed a slight improvement in UPDRS scores following 12 weeks of treatment (standard error of difference 1.039; p=0.01). In the single-dose crossover study, most (61%) patients liked Zydis Selegiline 5 mg; a significantly greater proportion than the null hypothesis of 50% (p<0.002). However, only 62 patients (46%) indicated that they liked the taste of Zydis Selegiline. Nevertheless, the proportion of patients who preferred Zydis Selegiline (65%) to their usual medication was significantly greater than the null hypothesis of 50% (p<0.001). Similar findings were demonstrated in the 12-week study where a higher proportion of patients who received up to 3 months of treatment indicated a preference for either Zydis Selegiline 1.25 mg (90%) or Zydis Selegiline 10 mg (86%) over conventional selegiline tablets 10 mg. More than 90% of patients found Zydis Selegiline easy to take, with 61% rating it as extremely easy. Most (81%) patients taking Zydis Selegiline 1.25 mg liked the taste compared with 45% taking Zydis Selegiline 5 mg (in the previous study). Zydis Selegiline did not potentiate the tyramine effect: a pressor effect was elicited after 400 mg tyramine both before and after 14 days of treatment with Zydis Selegiline 1.25 mg. In contrast, after 14 days treatment with conventional selegiline tablets 10 mg, the threshold dose required to elicit the tyramine pressor response was significantly (p<0.0001) reduced from 400 mg to 200 mg. In summary, Zydis Selegiline at doses of 1.25 mg and 10 mg was therapeutically equivalent to conventional selegiline tablets 10 mg. The Zydis Selegiline formulation was well-liked by all patients, with most preferring Zydis Selegiline 1.25 mg to their usual selegiline tablet. Furthermore, Zydis Selegiline was well tolerated and, unlike conventional selegiline tablets, appeared to retain specificity for inhibition of monoamine oxidase type B (MAO-B), since it did not potentiate the pressor response to tyramine.

Updated guidelines for the management of Parkinson's disease.

New data on diagnosis, drug therapy, surgery and psychosocial concerns have emerged since the publication of the 1998 Guidelines for the Management of Parkinson's Disease. This article reviews new data and addresses issues left unanswered in the previous guidelines.

Parkinson's disease nurse specialists: an important role in disease management.

A concerted effort by health-care professionals is central to delivering effective clinical management of patients with Parkinson's disease. Before the introduction of the first PD nurse specialist, a community study showed PD patients need basic nursing care: for instance, more than half experienced difficulties with constipation, micturition, or sleep patterns. The evolving role (particularly in the United Kingdom) of PD nurse specialists has started to address these problems. Nurse specialists are ideally placed to assess personal concerns and difficulties, furnish educational and emotional support, and facilitate referral to health or social care agencies. They can help physicians or neurologists in the assessment of physical and psychological status, they can monitor the effects and side-effects of the medications used to control the disease, and they can help in managing drug titration. The provision of a telephone support line, respite care facilities, and psychological support and counseling can help with depression, anxiety, hallucinations, and confusional states, some of which may be iatrogenic. An integrated multidisciplinary PD service that incorporates nurse specialists alongside their medical colleagues can offer support at the individual level, education to the wider community and training for a variety of clinical and lay staff. The cost-effectiveness of such a system is attracting considerable international interest and is currently being evaluated.

Practical approach to quality of life in Parkinson's disease: the nurse's role.

In recent years it has become apparent that nurses have several key roles in the treatment of Parkinson's disease. These include the practice of skilled clinical care, the provision of advice and education, communicating with patients and carers, and also between health and social care agencies. Their goals are to facilitate good clinical care, to reduce morbidity (both physical and psychological) and to achieve better informed patients by the reduction of misinformation, fear and distress caused by the diagnosis and consequences of this disease. The overall goal is to improve the prognosis and to reduce the impact of this disease on patients and their care givers. To achieve these goals the specialist nurse needs skills in assessment, reassessment and counselling in addition to knowledge of the disease and its management. The training needs have been established for the nursing profession to address these issues, and courses have been established and approved. A scale comprising four clinical management stages has been proposed: initially around the time of diagnosis; stable maintenance therapy; a more complex management stage, and palliative care. Nursing interventions and priorities differ in these arbitrary stages. Several models of nursing provision have been piloted in the United Kingdom, and results of evaluations are keenly awaited. Meanwhile, specialist nurses are proving to be popular with patients and carers, medical specialists, and the Parkinson's Disease Society which aims to see their provision in each Health District throughout the United Kingdom. In summary, the nursing role is complementary to those of the other members of the multi-disciplinary health team that aims to improve the quality of life of PD patients and their carers.

What's so special about being 65? The challenge facing eldercare departments.

There is no abrupt change in physiology, pathology or pharmacology occurring at or around the age of 65 years. There is some evidence of a change in the effect of illness, and of the prevalence of disability with advancing age. However, these changes are individual and gradual, and more associated with passing 75-80 years rather than 65. The main change occurring in the seventh decade arises from retirement from paid employment, and is therefore financial. Hence, in contrast to personal financial support, Health and Social Services departments would be ill advised to use the age of 65 as a threshold. Age-related admission policies may perpetuate ageism, and needs-related policies may therefore be preferable. The challenge facing departments of geriatric medicine and psychiatry is to present their services attractively to patients, carers and purchasers, who need to recognize the rationale for the purchase of these forms of care, with reference not only to benefit to patients, but also to their informal carers.

Simplification of the initiation of bromocriptine in elderly patients with advanced Parkinson's disease.

One hundred and seventy-three parkinsonian patients treated with levodopa entered a randomized multicentre comparison between two introductory schedules for adjuvant bromocriptine. A 2-week placebo run-in was followed by a double-blind 8-week titration phase of bromocriptine up to 15 mg daily, according to the standard seven-step, or a simpler three-step, regimen. They were maintained on this dose for a further 8 weeks and then followed for a further 12 weeks. One hundred and fifty-nine patients completed the placebo run-in period, and 132 completed 16 weeks. No significant differences were found between the standard and simplified regimens for efficacy, side-effects, withdrawals or deaths, nor for any of the clinical or functional assessments. The Webster score improved by 29% and the Cape ADL by 32%. The simpler schedule offers advantages to those elderly parkinsonian patients in whom bromocriptine is added to optimal levodopa dosage.

A comparison of the effects of controlled-release levodopa (Madopar CR) with conventional levodopa in late Parkinson's disease.

In this multicentre study a controlled-release formulation of levodopa and the decarboxylase inhibitor benserazide (Madopar CR) was evaluated in patients with Parkinson's disease exhibiting dose-related fluctuations in motor performance in response to conventional levodopa preparations. The effect of Madopar CR, with or without conventional levodopa/benserazide, on the proportion of time spent "on", "off" or "intermediate" was compared with that of previous conventional levodopa/decarboxylase inhibitor therapy. Evaluation of the two periods of optimum therapy was based on both patient diary data and investigator opinion. Forty seven patients completed the study but full patient diaries were available for only 37. The mean optimum total daily dosage of conventional Madopar was 820 mg taken in a mean of 6.4 doses, compared with a mean optimum daily dosage of combined Madopar CR and conventional Madopar of 1088 mg, taken in a mean of 5.2 doses. Conventional Madopar was taken in addition to Madopar CR in all but eight patients. Madopar CR was felt to be advantageous in 83% and disadvantageous in 11% of patients completing the study. Considering the 37 patients for whom diary data were available, Madopar CR therapy resulted in an increase in the mean time spent "on" (p = 0.016) and a decrease in the mean time spent "off" (p = 0.029) compared with conventional Madopar alone. Individually 25 out of 37 had an increase in "on" time and 19 out of 37 experienced a decrease in "off" time. Thus Madopar CR was found to be beneficial in a significant proportion of patients experiencing fluctuations in response to conventional levodopa.

Longitudinal study of thyroid function in acutely ill elderly patients using a sensitive TSH assay-defer testing until recovery.

A prospective longitudinal study of thyroid function was conducted in 180 consecutive admissions to an acute geriatric unit. The rest strategy included assay of TSH and TRH testing when appropriate. On admission TSH was suppressed (less than 0.1 mU/l) in 17 patients (9.4%) and elevated (greater than 4.0 mU/l) in 8 (4.4%). Follow-up of these initial abnormalities showed resolution in almost all cases. Our findings suggest that acute illness may interfere with the hypothalamic-pituitary-thyroid axis, causing either temporary suppression or stimulation of TSH release. Although no new cases of thyroid disease were diagnosed, the prevalence of established dysfunction was 3.3% (2.7% hypothyroid; 0.6% hyperthyroid). To avoid misleading results, testing of thyroid dysfunction should be delayed until recovery from illness.