Relationship Between Nonsteroidal Anti-inflammatory Drugs and Fall Risk in Older Adults.

Approximately 20% to 30% of older adults use nonsteroidal anti-inflammatory drugs (NSAIDs) daily. While some NSAIDs are known to cause adverse central nervous system effects, the risk of falls associated with NSAID use in older adults has not been as closely scrutinized as it has with other pain medications. This article reviews 16 studies evaluating NSAID use by older adults and subsequent fall risk. In the majority of evaluated studies, geriatric patients using NSAIDs had a higher occurrence of falls compared with those not takinG NSAIDS. It is important for pharmacists to understand this potential hazard of NSAID use by older adults to minimize the risk of falls by providing patient education, adjusting dosages, discontinuing medications, and closely monitoring patients.

A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis.

BACKGROUND: The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown. AIMS: To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up. METHODS: A multicentre, prospective, "real life" observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details. RESULTS: 198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p<0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started. CONCLUSIONS: This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

The Parkinson fatigue scale.

BACKGROUND: In recent years several studies have highlighted the clinical significance of fatigue in Parkinson's disease. While we are becoming aware of its prevalence and impact on the lives of patient, little progress has been made in understanding its nature or aetiology, nor on finding ways to manage the problem clinically. One possible reason for the slow pace of progress is the lack of an appropriate instrument to measure fatigue in Parkinson's disease and related disorders. While assessment tools have been developed for assessing fatigue associated with other diseases, their use in patients with Parkinsonism can pose problems and their validity cannot be assumed. OBJECTIVES: In an attempt to progress research and improve clinical management a new instrument is presented, the Parkinson Fatigue Scale. METHODS: This 16-item self-report instrument (the PFS-16) arose from statements by individuals with Parkinsonism experiencing fatigue. Initially tested on a sample of almost 500 patients, and subsequently on an independent sample of over 100. RESULTS: The PFS-16 scale was designed to tap a single construct encompassing the physical aspects fatigue and their impact on the patient's daily function. The scale deliberately excludes emotional and cognitive features that may occur as part of the fatigue experience but which may also occur independently in Parkinsonism. The scale has good intrinsic properties and satisfactory test-retest reliability. It shows reasonable associations with other measures of fatigue and is able to identify patients who self-report the presence of fatigue, and particularly those in whom fatigue is a problem. Cut-off scores are provided in both cases with good specificity and sensitivity. CONCLUSION: While further evaluation is required, the scale is offered to facilitate clinical practice and future research. It is hoped that its use will enable the improved understanding and clinical management of this important problem.

Blood transfusion in adult Jehovah's Witnesses. A case study of one congregation.

Jehovah's Witnesses, a religious group that prohibits certain types of medical treatment, eg, blood transfusions, tissue transplantations, and abortions, has 535,000 practicing members in the United States. We believe physicians should be informed of these beliefs to treat this large group of people properly. We studied one congregation's medical needs and beliefs in Denver by mailing a questionnaire to the 70 adult members. Their responses indicated that all of the members believe that accepting a blood transfusion is morally wrong. Seventeen members (29%) had refused a blood transfusion for themselves, and 27 members (46%) had had "bloodless" surgery performed on themselves or a family member. A majority of the congregation indicated they would consider suing a physician who would force them to receive a blood transfusion. Of the 43 members (73%) of the congregation who had regular physicians, eight members (19%) said their physicians were unaware of their refusal to accept blood products. The members of this congregation seek a physician who can respect their beliefs, understand bloodless surgical procedures, and vigorously treat every member within the limits of their religious beliefs.

Drivers with untreated sleep apnea. A cause of death and serious injury.

Three patients with untreated sleep apnea fell asleep while driving and caused serious automobile accidents. One person died, another became permanently paraplegic, and the three patients with sleep apnea were seriously injured in these crashes. This sequela of sleep apnea is not surprising, since subjects with sleep apnea may be poor drivers with a high accident rate and a high incidence of "near-miss" vehicular incidents. Because drivers with untreated sleep apnea may cause a large number of preventable automobile accidents, physicians have specific duties involving these drivers. First, physicians must try to identify impaired drivers with sleep apnea before they have an accident; routinely asking patients about loud snoring and hypersomnolence may help identify these impaired drivers. Second, physicians must consider the diagnosis of sleep apnea when examining patients who fall asleep while driving. Next, physicians must warn their patients with sleep apnea about the risks of driving with untreated sleep apnea. Finally, physicians must treat any seriously impaired driver with sleep apnea and keep these patients from driving until they can receive successful treatment.

Central sleep apnea. Improvement with acetazolamide therapy.

Respiratory rhythm during sleep may be dependent on blood pH with apneas being associated with alkalosis. Acidification may therefore have therapeutic value in some forms of sleep apnea. We administered acetazolamide to six patients with symptomatic central sleep apnea, a disorder of respiratory rhythm with little or no upper airway obstruction. Sleep studies were carried out before and after one week of drug therapy, during which time the mean arterial pH decreased from 7.42 to 7.34. All six patients had significant improvement, demonstrating a 69% reduction in total apneas. Five of the six patients reported better-quality sleep and decreased daytime hypersomnolence. Subsequent studies in normal subjects showed that acetazolamide, like other agents known to produce a metabolic acidosis, shifted the hypercapnic ventilatory response to the left 5 +/- 0.54 mm Hg. This may be important in mediating the observed decrease in apneas.

Interactions of levodopa with inhibitors of monoamine oxidase and L-aromatic amino acid decarboxylase.

Drug interactions between levodopa, tranylcypromine, and carbidopa have been studied in 4 patients with idiopathic parkinsonism. Pressor responses were induced by a combination of levodopa and tranylcypromine. These hypertensive reactions were inhibited by carbidopa, indicating that they are mediated at the periphery. Very small doses of levodopa induced an improvement in parkinsonism when patients were concomitantly taking carbidopa and tranylcypromine, but adverse reactions were prominent.

Effect of very-low-calorie diets with weight loss on obstructive sleep apnea.

To determine the effect of very-low-calorie diets (VLCDs) with weight loss on obstructive sleep apnea (OSA), we studied eight obese subjects with OSA, five males and three females. Subjects consumed a VLCD of 1760 kJ (420 kcal) (67% protein, 4% fat, 29% carbohydrate) or 3350 kJ (800 cal) (20% protein, 30% fat, 50% carbohydrate) with 100% of the recommended daily allowance of vitamins and minerals. Mean (+/- SD) values of weight and respiration before and after weight loss were, for weight, 153 +/- 37 and 132 +/- 29 kg (P less than 0.05); for BMI (kg/m2), 54 +/- 13 and 46 +/- 10 (P less than 0.05); for desaturations/h sleep, 106 +/- 50 and 52 +/- 45 (P less than 0.05); for apneas + hypopneas/h sleep, 90 +/- 32 and 62 +/- 49; for Pco2, 48 +/- 10 and 42 +/- 4 torr (P less than 0.05). Desaturation episodes/h and apnea + hypopneas/h improved in six patients. The most obese subject (female, BMI 81) who lost the most weight (47 kg) did not improve, nor did the subject who lost the least weight, 7 kg. The number of movements + arousals from sleep decreased in all patients (P less than 0.05). We conclude that VLCD with weight loss can produce improvement in OSA; subjects who lose a small amount of weight or subjects who are extraordinarily obese before and after weight loss may not improve.

A normative study of postural tremor of the hand.

In a normative study of amplitude, frequency, and variability of postural tremor of the hand in 97 normal subjects, 15 to 80 years old, tremor was transduced using accelerometers and characterized by power spectral analysis. Tremor amplitude ranged from a 0.0015- to 0.035-g peak at the dominant frequency. The modal tremor amplitude was 0.01-g peak, and the threshold for "visible tremor" was 0.007-g peak. The modal tremor frequency was constant at about 7 Hz in those subjects up to 70 years old and thereafter decreased to about 6 Hz. The mean range of variability of the dominant frequency was 2.5 Hz. The tremor pattern, characterized by the shape of spectra, varied greatly from a single finely tuned peak to multiple broad peaks. More than two thirds of normal subjects showed complex spectral patterns with more than one peak of significance. Passive resonance of the hand tissues was an important factor in determining dominant tremor frequencies in most subjects. Many subjects showed a strong, albeit variable , cardioballistic component. The results provide baseline data for studies of the effects of drugs on tremor, particularly in cases of "essential" tremor, and provide warnings that such studies require objective recording methods for adequate evaluation and need recourse to measurement of several factors of the tremor to elucidate the component of tremor affected by a drug. A scaling of tremor can be used in terms of reference to the strength of gravitational acceleration (1.0 g), which provides simple numerical relationships.

A novel method of recording arm movements. A survey of common abnormalities.

A novel technique uses a Schottky barrier photodetector to record abnormal movements of the arms in diseases of the nervous system. The method transduces displacement of the freely moving limbs, producing recordings that readily relate to clinical observation and provide quantification. This article gives examples of the use of the technique for examining ataxia in finger-to-nose testing, tremor, and cog-wheel phenomena in common neurological conditions.

A positron emission tomography study of cerebral activation associated with essential and writing tremor.

OBJECTIVE: To compare the abnormal patterns of cerebral activation associated with essential and writing tremors. DESIGN: Positron emission tomography using oxygen 15-labeled water was utilized to determine regional cerebral blood flow. Positron emission tomography images that were taken of the brain in individual patients were coregistered with magnetic resonance images of the same brain to ascertain accurate localization of cerebral activation in single patients. Patients with essential tremor underwent scanning at rest, during involuntary postural tremor, and during passive wrist oscillation. Normal control subjects underwent scanning at rest and during voluntary and passive wrist oscillation. Patients with writing tremor underwent scanning while they were holding a pen to paper with consequent involuntary tremor and again while they were holding a pen in the same supinated arm without tremor. SETTING: Research hospital. PATIENTS OR OTHER PARTICIPANTS: Seven patients with essential tremor, six patients with writing tremor, and six matched control subjects. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Regional cerebral blood flow. RESULTS: Essential tremor was associated with abnormal bilateral cerebellar, red nuclear, and thalamic activation. Writing tremor was also associated with abnormal bilateral cerebellar activation. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. These findings were evident in single patients, when positron emission tomography images were coregistered with magnetic resonance images and on group analysis of the pooled positron emission tomography data after transformation into stereotaxic space. CONCLUSION: These results indicate that both essential and writing tremors are associated with abnormal bilateral overactivity of cerebellar connections.

Epidemiology and genetics of essential tremor.

Essential tremor (ET) is probably the most common movement disorder and is a common cause of social, physical, and psychological handicaps. Its etiology and pathogenesis are unknown. Phenomenologically, ET overlaps and is associated with other disorders of movement, such as parkinsonism and dystonia. There is large variation in the stated prevalence of ET as well as limited availability of epidemiologic studies. Prevalence variations reflect differences in the definition of ET and the methodologies of investigation. The familial and sporadic forms of ET are generally assumed to be similar. The familial form appears to have a narrow phenotype. Wide variation in the reported percentage of patients with positive family history reflects ascertainment and classification differences. Linkage of ET to two different chromosome locations has been reported.

Phenobarbitone in essential tremor.

We conducted a double-blind, placebo-controlled trial of phenobarbitone on a fixed-dose regimen in 12 patients with essential tremor. The drug was better than placebo on accelerometric measurement and clinical assessment, but not according to patient self-assessment or measures of manual performance. Phenobarbitone may be an alternative to beta-adrenoreceptor antagonists in treating essential tremor.

PET before and after surgery for tumor-induced parkinsonism.

We studied a patient with left frontal meningioma and right-sided parkinsonism that resolved completely after operation. PET scans were performed before and after operation to measure regional cerebral blood flow, oxygen extraction ratio, oxygen utilization, and blood volume. A specific pattern of severe functional changes returned to normal postoperatively. The data suggest increased local tissue pressure due to edema, causing a functional disorder in the left basal ganglia that gave rise to reversible contralateral parkinsonism.

Post-traumatic tremor.

We present seven cases of tremor caused by mild head injury without loss of consciousness. The interval between head trauma to onset of symptoms was 1 to 4 weeks. A posture and kinetic tremor of the hands and head occurred unassociated with other neurologic signs. Myoclonic-like jerking was frequently present. Neuroimaging studies were normal. Clonazepam administration resulted in tremor reduction in three patients and propranolol decreased tremor in one patient. A tremor, similar to essential tremor, can be a rare complication of head trauma.

A positron emission tomography study of primary orthostatic tremor.

Primary orthostatic tremor (OT), a clinical syndrome in which a rapid (14 to 16 Hz), regular lower limb tremor causes unsteadiness on standing, may be associated with a postural upper limb tremor of similar frequency. We used H2 15O PET to analyze the abnormal pattern of cerebral activation associated with the postural upper limb tremor in four patients with primary OT. Patients had regional cerebral bloodflow (rCBF) measured during involuntary tremor while maintaining a posture with their outstretched right upper limb and again at rest. Tremor was associated with abnormal bilateral cerebellar and contralateral lentiform and thalamic activation. These findings were evident on group analysis of pooled PET data after transformation into standard stereotactic space and in single subjects when PET images were coregistered with structural MRI of the brain. At rest, cerebellar blood flow was significantly increased bilaterally in OT when compared with age- and sex-matched controls. We have previously demonstrated similar abnormal bilateral cerebellar activation in essential and writing tremors and conclude that abnormal bilateral overactivity of cerebellar connections is a common feature of tremulous disorders.

Electrophysiological aids in distinguishing organic from psychogenic tremor.

The clinical differentiation of tremors of organic and psychogenic origin can be difficult. We describe a patient with unilateral upper limb tremor that was initially considered to have a psychogenic cause, but subsequent frequency analysis of EMG signals and accelerometer recordings indicated that the tremor was organic in nature. An ischemic lesion in the contralateral lentiform nucleus found on MRI supported this conclusion. Quantitative electrophysiologic studies may thus be useful in distinguishing organic from psychogenic tremor.

Psychogenic tremors.

We diagnosed 24 patients, 9 men and 15 women ranging in age from 15 to 78 years, with clinically established or documented psychogenic tremors. Clinical presentations were unique, with complex tremors (often resting, postural, and kinetic), unusual temporal profiles (abrupt onset with a variable course), absence of other neurologic signs, inconsistent and incongruous symptomatology, selective disability with ability to perform some functions despite severe tremors, distractibility that lessens or abolishes tremor, atypical tremorgraphic recordings with changing amplitude and frequency, unusual handwriting and drawing specimens, presence of multiple undiagnosed somatizations, unresponsiveness to all treatments, absence of documented disease by laboratory or radiographic tests, presence of psychiatric disease, spontaneous remissions, or recovery with psychotherapy. We present criteria for the diagnosis of psychogenic tremor.

Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F-dopa PET study.

We measured striatal 18F-dopa influx constants (Ki) for 20 patients with isolated, predominantly postural, tremor (eight familial, 12 sporadic) and 11 with predominantly rest tremor. Results were compared with 30 controls and 16 Parkinson's disease (PD) patients. The eight familial essential tremor (ET) patients had normal striatal 18F-dopa uptake. Two of the 12 sporadic postural tremor patients had subnormal putamen 18F-dopa Ki, one (who later became akinetic) falling in the PD range. The mean putamen 18F-dopa uptake of the 11 rest tremor patients was reduced to PD levels (51% of normal). Our findings argue against an association between ET and PD, but support the existence of a "benign" tremulous variant of PD. The presence of low-amplitude rest tremor, cogwheel rigidity, reduced arm swing, and short tremor duration was not a useful predictor of nigral dysfunction in patients with postural tremor. In contrast, patients with predominantly rest tremor, particularly with onset in the leg, consistently showed reduced putamen 18F-dopa uptake.

Time-on-task decrements in "steer clear" performance of patients with sleep apnea and narcolepsy.

Loss of attention with time-on-task reflects the increasing instability of the waking state during performance in experimentally induced sleepiness. To determine whether patients with disorders of excessive sleepiness also displayed time-on-task decrements indicative of wake state instability, visual sustained attention performance on "Steer Clear," a computerized simple RT driving simulation task, was compared among 31 patients with untreated sleep apnea, 16 patients with narcolepsy, and 14 healthy control subjects. Vigilance decrement functions were generated by analyzing the number of collisions in each of six four-minute periods of Steer Clear task performance in a mixed-model analysis of variance and linear regression equations. As expected, patients had more Steer Clear collisions than control subjects (p=0.006). However, the inter-subject variability in errors among the narcoleptic patients was four-fold that of the apnea patients, and 100-fold that of the controls volunteers; the variance in errors among untreated apnea patients was 27-times that of controls. The results of transformed collision data revealed main effects for group (p=0.006), time-on-task (p=0.001), and a significant interaction (p=0.022). Control subjects showed no clear evidence of increasing collision errors with time-on-task (adjusted R2=0.22), while apnea patients showed a trend toward vigilance decrement (adjusted R2=0.42, p=0.097), and narcolepsy patients evidenced a robust linear vigilance decrement (adjusted R2=0.87, p=0.004). The association of disorders of excessive somnolence with escalating time-on-task decrements makes it imperative that when assessment of neurobehavioral performance is conducted in patients, it involves task durations and analyses that will evaluate the underlying vulnerability of potentially sleepy patients to decrements over time in tasks that require sustained attention and timely responses, both of which are key components in safe driving performance.