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 basic smell test is as sensitive as a dopamine transporter scan: comparison of olfaction, taste and DaTSCAN in the diagnosis of Parkinson's disease.

AIM: To evaluate relationship between odour identification, taste threshold, dopamine transporter scan (DaTSCAN) and motor function in early Parkinson's disease (PD) and their diagnostic accuracy. METHODS: Seventy-three patients with early parkinsonism were evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS), DaTSCAN, electrogustometry (EGM) threshold and University of Pennsylvania Smell Identification Test (UPSIT). Olfactory Event-Related potentials (OERP) were performed on 49 patients. At follow-up (mean 15.3 months), patients were diagnosed as 'PD' or 'non-PD'. DaTSCAN images were assessed visually and semi-quantitatively by QuantiSPECT. RESULTS: The sensitivity of UPSIT (86%) was not significantly different from that of the DaTSCAN (92%). UPSIT correlated moderately with DaTSCAN uptake (r = 0.44; P < 0.005) and UPDRS score (r = 0.43; P < 0.05) and weakly with symptom duration (r = 0.25; P < 0.05). In the PD group, OERP showed increased latency but no change in amplitude and no correlation with DaTSCAN. EGM thresholds were impaired in 22% of the PD group but they did not correlate with any other test parameters. DaTSCAN-UPSIT discordance was found in nine patients with PD, but neither was diagnostically superior. CONCLUSION: Our patients with early PD have a frequent and severe olfactory deficit that correlates with disease severity, symptom duration and DaTSCAN but not EGM. The sensitivities of UPSIT and DaTSCAN are high at 86% and 92%, respectively. Although DaTSCAN is superior for 'localization', UPSIT is considerably 'cheaper', and neither is disease specific. EGM threshold impairment in PD is independent of the smell deficit, and probably signifies advanced disease.

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.

A randomly assigned double-blind cross-over study examining the relative anti-parkinsonian tremor effects of pramipexole and pergolide.

This study examined the relative anti-Parkinson's disease (PD) tremor potencies of pergolide and pramipexole in people with PD, using a 3-month double-blind cross-over design. Patients were randomly assigned to receive either pergolide and then pramipexole (n=9) or vice versa (n=8). The dose of the respective dopamine agonist was increased according to a titration schedule up to a maximum 1.5 mg t.d.s., with cross-over at 10 weeks. Assessments were performed at baseline, 4, 8 and 12 weeks. The primary outcome measures were the differences in the clinical (rest and postural) tremor scores on pergolide versus pramipexole. Seventeen PD patients (11 females and six males) with a mean age 68.4 years (range: 55-84 years) and a mean disease duration of 3.9 years (range: 2 months to 13 years) participated in the study. Twelve of the patients were taking other anti-parkinsonian medications. Two patients dropped out of the study whilst on pergolide. Fifteen of 16 patients were able to cross-over from one dopamine agonist to the other, without major retitration. There were no significant differences between the effects of the two drugs on the primary outcome measures, suggesting that the anti-PD tremor efficacies of dopaminergic medications are not dependent on differential affinities for dopamine receptor types.

[Sleepy drivers have a high frequency of traffic accidents related to respiratory effort-related arousals]. / Los conductores somnolientos tienen alta frecuencia de accidentes de tráfico asociados a exceso de RERA.

INTRODUCTION: Respiratory effort-related arousals (RERA) are secondary to subtle obstructions of the upper airway during sleep and can appear in the absence of a predominance of apneas and hypopneas, causing excessive daytime sleepiness. Analyzing the possible consequences of these new respiratory events is of increasing interest. Habitually sleepy drivers are at high risk of having traffic accidents related to sleep disorders (apneas, hypopneas and RERA). OBJECTIVE: The aim of this study was to determine whether excess RERA alone is an independent risk factor among sleepy drivers. METHOD: We studied 40 habitually sleepy drivers and 23 age- and sex-matched controls selected from a sample of 4,002 automobile drivers. We surveyed sleep habits, daytime sleepiness and traffic accidents. Sleep studies of esophageal pressure were performed. RESULTS: The sleepy drivers with apneas (apnea/hypopnea index > 10) had a higher 5-year accident rate (0.33 0.50) than did control drivers (0.004 0.21; p < 0.05). However, a high RERA index, but not sleep apnea, was an independent risk factor among the habitually sleepy drivers. The adjusted odds ratio (OR) for a RERA index > or = 10 was 7.6 (confidence interval [CI], 1.2 to 48); for a RERA index > or = 15, the OR was 17 (CI 1.5 to 91). CONCLUSIONS: The high risk of traffic accidents among sleepy drivers is mainly determined by the presence of RERA rather than the presence of apneas and hypopneas. These findings verify the importance of identifying RERA in routine sleep laboratory studies.

Los conductores somnolientos tienen alta frecuenciade accidentes de tráfico asociados a exceso de RERA / Sleepy drivers have a high frequency of traffic accidents related to respiratory effort-related arousals

INTRODUCCIÓN: Los RERA (respiratory effort-related arousal) son secundarios a sutiles obstrucciones de la vía aérea superior durante el sueño, pueden aparecer sin predominio de apneas e hipopneas y causan somnolencia diurna excesiva. El análisis de las potenciales consecuencias de estos nuevos acontecimientos respiratorios tiene hoy un interés creciente. Los conductores habitualmente somnolientos tienen un riesgo alto de sufrir accidentes de tráfico asociados a trastornos respiratorios durante el sueño (apneas más hipopneas más RERA). OBJETIVO: El objetivo de este trabajo es determinar si exclusivamente el exceso de RERA es un factor independiente de riesgo de accidentes en los conductores somnolientos. MÉTODO: Estudiamos a 40 conductores habitualmente somnolientos y 23 controles (conductores no somnolientos) pareados por edad y sexo, y ambos extraídos de una muestra de 4.002 conductores de vehículos. Se estudiaron datos sobre hábitos de sueño, somnolencia diurna, accidentes de tráfico y se realizaron estudios de sueño con medida de presión esofágica. RESULTADOS: Los conductores somnolientos con apneas de sueño tienen una tasa de accidentes en 5 años mayor que los controles (índice de apneas-hipoapneas [IAH] > 10; 0,33 ñ 0,50 frente a 0,004 ñ 0,21 en los controles; p < 0,05), pero sólo el exceso de RERA y no el de apneas de sueño fue un factor independiente de riesgo de accidentes en conductores somnolientos. La odds ratio (OR) ajustada para un índice de RERA 10 fue de 7,6 (intervalo de confianza [IC] del 95 por ciento, 1,2-48) y para un índice de RERA 15 fue de 17 (IC, 1,5-91).CONCLUSIONES: El alto riesgo de accidentes de tráfico de los conductores somnolientos viene principalmente determinado por la presencia de RERA más que por la presencia de apneas e hipopneas de sueño. Estos datos ratifican la importancia y la necesidad de identificar RERA en la práctica habitual de los laboratorios de sueño (AU)

Nature vs. nurture: two brothers with schizophrenia.

TOPIC: The nature vs. nurture argument as it pertains to two brothers. PURPOSE: To explore the synergistic effects of heritability and environment in the cases of two brothers with schizophrenia. SOURCES: Review of the literature and the authors' clinical experience. CONCLUSIONS: The nature vs. nurture dichotomy may not be as relevant as looking at the interaction between these two forces.

Habitually sleepy drivers have a high frequency of automobile crashes associated with respiratory disorders during sleep.

Sleepiness is a common cause of traffic crashes with a cost of billions of dollars per year. A recent study has found that 2 to 3% of drivers are habitually sleepy while driving. However, there has not been a controlled study to define the characteristics, driving performance, or automobile crash rate of habitually sleepy drivers. The prevalence of respiratory disorders during sleep, and whether these respiratory disorders contribute to the increased automobile crash frequency, is unknown in habitually sleepy drivers. We interviewed 4,002 randomly selected drivers to define the prevalence of drivers who are habitually sleepy while driving. We studied the habitually sleepy drivers and an age- and sex-matched control group of drivers. These studies included reporting of daytime sleepiness, automobile crashes, driving performance and sleep studies. Of the 4, 002 drivers interviewed, 145 (3.6%, confidence interval [CI] = 3.1 to 4.3) were habitually sleepy while driving. The habitually sleepy drivers reported a significantly higher frequency of auto crashes than control subjects (the adjusted odds ratio [OR] was 13.3, CI = 4. 1 to 43). The habitually sleepy drivers had a significantly higher prevalence of respiratory sleep disorders than control subjects. For a total respiratory events index (apneas, hypopneas, and other respiratory effort-related arousals) >/= 15 the adjusted OR was 6.0, CI = 1.1 to 32. In the habitually sleepy drivers group, the frequency of sleep apnea (apnea-hypopnea index) between subjects with or without auto crashes was not statistically different. However, if we consider total respiratory events index, this frequency of respiratory sleep disorders was significantly higher in subjects with automobile crashes (the adjusted OR for a total respiratory event index >/= 15 was 8.5, CI = 1.2 to 59). Habitually sleepy drivers are a large group of drivers (1 of 30 drivers) who are involved in several fold more automobile crashes than control subjects. As these excess auto crashes can be explained in part by the presence of respiratory disorders during sleep, which are treatable, many automobile crashes in these sleepy drivers may be preventable. Our findings suggest that asking about excessive sleepiness while driving may better predict which subjects with breathing disorders during sleep have crashes than asking about overall sleepiness.

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.

Evaluation of three different ways of assessing tremor in multiple sclerosis.

OBJECTIVES: To examine the comparative reliability and validity of three simple ways of rating upper limb tremor in patients with multiple sclerosis. METHODS: Three examiners independently rated severity of upper limb tremor in patients with multiple sclerosis on a 0-10 scale by studying videotape recordings of patients' examinations, spiral drawings, and handwriting samples. The correlations of the tremor severity scores with scores from arm dexterity tests and a tremor related disability scale were also assessed. RESULTS: Rating tremor on posture had a good intrarater and interrater reliability. However, these reliabilities decreased when kinetic tremor was assessed, in part because dysmetria was a confounding factor. The intrarater reliabilities of rating tremor from spirals and handwriting were also good but the interrater reliabilities were only fair to moderate. Tremor severity scored by all three methods correlated highly with scores obtained from the nine hole peg test, finger tapping test, and a tremor related activities of daily living (ADL) questionnaire, indicating that all three methods were valid ways of assessing tremor in multiple sclerosis. CONCLUSION: Multiple sclerosis tremors in posture can be scored using a clinical rating scale in a valid and reliable way, and from spirals and handwriting samples if the ratings are carried out by the same examiner. However, scoring kinetic tremor was less reliable. In addition, the nine hole peg and finger tapping tests provide useful objective assessments of upper limb function in tremulous patients with multiple sclerosis.

Treatment with nasal CPAP decreases automobile accidents in patients with sleep apnea.

We studied 50 consecutive patients to test the hypothesis that successful treatment of obstructive sleep apnea with nasal continuous positive airway pressure (nasal CPAP) will decrease automobile accidents in patients with sleep apnea. Thirty-six (72%) of the patients reported using nasal CPAP regularly during 2 yr. Fourteen patients reported they had not used CPAP during 2 yr. The patients with sleep apnea in this study had a higher automobile crash rate than all drivers in the state of Colorado (0.07 versus 0. 01 crash per driver per year, p < 0.02). Patients who were treated with nasal CPAP had a lower crash rate while being treated than before treatment (0.07 versus 0 crash per driver per year, p < 0.03). Untreated patients with sleep apnea continued to have a high crash rate (0.07 crash per driver before and after diagnosis). Drivers with sleep apnea were reluctant to report their automobile crashes, for the drivers in this study reported only one-third of the crashes in which they were involved. This is the first study to confirm with traffic records that patients with sleep apnea have fewer automobile crashes while being treated with nasal CPAP.

The timing of primary orthostatic tremor bursts has a task-specific plasticity.

Primary orthostatic tremor is characterized by unsteadiness and shakiness of the legs while standing. It is due to a remarkably strong and regular EMG modulation at approximately 16 Hz that is thought to be of CNS origin. Previous studies have shown that the tremor frequency is the same in all involved muscles and that the time relation between bursts of activity in different muscles may be fixed (e.g. always co-contracting or always contracting in an alternating pattern). Here we have used frequency domain analysis of postural muscle EMG signals in five primary orthostatic tremor patients and in two normal controls to explore the nature of such fixed timing patterns. The timing is found not to relate simply to the relative conduction times for passage of rhythmic bursts from a central oscillation to different muscles. Indeed, although the timing pattern (expressed as phase) of the 16-Hz EMG bursts in different postural muscles remains constant while the subject adopts a certain steady posture, it is different for different subjects and also changes when the same subject adopts a different posture. It seems unlikely that such complex task-dependent timing relations of rhythmic postural muscle activity are due to the primary pathology of primary orthostatic tremor. Instead, we suggest that the abnormally strong peripheral manifestation of a 16-Hz CNS oscillation merely unmasks normal central processes so that the timing patterns may provide a clue to the nature of postural motor control.

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.

Lamotrigine monotherapy in newly diagnosed untreated epilepsy: a double-blind comparison with phenytoin.

PURPOSE: Lamotrigine is an effective add-on therapy against a range of epileptic seizure types. Comparative studies with carbamazepine (CBZ) as monotherapy in newly diagnosed epilepsy suggest similar efficacy. In this study, lamotrigine (LTG) and phenytoin (PHT) are compared. METHODS: In a double-blind parallel-groups study, 181 patients with newly diagnosed untreated partial seizures or secondarily or primary generalised tonic-clonic seizures were randomised to two treatment groups. One group (n = 86) received LTG titrated over 6 weeks from a starting dose of 100 mg/day. The other (n = 95) received PHT titrated from 200 mg/day. Treatment continued for < or =48 weeks. RESULTS: The percentages of patients remaining on each treatment and seizure free during the last 24 and 40 weeks of the study, and times to first seizure after the first 6 weeks of treatment (dose-titration period), did not differ significantly between the treatment groups. These were measures of efficacy. Time to discontinuation, a composite index of efficacy and safety, likewise did not distinguish between treatments. Adverse events led to discontinuation of 13 (15%) patients from LTG and 18 (19%) from PHT. The adverse-event profile for LTG was dominated by skin rash [discontinuation of 10 (11.6%) patients compared with five (5.3%) from PHT] rather than central nervous system side effects: asthenia, somnolence, and ataxia were each significantly more frequent in the PHT group. The high rate of rash with LTG was probably due to the high starting dose and may be avoidable. A quality-of-life instrument, the SEALS inventory, favoured LTG. Patients taking PHT showed the biochemical changes expected of an enzyme-inducing drug, whereas those taking LTG did not. CONCLUSIONS: LTG and PHT monotherapy were similarly effective against these seizure types in patients with newly diagnosed epilepsy. LTG was better tolerated, more frequently causing rash, but with a lower incidence of central nervous system side effects.