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Biomedical subjects

Richard B Lipton

Publications and source records attributed to Richard B Lipton.

At least 37 records · Page 2Linked to original sources

A clinical trial of trimethobenzamide/diphenhydramine versus sumatriptan for acute migraines.

BACKGROUND: Although various classes of medication are used to treat acute migraine in the emergency department (ED), no treatment offers complete pain relief without side effects or recurrence of headache. Consequently, even though several antiemetic medications as well as SQ sumatriptan have demonstrated efficacy and tolerability for the ED treatment of migraine, there remains a need for more effective parenteral therapies. Open-label studies suggest that the combination of trimethobenzamide and diphenhydramine (TMB/DPH) may provide effective relief in a high proportion of migraineurs. OBJECTIVE: To test the hypothesis that ED patients with acute migraine, given intramuscular TMB/DPH, would have a larger reduction in their pain scores than patients given SQ sumatriptan. METHODS: This was an ED-based, randomized, double-blind, "double-dummy" clinical trial comparing 2 parenteral treatments for acute migraine headaches. Subjects received a combination of TMB 200 mg and DPH 25 mg as a single intramuscular injection or 6 mg of SQ sumatriptan. Pain scores, disability scores, associated symptoms, and adverse effects were assessed for 2 hours in the ED and by telephone 24 hours after medication administration. The primary outcome was the between-group difference in reduction of pain intensity as measured by a validated numerical rating scale 2 hours after medication administration. This study was designed to detect superiority of TMB/DPH; therefore, a 1-tailed t-test was used. An interim analysis was planned to terminate the trial if predetermined endpoints in the primary outcome variable were reached. RESULTS: The trial was stopped by the data monitoring committee after 40 subjects were enrolled because a substantial benefit in the primary outcome was found favoring sumatriptan. Baseline pain scores were comparable between the 2 groups. By 2 hours, sumatriptan subjects had improved by a mean of 6.1 and the TMB/DPH subjects had improved by a mean of 4.4 (95% CI for difference of 1.7: -0.1 to 3.4). By 24 hours after medication administration, sumatriptan subjects had a mean improvement from baseline of 4.9 as compared to 5.3 for TMB (95% CI for difference of -0.4: -2.4 to 1.6). The need for rescue medication was comparable between the groups. No serious or frequent adverse effects were noted in either group. CONCLUSIONS: SQ sumatriptan is probably superior to TMB/DPH for treating the pain of acute migraine at 2 hours. However, TMB/DPH was well-tolerated, efficacious, and relieved pain comparably to sumatriptan at 24 hours. TMB/DPH might have a role in select populations in which sumatriptan is contraindicated or likely to be ineffective.

Acute Disease↗

Modifiable risk factors for migraine progression (or for chronic daily headaches)--clinical lessons.

Herein we summarize clinical issues gleaned from a full peer-reviewed article on modifiable risk factors for migraine. Since migraine is progressive in some but not in most individuals, identifying patients at risk for progression is crucial. Key interventions include: (1) Decrease headache frequency with behavioral and pharmacologic interventions; (2) Monitor the body mass index and encourage maintenance of normal weight; (3) Avoid medication overuse; (4) Avoid caffeine overuse; (5) Investigate and treat sleep problems and snoring; (6) Screen and treat depression and other psychiatric comorbidities. These recommendations have not been demonstrated to improve outcomes in longitudinal studies.

Disease Progression↗

Psychiatric comorbidity of migraine.

Migraine affects nearly 12% of the adult population in the United States and causes significant lost productivity and decrements in health-related quality of life. The burden of migraine and the challenge in managing it are increased by the comorbid psychiatric conditions that occur in association with it. Studies in both clinical and community-based settings have demonstrated an association between migraine and a number of specific psychiatric disorders. This review will focus on the relationships between migraine and depression, generalized anxiety disorder, panic disorder, and bipolar disorder. In large scale population-based studies, persons with migraine are from 2.2 to 4.0 times more likely to have depression. In longitudinal studies, the evidence supports a bidirectional relationship between migraine and depression, with each disorder increasing the risk of the other disorder. Migraine is also comorbid with generalized anxiety disorder (Odds Ratio [OR] 3.5 to 5.3), panic disorder (OR 3.7), and bipolar disorder (OR 2.9 to 7.3). A diagnosis of migraine should lead to a heightened level of diagnostic suspicion for these comorbid psychiatric disorders. Similarly, a diagnosis of one of these psychiatric disorders should increase vigilance for migraine. Treatment plans for migraine should be mindful of the comorbid conditions.

Comorbidity↗

Modifiable risk factors for migraine progression.

Migraine is a chronic-recurrent disorder that progresses in some individuals. Transformed migraine is the result of this progression. Since migraine does not progress in most patients, identifying the risk factors for progression has emerged as a very important public health priority. If risk factors can be identified, that might provide a foundation for more aggressive preventive intervention. Risk factors for progression may be divided into non-remediable (gender, age, race) and remediable categories. In this paper, we focus on several already identified remediable risk factors, including frequency of migraine attacks, obesity, acute medication overuse, caffeine overuse, stressful life events, depression, and sleep disorders. We present the evidence for each risk factor and discuss possible interventions to address them.

Anxiety Disorders↗

The comorbidity of headache with other pain syndromes.

In this article, we consider the possible reasons and supporting evidence for the comorbidity of chronic pain conditions. To simplify the discussion, we primarily focus on the epidemiology of headache with other pain conditions, dividing studies into those based on children or adolescents and those based on adults. We consider exogenous and endogenous factors, and methodological challenges, in understanding whether and how 2 pain conditions may be related.

Adaptation, Psychological↗

Epidemiology of gait disorders in community-residing older adults.

OBJECTIVES: To study the epidemiology of gait disorders in community-residing older adults and their association with death and institutionalization. DESIGN: Community-based cohort study. SETTING: Bronx County and the research center at Albert Einstein College of Medicine. PARTICIPANTS: The Einstein Aging study recruited 488 adults aged 70 to 99 between 1999 and 2001. At entry and during annual visits over 5 years, subjects received clinical evaluations to determine presence of neurological or nonneurological gait abnormalities. MEASUREMENTS: Prevalence and incidence of gait disorders based on clinical evaluations and time to institutionalization and death. RESULTS: Of 468 subjects (95.9%) with baseline gait evaluations, 168 had abnormal gaits: 70 neurological, 81 nonneurological, and 17 both. Prevalence of abnormal gait was 35.0% (95% confidence interval (CI) = 28.6-42.1). Incidence of abnormal gait was 168.6 per 1,000 person-years (95% CI = 117.4-242.0) and increased with age. Men had a higher incidence of neurological gait abnormalities, whereas women had a higher incidence of nonneurological gaits. Abnormal gaits were associated with greater risk of institutionalization and death (hazard ratio (HR) = 2.2, 95% CI =1.5-3.2). The risk was strongly related to severity of impairment; subjects with moderate to severe gait abnormalities (HR = 3.2, 95% CI = 1.9-5.2) were at higher risk than those with mild gait abnormalities (HR = 1.8, 95% CI = 1.0-2.8). CONCLUSION: The incidence and prevalence of gait disorders are high in community-residing older adults and are associated with greater risk of institutionalization and death.

Aged↗

When migraine progresses: transformed or chronic migraine.

Migraine may be conceptualized, not just as an episodic disorder, but as a chronic recurrent and sometimes chronic progressive disorder. Transformed migraine, often referred to as chronic migraine is the result of migraine progression. This article will review the clinical features of transformed migraine, highlighting that its phenotype varies according to stage. Early in the process of transformation, attacks with migraine features are very common. As the disease evolves, most attacks lack the migraine features. The risk factors for migraine progression and the mechanisms for progression will be discussed. This review concludes with the prospects for treating transformed migraine and avoiding migraine progression.

Analgesics↗

The global burden of migraine: measuring disability in headache disorders with WHO's Classification of Functioning, Disability and Health (ICF).

This overview of the published epidemiological evidence of migraine helps to identify the size of the public-health problem that migraine represents. It also highlights the need for further epidemiological studies in many parts of the world to gain full understanding of the scale of clinical, economic and humanistic burdens attributable to it. This paper presents some of the work on migraine undertaken by the World Health Organization (WHO) in the Global Burden of Disease study conducted in 2000 and reported in the World Health Report 2001. Migraine was not included in the first Global Burden of Disease 1990. The paper also discussed the measurement of disability attributable to headache disorders using WHO ICF Classification. Using disability-adjusted life years (DALYs) as a summary measure of population health (which adds disability to mortality), WHO have shown that mental and neurological disorders collectively account for 30.8% of all years of healthy life lost to disability (YLDs) whilst migraine, one amongst these, alone accounts for 1.4% and is in the top 20 causes of disability worldwide. This information is combined with the increasingly widely accepted belief that disability and functioning are relevant parameters for monitoring the health of nations and that there is an increasing need to measure them. WHO's Classification of Functioning, Disability and Health (ICF) provides a model of human functioning and disability, as well as a classification system, that allows us to highlight and measure all dimensions of disability. ICF applied to headache disorders allows comparability with other health conditions as well as evaluation of the role of the environment as a cause of disability amongst people with headache. Migraine causes a large proportion of the non-fatal disease-related burden worldwide. Our knowledge of headache related burden is incomplete and it is necessary to add to it epidemiological studies in many parts of the world and to combine this with measurements of disability using both DALYs and WHO's ICF Classification. The work described here has been the base for the Global Campaign against Headache disorders: "Lifting the Burden", launched in 2004 jointly by WHO, IHS (International Headache Society), WHA (World Headache Alliance) and EHF (European Headache Federation).

Cost of Illness↗

Obesity and migraine: a population study.

OBJECTIVE: To assess the influence of body mass index (BMI) on the prevalence, attack frequency, and clinical features of migraine. METHODS: In a population-based telephone interview study, the authors gathered information on headache, height, and weight. The 30,215 participants were divided into five categories, based on BMI: 1, underweight (< 18.5), normal weight (18.5 to 24.9), overweight (25 to 29.9), obese (30 to 24.9), and morbidly obese (> or = 35). Migraine prevalence and modeled headache features were assessed as a function of BMI, adjusting by covariates (age, sex, marital status, income, medical treatment, depression). RESULTS: Subjects were predominantly female (65% female) and in middle life (mean age 38.4). BMI group was not associated with the prevalence of migraine, but was associated with the frequency of headache attacks. In the normal weight group, 4.4% had 10 to 15 headache days per month, increasing to 5.8% of the overweight (odds ratio [OR] = 1.3), 13.6% of the obese (OR = 2.9), and 20.7% of the morbidly obese (OR = 5.7). The proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (OR = 1.9). Similar significant associations were demonstrated with BMI category for disability, photophobia, and phonophobia. CONCLUSION: Though migraine prevalence is not associated with body mass index, attack frequency, severity, and clinical features of migraine increase with body mass index group.

Adolescent↗

Assessment of potential drug-drug interactions with a prescription claims database.

PURPOSE: The prevalence of 25 clinically important potential drug-drug interactions (DDIs) in a population represented by the drug claims database of a pharmacy benefit management company (PBM) was studied. METHODS: A retrospective cross-sectional analysis of pharmaceutical claims for almost 46 million participants in a PBM was conducted to determine the frequency of 25 DDIs previously identified as clinically important. A DDI was counted when drugs in potentially interacting combinations were dispensed within 30 days of each other during a 25-month period between April 2000 and June 2002. RESULTS: The number of DDIs ranged from 37 for pimozide and an azole antifungal to 127,684 for warfarin and a nonsteroidal antiinflammatory drug (NSAID). The highest prevalence (278.56 per 100,000 persons) and highest case-exposure rate (242.7 per 1,000 warfarin recipients) occurred with the warfarin-NSAID combination. The combination with the lowest overall prevalence (cyclosporine and a rifamycin, 0.10/100,000) differed from the combination with the lowest case-exposure rate (pimozide and an azole antifungal, 0.028 per 1,000 azole antifungal recipients). Number of cases, prevalence, and case-exposure rates for both sexes generally increased with age. An estimated 374,000 plan participants were exposed to a clinically important DDI during a 25-month period. Between 20% and 46% of prescription drug claims were reversed (canceled) for a medication with a drug interaction when a warning about the interaction was sent to the pharmacy. CONCLUSION: Analysis of prescription claims data from a major PBM found that 374,000 of 46 million plan participants had been exposed to a potential DDI of clinical importance.

Adolescent↗

Tension-type headache: classification and diagnosis.

Tension-type headache (TTH) is the most prevalent form of primary headache in the general population. In this article, the diagnostic challenges of TTH are discussed. The classification of these headaches according to the second edition of the International Classification of Headache Disorders (ICHD-2) and the main differences between the ICHD-2 and the first edition of the classification (ICHD-1, 1988) are discussed. The typical features of TTH also are highlighted. Finally, the differential diagnosis of episodic and chronic TTH, emphasizing the situations more likely to raise doubts, is discussed. The wide clinical spectrum of TTH frequently challenges the physician's diagnostic acumen. A structured approach to the patient and a better comprehension of this variability of presentation should translate into better quality of care and a more specific diagnosis for TTH sufferers.

Acute Disease↗

Retinal migraine.

Retinal migraine is a primary headache disorder, clinically manifested by attacks of transient monocular visual loss associated with migraine headache. Although isolated reports suggest that retinal migraine is rare, it likely is under-recognized. Retinal migraine usually is reported in women of childbearing age who have a history of migraine with aura. It typically is characterized by negative monocular visual phenomena lasting less than 1 hour. More than half of reported cases with recurrent transient monocular visual loss subsequently experienced permanent monocular visual loss. Although the International Headache Society diagnostic criteria for retinal migraine require reversible visual loss, our findings suggest that irreversible visual loss is part of the retinal migraine spectrum, likely representing an ocular form of migrainous infarction.

Humans↗

The epidemiology of migraine.

This article provides a review of the epidemiology and risk factors for migraine in population studies, as well as patterns for healthcare use. The burden and costs of migraine, as well as risk factors for disease progression, are also discussed. Although migraine is a remarkably common cause of temporary disability, many persons with migraine, even those with disabling headache, have never consulted a physician for the problem. Prevalence is highest in women, in persons between the ages of 25 and 55 years, and, at least in the United States, in individuals from lower income households. However, prevalence is high in groups other than these high-risk groups. In a subgroup of patients, migraine may be a progressive disorder.

Adult↗

Decreased neprilysin immunoreactivity in Alzheimer disease, but not in pathological aging.

Although evidence suggests that extensive cortical beta-amyloid (Abeta) deposition is essential in Alzheimer disease (AD), it is also detected in nondemented elderly individuals with pathologic aging (PA). Given evidence that neutral endopeptidase (NEP) or neprilysin, a key enzyme for clearance of Abeta, is decreased in AD, the goal of the present study was to determine if NEP was also decreased in PA. We measured NEP immunoreactivity in frontal cortex of 12 AD and six PA cases and compared this with 10 normal (N) elderly individuals. None had any significant other pathology, and they were similar with respect to age, sex, and postmortem delay. In addition, Abeta1-40 and Abeta1-42 were measured by enzyme-linked immunosorbent assay (ELISA), whereas tau, synaptophysin, and alpha-synuclein were measured on Western blots. The AD cases had more neuritic plaques, neurofibrillary tangles, higher Braak stage, and more tau immunoreactivity in frontal cortex than both PA and N. In contrast, both PA and AD had more senile plaques and Abeta1-42 than N. NEP immunoreactivity was decreased in AD but not in PA. The decrease was unlikely the result of neuronal or synaptic loss because NEP immunoreactivity in frontotemporal degeneration with comparable degrees of synaptic loss as the AD cases was not different from control subjects. Although NEP enzyme activity was decreased in approximately half the AD cases, on average, it was not decreased compared with N or PA. The results add further evidence that PA is distinct from AD and indicate that decreased Abeta degradation by NEP is unlikely to contribute significantly to amyloid deposition in PA or, in many cases, of AD.

Aged↗

Assessment of cognitive function of the elderly population: effects of darifenacin.

PURPOSE: Overactive bladder is common in the elderly population, which is susceptible to cognitive disorders and drug induced cognitive impairment. Existing overactive bladder treatments may cause adverse events, such as cognitive impairment, due to antagonism of the M1 receptor in the central nervous system. In this study we evaluated the effect of darifenacin, an M3 selective antagonist, on cognitive function in elderly volunteers without clinical dementia. MATERIALS AND METHODS: This double-blind, 3-period crossover study randomized 129 volunteers 65 years or older with no/mild cognitive impairment to receive 3 of 5 treatments, namely darifenacin controlled release (3.75, 7.5 or 15 mg once daily), darifenacin immediate-release (5 mg 3 times daily) or matching placebo for 14 days. Each treatment period was separated by 7 days of washout. Cognitive function tests were completed at baseline and at treatment end. RESULTS: For the primary end points of memory scanning sensitivity, speed of choice reaction time and word recognition sensitivity, there were no statistically significant differences for darifenacin vs placebo. There were no statistically significant differences in secondary variables except memory scanning speed, which increased in all groups relative to baseline, but improvement was greater with placebo than with 3.75 mg darifenacin. Darifenacin treatment was not associated with changes in alertness, contentment or calmness, which are likely to be clinically relevant. Darifenacin was well tolerated. CONCLUSIONS: : In elderly volunteers 2 weeks of treatment with darifenacin had no effect on cognitive function compared with baseline and it was not significantly different from placebo. This may be related to its M3 receptor selectivity with negligible M1 receptor antagonism.

Aged↗