Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey.

BACKGROUND: Little is known about the costs of treating ataxia and whether treatment at a specialist ataxia centre affects the cost of care. The aim of this study was to investigate whether patients who attended specialist ataxia centres in three European countries reported differences in their health care use and costs compared with patients who did not attend a specialist ataxia centre. We compared mean resource use and health service costs per patient affected by ataxia in the United Kingdom, Italy and Germany over a 12-month period. Data were obtained from a survey distributed to people with ataxia in the three countries. We compared mean resource use for each contact type and costs, stratifying patients by whether they were currently attending a specialist ataxia centre or had never attended one. RESULTS: Responses were received from 181 patients from the United Kingdom, 96 from Italy and 43 from Germany. Differences in the numbers of contacts for most types of health service use between the specialist ataxia centre and non-specialist ataxia centre groups were non-significant. In the United Kingdom the mean total cost per patient was €2209 for non-specialist ataxia centre patients and €1813 for specialist ataxia centre patients (P = 0.59). In Italy these figures were €2126 and €1971, respectively (P = 0.84). In Germany they were €2431 and €4087, respectively (P = 0.19). Inpatient stays made the largest contribution to total costs. CONCLUSIONS: Within each country, resource use and costs were broadly similar for specialist ataxia centre and non-specialist ataxia centre groups. There were differences between countries in terms of health care contacts and costs.

Patient pathways for rare diseases in Europe: ataxia as an example.

BACKGROUND: Progressive ataxias are rare and complex neurological disorders that represent a challenge for the clinicians to diagnose and manage them. This study explored the patient pathways of individuals attending specialist ataxia centres (SAC) compared with non-specialist settings. We investigated specifically how diagnosis was reached, the access to healthcare services, treatments, and care satisfaction. The focus of this study was on early intervention, coordination of treatment to understand the care provision in different countries. METHODS: A patient survey was done in the UK, Germany and Italy to gather information about diagnosis and management of the ataxias in specialist (SAC) and non-specialist settings, utilisation of other primary and secondary health care services, and patients' satisfaction of received treatment. RESULTS: Patients gave positive feedback about the role of SAC in understanding their condition, ways to manage their ataxia (p < 0.001; UK) and delivering care adapted to their needs (p < 0.001; UK), in coordinating referrals to other healthcare specialists, and in offering opportunities to take part in research studies. Similar barriers for patients were identified in accessing the SACs among the selected countries, UK, Germany, and Italy. CONCLUSIONS: This study provides crucial information about the ataxia patients care pathways in three European countries. Overall, the results showed a trend in patients' satisfaction being better in SAC compared to non-SAC. The outcomes can be used now for policy recommendations on how to improve treatment and care for people with these very rare and complex neurological diseases across Europe.

Assessing What Matters to People Affected by Alzheimer's Disease: A Quantitative Analysis.

INTRODUCTION: In this phase of the ongoing What Matters Most study series, designed to evaluate concepts that are meaningful to people affected by Alzheimer's disease (AD), we quantified the importance of symptoms, impacts, and outcomes of AD to people at risk for or with AD and care partners of people with AD. METHODS: We administered a web-based survey to individuals at risk for or with AD (Group 1: unimpaired cognition with evidence of AD pathology; Group 2: AD risk factors and subjective cognitive complaints/mild cognitive impairment; Group 3: mild AD) and to care partners of individuals with moderate AD (Group 4) or severe AD (Group 5). Respondents rated the importance of 42 symptoms, impacts, and outcomes on a scale ranging from 1 ("not at all important") to 5 ("extremely important"). RESULTS: Among the 274 respondents (70.4% female; 63.1% white), over half of patient respondents rated all 42 items as "very important" or "extremely important," while care partners rated fewer items as "very important" or "extremely important." Among the three patient groups, the minimum (maximum) mean importance rating for any item was 3.4 (4.6), indicating that all items were at least moderately to very important. Among care partners of people with moderate or severe AD, the minimum (maximum) mean importance rating was 2.1 (4.4), indicating that most items were rated as at least moderately important. Overall, taking medications correctly, not feeling down or depressed, and staying safe had the highest importance ratings among both patients and care partners, regardless of AD phase. CONCLUSION: Concepts of importance to individuals affected by AD go beyond the common understanding of "cognition" or "function" alone, reflecting a desire to maintain independence, overall physical and mental health, emotional well-being, and safety. Preservation of these attributes may be key to understanding whether interventions deliver clinically meaningful outcomes.

Technical Review of Clinical Outcomes Assessments Across the Continuum of Alzheimer's Disease.

INTRODUCTION: Insight into the relationship between concepts that matter to the people affected by Alzheimer's disease (AD) and the clinical outcome assessments (COAs) commonly used in AD clinical studies is limited. Phases 1 and 2 of the What Matters Most (WMM) study series identified and quantitatively confirmed 42 treatment-related outcomes that are important to people affected by AD. METHODS: We compared WMM concepts rated as "very important" or higher to items included in COAs used commonly in AD studies. RESULTS: Twenty COAs designed to assess signs, symptoms, and impacts across the spectrum of AD were selected for review. Among these 20 COAs, only 5 reflected 12 or more WMM concepts [Integrated Alzheimer's Disease Rating Scale (iADRS), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory-Mild Cognitive Impairment (ADCS-ADL-MCI), Alzheimer's Disease Composite Scores (ADCOMS), and Clinical Dementia Rating; Clinical Dementia Rating-Sum of Boxes (CDR/CDR-SB)]. Multiple symptoms and impacts of AD identified as important and meaningful in the WMM studies map only indirectly at best to 7 of the 20 most widely used COAs. CONCLUSION: While many frequently used COAs in AD capture some concepts identified as important to AD populations and their care partners, overlap between any single measure and the concepts that matter to people affected by AD is limited. The highest singly matched COA reflects fewer than half (45%) of WMM concepts. Use of multiple COAs expands coverage of meaningful concepts. Future research should explore the content validity of AD COAs planned for AD trials based on further confirmation of the ecological validity of the WMM items. This research should inform development and use of core outcome sets that capture WMM items and selection or development of new companion tools to fully demonstrate clinically meaningful outcomes spanning WMM.

From Genotype to Phenotype-A Review of Kabuki Syndrome.

Kabuki syndrome (KS) is a rare neuro-developmental disorder caused by variants in genes of histone modification, including KMT2D and KDM6A. This review assesses our current understanding of KS, which was originally named Niikawa-Kuroki syndrome, and aims to guide surveillance and medical care of affected individuals as well as identify gaps in knowledge and unmet patient needs. Ovid MEDLINE and EMBASE databases were searched from 1981 to 2021 to identify reports related to genotype and systems-based phenotype characterization of KS. A total of 2418 articles were retrieved, and 152 were included in this review, representing a total of 1369 individuals with KS. Genotype, phenotype, and the developmental and behavioral profile of KS are reviewed. There is a continuous clinical phenotype spectrum associated with KS with notable variability between affected individuals and an emerging genotype-phenotype correlation. The observed clinical variability may be attributable to differences in genotypes and/or unknown genetic and epigenetic factors. Clinical management is symptom oriented, fragmented, and lacks established clinical care standards. Additional research should focus on enhancing understanding of the burden of illness, the impact on quality of life, the adult phenotype, life expectancy and development of standard-of-care guidelines.

A Qualitative Study to Characterize the Humanistic Burden of Kabuki Syndrome in the United States and Canada.

INTRODUCTION: Kabuki syndrome is a rare congenital condition characterized clinically by unique facial features, abnormalities in the skeleton, finger pad abnormalities, and developmental delays, as well as a range of other health issues. Existing research lacks information on the daily burden of living with Kabuki syndrome. METHODS: A survey collected caregiver- and patient-reported data about the experience of living with Kabuki syndrome in order to better understand its presentation and effect on patients and their psychosocial well-being. RESULTS: A total of 68 participants (n = 57 caregivers and n = 11 adolescents) were recruited from the USA and Canada. Caregiver survey participants reported developmental delays and lower IQ in individuals with Kabuki syndrome compared to the general population, as well as difficulty with cognitive-related tasks, need for educational accommodations, and difficulty with particular school subjects and with daily tasks. Additionally, participants reported significant emotional, social, and communication-related impacts of Kabuki syndrome. Adolescent data largely corroborated the information collected from caregivers, with the exception of adolescents reporting the emotional and social impacts as occurring less frequently. CONCLUSIONS: Kabuki syndrome is a multidimensional disease which has substantial negative effects on physical, mental, emotional, and social aspects of health-related quality of life. This research adds to the limited existing body of literature on the clinical presentation of Kabuki syndrome and provides a novel perspective into the caregiver and adolescent perception of the burden of Kabuki syndrome.

Caregiver-reported clinical characteristics and the burden associated with Kabuki syndrome.

Kabuki syndrome is a genetic disorder that can affect multiple body systems and manifest as congenital abnormalities and both developmental and socio-emotional delays. The condition is largely unknown by most primary care physicians and has no available treatment other than symptomatic management. This research sought to obtain caregiver-reported data about the experience of living with and caring for someone with Kabuki syndrome to fill a gap in the available literature. Fifty-seven caregivers participated in an online survey and reported that Kabuki syndrome affected their children in a wide variety of ways, including a high frequency of visits to various healthcare professionals. Caregivers reported their child experienced problems with hearing, eating, eyes, mouth, immune system, anxiety, depression, autism, teeth, joints, seizures, kidneys, and heart. Caregivers also described the challenges of caring for someone with Kabuki syndrome, including an impact on emotional well-being and the ability to work outside the home. This unique research characterizes the caregiver experience of living with and caring for someone with Kabuki syndrome, both through observed manifestations of Kabuki syndrome in their own children and their experience managing their treatment. Additional research is needed to investigate the patient experience of living with Kabuki syndrome.

Measuring the impact of trigeminal neuralgia pain: the Penn Facial Pain Scale-Revised.

BACKGROUND AND OBJECTIVE: The Penn Facial Pain Scale (Penn-FPS) was originally developed as a supplemental module to the Brief Pain Inventory Pain Interference Index (BPI-PII) in order to fully assess the impact of trigeminal neuralgia (TN) pain on patients' health-related quality of life (HRQoL). The current objective is to create and establish the content validity of a new stand-alone version of the measure, the Penn-FPS-Revised (Penn-FPS-R). METHODS: Twenty participants (15 USA and 5 UK) with confirmed TN engaged in concept elicitation and cognitive debriefing interviews. These semi-structured interviews allowed participants to spontaneously describe the ways in which TN impacts on HRQoL and report on the extent to which the Penn-FPS and BPI-PII measure concepts are most relevant to them. Participants were also asked to report on the suitability of the instructions, recall period, and response options. RESULTS: Concept elicitation revealed nine themes involving TN restrictions on daily activities and HRQoL, including: "talking," "self-care," "eating," "eating hard foods/chewing foods," "daily activities," "activities with temperature change," "touching," "mood," and "relationships." Cognitive debriefing confirmed that all of the Penn-FPS concepts and some of the BPI-PII concepts ("mood," "general activities," and "relations with others") were relevant, although some items required edits to better capture individuals' experiences. The impact of temperature and/or weather on activities was also identified as an important concept that is not captured by the Penn-FPS or BPI-PII. Participants confirmed the acceptability of recall period, instructions, and response options. Results from the interviews were applied to create the Penn-FPS-R, a new brief outcome measure that assesses the impacts of TN most important to patients. CONCLUSION: The Penn-FPS-R is a new 12-item HRQoL outcome measure with content validity that can be used to assess and monitor the impact of TN treatment interventions in both clinical practice and research.

Characterizing Treatment Utilization Patterns for Trigeminal Neuralgia in the United States.

BACKGROUND AND AIM: Trigeminal neuralgia (TN) is a rare orofacial disorder characterized by severe unilateral paroxysmal pain in the region of the fifth cranial nerve. Clinical guidelines recommend carbamazepine (only US Food and Drug Administration-approved drug for TN) and oxcarbazepine as first-line therapies. We utilized the US Truven Health MarketScan database to examine treatment patterns among patients with TN. METHODS: Included patients were aged 18 years and above, newly diagnosed with TN (≥2 TN diagnoses ≥14 days apart; no diagnosis in the previous year), continuously enrolled 1 year before index, with ≥3 years' follow-up postindex. We assessed utilization of selected pharmacotherapies (carbamazepine, oxcarbazepine, pregabalin, gabapentin, baclofen, duloxetine, topiramate), surgery (posterior fossa, radiosurgery), and injections (peripheral anesthetic injections, Gasserian ganglion procedures) for TN. RESULTS: In total, 3685 patients were included (2425 commercial, 1260 Medicare; 71.8% female; age, mean [SD], 59 [15] y). Overall, 72.5% of patients received at least 1 studied medication, most commonly carbamazepine (51.7%) or gabapentin (48.6%). In total, 65% of pharmacologically treated patients had ≥2 treatment episodes; 41.6% had ≥3 (defined by a change in pharmacotherapy [monotherapy/combination] regimen). Overall, 12.3% had surgery and 7.3% injections; 42.9% received opioids for TN. CONCLUSIONS: In the 3 years after diagnosis, patients with TN in the United States receive a variety of pharmacological treatments, including opioids, despite carbamazepine being the only approved medication. A notable proportion utilize surgeries/injections. A high proportion of pharmacologically treated patients receive multiple treatment episodes, suggesting frequent therapy switching, perhaps because of suboptimal efficacy/tolerability. Our data suggest a high burden of illness associated with TN.

Clinical meaningfulness of Alzheimer's Disease Assessment Scale-Cognitive subscale change in relation to goal attainment in patients on cholinesterase inhibitors.

INTRODUCTION: The clinical meaningfulness of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) subscale change is disputed. We compared 2- to 4-point ADAS-Cog changes with changes in Goal Attainment Scaling (GAS) and everyday function across initial ADAS-Cog scores and treatment responses. METHODS: This exploratory analysis evaluated mild-moderate Alzheimer's disease patients treated with donepezil (12 months) or galantamine (8 months). Clinical meaningfulness was defined as concomitant ADAS-Cog and GAS changes of ±3 points and/or functional improvement. RESULTS: Patients with ≥3-point ADAS-Cog improvement significantly improved on GAS but not on standard tests of everyday function. ADAS-Cog "no change" (≤±3 points) was seen with mean GAS improvement. Initial ADAS-Cog improvement made endpoint improvement (ADAS-Cog 3 points and GAS 1 point) more likely (odds ratio = 6.9; 95% confidence interval = 2.5-19.5). In contrast, initial deterioration made endpoint improvement unlikely (0.33; 0.14-0.64). DISCUSSION: ADAS-Cog improvement and no change were each associated with GAS improvement. Initial ADAS-Cog worsening was unlikely to result in later improvement. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN26167328.

How do changes in pain severity levels correspond to changes in health status and function in patients with painful diabetic peripheral neuropathy?

The current analysis compares changes in pain with changes in function and health status in individuals with painful diabetic peripheral neuropathy (DPN). The post hoc analysis is based on a 12week, multinational, placebo-controlled trial of pregabalin in which 401 patients were randomized to treatment. Study measures included the Brief Pain Inventory short-form (BPI-sf), EQ-5D and other patient-reported outcomes. Cutpoints were derived on the BPI-sf 0-10 average pain numeric rating scale [NRS] to classify pain grades of "mild" (1-3), moderate (4-6) and severe (7-10), adjusting for geographical regions where data were collected. Two different metrics were used to classify the importance of change in pain severity from baseline to 12weeks: changes in pain severity grades (defined by cutpoint categories) and percent reduction in the NRS (categories ranging from 0-9% to 50%). An improvement in one pain grade or a 30% reduction in the NRS served as determinants of a clinically important difference. Patients with a one-grade reduction in pain severity, either from "severe-to-moderate" or "moderate-to-mild," had a 3-point improvement the BPI-sf Pain Interference Index (PII; a composite measure of function); a reduction from "severe-to-mild" pain corresponded to a 6-point improvement in the PII. Similarly, a reduction in the NRS of 30% and 50% corresponded to a 3-point and a 5-point improvement in the PII, respectively. Changes in pain were also associated with changes in health status. Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinically important changes in function and health status.

Altered eyeblink reflex conditioning in restless legs syndrome patients.

BACKGROUND: Restless legs syndrome (RLS) is characterized by abnormal leg sensations and an uncontrollable urge to move the lower extremities during rest periods. Evidence suggests that reflex tasks that involve sensory-motor integration may be altered in RLS patients. This led us to determine if RLS patients show alterations in a sensory-motor reflex conditioning task called differential eyeblink conditioning. METHODS: RLS subjects were washed out of treatment medication for 7 days prior to testing. Subjects (20 RLS and 19 Control) received 120 discrimination conditioning trials consisting of 60 CS+ trials (i.e., an auditory stimulus paired with the airpuff-US separated by a silent 900 ms trace interval) and 60 CS- trials (i.e., a different auditory stimulus that was NOT paired with the US). RESULTS: Control subjects showed normal differential responding to the CS+ and CS-, but the RLS patients showed little or no differential responding. A post-test questionnaire provides evidence that symptomatic interference was not responsible for the eyeblink conditioning deficits in the RLS subjects, and further suggests that neurophysiological factors were responsible for these deficits. CONCLUSIONS: Together these results suggest that deficits in eyeblink conditioning are related to the pathophysiology of RLS. The eyeblink conditioning test may also be useful for supporting a clinical diagnosis or treatment strategy for RLS.

Cross-national burden of painful diabetic peripheral neuropathy in Asia, Latin America, and the Middle East.

The burden of painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes. This study expanded on the human burden of painful DPN by quantifying functional and health status impairments among international patients from a randomized, double-blind, placebo-controlled trial of painful DPN. Evaluated outcomes measures included: Brief Pain Inventory-Short Form (mBPI-sf), EuroQOL 5D, Hospital Anxiety and Depression Scale, and Medical Outcomes Study Sleep Scale. Outcomes were stratified by pain severity using cut-points: 0 to 10 numeric rating scale (NRS) for average pain (0 to 3: none/mild, 4 to 6: moderate, 7 to 10: severe). Study sample is: 401 patients (163 in Asia, 110 in Latin America and 128 in the Middle East), mostly female (61%) (+/- standard deviation, SD), age of 57 +/- 10 years. Participants reported at least moderate levels of pain severity (mean [+/- SD] scores on a 0 to 10 NRS for average pain of 5.9 +/- 1.8 for Asia, 6.7 +/- 1.6 for Latin America, and 6.6 +/- 1.7 for the Middle East). Mean (+/- SD) values on the mBPI-sf Pain Interference Index were 4.7 +/- 2.3 for Asia, 5.6 +/- 2.1 for Latin America, and 5.5 +/- 2.3 for the Middle East. Patients in all 3 regions reported difficulties with functioning, sleep, and overall health status, which increased with higher pain severity levels. Patients in Asia had substantial impairments; however, they reported less serious problems than the other regions. These data are consistent with painful DPN being a burdensome condition worldwide: people with poorly managed neuropathic pain report a substantial burden of disease.

Human and economic burden of generalized anxiety disorder.

The goal of the current work is to provide a comprehensive review and interpretation of the literature on the human and economic burden of generalized anxiety disorder (GAD) and how it compares with that of other mental disorders. The term "human burden" is used to describe quantified impairments in role functioning and quality of life (QOL). "Economic burden" describes costs related to health care resource utilization and lost work. A review of 34 studies reporting original quantitative data on associations between GAD and role functioning, QOL, and/or economic costs was undertaken. GAD was defined by DMS-III-R, DSM-IV, or ICD-10 DCR. Persons with GAD (both with and without a comorbid mental disorder) described significant impairments due to both physical and emotional problems. Studies typically showed that role and QOL impairments of GAD were at least comparable in magnitude to those of other anxiety disorders, somatoform disorders, and physical conditions, and greater than those of substance use disorders. Large representative studies showed that role impairments of pure GAD were similar in magnitude to those of pure MDD. Studies of DSM-IV disorders showed that QOL impairments of GAD were at least comparable in magnitude to those of MDD; studies of DSM-III-R disorders showed the opposite pattern. GAD was associated with considerable economic costs owing to lost work productivity and high medical resource use. Quality of care initiatives that have been implemented to increase recognition and improve treatment outcomes for persons with MDD should be extended to the effective management of GAD.

Burden of illness in painful diabetic peripheral neuropathy: the patients' perspectives.

UNLABELLED: Our goal was to assess the patient-level burden among subjects with painful diabetic peripheral neuropathy (DPN). Community-based physicians recruited patients with painful DPN (N = 255) between April and October 2003. Patients completed a survey on pain experience (Brief Pain Inventory-DPN [BPI-DPN]), health status (EuroQoL [EQ-5D]), healthcare utilization (consults, prescription [Rx], and over-the-counter [OTC] medications), and work productivity/functioning. Patients were 61 +/- 12.8 years old and had diabetes for 12 +/- 10.3 years and painful DPN for 6.4 +/- 6.4 years; 25.5 and 62.7% had other neuropathic and musculoskeletal pain conditions. Average and worst pain scores (BPI-DPN, 0-10 scales) were 5.0 +/- 2.5 and 5.6 +/- 2.8. The mean EQ-5D utility was .5 +/- .3 (range = -.594-1). A majority (87.4%) took pain medications (Rx/OTC) in the preceding week: an average of 3.8 +/- 3.9 Rx and 2.1 +/- 1.3 OTC medications. Nearly half (46.7%) received NSAIDs. Other frequently reported medications were short/long-acting opioids (43.1%), anticonvulsants (27.1%), selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors (18%), and tricyclic antidepressants (11.4%). During the preceding 3 months, 59.6% had >or=2 health professional consults; 59% reported decreased home productivity; 85.5% reported activity limitations; and 64.4% of patients who worked (N = 73) reported missing work/decreased work productivity due to painful DPN. Our results underscore a substantial patient-level burden among subjects with painful DPN. PERSPECTIVE: Information on the patient-level burden among painful DPN sufferers in the U.S. was previously lacking. Our results suggest that this burden is significant, evidenced by moderate-to-high pain levels, polypharmacy, health resource use, and work/activity limitations. Results also suggest suboptimal pain management and low levels of satisfaction with treatments.

Infiltração marginal utilizando três tipos de adesivos dentinários com restaurações de resina composta / Marginal leakage using tree types of dentinal adhesives with resin composite restorations

O propósito desta pesquisa foi verificar o grau de infiltração marginal em cavidades classe V, vestibular e lingual, em 40 dentes pré-molares humanos recém-extraídos,divididos em quatro grupos, e que, após ciclagem térmica a 5ºC/55ºC, foram imersos no corante azul de metileno a 2 por cento por 24 horas, lavados e seccionados ao meio, no sentido vestíbulo-lingual, longitudinalmente, com um disco diamantado. A avaliação deles contemplou dois aspectos: 1. tipos de adesivos dentinários: adesivo autocondicionante (Clearfil SE Bond); adesivo de frasco único com ácido (Single Bond) e adesivo convencional (Scotchbond Multi-Purpose), sendo todas as cavidades restauradas posteriormente com resina micro-híbrida(Z 250); e 2. localização da parede cavitária (parede gengival em cemento e parede oclusal em esmalte). Os dados foram mensurados por meio de escores de 0 a 4 e processados estatísticamente pelo teste não paramétrico de Kruskal-Wallis. Os três tipos de sistemas adesivos-convencional, simplificado e autocondicionante - não mostraram diferença estatística significante entre si. Também não houve diferença estatística significante entre parede oclusal e cervical

Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep.

Our goal was to evaluate pain severity, pain-related interference with function, sleep impairment, symptom levels of anxiety and depression, and quality of life among patients with painful diabetic peripheral neuropathy (DPN). Participants in a burden of illness survey (n = 255) completed the modified Brief Pain Inventory-DPN (BPI-DPN), MOS Sleep Scale, Hospital Anxiety and Depression Scale (HADS), Short Form Health Survey-12v2 (SF-12v2), and the EuroQoL (EQ-5D). Patients were 61 +/- 12.8 years old (51.4% female), had diabetes for 12 +/- 10.3 years and painful DPN for 6.4 +/- 6.4 years. Average and Worst Pain scores (BPI-DPN, 0-10 scales) were 5.0 +/- 2.5 and 5.6 +/- 2.8. Pain substantially interfered (>or=4 on 0-10 scales) with walking ability, normal work, sleep, enjoyment of life, mood, and general activity. Moderate to severe symptom levels of anxiety and depression (HADS-A and HADS-D scores >or=11 on 0-21 scales) occurred in 35% and 28% of patients, respectively. Patients reported greater sleep problems compared with the general U.S. population and significant impairment in both physical and mental functioning (SF-12v2) compared with subjects with diabetes. The mean EQ-5D utility score was 0.5 +/- 0.3. Greater pain levels in DPN (mild to moderate to severe) corresponded with higher symptom levels of anxiety and depression, more sleep problems, and lower utility ratings and physical and mental functioning, (all Ps < 0.01). Painful DPN is associated with decrements in many aspects of patients' lives: physical and emotional functioning, affective symptoms, and sleep problems. The negative impact is higher in patients with greater pain severity.

Acceptable, manageable, and tolerable days: patient daily goals for medication management of persistent pain.

Although the construct of "a symptom-free day" has been widely applied in asthma and gastric reflux disease, there is no analogous concept in the field of pain management. This study represents the initial development of a "day of acceptable or manageable pain control," a construct which reflects patients' daily strategic use of pain medication in order to allow the accomplishment of desired activities while minimizing side effects. Focus group methodology was used to extract patient-generated themes of "an acceptable day of pain control." Fifty-three outpatients with persistent moderate to severe average pain intensity due to osteoarthritis (n=18), metastatic cancer (n=15), and low back pain (n=20) participated. Participants preferred the term "manageable" or "tolerable" to "acceptable." Thematic analysis revealed components of a manageable/tolerable day of pain control as including: 1) taking the edge off the pain, 2) performing valued activities; 3) relief from dysphoria and irritability; 4) reduced medication side effects; 5) feeling well enough to socialize. Additional cancer-specific themes included relief from fatigue and ability to have a positive day when one's future days were perceived as being limited. The set of themes is presented and their relevance for developing a measure of "a manageable day of pain control" discussed. Study findings identify a novel construct that can inform development of an outcome for evaluating the effectiveness of different pharmacotherapies for pain management.

Therapy switching in patients receiving long-acting opioids.

BACKGROUND: Patterns of therapy switching in patients receiving long-acting opioids have not been well documented. OBJECTIVE: To compare therapy switching among patients beginning treatment with controlled-release (CR) oxycodone, transdermal fentanyl, or CR morphine sulfate. METHODS: Using a US healthcare claims database, we identified patients beginning treatment with CR oxycodone, transdermal fentanyl, or CR morphine sulfate between July 1, 1998, and December 31, 1999. We compiled claims for each patient for 6 months following therapy initiation and compared the incidence of therapy switching among the 3 groups. We also estimated total healthcare charges for patients who switched therapy versus those who did not. RESULTS: We identified 1931, 668, and 449 patients beginning therapy with CR oxycodone, transdermal fentanyl, and CR morphine sulfate, respectively; 16.7%, 25.0%, and 35.9%, respectively, had cancer. For patients without cancer, rates of therapy switching at 6 months were 10.6% (CR oxycodone), 19.0% (transdermal fentanyl), and 26.0% (CR morphine sulfate); for those with cancer, rates were 23.8%, 24.6%, and 29.8%, respectively. Multivariate hazard ratios (vs CR morphine sulfate) for therapy switching in patients without cancer were 0.36 (95% CI, 0.27 to 0.47) for CR oxycodone and 0.69 (0.51 to 0.94) for transdermal fentanyl; for those with cancer, corresponding hazard ratios were 0.72 (0.50 to 1.03) and 0.76 (0.50 to 1.16). Total healthcare charges were significantly (p < 0.01) higher for patients who switched therapy than those who did not (23,965 US dollars vs 14,299 US dollars in pts. without cancer; 58,259 US dollars vs 39,618 US dollars for those with cancer). CONCLUSIONS: Patients without cancer who receive CR oxycodone or transdermal fentanyl are less likely to switch therapy than those receiving CR morphine sulfate. Total healthcare charges are higher for patients who switch therapy.

Development of a metric for a day of manageable pain control: derivation of pain severity cut-points for low back pain and osteoarthritis.

The objective of this study was to adapt the concept of 'episode-free day', a metric for measuring symptom relief in daily units, to the clinical outcome literature for persistent pain. The episode-free day metric is widely used in other medical literature, but no analogous measure exists in pain literature. Prior focus groups with this population suggested that a 'Day of Manageable Pain Control' was an appropriate name for the metric. In the present study, in order to derive a statistical criterion for 'Manageable Day', we used Serlin et al.'s (Pain 61 (1995) 277) cut-point derivation method to derive a single cut-point on a 0-10 scale of average pain that divided groups with significant persistent pain optimally on pain-related functional interference. Participants were 194 patients with moderate-severe low back pain (n=96) or osteoarthritis (n=98). For both patient samples, '5' was the cut-point that optimally distinguished groups on pain-related interference. '5-8' and '5-7' were double cut-point solutions that optimally divided LBP and OA samples into three categories (e.g. lowest, medium and highest average pain), respectively. Derived cut-points were confirmed using a variety of measures of functional disability. Together with research that showed that average pain ratings of approximately 5 and below permit increased function and quality of life in patients with moderate to severe low back pain and osteoarthritis, our findings provide support for the use of 0-5 on a 0-10 numeric average pain severity scale as one possible criterion for a Manageable Day.