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1.
J Gerontol Soc Work ; 64(1): 78-87, 2021.
Article in English | MEDLINE | ID: mdl-33402055

ABSTRACT

The author reminisces about her collegial relationships and friendship with Rosalie Kane over a span of nearly 40 years. She also reflects on the main themes of Rosalie's scholarly work as a social gerontologist, highlighting seminal publications and why Rosalie's insights remain valuable and "evergreen" decades later.

2.
Gerontologist ; 58(5): 863-871, 2018 09 14.
Article in English | MEDLINE | ID: mdl-28591784

ABSTRACT

Background and Objectives: We examine trends in informal care from the perspective of both community-dwelling disabled older Americans and their caregivers from 1982 to 2012. We decompose hours of care received from spouses and children according to changes in: (a) the number of potential spousal and child caregivers ("family structure"), (b) the likelihood that existing spouses and children are caregivers ("caregiving propensity"), and (c) the amount of care provided by individual caregivers ("time burden"). Research Design and Methods: We examine two sets of time trends based on distinct samples of community-dwelling disabled older Americans from the 1982-2004 waves of the National Long-Term Care Survey (NLTCS) and the 2000-2012 waves of the Health and Retirement Study (HRS). Results: Existing spouses' and children's decreasing likelihood of being caregivers led to fewer spousal and child caregivers per disabled older person in the 2004 NLTCS than the 1982 NLTCS. However, the NLTCS and HRS time trends suggest that the amount of care provided by individual caregivers was similar from 1989 to 2012. Discussion and Implications: Because individual caregivers' time burden has remained fairly constant since at least 1989, advocacy on behalf of policies that promote more and better support for caregivers is appropriate.


Subject(s)
Caregivers/trends , Disabled Persons , Aged , Caregivers/psychology , Health Care Surveys , Humans , Intergenerational Relations , Middle Aged , Models, Theoretical , United States , Workload
3.
Gerontologist ; 58(3): 588-597, 2018 May 08.
Article in English | MEDLINE | ID: mdl-28379357

ABSTRACT

BACKGROUND AND OBJECTIVES: Since 1995, Germany has operated one of the longest-running public programs providing universal support for the cost of long term services and supports (LTSS). Its self-funding, social insurance approach provides basic supports to nearly all Germans. We discuss its design and development, including recent reforms expanding the program and ensuring its ongoing sustainability. RESEARCH DESIGN AND METHODS: The study reviews legislative and programmatic changes, using program data, as well as legislative documents and program reports. RESULTS: The program is widely accepted among citizens and has achieved many of its original goals: ensuring access to LTSS and reducing reliance on the locally-funded safety-net social assistance program, which can be used to cover nursing home costs. It also strengthened the LTSS provider infrastructure and expanded access to home care. Recent reforms have addressed some of the program's key issues: the benefit's decreasing value, the eligibility and benefit structure that largely excluded cognitive impairment, and the program's longer-term financial sustainability-particularly its ability to sustain newly expanded benefits, which provide stronger protections to caregivers, index-link benefits, and more systematically incorporate cognitive impairment via a new assessment system. It has addressed financing issues by increasing premiums, introducing subsidies for the purchase of private insurance, and creating a "demographic reserve fund." DISCUSSION AND IMPLICATIONS: The reforms constitute a significant strengthening of the program, remarkable in an era of retrenchment. Overall, the program provides evidence for the financial viability of a social insurance model, although longer-term challenges may yet arise.


Subject(s)
Insurance, Long-Term Care/legislation & jurisprudence , Social Security/legislation & jurisprudence , Aged , Aged, 80 and over , Germany , Health Policy , Humans , Insurance , Long-Term Care , Middle Aged , Social Security/organization & administration
4.
J Clin Psychopharmacol ; 37(6): 675-683, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28926353

ABSTRACT

PURPOSE: This phase 1, randomized, double-blind, placebo- and active comparator-controlled crossover study assessed the abuse potential of the antiepileptic drug, lacosamide. METHODS: After a qualification phase, 38 healthy, recreational central nervous system-depressant users were randomized to treatment sequences comprising single oral therapeutic (200 mg) and supratherapeutic (800 mg) doses of lacosamide, alprazolam (1.5 and 3 mg), and placebo. Subjective effects were assessed for 24 hours following each dose using a range of scales, with a 5- to 9-day washout between treatments. FINDINGS: Mean subjective effects for 200 mg lacosamide were statistically similar to placebo and significantly lower than with alprazolam for most end points. Lacosamide 800 mg elicited transient, statistically significant positive effects compared with placebo, but also persistent Bad Drug Effects including statistically greater maximum effect (Emax) scores for Nausea and Dysphoria compared with other treatments (P < 0.0002). Consistent with this, the 800 mg lacosamide dose showed a significantly lower "at this moment" Drug Liking visual analog scale (VAS) Emax compared with 3 mg alprazolam, but was not different from 1.5 mg alprazolam (73.1/100, 85.4/100, and 78.9/100, respectively, where 50 is neutral). Overall Drug Liking VAS and Take Drug Again VAS Emax for 800 mg lacosamide were not significantly different from placebo and were lower than those for both alprazolam doses (P < 0.0001). IMPLICATIONS: These results suggest that in recreational central nervous system-depressant users, lacosamide has detectable abuse-related subjective effects, but a relatively low potential for abuse compared with alprazolam. These findings contributed toward placement of lacosamide into Schedule V of the US Controlled Substances Act.


Subject(s)
Acetamides/pharmacology , Alprazolam/pharmacology , Anticonvulsants/pharmacology , Central Nervous System Depressants/pharmacology , Drug-Related Side Effects and Adverse Reactions , Substance-Related Disorders , Acetamides/administration & dosage , Acetamides/adverse effects , Adult , Alprazolam/administration & dosage , Alprazolam/adverse effects , Anticonvulsants/administration & dosage , Anticonvulsants/adverse effects , Central Nervous System Depressants/administration & dosage , Central Nervous System Depressants/adverse effects , Cross-Over Studies , Double-Blind Method , Female , Humans , Lacosamide , Male , Middle Aged , Young Adult
5.
Epileptic Disord ; 19(2): 186-194, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28597842

ABSTRACT

To evaluate the safety and effectiveness of lacosamide in a real-life setting with the use of a flexible dose titration schedule and individualised maintenance doses up to the maximum approved dose of 400 mg/day. Adults with a diagnosis of focal seizures, with or without secondary generalization, were enrolled in this open-label Phase IV trial (NCT01235403). Lacosamide was initiated at 100 mg/day (50 mg bid) and uptitrated over a 12-week period to 200, 300 or 400 mg/day, based on safety and seizure control. Although dose increases were to be in increments of 100 mg/day, intermediate doses were permitted at each escalation step for one week for patients known to be particularly sensitive to starting new AEDs. After receiving a stable, effective dose for three weeks, patients entered the 12-week maintenance period. Primary outcomes were incidence of treatment-emergent adverse events (TEAEs) and withdrawal due to TEAEs. Seizure outcomes, all secondary, were median focal seizure frequency, ≥50% reduction in focal seizure frequency, and seizure freedom. One hundred patients with a mean age of 44 years were enrolled and 74 completed the trial. The incidence of TEAEs was 64.0% (n=100), with the most frequently reported (≥5% of patients) being dizziness, headache, and asthenia. Fourteen patients withdrew due to TEAEs, most frequently due to dizziness (six patients; 6.0%), vomiting (two patients; 2%), and tremor (two patients; 2%). Among patients with baseline and maintenance phase seizure data (n=75), median reduction in focal seizure frequency from baseline was 69.7% and the ≥50% responder rate was 69.3%. Among 74 patients who completed the maintenance phase, 21 (28.4%) were seizure-free. Flexible lacosamide dosing in this open-label trial was associated with a favourable tolerability and safety profile; the nature of the TEAEs was consistent with that observed in previous pivotal trials. Treatment with lacosamide was also associated with effective seizure control.


Subject(s)
Acetamides/pharmacology , Anticonvulsants/pharmacology , Epilepsies, Partial/drug therapy , Outcome Assessment, Health Care , Acetamides/administration & dosage , Acetamides/adverse effects , Adult , Aged , Anticonvulsants/administration & dosage , Anticonvulsants/adverse effects , Drug Administration Schedule , Female , Humans , Lacosamide , Male , Middle Aged , Young Adult
6.
Epilepsy Res ; 130: 13-20, 2017 02.
Article in English | MEDLINE | ID: mdl-28086164

ABSTRACT

OBJECTIVE: Assess the safety of adjunctive lacosamide for the treatment of uncontrolled primary generalized tonic-clonic seizures in patients (16-65 years) with primary generalized (genetic) epilepsy (PGE). METHODS: An open-label pilot safety study (SP0961; NCT01118949), comprising 12 weeks' historical baseline, 4 weeks' prospective baseline, 3 weeks' titration (target: 400mg/day adjunctive lacosamide) and 6 weeks' maintenance. Patients who continued to the extension study (SP0962; NCT01118962) then received ≤59 weeks of flexible treatment (100-800mg/day lacosamide with flexible dosing of concomitant antiepileptic drugs). The primary outcomes for SP0961 were the mean change (±standard deviation) in absence seizure or myoclonic seizure days per 28days from prospective baseline to maintenance; for SP0962, the incidence of treatment-emergent adverse events (TEAEs) and withdrawals because of TEAEs. RESULTS: Of the 49 patients who enrolled, 40 (82%) completed the pilot study and 9 discontinued (5 because of adverse events). Of the 39 patients who continued to the extension study, 10 discontinued (2 owing to TEAEs) and 29 (74%) completed the study. During the pilot study, patients reported a reduction in mean (±standard deviation) absence and myoclonic seizure days per 28days (-0.37±4.80, -2.19±5.80). Reductions were also observed during the extension study (-2.38±5.54, -2.78±6.43). Five patients in SP0961 and 2 patients in SP0962 experienced TEAEs of new or increased frequency of absence seizures or myoclonic seizures. The most common TEAEs during SP0961 were dizziness (39%) and nausea (27%), and during SP0962 were dizziness (26%) and upper respiratory tract infection (26%). CONCLUSIONS: The safety profile of adjunctive lacosamide was similar to that previously published. Adjunctive lacosamide did not systematically worsen absence or myoclonic seizures, and appears to be well tolerated in patients with PGE.


Subject(s)
Acetamides/therapeutic use , Anticonvulsants/therapeutic use , Seizures/drug therapy , Acetamides/adverse effects , Adolescent , Adult , Aged , Anticonvulsants/adverse effects , Epilepsy, Generalized/drug therapy , Female , Follow-Up Studies , Humans , Lacosamide , Male , Middle Aged , Pilot Projects , Treatment Outcome , Young Adult
7.
Epilepsy Behav ; 58: 35-43, 2016 05.
Article in English | MEDLINE | ID: mdl-27054272

ABSTRACT

This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were reported by four patients who added lacosamide (two cases of depression, two of suicide attempt) and one who added another AED (depression). Seven deaths occurred, all of which were considered unrelated/unlikely related to study medication. This thorough evaluation revealed a low incidence of predefined CV- and psychiatric-related TEAEs in patients taking adjunctive AED therapy according to standard medical practice. No specific safety concerns related to adjunctive lacosamide therapy were noted.


Subject(s)
Acetamides/therapeutic use , Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Piracetam/analogs & derivatives , Seizures/drug therapy , Adult , Aged , Combined Modality Therapy , Drug Therapy, Combination , Female , Humans , Lacosamide , Levetiracetam , Longitudinal Studies , Male , Middle Aged , Piracetam/therapeutic use , Treatment Outcome
8.
Epilepsy Behav ; 52(Pt A): 119-27, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26414341

ABSTRACT

OBJECTIVE: The objective of this study was to describe a priori protocol-defined analyses to evaluate the safety and tolerability of adjunctive oral lacosamide (200-600 mg/day) in adults (ages 16-70 years) with partial-onset seizures (POS) using data pooled from three similarly designed randomized, double-blind, placebo-controlled trials (SP667, SP754 [NCT00136019], SP755 [NCT00220415]). METHODS: Patients with POS (≥2 years' duration, ≥2 previous antiepileptic drugs [AEDs]) uncontrolled by a stable dosing regimen of 1-3 concomitant AEDs were randomized to treatment with lacosamide at doses of 200 mg/day, 400 mg/day, or 600 mg/day, or placebo. Studies comprised a 4- to 6-week titration phase to target dose followed by a 12-week maintenance phase. Safety outcomes included treatment-emergent adverse events (TEAEs) of particular relevance to patients with POS, overall TEAEs, and discontinuations due to TEAEs. Post hoc analyses included evaluation of TEAEs potentially related to cognition and TEAEs leading to discontinuation analyzed by concomitant AEDs. RESULTS: One thousand three hundred eight patients were randomized to and received treatment; 944 to lacosamide and 364 to placebo. Most patients (84.4%) were taking 2 or 3 concomitant AEDs. The most common drug-associated TEAEs (reported by ≥5% of patients in any lacosamide dose group and with an incidence at least twice that reported for placebo during the treatment phase) were dizziness (30.6% for lacosamide vs 8.2% for placebo), nausea (11.4% vs 4.4%), and diplopia (10.5% vs 1.9%). Common drug-associated TEAEs generally appeared to be dose-related, and the incidence of each was lower during the 12-week maintenance phase than during the titration phase. Most TEAEs were either mild or moderate in intensity; severe TEAEs were predominantly observed with lacosamide 600 mg/day. No individual serious TEAE occurred in ≥1% of all lacosamide-treated patients. Treatment-emergent adverse events led to discontinuation in 8.1%, 17.2%, and 28.6% of the lacosamide 200-, 400-, and 600-mg/day groups, respectively (vs 4.9% of placebo). Few TEAEs were related to rash, weight loss/gain, changes in clinical chemistry parameters, or psychiatric disturbances, or were seizure-related. The odds of reporting any potential cognition-related TEAE vs placebo increased with dose and were similar between lacosamide doses of 200 and 400mg/day and placebo (odds ratio 1.3, 95% confidence interval 0.7-2.4). Discontinuations due to TEAEs based on most commonly used AEDs taken in combination with lacosamide (all doses combined) were carbamazepine (15.3% [51/334] vs 3.9% [5/129] placebo), lamotrigine (19.2% [56/291] vs 4.3% [5/117]), and levetiracetam (10.1% [28/278] vs 3.9% [4/103]). CONCLUSIONS: The safety and tolerability profile of adjunctive lacosamide in this detailed evaluation was similar to that observed in the individual double-blind trials. Adjunctive lacosamide was associated with TEAEs related to the nervous system and gastrointestinal tract, predominantly during titration.


Subject(s)
Acetamides/adverse effects , Acetamides/therapeutic use , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Seizures/drug therapy , Acetamides/administration & dosage , Adolescent , Adult , Aged , Anticonvulsants/administration & dosage , Body Weight , Cognition/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Eruptions/epidemiology , Drug Therapy, Combination , Epilepsies, Partial/psychology , Female , Humans , Lacosamide , Male , Middle Aged , Seizures/psychology , Substance Withdrawal Syndrome/psychology , Young Adult
9.
Milbank Q ; 93(2): 359-91, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26044633

ABSTRACT

UNLABELLED: POLICY POINTS: France's model of third-party coverage for long-term services and supports (LTSS) combines a steeply income-adjusted universal public program for people 60 or older with voluntary supplemental private insurance. French and US policies differ: the former pay cash; premiums are lower; and take-up rates are higher, in part because employer sponsorship, with and without subsidization, is more common-but also because coverage targets higher levels of need and pays a smaller proportion of costs. Such inexpensive, bare-bones private coverage, especially if marketed as a supplement to a limited public benefit, would be more affordable to those Americans currently most at risk of "spending down" to Medicaid. CONTEXT: An aging population leads to a growing demand for long-term services and supports (LTSS). In 2002, France introduced universal, income-adjusted, public long-term care coverage for adults 60 and older, whereas the United States funds means-tested benefits only. Both countries have private long-term care insurance (LTCI) markets: American policies create alternatives to out-of-pocket spending and protect purchasers from relying on Medicaid. Sales, however, have stagnated, and the market's viability is uncertain. In France, private LTCI supplements public coverage, and sales are growing, although its potential to alleviate the long-term care financing problem is unclear. We explore whether France's very different approach to structuring public and private financing for long-term care could inform the United States' long-term care financing reform efforts. METHODS: We consulted insurance experts and conducted a detailed review of public reports, academic studies, and other documents to understand the public and private LTCI systems in France, their advantages and disadvantages, and the factors affecting their development. FINDINGS: France provides universal public coverage for paid assistance with functional dependency for people 60 and older. Benefits are steeply income adjusted and amounts are low. Nevertheless, expenditures have exceeded projections, burdening local governments. Private supplemental insurance covers 11% of French, mostly middle-income adults (versus 3% of Americans 18 and older). Whether policyholders will maintain employer-sponsored coverage after retirement is not known. The government's interest in pursuing an explicit public/private partnership has waned under President François Hollande, a centrist socialist, in contrast to the previous center-right leader, President Nicolas Sarkozy, thereby reducing the prospects of a coordinated public/private strategy. CONCLUSIONS: American private insurers are showing increasing interest in long-term care financing approaches that combine public and private elements. The French example shows how a simple, cheap, cash-based product can gain traction among middle-income individuals when offered by employers and combined with a steeply income-adjusted universal public program. The adequacy of such coverage, however, is a concern.


Subject(s)
Insurance, Long-Term Care/economics , Long-Term Care/economics , Universal Health Insurance/economics , Aged , Aging , Cross-Cultural Comparison , Financing, Government , Financing, Personal , France , Humans , Income , Insurance, Long-Term Care/legislation & jurisprudence , Middle Aged , Models, Economic , Population Dynamics/trends , Public-Private Sector Partnerships , United States , Universal Health Insurance/legislation & jurisprudence
10.
Epilepsy Behav ; 41: 164-70, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25461210

ABSTRACT

Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained.


Subject(s)
Acetamides/adverse effects , Acetamides/pharmacology , Anticonvulsants/adverse effects , Anticonvulsants/pharmacology , Epilepsies, Partial/drug therapy , Seizures/drug therapy , Acetamides/administration & dosage , Adult , Anticonvulsants/administration & dosage , Drug Therapy, Combination , Female , Humans , Lacosamide , Male , Middle Aged , Time Factors , Treatment Outcome
11.
Epilepsy Res ; 108(8): 1392-8, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25082395

ABSTRACT

The purpose of this post hoc exploratory analysis was to determine the effects of the antiepileptic drug, lacosamide, on focal (partial-onset) seizure subtypes. Patient data from the three lacosamide pivotal trials were grouped and pooled by focal seizure subtype at Baseline: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized partial seizures (SGPS). Both efficacy outcomes (median percent change from Baseline to Maintenance Phase in seizure frequency per 28 days and the proportion of patients experiencing at least a 50% reduction in seizures) were evaluated by lacosamide dose (200, 400, or 600 mg/day) compared to placebo for each seizure subtype. An additional analysis was performed to determine whether a shift from more severe focal seizure subtypes to less severe occurred upon treatment with lacosamide. In patients with CPS or SGPS at Baseline, lacosamide 400 mg/day (maximum recommended daily dose) and 600 mg/day reduced the frequency of CPS and SGPS compared to placebo. Likewise, a proportion of patients with CPS and SGPS at Baseline experienced at least a 50% reduction in the frequency of CPS and SGPS (≥50% responder rate) in the lacosamide 400 and 600 mg/day groups compared with placebo. For both outcomes, numerically greatest responses were observed in the lacosamide 600 mg/day group among patients with SGPS at Baseline. In patients with SPS at Baseline, no difference between placebo and lacosamide was observed for either efficacy outcome. An additional exploratory analysis suggests that in patients with SPS at Baseline, CPS and SGPS may have been shifted to less severe SPS upon treatment with lacosamide. The results of these exploratory analyses revealed reductions in CPS and SGPS frequency with adjunctive lacosamide. Reduction in CPS and SGPS may confound assessment of SPS since the CPS or SGPS may possibly change to SPS by effective treatment.


Subject(s)
Acetamides/administration & dosage , Anticonvulsants/administration & dosage , Epilepsies, Partial/classification , Epilepsies, Partial/drug therapy , Adult , Dose-Response Relationship, Drug , Double-Blind Method , Epilepsies, Partial/diagnosis , Female , Humans , Lacosamide , Male , Treatment Outcome
12.
Ann N Y Acad Sci ; 1291: 56-68, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23859801

ABSTRACT

Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug-drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures in those with idiopathic generalized epilepsy.


Subject(s)
Acetamides/therapeutic use , Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Acetamides/pharmacokinetics , Animals , Anticonvulsants/pharmacokinetics , Dose-Response Relationship, Drug , Epilepsies, Partial/metabolism , Humans , Lacosamide , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/trends , Treatment Outcome
13.
Epilepsia ; 54(1): 58-65, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22708895

ABSTRACT

PURPOSE: To examine the safety and tolerability of rapidly initiating adjunctive lacosamide via a single intravenous loading dose followed by twice-daily oral lacosamide in lacosamide-naive adults with partial-onset seizures. METHODS: This open-label, multicenter trial, enrolled patients with epilepsy who were taking 1-2 antiepileptic drugs (AEDs) in one of four sequential cohorts containing 25 subjects each. An intravenous lacosamide loading dose (200, 300, or 400 mg) was administered over 15 min followed 12 h later by initiation of oral dosing consisting of one-half of the loading dose administered twice daily for 6.5 days. The first cohort was administered lacosamide 200 mg/day, followed by a cohort at 300 mg/day, and then a cohort at 400 mg/day. The results from each cohort were evaluated before enrolling the next highest dose level. The fourth cohort enrolled patients at the highest dose with clinically acceptable safety and tolerability results. Safety evaluations included treatment-emergent adverse events (TEAEs), patient withdrawals due to TEAEs, and changes in vital signs, 12-lead electrocardiography (ECG) studies, laboratory parameters, and clinical examinations. Postinfusion lacosamide plasma concentrations were also evaluated. KEY FINDINGS: A total of 100 patients were enrolled, 25 in each cohort. The loading dose for the repeat cohort was 300 mg; therefore, 25 patients were enrolled at 200 mg/day, 50 at 300 mg/day, and 25 at 400 mg/day. Most TEAEs occurred within the first 4 h following infusion; dose-related TEAEs (incidence ≥10%) during this timeframe included dizziness, somnolence, and nausea. Seven patients withdrew, all due to TEAEs: three (6%) from the combined 300 mg group and four (16%) from the 400 mg group; four of these patients discontinued within 4 h following infusion. The most common TEAEs leading to discontinuation (overall incidence >1%) were dizziness (6%), nausea (5%), and vomiting (3%). No clinically relevant pattern of changes from baseline ECG, clinical laboratory parameters, or vital signs were observed. Trough plasma concentrations suggested that near steady-state lacosamide concentrations were achieved with a single intravenous loading dose. SIGNIFICANCE: Intravenous loading doses of 200 and 300 mg lacosamide administered over 15 min followed by oral lacosamide were well tolerated in lacosamide-naive patients. The 400-mg loading dose was less well tolerated due to a higher frequency of dose-related TEAEs. These results support the feasibility of rapid initiation of adjunctive lacosamide treatment.


Subject(s)
Acetamides/therapeutic use , Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Acetamides/administration & dosage , Acetamides/adverse effects , Administration, Oral , Adolescent , Adult , Anticonvulsants/administration & dosage , Anticonvulsants/adverse effects , Drug Administration Schedule , Female , Humans , Injections, Intravenous , Lacosamide , Male , Middle Aged , Young Adult
14.
Epilepsia ; 53(3): 521-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22372628

ABSTRACT

PURPOSE: To evaluate the long-term (up to 5 years exposure) safety and efficacy of lacosamide as adjunctive therapy in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs) in open-label extension trial SP756 (NCT00522275). METHODS: Patients who completed the double-blind trial SP754 (NCT00136019) were eligible to participate in this open-label extension trial (SP756). At the conclusion of trial SP754, patients had transitioned to lacosamide 200 mg/day. Subsequent dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant AEDs were allowed to optimize tolerability and seizure reduction. Treatment-emergent adverse events (TEAEs), vital signs, body weight, clinical laboratory data, electrocardiography studies, and seizure frequency were evaluated. KEY FINDINGS: A total of 308 patients received open-label lacosamide and 138 patients (44.8%) completed the long-term trial. The median modal dose (defined as the daily lacosamide dose a patient received for the longest duration during the treatment period) was 500 mg/day. The percentages of patients with lacosamide exposure >1, >2, >3, or >4 years were 75%, 63%, 54%, and 29%, respectively. Primary reasons for discontinuation were lack of efficacy (26%) and adverse events (11%). Common TEAEs (≥15%) were dizziness, headache, contusion, nausea, convulsion, nasopharyngitis, fall, vomiting, and diplopia. TEAEs that led to discontinuation in ≥1.0% of patients were dizziness (1.6%) and convulsion (1.0%). The median percent reductions from baseline of trial SP754 in 28-day seizure frequency were 53.4%, 55.2%, 58.1%, and 62.5%, respectively, for 1-, 2-, 3-, and 4-year completers. The ≥50% responder rates were 52.8%, 56.5%, 58.7%, and 62.5% for 1-, 2-, 3-, and 4-year completers, respectively. Seven of eight patients on lacosamide monotherapy for ≥12 months were deemed 50% responders. Of patients exposed to lacosamide ≥2 years, 3.1% remained seizure-free for a period ≥2 years. SIGNIFICANCE: Long-term (up to 5 years) lacosamide treatment was generally well tolerated. The safety profile of lacosamide observed in this trial is consistent with that established in previous double-blind, placebo-controlled trials. Although the open-label trial design limits the analysis of efficacy, long-term reduction in seizure frequency and maintenance of efficacy was observed.


Subject(s)
Acetamides/administration & dosage , Acetamides/adverse effects , Anticonvulsants/administration & dosage , Anticonvulsants/adverse effects , Drug Therapy, Combination/methods , Epilepsies, Partial/drug therapy , Adult , Dizziness/chemically induced , Dose-Response Relationship, Drug , Drug Resistance/physiology , Drug Synergism , Epilepsies, Partial/physiopathology , Female , Humans , Lacosamide , Male , Middle Aged , Nausea/chemically induced , Time , Treatment Outcome
15.
Gerontologist ; 52(4): 517-30, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22012960

ABSTRACT

PURPOSE OF THE STUDY: Medicaid service use and expenditure and quality of care outcomes in California's personal care program known as In-Home Supportive Service (IHSS) are described. Analyses investigated Medicaid expenditures, hospital use, and nursing home stays, comparing recipients who have paid spouse caregivers with those having other relatives or unrelated individuals as their caregivers. DESIGN AND METHODS: Medicaid claims and IHSS assessment data for calendar year 2005 were linked for IHSS recipients aged 18 years or older (n = 386,447) RESULTS: The rates of ambulatory care-sensitive hospital admissions and Medicaid-covered nursing home placements were at least comparable among IHSS recipients' with spouse, parent, other relative, or nonrelative caregivers. Statistically significant differences reflected more desirable outcomes for those with relatives as paid caregivers. In no comparisons did those with spouse providers have worse outcomes than those with nonrelative providers. Average monthly Medicaid expenditures for all services were also lower for IHSS recipients with family provider. IMPLICATIONS: There were no financial disadvantages and some advantages to Medicaid in terms of lower average Medicaid expenditures and fewer nursing home admissions when using spouses, parents, and other relatives as paid IHSS providers. This argues in favor of honoring the recipient's and family's preference for such providers.


Subject(s)
Caregivers/economics , Long-Term Care/economics , Medicaid/economics , Medicaid/statistics & numerical data , Nursing Homes/economics , Spouses , Adolescent , Adult , Aged , Aged, 80 and over , California , Family , Female , Health Expenditures , Humans , Male , Middle Aged , Nursing Homes/statistics & numerical data , Quality of Health Care , Self Care , United States , Workforce , Young Adult
16.
Health Serv Res ; 47(1 Pt 1): 309-28, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22091672

ABSTRACT

OBJECTIVE: To uncover lessons from abroad for Community Living Assistance Services and Supports (CLASS), a federally run voluntary public long-term care (LTC) insurance program created under the Accountable Care Act of 2010. DATA SOURCES: Program administrators and policy researchers from Austria, England, France, Germany, and the Netherlands. STUDY DESIGN: Qualitative methods focused on key parameters of cash for care: how programs set benefit levels; project expenditures; control administrative costs; regulate the use of benefits; and protect workers. DATA COLLECTION/EXTRACTION METHODS: Structured discussions were conducted during an international conference of LTC experts, followed by personal meetings and individual correspondence. PRINCIPAL FINDINGS: Germany's self-financing mandate and tight targeting of benefits have resulted in a solvent program with low premiums. Black markets for care are likely in the absence of regulation; France addresses this via a unique system ensuing legal payment of workers. CONCLUSIONS: Programs in the five countries studied have lessons, both positive and negative, relevant to CLASS design.


Subject(s)
Independent Living , Long-Term Care , Austria , Cost Control , England , France , Germany , Health Care Costs , Humans , Independent Living/economics , Independent Living/standards , Long-Term Care/organization & administration , Long-Term Care/standards , Netherlands , Quality of Health Care
17.
CNS Drugs ; 24(12): 1041-54, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21090838

ABSTRACT

BACKGROUND: Lacosamide is an antiepileptic drug (AED) approved for the adjunctive treatment of partial-onset seizures in adults. Completed phase II/III clinical trials of lacosamide provide a valuable opportunity to evaluate clinically relevant aspects of the resulting large patient pool. OBJECTIVE: To provide insight into the clinical utility of lacosamide by performing a priori-defined and post hoc analyses on a large, pooled patient population. STUDY DESIGN: Pooled data from three randomized, double-blind, multicentre, placebo-controlled phase II/III trials. PATIENTS: Adult patients with partial-onset seizures with or without secondary generalization (N = 1294). INTERVENTION: Four- to six-week titration followed by 12-week maintenance treatment with lacosamide (Vimpat®) 200, 400 or 600 mg/day or placebo. MAIN OUTCOME MEASURE: A priori-defined primary efficacy variables for the pooled analysis were change in seizure frequency per 28 days and the proportion of patients experiencing a ≥50% reduction in seizure frequency (50% responder rate) from Baseline to the Maintenance Phase; a priori-defined secondary efficacy variables were the proportion of patients achieving a ≥75% reduction in seizure frequency from Baseline to the Maintenance Phase (75% responder rate), the proportion of Maintenance Phase completers remaining seizure free throughout the entire Maintenance Phase and the percentage of seizure-free days during the Maintenance Phase for patients entering the Maintenance Phase. The pooled analyses of the change in seizure frequency, and 50% and 75% responder rates were performed with an intent-to-treat (ITT) approach, including all patients receiving at least one dose of trial medication and having at least one post-baseline efficacy assessment. Similar analyses of the two primary efficacy variables and 75% responder rates were also performed using a modified ITT population (ITTm) that included ITT patients who entered the Maintenance Phase. Additional post hoc efficacy analyses were an evaluation of onset of efficacy and assessment of efficacy in patients grouped by prior surgical history and individual concomitant AED use. In addition, pharmacokinetic-pharmacodynamic modelling was performed, and safety data were assessed. RESULTS: In this pooled analysis of 1294 difficult-to-treat patients, all three dosages of lacosamide (200, 400 and 600 mg/day) showed a significant improvement compared with placebo for median percent seizure reduction (ITT and ITTm; p < 0.05 for 200 mg/day, p < 0.001 for 400 and 600 mg/day), as well as for 50% responder rate (ITT and ITTm; p < 0.05 for 200 mg/day, p < 0.001 for 400 and 600 mg/day). Evaluation of 75% responder rate in the phase II/III pooled population showed that a significantly higher proportion of patients randomized to lacosamide 400 or 600 mg/day achieved a ≥75% reduction in seizure frequency compared with placebo (ITT and ITTm; p < 0.001); statistical significance was not observed for lacosamide 200 mg/day (ITT and ITTm). A total of 2.7%, 3.3% and 4.8% of patients completing the Maintenance Phase in the lacosamide 200, 400 and 600 mg/day groups, respectively, experienced no seizures throughout the entire Maintenance Phase (placebo group = 0.9%). The mean change from baseline in the percentage of seizure-free days in patients entering the Maintenance Phase for the phase II/III pool was 8.0%, 11.6% and 14.7% with lacosamide 200 (p = 0.077), 400 (p < 0.001) and 600 (p < 0.001) mg/day groups, respectively, compared with 6.1% in the placebo group. The onset of efficacy relative to placebo was evident by the first week of treatment with lacosamide. Efficacy was similar in lacosamide-treated patients reporting prior surgical intervention for epilepsy compared to lacosamide-treated patients with no prior surgical intervention. Lacosamide showed a reduction in seizures, regardless of the concomitant AEDs used. The preferred pharmacokinetic-pharmacodynamic model (E(max)) supported the therapeutic dose range of lacosamide, and no additional safety concerns were identified in the phase II/III pooled analysis. CONCLUSIONS: Results of these a priori-defined and post hoc pooled data analyses from phase II/III trials demonstrate that lacosamide effectively reduces seizures in patients at all three dosages evaluated with an early onset of efficacy, regardless of patient surgical history and concomitant AED regimen.


Subject(s)
Acetamides/therapeutic use , Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Acetamides/administration & dosage , Acetamides/pharmacokinetics , Adult , Anticonvulsants/administration & dosage , Anticonvulsants/pharmacokinetics , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Dose-Response Relationship, Drug , Double-Blind Method , Epilepsies, Partial/physiopathology , Epilepsies, Partial/surgery , Female , Humans , Lacosamide , Male , Models, Biological , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Time Factors , Treatment Outcome
18.
CNS Drugs ; 24(12): 1055-68, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21090839

ABSTRACT

BACKGROUND: Lacosamide, a new antiepileptic drug (AED) with a different pharmacological action that enhances sodium channel slow inactivation, is approved for the adjunctive treatment of partial-onset seizures in adults. Previous analyses of pooled phase II/III trials have demonstrated that lacosamide provides additional efficacy when added to a broad range of AEDs. OBJECTIVE: To further evaluate the efficacy and safety of lacosamide by grouping patients based upon the sodium channel-blocking properties of their concomitant AEDs. STUDY DESIGN: Post hoc exploratory analyses were performed on pooled data in which patients were grouped based upon inclusion or non-inclusion of at least one 'traditional' sodium channel-blocking AED (defined as carbamazepine, lamotrigine, oxcarbazepine and phenytoin derivatives) as part of their concomitant AED regimen. SETTING: Data pooled from previously conducted phase II/III clinical trials of lacosamide. PATIENTS: Adult patients with partial-onset seizures with or without secondary generalization (N = 1308). INTERVENTION: Four- to six-week Titration Phase followed by 12-week maintenance treatment with adjunctive lacosamide (Vimpat®) [200, 400 or 600 mg/day] or placebo. MAIN OUTCOME MEASURE: Efficacy variables included change in seizure frequency per 28 days and the proportion of patients experiencing a ≥50% reduction in seizure frequency (50% responder rate) from Baseline to the Maintenance Phase. The proportion of patients experiencing a ≥75% reduction in seizure frequency from Baseline to the Maintenance Phase (75% responder rate) was also assessed. Safety parameters assessed were treatment-emergent adverse events (TEAEs) and discontinuation due to TEAEs. Additional safety assessments were changes in ECG and laboratory parameters as well as vital signs (including bodyweight). RESULTS: Of 1308 patients in the pooled phase II/III population, the majority (82%) were using at least one 'traditional' sodium channel-blocking concomitant AED. In this subgroup of patients, adjunctive lacosamide showed significant reductions in seizure frequency (p < 0.01, all dosages) and significantly greater 50% and 75% responder rates (p < 0.01 for 400 mg/day; p < 0.01 [50% responder rate] and p < 0.05 [75% responder rate] for 600 mg/day) compared with placebo; these effects were similar to the results seen in the pooled phase II/III population. TEAEs and discontinuations due to TEAEs in this subgroup were dose related and similar to the pooled phase II/III population. In the remaining subgroup of patients, i.e. those not taking 'traditional' sodium channel-blocking AEDs as part of their concomitant AED regimen (n = 231; 18%), a pronounced, dose-related seizure reduction was observed with lacosamide (p < 0.01, 400 and 600 mg/day for median percent seizure reduction and 50% or 75% responder rates). Also in this group, incidences of TEAEs were low, and discontinuations due to TEAEs did not appear to increase with dose. Analyses of ECG, laboratory and vital signs (including bodyweight) assessments did not identify abnormalities in either subgroup that were outside of the known safety profile of lacosamide observed in the pooled phase II/III population. CONCLUSION: In this post hoc exploratory analysis, adjunctive lacosamide demonstrated significant seizure reduction over placebo regardless of the inclusion of 'traditional' sodium channel blockers in the concomitant AED regimen. Future prospective studies evaluating single AED combinations (e.g. lacosamide plus one other drug) are needed to better evaluate the potential for additive or synergistic effects of lacosamide in combination with AEDs not considered 'traditional' sodium channel blockers.


Subject(s)
Acetamides/therapeutic use , Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Acetamides/adverse effects , Acetamides/pharmacology , Adult , Anticonvulsants/adverse effects , Anticonvulsants/pharmacology , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Epilepsies, Partial/physiopathology , Female , Humans , Lacosamide , Male , Middle Aged , Randomized Controlled Trials as Topic , Sodium Channel Blockers/adverse effects , Sodium Channel Blockers/pharmacology , Sodium Channel Blockers/therapeutic use , Treatment Outcome
19.
Gerontologist ; 50(5): 613-22, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20299425

ABSTRACT

PURPOSE: The purpose of this study was to obtain a profile of individuals with private long-term care (LTC) insurance as they begin using paid LTC services and track their patterns of service use, satisfaction with services and insurance, claims denial rates, and transitions over a 28-month period. DESIGN AND METHODS: Ten LTC insurance companies contributed a random sample of 1,474 qualified individuals who were interviewed in-person by a trained nurse and then interviewed telephonically every 4 month for a 28-month period. Used in the analysis were descriptive statistics and techniques for analyzing longitudinal panel data. RESULTS: About 96% of those filing claims were approved for payment. At baseline, 37% received home care, 23% assisted living care, 14% were in a nursing home, and 26% had not yet begun using paid care. Few claimants reported that their policies restricted their choice of providers and most care costs were covered. The average number of care transitions was 1, typically occurring within 4 month of baseline. The less impaired and those in home care settings were most likely to transition between service settings. IMPLICATIONS: Having private LTC coverage enabled claimants to exercise their preference for alternatives to nursing home care.


Subject(s)
Financing, Personal/methods , Health Services for the Aged/statistics & numerical data , Insurance Benefits , Insurance, Long-Term Care/economics , Long-Term Care/economics , Patient Satisfaction , Aged , Aged, 80 and over , Health Expenditures , Humans , Insurance Claim Review , Male , Residential Facilities/statistics & numerical data , Socioeconomic Factors , United States
20.
Epilepsia ; 51(6): 958-67, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20132285

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of lacosamide (400 and 600 mg/day) as adjunctive treatment in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs). METHODS: This multicenter, double-blind, placebo-controlled trial randomized patients 1:2:1 to placebo, lacosamide 400 mg, or lacosamide 600 mg/day. After an 8-week baseline period, patients began treatment with placebo or lacosamide 100 mg/day, were force-titrated weekly (100 mg/day increments) to the target dose, and entered a 12-week maintenance period. RESULTS: A total of 405 patients were randomized and received trial medication. Most (82.1%) were taking two to three concomitant AEDs. Median percent reductions in seizure frequency per 28 days from baseline to maintenance (intention-to-treat, ITT) were 37.3% for lacosamide 400 mg/day (p = 0.008) and 37.8% for lacosamide 600 mg/day (p = 0.006) compared to 20.8% for placebo, with responder rates of 38.3% and 41.2%, respectively, compared to placebo (18.3%, p < 0.001; ITT). Patients randomized to lacosamide showed large reductions in secondarily generalized tonic-clonic seizures, with median percent reductions in seizure frequency of 59.4% for lacosamide 400 mg/day and 93.0% for lacosamide 600 mg/day compared to 14.3% for placebo, and responder rates of 56.0% and 70.2% compared to placebo (33.3%). Dose-related adverse events included dizziness, nausea, and vomiting. DISCUSSION: Adjunctive treatment with lacosamide 400 and 600 mg/day reduced seizure frequency for patients with uncontrolled partial-onset seizures. Lacosamide 400 mg/day provided a good balance of efficacy and tolerability; lacosamide 600 mg/day may provide additional benefit for some patients as suggested by secondary efficacy analyses, including response in patients with secondarily generalized tonic-clonic seizures.


Subject(s)
Acetamides/administration & dosage , Epilepsies, Partial/drug therapy , Seizures/drug therapy , Acetamides/adverse effects , Acetamides/pharmacokinetics , Adolescent , Adult , Aged , Dizziness/chemically induced , Double-Blind Method , Drug Therapy, Combination , Epilepsies, Partial/metabolism , Epilepsies, Partial/physiopathology , Female , Humans , Lacosamide , Male , Middle Aged , Seizures/metabolism , Seizures/physiopathology , Young Adult
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