Health-related quality of life in patients with triple-class exposed relapsed and refractory multiple myeloma treated with idecabtagene vicleucel or standard regimens: patient-reported outcomes from the phase 3, randomised, open-label KarMMa-3 clinical trial.

BACKGROUND: Chimeric antigen receptor T-cell therapy idecabtagene vicleucel (ide-cel) showed significantly improved progression-free survival compared with standard regimens in adults with relapsed and refractory multiple myeloma who had received two to four previous regimens in the ongoing phase 3 KarMMa-3 trial (NCT03651128). This study analysed patient-reported outcomes (PROs), a KarMMa-3 secondary endpoint. METHODS: In the randomised, open-label, phase 3 KarMMa-3 trial, 386 patients in hospitals (≥18 years of age, with measurable disease and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who had received two to four previous regimens-including an immunomodulatory agent, a proteasome inhibitor, and daratumumab-and had documented disease progression after receiving their last dose of the last therapy) were randomly assigned to ide-cel (n=254) or standard regimens (daratumumab, pomalidomide, and dexamethasone; daratumumab, bortezomib, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; carfilzomib and dexamethasone; or elotuzumab, pomalidomide, and dexamethasone; n=132). Patients were expected to complete the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire (QLQ-C30), Multiple Myeloma Module (QLQ-MY20), EQ 5 dimensions (EQ-5D), and EQ-5D visual analogue scale (VAS) at baseline and follow-up timepoints (data cutoff April 18, 2022). PROs included nine prespecified primary domains: EORTC QLQ-C30 GHS-quality of life (QoL), physical functioning, cognitive functioning, fatigue, and pain; QLQ-MY20 disease symptoms and side effects of treatment; and five-level EQ-5D (EQ-5D-5L) index score and EQ-5D visual VAS. Differences in overall least-squares mean changes from baseline to month 20 were analysed using post-hoc constrained longitudinal data analysis. Time to confirmed improvement or deterioration from baseline was analysed using Cox proportional hazard models. FINDINGS: Patients were randomly assigned between May 6, 2019, and April 8, 2022. Overall, the median age was 63 years (IQR 55-68); 151 (39%) patients were female; and 250 (65%) patients were White, 36 (9%) Black or African American, 19 (5%) Hispanic or Latino, 12 (3%) Asian, and seven (2%) of other race. The median follow-up was 18·6 months (IQR 14·0-26·4). PRO compliance was higher than 75% throughout. Overall least-squares mean changes from baseline favoured ide-cel with Hedges' g effect sizes from 0·3 to 0·7 for most domains. Patients in the ide-cel group showed statistically significant and clinically meaningful improvements across the primary PRO domains of interest, with the exception of QLQ-MY20 disease symptoms, side effects of treatment, and EQ-5D-5L index score, which showed improvement across assessment visits but did not exceed the within-group minimally important difference thresholds. The ide-cel group had shorter times to clinically meaningful improvement than the standard regimens group in QLQ-C30 domains except in role functioning, diarrhoea, and financial difficulties; in QLQ-MY20 domains except body image; and in EQ-5D-VAS. INTERPRETATION: Ide-cel offers improved health-related quality of life compared with standard regimens for patients with relapsed and refractory multiple myeloma after previous lines of therapy. The PRO data highlight the extended QoL benefits of a one-time infusion with ide-cel compared with continuous treatment with standard regimens in the treatment of triple-class exposed patients with relapsed and refractory multiple myeloma. FUNDING: 2seventy bio and Celgene, a Bristol Myers Squibb Company.

The Social Value of Improvement in Activities of Daily Living among the Advanced Parkinson's Disease Population.

OBJECTIVES: Quantify the value of functional status (FS) improvements consistent in magnitude with improvements due to levodopa-carbidopa intestinal gel (LCIG) treatment, among the advanced Parkinson's disease (APD) population. METHODS: The Health Economic Medical Innovation Simulation (THEMIS), a microsimulation that estimates future health conditions and medical spending, was used to quantify the health and cost burden of disability among the APD population, and the value of quality-adjusted life-years gained from FS improvement due to LCIG treatment compared to standard of care (SoC). A US-representative Parkinson's disease (PD)-comparable cohort was constructed in THEMIS based on observed PD patient characteristics in a nationally representative dataset. APD was defined from the literature and clinical expert input. The PD and APD cohorts were followed from 2010 over their remaining lifetimes. All individuals were ages 65 and over at the start of the simulation. To estimate the value of FS improvement due to LCIG treatment, decreases in activities of daily living (ADL) limitations caused by LCIG treatment were calculated using data from a randomized, controlled, double-blind, double-dummy clinical trial and applied to the APD population in THEMIS. RESULTS: Total burden of disability associated with APD was $17.7 billion (B). From clinical trial data, LCIG treatment versus SoC lowers the odds of difficulties in walking, dressing, and bathing by 76%, 42% and 39%, respectively. Among the APD population, these reductions generated $2.6B in value to patients and cost savings to payers. The added value was 15% of the burden of disability associated with APD and offsets 15% of the cost of LCIG treatment. CONCLUSIONS: FS improvements, consistent with improvements due to LCIG treatment, in the APD population created health benefits and reduced healthcare costs in the US.

The effect of functional status impairment on nursing home admission risk among patients with advanced Parkinson's disease.

Aims: To estimate the relationship between functional status (FS) impairment and nursing home admission (NHA) risk in Parkinson's disease (PD) patients, and quantify the effect of advanced PD (APD) treatment on NHA risk relative to standard of care (SoC).Materials and methods: PD patients were identified in the Medicare Current Beneficiary Survey (MCBS) (1992-2010). A working definition based on the literature and clinical expert input determined APD status. A logit model estimated the relationship between FS impairment and NHA risk. The effect of levodopa-carbidopa intestinal gel (LCIG) on NHA risk relative to SoC was simulated using clinical trial data (control: optimized oral levodopa-carbidopa IR, ClinicalTrials.gov NCT00660387 and NCT0357994).Results: Non-advanced PD and APD significantly increased NHA risk when controlling for demographics (p < 0.01). APD status was no longer significant after controlling for FS limitations, implying that FS limitations explain the increased NHA risk in APD patients. Reduced impairment in FS in patients with APD treated with LCIG reduced risk of NHA by 13.5% relative to SoC.Limitations: This study applies clinical trial results to real-world data. LCIG treatment might have a different effect on NHA risk for the nationally representative population than the effect measured in the trial. Both data sources employ different instruments to measure FS, instrument wording and study follow-up differed, which might bias our estimates. Finally, there lacks consensus on a definition of APD. The prevalence of APD in this study is high, perhaps due to the specific definition used.Conclusions: Patients with APD experience a higher risk in NHA than those with non-advanced disease. This increased risk in NHA in patients with APD is explained by greater limitations in FS. The relative reduction in risk of NHA for the APD population treated with LCIG is quantitatively similar to doubling Medicaid home care services.

Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson's disease: a multi-country Delphi-panel approach.

BACKGROUND: Lack of a global consensus on the definition of advanced Parkinson's disease (APD) and considerations for timing of device-aided therapies may result in heterogeneity in care. OBJECTIVES: To reach consensus among movement disorder specialists regarding key patient characteristics indicating transition to APD and guiding appropriate use of device-aided therapies in the management of PD symptoms. METHODS: A Delphi-panel approach was utilized to synthesize opinions of movement disorder specialists and build consensus. RESULTS: A panel was comprised of movement disorder specialists from 10 European countries with extensive experience of treating PD patients (mean =24.8 ± 7.2 years). Consensus on indicators of suspected APD and eligibility for device-aided therapies were based on motor symptoms, non-motor symptoms, and functional impairments. Key indicators of APD included: (i) motor-moderate troublesome motor fluctuations, ≥1 h of troublesome dyskinesia/day, ≥2 h "off" symptoms/day, and ≥5-times oral levodopa doses/day; (ii) non-motor-mild dementia, and non-transitory troublesome hallucinations; (iii) functional impairment-repeated falls despite optimal treatment, and difficulty with activities of daily living. Patients with good levodopa response, good cognition, and <70 years of age were deemed as good candidates for all three device-aided therapies. Patients with troublesome dyskinesia were considered good candidates for both levodopa-carbidopa intestinal gel and Deep Brain Stimulation (DBS). PD patients with levodopa-resistant tremor were considered good candidates for DBS. CONCLUSION: Identifying patients progressing to APD and suitable for device-aided therapies will enable general neurologists to assess the need for referral to movement disorder specialists and improve the quality of care and patient outcomes.

The cost-effectiveness of levodopa/carbidopa intestinal gel compared to standard care in advanced Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is an incurable, progressive neurological condition, with symptoms impacting movement, walking, and posture that eventually become severely disabling. Advanced PD (aPD) has a significant impact on quality-of-life (QoL) for patients and their caregivers/families. Levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of advanced levodopa-responsive PD with severe motor fluctuations and hyper-/dyskinesia when available combinations of therapy have not given satisfactory results. AIMS: To determine the cost-effectiveness of LCIG vs standard of care (SoC) for the treatment of aPD patients. METHODS: A Markov model was used to evaluate LCIG vs SoC in a hypothetical cohort of 100 aPD patients with severe motor fluctuations from an Irish healthcare perspective. Model health states were defined by Hoehn & Yahr (H&Y) scale-combined with amount of time in OFF-time-and death. SoC comprised of standard oral therapy ± subcutaneous apomorphine infusion and standard follow-up visits. Clinical efficacy, utilities, and transition probabilities were derived from published studies. Resource use was estimated from individual patient-level data from Adelphi 2012 UK dataset, using Irish costs, where possible. Time horizon was 20 years. Costs and outcomes were discounted at 4%. Both one-way and probabilistic sensitivity analyses were conducted. RESULTS: The incremental cost-effectiveness ratio for LCIG vs SOC was €26,944/quality adjusted life year (QALY) (total costs and QALYs for LCIG vs SoC: €537,687 vs €514,037 and 4.37 vs 3.49, respectively). LCIG is cost-effective at a payer threshold of €45,000. The model was most sensitive to health state costs. CONCLUSION: LCIG is a cost-effective treatment option compared with SoC in patients with aPD.

Adherence to disease-modifying therapies and its impact on relapse, health resource utilization, and costs among patients with multiple sclerosis.

PURPOSE: To evaluate adherence to disease-modifying therapies (DMTs) among patients with multiple sclerosis (MS) initiating oral and injectable DMTs, and to estimate the impact of adherence on relapse, health resource utilization, and medical costs. PATIENTS AND METHODS: Commercially insured MS patients (aged 18-65 years, two or more MS diagnoses, one or more DMT claims) with continuous eligibility 12 months before and after the first DMT claim date (index date) and no DMT claim during the pre-index period were identified from a large commerical claims database for the period from January 1, 2008, to September 30, 2015. Adherence to the index DMT was measured by the 12-month post-index proportion of days covered (PDC) and compared between oral and injectable DMT initiators. After adjustment for sex, age at index DMT, and comorbidities, regression models examined the relationship between adherence and relapse risk, MS-related health resource utilization, and non-drug medical costs (2015 US$). RESULTS: The study covered 12,431 patients and nine DMTs. Adherence to the index DMT did not differ significantly between oral (n=1,018) and injectable (n=11,413) DMTs when assessed by mean PDC (0.7257±0.2934 vs 0.7259±0.2869, respectively; P=0.0787), or percentages achieving PDC ≥0.8 (61.4% vs 58.6%, respectively; P=0.0806). Compared to non-adherence, adherence to DMT significantly reduced the likelihood of relapse in the post-index 12 months by 42%, hospitalization by 52%, and emergency visits by 38% (all, P<0.0001). Adherent patients would be expected to have on average 0.7 fewer outpatient visits annually versus non-adherent patients (P<0.0001). Based on the differences in predicted mean costs, adherence (vs non-adherence) would decrease the total annual medical care costs by $5,816 per patient, including hospitalization costs by $1,953, emergency visits by $171, and outpatient visits by $2,802. CONCLUSION: Adherence remains suboptimal but comparable between oral and injectable DMTs. Potential health and economic benefits underscore the importance of improving adherence in MS.

Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinson's disease: An open-label prospective observational study of effectiveness, tolerability and healthcare costs.

BACKGROUND: Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinson's disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG. METHODS: The seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naïve (N = 37), or had previous LCIG treatment for <2 (N = 22), or ≥2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored. RESULTS: Mean monthly costs per patient (€8226 ± 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naïve patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations. CONCLUSIONS: Costs in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naïve patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The long-term safety was consistent with the established LCIG profile.

Health economic evaluation of paricalcitol(®) versus cinacalcet + calcitriol (oral) in Italy. [corrected].

BACKGROUND AND OBJECTIVE: Chronic kidney disease (CKD) is a highly morbid disorder. The most severe form of CKD is end-stage renal disease (ESRD), in which the patient requires some form of renal replacement therapy to survive. The increasing incidence, prevalence, and costs of ESRD are major national healthcare concerns. The objective of this study was to determine the cost effectiveness of two innovative therapies, paricalcitol versus cinacalcet + calcitriol (oral) in patients with CKD stage 5 (CKD 5) in the healthcare setting in Italy in 2013. METHODS: A Markov process model was developed employing data sources from the published literature, paricalcitol clinical trials, official Italian price/tariff lists, and national population statistics. The analysis is based on a comparison of treatment with paricalcitol versus cinacalcet + calcitriol (oral) in CKD 5. The perspective of the study was that of the payer [Italian National Health Service (INHS)]. The primary efficacy outcomes in the paricalcitol and cinacalcet + calcitriol (oral) clinical trials (reduction of secondary hyperparathyroidism, complications, and mortality) were extrapolated to effectiveness outcomes: number of life-years gained (LYG) and number of quality-adjusted life-years (QALYs). Clinical and economic outcomes were discounted at 3 %. RESULTS: The base-case analysis is based on a 5-year time horizon. From the INHS perspective, the use of paricalcitol leads to a cost saving of €1,853 and an increase in LYG (0.136) and a gain in QALYs (0.089). Consequently, the use of paricalcitol is dominant over the use of combination cinacalcet + calcitriol (oral paricalcitol leads to cost savings and a higher effectiveness). Sensitivity analyses confirmed the robustness of the model. CONCLUSION: The results showed that the favorable clinical benefit of paricalcitol results in positive health economic benefits. This study suggests that the use of paricalcitol in patients with ESRD may be cost effective from the perspective of the INHS.

Cost effectiveness of paricalcitol versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients in the USA.

BACKGROUND: The IMPACT SHPT [Improved Management of Intact Parathyroid Hormone (iPTH) with Paricalcitol-Centered Therapy Versus Cinacalcet Therapy with Low-Dose Vitamin D in Hemodialysis Patients with Secondary Hyperparathyroidism] study compared the effectiveness of paricalcitol and cinacalcet in the management of secondary hyperparathyroidism in haemodialysis patients but did not report the costs or cost effectiveness of these treatments. AIM: The aim of this study was to compare the cost effectiveness of a paricalcitol-based regimen versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients from a US payer perspective, using a 1-year time horizon. METHODS: This was a post hoc cost-effectiveness analysis of data collected for US patients enrolled in the IMPACT SHPT study-a 28-week, randomized, open-label, phase 4, multinational study (ClinicalTrials.gov identifier: NCT00977080). Patients eligible for the IMPACT SHPT study were aged≥18 years with stage 5 chronic kidney disease, had been receiving maintenance haemodialysis three times weekly for at least 3 months before screening and were to continue haemodialysis during the study. Only US patients who reached the evaluation period (weeks 21-28) were included in this secondary analysis. US subjects in the IMPACT SHPT study were randomly assigned to receive intravenous paricalcitol, or oral cinacalcet plus fixed-dose intravenous doxercalciferol, for 28 weeks. Patients in the paricalcitol group could also receive supplemental cinacalcet for hypercalcaemia. The primary effectiveness endpoint in the IMPACT SHPT study was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) level of 150-300 pg/mL during the evaluation period. In this secondary analysis, we estimated the incremental cost-effectiveness ratio (ICER), comparing paricalcitol-treated patients with cinacalcet-treated patients on the basis of this primary endpoint and several secondary endpoints. Costs were estimated by examining the dosage of the study drug (paricalcitol or cinacalcet) and phosphate binders used by each participant during the trial. Nonparametric bootstrap analysis was used to examine the accuracy of the ICER point estimates. RESULTS: The percentages of patients achieving the treatment goal of a mean iPTH level between 150-300 pg/mL during weeks 21-28 of therapy were 56.9% in the paricalcitol group and 34.0% in the cinacalcet group (a difference of 23%, p=0.0235). Paricalcitol was also more effective for each of the secondary endpoints. When annualized, the total drug costs were US$10,153 in the paricalcitol group and US$15,967 in the cinacalcet group, a difference of US$5,814 (57.3%, p=0.0053). Because the paricalcitol-based treatment was less expensive and more effective, it was 'dominant', compared with cinacalcet, in this cost-effectiveness analyses. In our bootstrap analysis, 99.1% of bootstrap replicates for the ICER of the primary endpoint fell within the lower right quadrant of the cost-effectiveness plane-where paricalcitol is considered dominant. For all of the other endpoints, paricalcitol was dominant in 100% of replicates. CONCLUSION: On the basis of dosing and effectiveness data from US patients in the IMPACT SHPT study, we found that a regimen of intravenous paricalcitol was more cost effective than cinacalcet plus low-dose vitamin D in the management of iPTH in patients with SHPT requiring haemodialysis.

Antimuscarinic use among individuals with urinary incontinence who reside in long-term care facilities.

PURPOSE: To assess appropriateness of antimuscarinic use in long-term care facilities (LTCFs) among treated and untreated urinary incontinence (UI) residents from 2007 to 2009. METHODS: We conducted a retrospective analysis using the AnalytiCare(SM) database consisting of minimum data sets (MDS) assessments and prescription records of 90,660 residents from 2007 to 2009. UI (MDS H1b ≥ 1) residents with ≥ 14-day LTCF stay were identified and categorized as treated if they had ≥ 1 antimuscarinic prescription and untreated if they had no antimuscarinics. A random sample of untreated residents was matched based on treated residents' type of MDS assessment. We defined appropriate antimuscarinic use if residents had adequate cognitive function [≤ 4 on the cognitive performance scale (0 = intact to 6 = very severe impairment)] and mobility [scoring <4 on mobility for toileting scale (MDS item G1iA 0 = independent to 4 = total dependent)]. Chi-square tests were used to detect statistical difference between cohorts. RESULTS: A total of 5,327 residents (2,840 treated; 2,487 untreated) were selected [mean age (standard deviation) 80 (8), 81 (8) years; female (76, 65 %), respectively]. On study-defined MDS assessment, 63 % of treated and 69 % of untreated residents had UI (P < 0.01). Approximately 84 % of treated and 74 % of untreated residents may have had cognitive function and mobility sufficient for appropriate antimuscarinic use (P < 0.01). CONCLUSIONS: Our study identified a high percentage of LTCF residents with UI who may have been candidates for antimuscarinics. However, due to the MDS limitation, we were unable to identify overactive bladder patients among these untreated residents with UI. It is possible that untreated control residents had UI due to other factors not amenable to treatment with antimuscarinic agents. Therefore, choice of treatment for each resident needs to be individualized and carefully monitored for efficacy and adverse effects. This retrospective analysis requires prospective confirmation. Proper patient selection for antimuscarinic treatment requires careful assessment of underlying physical status including cognitive function, mobility, and comorbidities.

Comparative cost analysis of management of secondary hyperparathyroidism with paricalcitol or cinacalcet with low-dose vitamin D in hemodialysis patients.

OBJECTIVE: The objective of this analysis was to compare costs of paricalcitol or cinacalcet plus low dose vitamin D, and of phosphate binders, in patients in the IMPACT SHPT study; and to extrapolate those to estimate expected annual maintenance costs. METHODS: IMPACT SHPT was a 28-week, randomized, open-label trial. Subjects from 12 countries received intravenous (IV) or oral paricalcitol, or oral cinacalcet plus fixed IV doxercalciferol or oral alfacalcidol. The primary end-point was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) value of 150-300 pg/mL during weeks 21-28 (evaluation period). This study compares the costs of study drugs and phosphate binders among participants during the study and annualized. This analysis includes only those subjects that reached the evaluation period (134 in each group). RESULTS: The mean total drug costs over the study period were €2606 (SD = €2000) in the paricalcitol group and €3034 (SD = €3006) in the cinacalcet group (difference €428, p = 0.1712). The estimated annualized costs were €5387 (SD = €4139) in the paricalcitol group and €6870 (SD = €6256) in the cinacalcet group (difference €1492, p = 0.0395). In addition, a significantly greater proportion (p = 0.010) of subjects in the paricalcitol arm (56.0%) achieved an iPTH of 150-300 pg/mL during the evaluation period compared to the cinacalcet arm (38.2%). LIMITATIONS: This was a secondary analysis of the IMPACT SHPT study which was not designed or powered for costs as an outcome. The dosing of study drugs and phosphate binders in the IMPACT study may not reflect actual practice, and patients were followed for 28 weeks, while the treatment of SHPT is long-term. CONCLUSION: Patients with SHPT requiring hemodialysis who were treated with a paricalcitol-based regimen for iPTH control had lower estimated annual drug costs compared to those treated with cinacalcet plus low-dose vitamin D.

Content validity and test-retest reliability of Patient Perception of Intensity of Urgency Scale (PPIUS) for overactive bladder.

BACKGROUND: The Patient Perception of Intensity of Urgency Scale (PPIUS) is a patient-reported outcome instrument intended to measure the intensity of urgency associated with each urinary or incontinence episode. The objectives of this study were to assess the content validity, test-retest reliability, and acclimation effect of the PPIUS in overactive bladder (OAB) patients. METHODS: Patients undergoing treatment for OAB were recruited to participate in a non-interventional study by completing a three-day micturition diary including the PPIUS for three consecutive weeks. Following completion of the three-week study, participants from two select sites also completed a cognitive interview to assess their comprehension of the PPIUS. RESULTS: Thirty-nine participants successfully completed the three-week test-retest study; twelve of these participants completed the cognitive interview. Test-retest reliability was high based on intra-class correlation coefficient of 0.95. Among stable patients, the difference between the mean ratings of any two weeks was non-significant. Among the twelve interview participants, nine found it simple to choose a PPIUS rating for each of their micturition episodes and most found the urgency rating definitions consistent with their urgency experiences. CONCLUSIONS: The results demonstrated content validity based on qualitative interviews, and excellent test-retest reliability among stable patients. In addition, no acclimation effect was observed among stable patients. These findings support the use of the PPIUS as a reliable measure of urgency in both clinical trial and real life settings. The validity of PPIUS could be further established with future studies investigating the relationship between discretely graded urgency and incontinence continuum.

Supplementing retention through crown/preparation modification: an in vitro study.

STATEMENT OF PROBLEM: The best treatment for a crown that has come loose but has appropriate marginal fit and form is not clear. PURPOSE: This study was designed to determine whether the retention of such crowns can be increased without remaking the crown or by extensively modifying the tooth preparation. MATERIAL AND METHODS: Ninety cast metal complete crowns, divided into 9 groups of 10, were fabricated to be slightly loose in their internal adaptation to metal dies with an optimal tooth preparation. Horizontal grooves were formed around the circumference of the internal crown surface and the external surface of the metal die, the control being the unaltered crown and die. The crowns were cemented with resin-modified glass ionomer cement and then subjected to a tensile force until they were dislodged. The data were subjected to a 2-way ANOVA to determine the significance of the differences between crowns and dies, and 2 t tests were then used to compare each crown/die combination to the control (α=.05). RESULTS: The mean retention was significantly higher when 1 horizontal groove was placed inside the crowns (P<.001) and was even higher when 2 grooves were placed inside the crowns (P<.001). Placing 1 or 2 grooves in the metal die or in both the crown and die was not significantly more retentive than placing grooves only in the crown. CONCLUSIONS: Placing 1 or 2 horizontal circumferential grooves into the internal surface increased the retention of metal complete crowns made for optimal tooth preparations. Grooves placed into the crown were as effective as or more effective than grooves placed into the tooth / die.

Cost-effectiveness of tacrolimus ointment versus pimecrolimus cream in adults with atopic dermatitis.

BACKGROUND: Tacrolimus 0.1% and pimecrolimus 1.0% are used for short-term and noncontinuous treatment of atopic dermatitis (AD) in patients unresponsive to conventional therapies. OBJECTIVE: To assess the cost-effectiveness of tacrolimus versus pimecrolimus in adults with AD. METHODS: Using a Markov cohort model, the authors projected clinical and economic outcomes over six weeks in adults receiving tacrolimus versus pimecrolimus. Cost-effectiveness was assessed in terms of the ratio of the expected cost of AD-related care to the expected number of days with resolved AD. RESULTS: Patients receiving tacrolimus had an estimated 4.9 fewer days with active AD over six weeks (30.0 versus 34.9 for pimecrolimus). Expected costs (per patient) of AD-related care also were lower for tacrolimus patients ($501.27 versus $546.14, respectively). LIMITATION: While pimecrolimus is indicated for use solely in patients with mild-to-moderate AD, the trial on which this study was based included some patients with severe AD. CONCLUSION: In adults with AD, tacrolimus 0.1% may yield better clinical outcomes and lower costs of care than pimecrolimus 1.0%.

Estimating the prevalence and economic burden of overactive bladder among Medicare beneficiaries prior to Medicare Part D coverage.

OBJECTIVE: The goal of this study is to provide annual estimates for the treated prevalence and expenditures attributable to overactive bladder (OAB) in the elderly prior to Medicare Part D drug coverage. RESEARCH DESIGN AND METHODS: All Medicare claims were extracted for beneficiaries over 65 with continuous coverage for Medicare Parts A and B during 2003-2004. Two OAB definitions were created: (1) the base case included diagnosis codes that narrowly defined OAB, and (2) the sensitivity variant included additional codes indicative of OAB. Descriptive comparisons of baseline characteristics, annual expenditures, and events and procedures were performed for OAB vs. non-OAB subjects meeting the inclusion criteria. CMS expenditures (2004 US dollars) for individuals were totaled and multiple regression techniques were used to estimate costs attributable to OAB after adjusting for demographic characteristics and comorbid conditions. RESULTS: The prevalence of subjects with an OAB diagnosis ranged from 8.8 to 13.6% for the base and sensitivity definitions, respectively. While mean total annual expenditures ranged from $9331 to $9655, mean annual expenditures attributable to OAB ranged from $825 to $1184 per subject (9-12% of total medical expenditures for OAB subjects), with aggregate total OAB-attributable expenditures of $1.8-3.9 billion per year. CONCLUSIONS: The treated prevalence of individuals seeking treatment for OAB in the elderly Medicare population is comparable to some common chronic conditions in that population, and OAB-attributable CMS expenditures are considerable. However, due to study limitations this is a conservative estimate of the direct cost of OAB in the elderly population. The reported estimates exclude pharmacy and out-of-pocket costs, are extrapolated to only two-thirds of the elderly Medicare population, and do not include expenditures by Medicaid for long-term care. Additionally, claims data limits detection of chronic conditions to patients who receive treatment or consultation for OAB; diagnosis codes used were based on expert opinion rather than a review of medical records to identify OAB patients; and long-term care costs are not included.

Impact of patient selection criteria and treatment history on comparisons of alternative therapies: a case study of atypical antipsychotics.

BACKGROUND: Comparative effectiveness analyses using retrospective databases may be highly sensitive to common design decisions employed by researchers. OBJECTIVE: To test the sensitivity of statistical results to common research methods in retrospective database analyses. Comparisons of time to all-cause discontinuation (TTAD) across antipsychotic drug therapies are used to illustrate these effects. METHODS: Data from the California Medicaid Program were used to identify 231,635 episodes of antipsychotic drug therapy. Four sequential analyses of TTAD were performed on all patients, patients with 1 year of post-treatment data, and patients with schizophrenia and using models that included variables documenting drug treatment history. RESULTS: Patients using atypical antipsychotics consistently achieve longer TTAD than patients treated with conventional antipsychotics. Nevertheless, estimated differences narrowed when analyses included only patients with schizophrenia. Risperidone performed better than olanzapine when diagnosis was not limited to schizophrenia, and quetiapine outperformed olanzapine and risperidone when the analysis did not control for treatment history. This latter result reflects the disproportionate use of quetiapine in long-duration augmentation episodes. There were no statistical differences across alternative atypical antipsychotics once the analysis excluded patients without a diagnosis of schizophrenia and included patient treatment history in the analysis. CONCLUSIONS: Comparative effectiveness analyses of alternative drug therapies are sensitive to diagnosis and patient drug treatment history. Data on these factors can be derived from paid claims data and should be used to provide more accurate comparisons of effectiveness across drugs and to provide results that cover the full range of clinical scenarios that clinicians face.