Real-world antiseizure medication treatment outcomes in drug-resistant focal epilepsy patients.

OBJECTIVE: To gather real-world evidence on antiseizure medications (ASMs) treatment patterns and related outcomes in patients with drug-resistant focal epilepsy. METHODS: Medical insurance claims from the start of 2014 till the end of 2019 were used. Patient selection criteria included International Classification of Diseases (ICD) codes followed by documented ASM use. Baseline patient demographics along with ASM and rescue medication use patterns and related patient outcome were documented for first (index) ASM regimen. Patients who failed the first regimen and then failed the second regimen were considered drug resistant. Multivariate analyses were performed to identify risks and other characteristics for positive or negative treatment outcomes. RESULTS: Study cohort consisted of 46 474 patients with a mean age of 47.23 (SD: 16.94). Levetiracetam was the most first-encountered ASM (37.94%). At baseline, 87.14% were treated with ASMs prior to having study-confirmed diagnoses. Mental comorbidities were present in 37.86% of patients. After first-year ASM treatment, 34.61% of patients persisted on their index regimen and 5.91% were seizure-free. Patients failing first ASM regimen numbered 12 868 (27.69%). Drug-resistant patients who failed first and then second ASM regimens numbered 6335 (49.23%). Percentages of patients who had successful second treatment and seizure-free were 21.32 and 3.65, respectively. Initiating patients on lamotrigine or carbamazepine (relative to levetiracetam), baseline use of index ASM, rescue medications, and older age or male gender all lowered the risk for treatment failure. Having higher comorbidity, comorbid mental illness, headache, or neoplasty increased such a risk. Baseline use of index ASM, depressive episode, or anxiety disorder all entailed higher risk of failing second ASM treatment. SIGNIFICANCE: Overall, reported findings indicated that patient history at baseline and the early selection of an ASM all influenced treatment outcomes. Findings pointed to the complex nature of ASM treatment in drug-resistant focal epilepsy patients calling for additional research to identify the optimal treatment to achieve beneficial patient outcomes.

Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder of life-threatening hyperphagia, obesity, intellectual deficits, compulsivity, and other behavioral problems. The efficacy and safety of i.n. carbetocin, an oxytocin analog, was evaluated in a prospective, randomized, double-blinded trial in adolescents with PWS. METHODS: Eligible patients aged 10-18 years with genetically confirmed PWS were randomized (1:1) to i.n. carbetocin or placebo 3 times daily for 14 days. The primary efficacy endpoint was change in parent/caregiver-rated Hyperphagia in PWS Questionnaire-Responsiveness (HPWSQ-R) total score. Secondary efficacy endpoints included HPWSQ-R behavior, drive, and severity domains; clinician-rated HPWSQ; Children's Yale-Brown Obsessive-Compulsive Severity Scale; food domain of the Reiss Profile; and Clinical Global Impression-Improvement scale. Endpoints were assessed using analysis of covariance. Relationship between primary and secondary endpoints was assessed using Pearson correlation coefficients. Safety was assessed throughout the study. RESULTS: Demographics and clinical characteristics were similar between treatment groups (carbetocin, n = 17; placebo, n = 20). Patients receiving carbetocin had statistically significant reductions in HPWSQ-R total score at study end (-15.6) versus patients receiving placebo (-8.9; P = 0.029); several secondary efficacy endpoints also demonstrated significant differences (P < 0.05). Treatment effects for the primary and secondary endpoints were highly correlated (P ≤ 0.0001). Incidence of adverse events (AEs) was similar between treatment groups. CONCLUSION: I.n. carbetocin was well tolerated and improved hyperphagia and behavioral symptoms of PWS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01968187FUNDING. The study was funded by Ferring Pharmaceuticals. Recruitment was aided by ongoing work in PWS performed through Eunice Kennedy Shriver National Institute of Child Health and Human Development grant U54 HD083211.

The relationship between patients' knowledge of diabetes therapeutic goals and self-management behaviour, including adherence.

Background The Middle East region has one the highest prevalence rates of diabetes in the world. Little is known about the determinants of adherence and the role of knowledge in diabetes self-management within these populations. Objective To investigate the relationship between patients knowledge of diabetes therapeutic targets with adherence to self-care measures in a sample of patients with type 2 diabetes in Kuwait. Setting Primary care chronic care clinics within the Ministry of Health of Kuwait. Methods A cross sectional survey was carried out with 238 patients from six clinics. A multistage stratified clustered sampling method was used to first randomly select the clinics and the patients. MAIN OUTCOME MEASURE: Self-reported adherence to three behaviours: medication taking, diet and physical activity. Results Respondents were able to correctly report a mean (SD) of 1.6 (1.3) out of 5 of the pre-specified treatment targets. Optimal adherence to physical activity, diet and medications was reported in 25, 33 and 47 % of the study cohort, respectively. A structural equation model analysis showed better knowledge of therapeutic goals and own current levels translated into better adherence to medications, diet and physical activity. Conclusion Knowledge of therapeutic goals and own recent levels is associated with adherence to medications, diet, or physical activity in this Kuwaiti cohort of patients with diabetes. Low adherence to self-care management and poor overall knowledge of diabetes is a big challenge to successful diabetes care in Kuwait.

Validation of a Patient Satisfaction Scale in Patients Undergoing Bowel Preparation Prior to Colonoscopy.

BACKGROUND: Colonoscopy is the most widely used test to screen for colorectal cancer but its use may be hindered by patients' inability to complete the bowel preparation. Patient-reported satisfaction with bowel-cleansing preparations has received little attention. We assessed the reliability and validity of a patient satisfaction survey used in two large, multicenter, randomized, assessor-blinded colonoscopy trials. METHODS: Datasets from two pivotal trials were combined. Patients in both trials included men and women aged 18-80 years who were scheduled for an elective outpatient colonoscopy. Questions relevant to satisfaction with bowel preparation prior to colonoscopy were identified from the literature and incorporated into a 7-item survey administered to patients on the day of colonoscopy. Domain 1 of the satisfaction measure assessed difficulty using bowel-cleansing preparations, ability to consume preparations, acceptability of taste, and overall experience; questions regarding acceptance or refusal of future use of the same bowel preparation were asked in Domain 2. Responses from each item of Domain 1 were transformed on a scale ranging from 0 to 100 and summed as total satisfaction scores. Cronbach's alpha was used to measure reliability; validity was assessed by evaluating relationship between total satisfaction (Domain 1) and willingness to use preparation in the future (Domain 2). RESULTS: Mean age of the 1211 trial participants was 56: 61 % female, 89.5 % Caucasian. Domain 1 had a Cronbach's alpha of 0.79, with higher satisfaction predicting higher future acceptability (p < 0.0001). CONCLUSION: The patient-reported satisfaction measure of bowel-cleansing preparations possesses good validity and reliability.

Cost-effectiveness analysis of intra-articular injections of a high molecular weight bioengineered hyaluronic acid for the treatment of osteoarthritis knee pain.

OBJECTIVE: To determine the cost-effectiveness of bioengineered hyaluronic acid (BioHA, 1% sodium hyaluronate) intra-articular injections in treating osteoarthritis knee pain in poor responders to conventional care (CC) including non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. METHODS: Two decision analytic models compared BioHA treatment with either continuation of patient's baseline CC with no assumption of disease progression (Model 1), or CC including escalating care costs due to disease progression (NSAIDs and analgesics, corticosteroid injections, and surgery; Model 2). Analyses were based on patients who received two courses of 3-weekly intra-articular BioHA (26-week FLEXX Trial + 26-week Extension Study). BioHA group costs included fees for physician assessment and injection regimen, plus half of CC costs. Cost-effectiveness ratios were expressed as averages and incremental costs per QALY. One-way sensitivity analyses used the 95% confidence interval (CI) of QALYs gained in BioHA-treated patients, and ±20% of BioHA treatment and CC costs. Probabilistic sensitivity analyses were performed for Model 2. RESULTS: For 214 BioHA patients, the average utility gain was 0.163 QALYs (95% CI = -0.162 to 0.488) over 52 weeks. Model 1 treatment costs were $3469 and $4562 for the BioHA and CC groups, respectively; sensitivity analyses showed BioHA to be the dominant treatment strategy, except when at the lower end of the 95% CI. Model 2 annual treatment costs per QALY gained were $1446 and $516 for the BioHA and CC groups, respectively. Using CC as baseline strategy, the incremental cost-effectiveness ratio (ICER) of BioHA was $38,741/QALY gained, and was sensitive to response rates in either the BioHA or CC groups. CONCLUSION: BioHA is less costly and more effective than CC with NSAIDs and analgesics, and is the dominant treatment strategy. Compared with escalating CC, the $38,741/QALY ICER of BioHA remains within the $50,000 per QALY willingness-to-pay threshold to adopt a new technology.

Review of the economic evaluations of hormonal therapy for patients with locally advanced prostate cancer.

Androgen deprivation therapy (ADT) is used as first-line therapy for locally advanced or metastatic prostate cancer aiming to reduce testosterone to castrate levels. The authors present an overview of the existing cost-effectiveness studies of ADT in prostate cancer. Cost-effectiveness of ADT was reviewed using a systematic search of the peer-reviewed literature, as well as research abstracts presented at various scientific and industry meetings. Most cost-effectiveness analyses of ADT reported results within the accepted societal threshold of US$50,000 cost/quality-adjusted life year needed to adopt new technology.

Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer.

Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study.

BACKGROUND: 1st generation 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), and palonosetron, a 2nd generation 5-HT3 RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT3 RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions. METHODS: Patients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics' (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT3 RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables. RESULTS: Eligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT3 RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT3 RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT3 RAs, the palonosetron groups incurred 22%-51% fewer 5-HT3 RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p<0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT3 RA group (p<0.05). CONCLUSIONS: Patients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV.

Effectiveness of adjuvant imatinib in patients with gastrointestinal stromal tumor: results of a population-based, matched-cohort study.

OBJECTIVE: Data are limited on the use of adjuvant imatinib in patients with gastrointestinal stromal tumor (GIST) outside of clinical trials. This retrospective, population-based, matched-cohort study evaluated adjuvant imatinib treatment patterns, assessed impact on clinical outcomes, and estimated effectiveness based on number needed to treat (NNT). RESEARCH DESIGN AND METHODS: GIST-related claims from the PharMetrics claims database were included (2000-2010). A stepwise identification algorithm identified appropriate patients based on GIST-related ICD-9-CM codes, who were classified as 'imatinib (IM) patients' receiving imatinib within 84 days post-surgery and 'non-imatinib (non-IM) patients' undergoing surgery but not receiving imatinib during the study period. The primary composite outcome was based on incidence of a second GIST-related surgery and long-term follow-up in the matched cohorts. IM patients were matched with up to eight non-IM patients on age, gender, ICD-9-CM code, and first surgery date. RESULTS: A total of 118 IM and 4088 non-IM patients with possible GIST ICD-9s and surgery were included. The median duration between first and second surgeries was significantly longer in IM than non-IM patients (488 vs. 290 days; p = 0.0005). IM patients also had longer median follow-up from initial surgery to composite outcome (433 vs. 320 days; p = 0.002). Adherence to IM, measured by medication possession ratio, was 0.83 and 0.73 during the first and second years of treatment, respectively. IM patients were less likely to have the composite outcome compared with non-IM patients (hazard ratio = 0.501; p = 0.0005). The NNT to prevent one outcome was 4. CONCLUSIONS: Patients receiving adjuvant imatinib treatment were less likely to have second surgery or be lost to follow-up, and had a longer interval to second surgery. Although treatment with adjuvant imatinib in patients with primary GIST is effective, adherence to imatinib and treatment duration are less than recommended by current treatment guidelines.

Comparative clinical effectiveness of various 5-HT3 RA antiemetic regimens on chemotherapy-induced nausea and vomiting associated with hospital and emergency department visits in real world practice.

PURPOSE: The aim of this study was to compare the risk of chemotherapy-induced nausea and vomiting (CINV) events for various 5-HT(3) RAs in patients who received moderately (MEC) or highly emetogenic chemotherapy (HEC) by evaluating hospital or emergency department (ED) admissions. METHODS: PharMetrics claims database was used to identify patients diagnosed with breast cancer (BC) who were initiated on cyclophosphamide-based adjuvant chemotherapy or with lung cancer (LC) initiated on carboplatin-based or cisplatin-based chemotherapy between 2005 and 2008. Patients were stratified in two groups: those initiated and maintained on palonosetron versus those treated with any other 5-HT(3) RA regimens in the 6-month post first chemotherapy. Risk for CINV events, identified by ICD-9-CM for nausea, vomiting, and/or dehydration, were estimated using logistic regressions, controlling for age, gender, comorbidity, and total chemotherapy doses or days. RESULTS: Of the 4,868 cyclophosphamide-treated BC, 5,414 carboplatin-treated LC, and 1,692 cisplatin-treated LC identified, there were 1,864 BC (38.5%), 1,806 carboplatin-treated LC (33.4%), and 390 cisplatin-treated LC (23.0%) in the palonosetron-only group. Palonosetron-only group had significantly lower probability of CINV events associated with ED/hospital admissions in all three cohorts (3.5% vs. 6.3% in BC, 9.5% vs. 13.8% in carboplatin-treated LC, and 16.4% vs. 22.6% in cisplatin-treated LC, all at p < 0.05). Logistic regressions found palonosetron-only group had significantly lower risk of CINV events (odds ratios = 0.550, 0.653, and 0.689 in BC, carboplatin-treated LC and cisplatin-treated LC, respectively, p < 0.05). CONCLUSION: Patients with lung or breast cancer receiving MEC or HEC had significantly lower risk of CINV events associated with hospital/ED admissions if initiated and maintained on palonosetron relative to patients receiving 5-HT(3) RA regimens.

Treatment persistence with monthly zoledronic acid is associated with lower risk and frequency of skeletal complications in patients with breast cancer and bone metastasis.

BACKGROUND: Zoledronic acid (ZA) reduces skeletal complications in breast cancer patients with bone metastases. This study explored relationships between ZA treatment persistence and patient outcomes. METHODS: Two thousand three hundred ninety-four female patients with breast cancer and bone metastasis were identified from the PharMetrics(®) Integrated Database between January 2003 and October 2006. Of these women, 714 (29.7%) received ZA; the remainder received no intravenous (IV) bisphosphonate (untreated). ZA treatment persistence was measured from first treatment to the first treatment gap > 45 days. Treatment persistence was categorized as short (≤ 90 days, n = 230), medium (91-180 days, n = 171), or long (> 180 days, n = 313). Relationships between ZA treatment and persistence on outcomes were assessed in regression models adjusted for age, comorbidities, and propensity to receive treatment. RESULTS: Compared with untreated patients, after multivariate adjustment, ZA-treated patients experienced a 25% lower rate of skeletal complications (P < .05), were at lower risk for skeletal complications or loss to follow-up (hazard ratio [HR] = 0.67; P < .001), and had 41% longer follow-up time (P < .001). The skeletal complication risk was lower in the long-persistence group than in the short-persistence group (HR = 0.576; P < .05). In patients with ≥ 1 skeletal complication, the long-persistence group had 39% fewer skeletal complications than the short-persistence group (P < .01). The medium- and long-persistence groups had 40% and 139% longer follow-up than the short-persistence group (both P < .001). CONCLUSIONS: ZA treatment was associated with lower risk and frequency of skeletal complications and longer follow-up time. Greater persistence with ZA treatment was associated with better outcomes.

Use of hypomethylating agents and associated care in patients with myelodysplastic syndromes: a claims database study.

OBJECTIVE: The purpose of this study is to describe patterns of hypomethylating agents (HMA) use and to compare treatment outcomes of decitabine (DAC) and azacitidine (AZA) with respect to transfusion dependence and the use of erythropoiesis-stimulating agents (ESA) treatment in commercially-insured patients with Myelodysplastic Syndromes (MDS). RESEARCH DESIGN AND METHODS: A retrospective study using MarketScan Research Data, a large claims database studied patients who received DAC, AZA, or Supportive Care (SC) with at least two claims for MDS between January 1, 2006 and December 31, 2008. Poisson regressions were used to compare DAC and AZA on post-index number of red blood cell/platelet (RBC/PLT) transfusions and ESA treatment, controlling for age, gender, Charlson Comorbidity Index (CCI), time to HMA initiation, number of HMA cycles, and pretreatment RBC/PLT or ESA claims. No other adjustment for disease severity was made. RESULTS: Approximately 48% of the patients were males with a mean age of 73 years (N = 2525). There were 37 DAC-treated and 60 AZA-treated patients. The length of follow-up did not significantly differ between the DAC- and AZA-treated groups (DAC = 349.2; AZA = 350.5 days); however, the number of days from MDS diagnosis to HMA therapy initiation was longer in the DAC cohort than in the AZA cohort (mean 93.7 days vs. 50.8 days, respectively, p = 0.029). Both DAC- and AZA-treated patients received similar number of treatment cycles (mean: 4.8 vs. 5.6 in DAC vs. AZA, p > 0.05), with means of 4.6 days per cycle for patients receiving DAC and 7.4 days for those receiving AZA (p = 0.003). Following treatment with HMA using Poisson regression analysis, DAC-treated patients had significantly lower use of RBC/PLT transfusions (RR 0.206, p = 0.034) and similar use of ESAs compared with AZA-treated patients. Limitations of the study included the small sample size, and the fact that the majority of patients were unspecified regarding their International Prognostic Scoring System (IPSS) risk category, which did not allow for accounting for differences in disease severity. CONCLUSIONS: In MDS patients treated with an HMA, treatment with DAC was associated with less frequent transfusions than with AZA treatment. Further studies with the ability to control for disease severity are warranted.

Zoledronic acid therapy impacts risk and frequency of skeletal complications and follow-up duration in prostate cancer patients with bone metastasis.

PURPOSE: To evaluate the effects of timing and length of zoledronic acid (ZA) treatment on outcomes for patients with prostate cancer in clinical practice. MATERIALS AND METHODS: Patients with prostate cancer and first bone metastasis diagnosed from January 2003 to October 2006 were included. Patients were considered 'untreated' if no ZA was given, 'early ZA-treated' if ZA was initiated before skeletal complication (SC) occurrence or 'late ZA-treated' if one or more SC was documented before or at ZA initiation. Patients were classified with short (≤ 90 days), medium (91-180 days) or long (>180 days) treatment persistence. Assessments included follow-up duration (FUP) and risk of developing one or more SC. RESULTS: Among eligible patients, 847 were untreated, 243 were early ZA-treated and 218 were late ZA-treated. For untreated versus early ZA-treated groups, median FUP was 263 versus 357 days (p < 0.0001), respectively, and time to first SC was 199 versus 273 days (p < 0.0001), respectively. ZA treatment was associated with significantly longer FUP and lower SC risk. The early ZA-treated group had significantly longer FUP versus the late ZA-treated group (median days, 357 vs. 299.5); the late ZA-treated group experienced significantly higher SC risk vs. the early ZA-treated group (odds ratio, 1.51). Compared with the long-persistence group, FUP was 56% and 40% shorter in the short and medium groups, respectively (p < 0.0001). CONCLUSION: Treatment with and early initiation of ZA for patients with prostate cancer and bone metastasis significantly prolonged time to and reduced risk of developing SC, while extending FUP.

Outcomes and management costs in patients hospitalized for skin and skin-structure infections.

BACKGROUND: This study was conducted to determine outcomes and costs of treating complicated skin and skin-structure infections (cSSSIs) due to gram-positive only, gram-negative only, or mixed pathogens (gram-positive and gram-negative), including those with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. METHODS: Data on length of stay (LOS), mortality, and charges for cSSSIs were compiled from claims in the multihospital Solucient database from 2002 to 2006. RESULTS: Among the 5156 cases with pathogens identified, 59.7% were gram-positive, 21.5% were gram-negative, and 18.8% were mixed. Patients with mixed pathogens incurred significantly higher LOS (17.2 days), mortality (10.2%), and charges ($80,093) than those with cSSSIs due to gram-negative pathogens (10.1 days, 6.5%, and $41,634, respectively) or to gram-positive pathogens (9.5 days, 4.8%, and $40,046, respectively). MRSA was isolated from 21.6% of all cases and from 26.3% of cases involving mixed pathogens. MRSA cases had significantly longer LOS and greater mortality than non-MRSA cases, but similar total charges. P aeruginosa occurred in 13.3% of all cases and in 36.3% of cases involving mixed pathogens. P aeruginosa cases had significantly higher LOS and charges compared with non‒P aeruginosa cases. CONCLUSION: Although gram-positive pathogens were the most common causes of cSSSIs, cases involving mixed and resistant pathogens were associated with longer LOS, greater mortality, and higher total charges.

The attributable clinical and economic burden of skin and skin structure infections in hospitalized patients: a matched cohort study.

We estimated the incremental clinical and economic burden of skin and skin structure infections (SSSI) in hospitalized patients using a matched cohort study design. Cases with SSSI as secondary diagnosis were matched with up to 4 randomly selected non-SSSI controls by age, gender, admission date, and ICD-9 code of principal diagnosis. Among the 1 472 965 hospitalizations episodes, 23 026 had SSSI as their secondary diagnosis. Matching was successful in 22 551 (98%) cases. Compared with controls (n = 87 811), the cases had an average mean unadjusted length of hospital stay (LOS) of 5 days longer and excess hospital charges over $21 000 and higher mortality rate (5.4% versus 3.5%). Adjusted estimates from regression models revealed that SSSI incurred on average 3.81 additional days and $14 794 excess hospitalization charges. Risk of mortality was significantly higher in the cases (odds ratio, 1.32). P value was <0.0001 for all unadjusted and adjusted outcomes. Compared with their matched controls, patients with SSSI had significantly longer LOS, higher mortality, and higher hospital charges.

Predicting time to nursing home placement based on activities of daily living scores--a modelling analysis using data on Alzheimer's disease patients receiving rivastigmine or donepezil.

OBJECTIVE: To quantify the impact of activities of daily living (ADL) scores on the risk of nursing home placement (NHP) in Alzheimer's disease (AD) patients. SETTING: Models predicting NHP for AD patients have depended on cognitive deterioration as the primary measure. However, there is increased recognition that both patient functioning and cognition are predictive of disease progression. METHODS: Using the database from a prospective, randomised, double-blind trial of rivastigmine and donepezil, two treatments indicated for AD, Cox regression models were constructed to predict the risk of NHP using age, gender, ADL and MMSE (Mini-Mental State Examination) scores as independent variables. PARTICIPANTS: Patients aged 50-85 years, with MMSE scores of 10-20, and a diagnosis of dementia of the Alzheimer type. RESULTS: Cox regression analyses indicated that being female, older age, lower ADL score at baseline, and deterioration in ADL all significantly increased the risk of NHP. Over 2 years, risk of NHP increased by 3% for each 1-point deterioration in ADL score independent of cognition. CONCLUSION: Data analyses from this long-term clinical trial established that daily functioning is an important predictor of time to NHP. Further research may be required to confirm whether this finding translates to the real world.

A double-blind, randomized, saline-controlled study of the efficacy and safety of EUFLEXXA for treatment of painful osteoarthritis of the knee, with an open-label safety extension (the FLEXX trial).

OBJECTIVE: To report the FLEXX trial, the first well-controlled study assessing the safety and efficacy of Euflexxa (1% sodium hyaluronate; IA-BioHA) therapy for knee osteoarthritis (OA) at 26 weeks. METHODS: This was a randomized, double-blind, multicenter, saline-controlled study. Subjects with chronic knee OA were randomized to 3 weekly intra-articular (IA) injections of either buffered saline (IA-SA) or IA-BioHA (20 mg/2 ml). The primary efficacy outcome was subject recorded difference in least-squares means between IA-BioHA and IA-SA in subjects' change from baseline to week 26 following a 50-foot walk test, measured via 100-mm visual analog scale (VAS). Secondary outcome measures included Osteoarthritis Research Society International responder index, Western Ontario McMaster University Osteoarthritis Index VA 3.1 subscales, patient global assessment, rescue medication, and health-related quality of life (HRQoL) by the SF-36. Safety was assessed by monitoring and reporting vital signs, physical examination of the target knee following injection, adverse events, and concomitant medications. RESULTS: Five hundred eighty-eight subjects were randomized to either IA-BioHA (n = 293) or IA-SA (n = 295), with an 88% 26 week completion rate. No statistical differences were noted between the treatment groups at baseline. In the IA-BioHA group, mean VAS scores decreased by 25.7 mm, compared with 18.5 mm in the IA-SA group. This corresponded to a median reduction of 53% from baseline for IA-BioHA and a 38% reduction for IA-SA. The difference in least-squares means was -6.6 mm (P = 0.002). Secondary outcome measures were consistent with significant improvement in Osteoarthritis Research Society International responder index, HRQoL, and function. Both IA-SA and IA-BioHA injections were well tolerated, with a low incidence of adverse events that were equally distributed between groups. Injection-site reactions were reported by 1 (<1%) subject in the IA-SA group and 2 (1%) in the IA-BioHA group. CONCLUSIONS: IA-BioHA therapy resulted in significant OA knee pain relief at 26 weeks compared with IA-SA. Subjects treated with IA-BioHA also experienced significant improvements in joint function, treatment satisfaction, and HRQoL.

Zoledronic acid and skeletal complications in patients with solid tumors and bone metastases: analysis of a national medical claims database.

BACKGROUND: Bone is among the most common sites of metastasis in patients with advanced cancer, and the development of bone metastases places patients at increased risk for skeletal complications. METHODS: This retrospective claims analysis included only patients with a diagnosis of bone metastasis who had a single type of solid tumor of the breast (women), prostate, or lung and experienced >or=1 skeletal complication between January 2002 and October 2005. RESULTS: The mean follow-up (+/-standard deviation) for zoledronic acid (ZA)-treated patients versus untreated patients was 12.2 +/- 9.05 months versus 8.7 +/- 9.28 months, respectively (P < .001). The monthly rate of skeletal complications in ZA-treated patients versus untreated patients was 0.29 +/- 0.3 per month versus 0.43 +/- 0.4 per month, respectively (P < .001). Persistent ZA use was associated with longer follow-up duration (P < .05) and a greater probability of continuing follow-up. Greater persistency was associated with lower monthly rates of skeletal complications (P < .05). The length of follow-up for ZA use according to the recommended dosing schedule was 17.11 months compared with 9.93 months for nonrecommended schedules and 8.68 months for no treatment (analysis of variance; P < .001). The rate of skeletal complications with ZA use on the recommended schedule was 0.16 events per month versus 0.31 events per month for nonrecommended schedules and 0.43 events per month for no treatment. In the subgroup analysis, the mean time to first complication was 185 +/- 210 days in the ZA-treated group versus 98 +/- 161 days in the untreated group (P < .0001). The mean time from the first complication to the second complication was 111 +/- 124 days in the ZA-treated group versus 86 +/- 114 days in the untreated group (P < .05). CONCLUSIONS: Real-world evidence indicated that ZA reduced the skeletal morbidity rate and delayed the time to skeletal complications.

The use of the occupational disruptiveness scale of the neuropsychiatric inventory-nursing home version to measure the impact of rivastigmine on the disruptive behavior of nursing home residents with Alzheimer's disease.

OBJECTIVES: The Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) was used to study the impact of rivastigmine (Exelon; Novartis Pharmaceuticals Corporation, East Hanover, NJ), on occupational disruptiveness (OD), a proxy measure for professional caregiver burden. METHODS: The study was a prospective, multicenter, open-label, single-arm trial with NH residents prescribed rivastigmine (up to 6 mg bid) for Alzheimer's disease (AD) treatment. The NPI-NH was completed by NH staff caregivers at time of initiation of treatment with rivastigmine (T1), at treatment weeks 10 to 14 (T2), at treatment weeks 24 to 28 (T3), and at treatment weeks 50 to 54 (T4). RESULTS: Observations ranged from 173 at baseline to 73 at week 52. All but one patient had either moderate or severe dementia. Total OD score means were 4.7 +/- 6.1, 3.9 +/- 5.0, 4.19 +/- 5.6, and 2.79 +/- 2.8 at baseline, and weeks 12, 26, and 52 (T1-T4), respectively, with significant difference found between T1 and T4. Except for euphoria and disinhibition at T3 and T4, all correlations between OD scores and the domain scores of the NPI, were significant. Rivastigmine dose was an independent variable that affected OD change. CONCLUSION: Treatment with rivastigmine was associated with a reduction in the self-reported professional caregiver burden, as assessed by the NPI-NH OD scale.