Sum Of Days Research Articles

Productivity cost due to postpartum ill health: A cross-sectional study in Sri Lanka.

ObjectiveEven though postpartum morbidity continues to cause high disease burden in maternal morbidity and mortality across the globe, the literature pertaining to resultant productivity loss is scarce. Hence, the present study aimed at determining the productivity loss and associated cost of episodes of postpartum ill health.MethodsA cross sectional study was conducted in two Medical Officer of Heath areas in the Anuradhapura district, Sri Lanka in 2011, among 407 women residing in Anuradhapura district with an infant aged between 8 to 24 weeks. Validated interviewer administered questionnaires, including the IMMPACT productivity cost tool, were used to collect data on self-reported episodes of postpartum ill health. The productivity loss was calculated as the sum of days lost due to partial and total incapacitation. The adjusted productivity loss for coping strategies was calculated. Productivity cost, both total and adjusted, were calculated based on the mean daily per capita income of the study sample.ResultsOf the 407 participants, 161(39.6%) reported at least one episode of postpartum illness. Hospitalisations were reported by 27 (16.8%) of all symptomatic postpartum women. Common symptoms of postpartum ill health were pain/infection at either episiotomy or surgical site (n = 44, 27.3%), lower abdominal pain (n = 40, 24.8%) and backache (n = 27, 16.8%). The mean productivity loss per episode of ill health was 15 days (SD = 7.8 days) and the mean productivity loss per episode after adjusting for coping strategies was 7.9 days (SD = 4.4 days). The mean productivity cost per an episode was US$ 34.2(95%CI US$ 26.7–41.6) and the mean productivity cost per an episode after adjusting for coping strategies was US$ 18.0 (95%CI US$ 14.1–22.0)ConclusionsThe prevalence of self-reported postpartum ill health, associated productivity loss and cost were high in the study sample and the main contributors were preventable conditions including pain and infection. Thus, effective pain management and proper infection prevention and control measures are important in reducing the burden of postpartum illness and resultant productivity cost.

Trends in the use and costs of round-the-clock long-term care in the last two years of life among old people between 2002 and 2013 in Finland

BackgroundThe structure of long-term care (LTC) for old people has changed: care has been shifted from institutions to the community, and death is being postponed to increasingly old age. The aim of the study was to analyze how the use and costs of LTC in the last two years of life among old people changed between 2002 and 2013.MethodsData were derived from national registers. The study population contains all those who died at the age of 70 years or older in 2002–2013 in Finland (N = 427,078). The costs were calculated using national unit cost information. Binary logistic regression and Cox proportional hazard models were used to study the association of year of death with use and costs of LTC.ResultsThe proportion of those who used LTC and the sum of days in LTC in the last two years of life increased between 2002 and 2013. The mean number of days in institutional LTC decreased, while that for sheltered housing increased. The costs of LTC per user decreased.ConclusionsUse of LTC in the last two years of life increased, which was explained by the postponement of death to increasingly old age. Costs of LTC decreased as sheltered housing replaced institutional LTC. However, an accurate comparison of costs of different types of LTC is difficult, and the societal costs of sheltered housing are not well known.

Adherence to Antihypertensive Medications and Stroke Risk: A Dose-Response Meta-Analysis.

BackgroundInconsistent findings have been obtained for previous studies evaluating the association between antihypertensive medication (AHM) adherence and the risk of stroke. This dose‐response meta‐analysis was designed to investigate the association between AHM adherence and stroke risk.Methods and ResultsMEDLINE and Embase databases were systematically searched to identify relevant studies. The quantification of adherence to AHM was calculated as the percentage of the sum of days with AHM actually taken divided by the total number of days in a specific period. Summary relative risks (RR) and 95% CIs were estimated using a random‐effects model. Stratified and dose‐response analyses were also performed. A total of 18 studies with 1 356 188 participants were included. The summary RR of stroke for the highest compared with the lowest AHM adherence level was 0.73 (95% CI, 0.67–0.79). Stratified by stroke subtype, a higher AHM adherence was associated with lower risks of ischemic stroke (RR, 0.74; 95% CI, 0.69–0.79) and hemorrhagic stroke (RR, 0.55; 95% CI, 0.42–0.72). Moreover, both fatal (RR, 0.51; 95% CI, 0.36–0.73) and nonfatal stroke (RR, 0.52; 95% CI, 0.28–0.94) were lower in participants with higher AHM adherence. The results of a dose‐response analysis indicated that a 20% increment in AHM adherence level was associated with a 9% lower risk of stroke (RR, 0.91; 95% CI, 0.86–0.96).ConclusionsHigher AHM adherence is dose‐dependently associated with a lower risk of stroke in patients with hypertension.

Genome-wide association studies for reproductive seasonality traits in Rasa Aragonesa sheep breed

Sheep breeds from Mediterranean area show reproductive seasonal patterns of oestrous behaviour and ovulatory activity, mainly regulated by variation in the photoperiod. Maximal reproductive activity is associated with short days from August to March. The aim of this study therefore was, to identify new SNPs and genes associated to reproductive seasonality in sheep by using the Illumina OvineSNP50 Beadchip. A total of 239 adult Rasa Aragonesa breed ewes from one flock were controlled from January to August. Three reproductive seasonality traits were considered: the total days of anoestrus (TDA), based on weekly individual plasma progesterone levels and defined as the sum of days in anoestrus, considering anoestrus those periods with three or more consecutive P4 concentrations lower than 0.5 ng/ml; the progesterone cycling months (P4CM), defined for each ewe as the rate of cycling months between January and August based on progesterone determinations and the oestrus cycling months (OCM), defined for each ewe as the rate of months cycling between January and August based on oestrus records. Genotyping of 123 ewes was performed with the OvineSNP50 Infinium Beadchip. After the quality control (QC) performed on the raw genotypes, a total of 47,206 SNPs distributed over the 27 ovine chromosomes and 110 ewes were included in subsequent analyses. Principal component analysis revealed a substructure within the total dataset and identified 4 principal clusters in the experimental flock. None of the SNPs overcame the genome-wide significance level (P = 1.06 × 10−6). However, the SNPs OAR4_66002395 (9.41E-6), and OAR8_25877010 (1.86E-5) reached the genome-wide suggestive significance level (set to 2.32 × 10−5) for TDA and P4CM traits, respectively, while OAR23_14608581 was significant for both TDA (2.02E-5) and P4CM (1.05E-5) traits. Five SNPs evidenced association at chromosome-wise level: SNPs OAR4_66002395, OAR23_14608581 and s20800 (DTA), and OAR8_25877010, OAR23_14608581 and s48474 (P4CM). Several genes related to circadian and circannual rhythms were found close to these SNPs: NPSR1 (SNP OAR4_66002395), HS3ST5 (SNP OAR8_25877010), RPTOR (SNP s48474), and NPTX1 (SNP s48474) and could be considered as candidate gene related to TDA and P4CM traits.

Outpatient parenteral antimicrobial therapy for orthopedic infections – a successful public healthcare experience in Brazil

Treatment of orthopedic infections usually requires prolonged antimicrobial therapy, ranging from 14 days up to 6 months. Nowadays, rising levels of antimicrobial resistance demands parenteral therapy for many patients. Outpatient parenteral antimicrobial therapy (OPAT) is a modality that allows treatment out of hospital in these situations. In Brazil, where a public universal healthcare system allows full coverage for all citizens, implantation and dissemination of OPAT programs would be beneficial for patients and for the system, because it would allow a better allocation of health resources. The Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da USP (IOT) started, in July 2013, a partnership with municipal health authorities in Sao Paulo, Brazil, in order to initiate an OPAT program in which patients discharged from that hospital would be able to continue antimicrobial therapy at primary care facilities. When necessary, patients could also receive their therapy at the day-hospital located at IOT. Primary care nursing and physician staff were trained about antimicrobial infusion and peripherally inserted central catheter manipulation. An OPAT specific antimicrobial protocol was designed and a special reference and counter-reference organized. As a result, 450 primary healthcare professionals were trained. In the first year of this program, 116 patients were discharged for OPAT. Chronic and acute osteomyelitis were most frequent diagnosis. Teicoplanin, ertapenem and tigecycline were the most used drugs. Duration of treatment varied from 10 to 180 days (average 101, median 42). Total sum of days in OPAT regimen was 11,698. Only 3 patients presented adverse effects. Partnership between services of different levels of complexity allowed implantation of a safe and effective public healthcare OPAT program for treatment of orthopedic infections. This program can serve as a model for developing similar strategies in other regions of Brazil and Latin America.

Predictors of bigheaded carp drifting egg density and spawning activity in an invaded, free-flowing river

Abstract Successful reproduction of non-native species is a critical step in the invasion process, influencing establishment and spread. Predicting invasive species' reproduction is often based on information collected from species' native ranges; however, environmental variables within the invaded range may provoke different responses. Bigheaded carp ( Hypophthalmichthys spp.) have successfully invaded many water bodies worldwide and are currently threatening the Laurentian Great Lakes. We examined bigheaded carp spawning in a mostly unregulated, invaded ecosystem (Wabash River, IN, USA) which has similarities to multiple Great Lakes tributaries; it can therefore provide insights into the potential spawning of bigheaded carp in the Great Lakes. Spawning was protracted, and while initiation of spawning has been reported to require changes in discharge in their native ranges, this association was not observed in the Wabash River. However, changing discharges did appear to influence egg density, with rises in late spring producing high drifting egg densities. Cumulative growing degree-day (sum of days where [(max temperature − min temperature / 2) − 10 °C base temperature] is > 0) was the most influential factor predicting spawning initiation. Overall, it appears that bigheaded carp exhibit the ability to spawn under a variety of environmental conditions, with changing discharges targeting spawning to periods when reproductive success may be more likely. The successful establishment of invasive species may hinge on their ability to reproduce across wide-ranging environmental conditions. The reproductive plasticity displayed by bigheaded carp could therefore contribute to their successful reproduction in multiple invaded ecosystems, including Great Lakes tributaries.

Effect of calving interval and parity on milk yield per feeding day in Danish commercial dairy herds

The idea of managing cows for extended lactations rather than lactations of the traditional length of 1 yr primarily arose from observations of increasing problems with infertility and cows being dried off with high milk yields. However, it is vital for the success of extended lactation practices that cows are able to maintain milk yield per feeding day when the length of the calving interval (CInt) is increased. Milk yield per feeding day is defined as the cumulated lactation milk yield divided by the sum of days between 2 consecutive calvings. The main objective of this study was to investigate the milk production of cows managed for lactations of different lengths, and the primary aim was to investigate the relationship between CInt, parity, and milk yield. Five measurements of milk yield were used: energy-corrected milk (ECM) yield per feeding day, ECM yield per lactating day, cumulative ECM yield during the first 305d of lactation, as well as ECM yield per day during early and late lactation. The analyses were based on a total of 1,379 completed lactations from cows calving between January 2007 and May 2013 in 4 Danish commercial dairy herds managed for extended lactation for several years. Herd-average CInt length ranged from 414 to 521d. The herds had Holstein, Jersey, or crosses between Holstein, Jersey, and Red Danish cows with average milk yields ranging from 7,644 to 11,286kg of ECM per cow per year. A significant effect of the CInt was noted on all 5 measurements of milk yield, and this effect interacted with parity for ECM per feeding day, ECM per lactating day and ECM per day during late lactation. The results showed that cows were at least able to produce equivalent ECM per feeding day with increasing CInt, and that first- and second-parity cows maintained ECM per lactating day. Cows with a CInt between 17 and 19mo produced 476kg of ECM more during the first 305d compared with cows with a CInt of less than 13mo. Furthermore, early-lactation ECM yield was greater for all cows and late-lactation ECM yield was less for second-parity and older cows when undergoing an extended compared with a shorter lactation. Increasing CInt increased the dry period length with 3 to 5d. In conclusion, the group of cows with longer CInt were able to produce at least equivalent amounts of ECM per feeding day when the CInt was up to 17 to 19mo on these 4 commercial dairy farms.

Severity of White Matter Hyperintensities and Length of Hospital Stay in Patients with Cognitive Impairment: A CREDOS (Clinical Research Center for Dementia of South Korea) Study.

White matter hyperintensities (WMHs) contribute to aggravation of dementia or geriatric syndrome, thereby resulting in functional impairment. However, evidence of direct association between WMHs and medical resource utilization indicated by length of hospital stay (LOS) is scarce in patients with cognitive impairment. This study aimed to examine the relationship between the severity of WMHs and LOS in patients with cognitive impairment. 4,253 older adults with cognitive impairment were enrolled in this study. We defined LOS as the total sum of days from January 1, 2008 to December 31, 2012. The severity of periventricular (PVWMHs), deep (DWMHs), and overall white matter hyperintensities (Overall WMHs) was evaluated by a visual rating scale. We conducted multinomial logistic regression to demonstrate the relationship between LOS and severity of PVWHMs, DWHMs, and Overall WMHs, respectively. The median LOS was 20 days. Severe PVWMHs had a higher likelihood of longer LOS (Q3: odd ratio/OR = 1.32, 95% confidence interval/CI = 1.06-1.64; Q4: OR = 1.33, 95% CI = 1.07-1.65; Q5: OR = 1.55, 95% CI = 1.26-1.91). As for DWMHs, moderate DWMHs were related to longer LOS (Q4: OR = 1.33, 95% CI = 1.03-1.71; Q5: OR = 1.63, 95% CI = 1.26-2.11). Finally, severity of overall WMHs was independently associated with LOS, which was similar to the results of DWMHs. These findings would advocate for prevention of WMHs to stave off excess medical resource utilization in patients with cognitive impairment.

Can the Canadian drought code predict low soil moisture anomalies in the mineral soil? An analysis of 15 years of soil moisture data from three forest ecosystems in Eastern Canada

AbstractThe Canadian Drought Code (CDC) is an empirical soil‐drying model adapted to high‐latitude forests and commonly used by Canadian fire managers and researchers to predict the water content of the organic soil layer. Better knowledge of the capacity of the CDC to predict the effect of droughts on the water content of the mineral soil could improve our capacity to predict the future response of Canadian boreal forests to future changes in drought frequency and intensity.We tested the capacity of the CDC to predict mineral soil water content (SWC) and droughts against long‐term (14–16 years) daily mineral SWC data from time domain reflectometry probes in multiple stations within three forest ecosystems of Eastern Canada respectively dominated by sugar maple, balsam fir and black spruce. Droughts were defined as SWC values lower than one standard deviation from their historical mean. The drought intensity and frequency of each growing season were computed as the sum of daily SWC departures from normal and the sum of days of drought, respectively.Our results show that the CDC is a reliable predictor of mineral SWC (r = 0.6–0.8), drought frequency (r = 0.5–0.9) and intensity (r = 0.7–0.9) for high‐latitude forest ecosystems of Eastern Canada. Lower correlations were due to the poor accuracy of the model at predicting mild droughts at the sugar maple stand due to the SWC values close to the drought threshold. We detected a higher susceptibility to droughts at the black spruce stand due to a 1‐month‐earlier occurrence of severe droughts. Copyright © 2015 John Wiley & Sons, Ltd.

Adherence patterns for abiraterone acetate and concomitant prednisone use in patients with prostate cancer.

With the growing use of oral anticancer medications, understanding adherence patterns has become increasingly important. Abiraterone acetate (AA) is a prodrug of abiraterone, a novel androgen biosynthesis inhibitor. AA is approved for use in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer. To evaluate AA and concomitant prednisone utilization and adherence patterns for patients with prostate cancer in the United States. This study used data from 2 administrative health care claims databases--Dataset 1: Truven Health Analytics MarketScan (December 2010 to August 2012) and Dataset 2: Symphony Health Solutions' ProMetis Lx (June 2009 to March 2013). To evaluate the consistency of medication-taking behavior, adherence was measured using medication possession ratio (MPR), which was calculated as the sum of days of supply divided by the days on therapy in patients with at least 2 AA prescriptions. Additional outcomes included the proportion of patients taking prednisone, mean and median daily dose of AA, and concomitant prednisone use. Adherence was also studied by age, health care plan type, or previous recent chemotherapy subgroups. 515 patients (mean age: 72.2) and 3,228 patients (mean age: 72.2) with at least 1 AA claim were selected from Dataset 1 and Dataset 2, respectively. The mean (median) daily AA dose per person per prescription was 998.8 (1,000) mg for Dataset 1 and 994.2 (1,000) mg for Dataset 2, which is within 1% of the recommended daily dose (1,000 mg). Mean (median) MPR was 93% (98%; n = 492) in Study Population 1 and 93% (100%; n = 2,449) in Study Population 2. The mean (median) daily prednisone dose per person per prescription was similar in both datasets with 10.1 (10.0; n = 488) mg and 10.6 (10.0; n = 2,425) mg in Dataset 1 and 2, respectively. Similar adherence patterns were observed for patients in different age groups, for patients with commercial health care plans versus patients with Medicare coverage, and for patients with recent chemotherapy compared with patients without. Results from 2 observational studies reported high levels of adherence to AA dosing and administration patterns consistent with prescribing information. These findings provide useful insights into the treatment patterns in patients with prostate cancer treated with AA and can contribute to the current discussion in oncologic research and practice.

Trends in Anxiolytic-Hypnotic Use and Polypharmacy in Taiwan, 2002–2009: A Nationwide, Population-Based Survey

Use of anxiolytics-hypnotics, including benzodiazepines and "z" hypnotics, is a public health concern. This study aimed to investigate the trends in prevalence of anxiolytic-hypnotic drug use and polypharmacy (simultaneous use of two or more anxiolytics-hypnotics) in Taiwan. A dynamic sample of one million individuals who were randomly selected from the National Health Insurance database was used to detect populationwide trends in the use of anxiolytics-hypnotics in Taiwan between 2002 and 2009. The analyses included drugs that are administered orally, intravenously, or intramuscularly as well as single or compound drugs. The authors identified the number of individuals who used the drugs, the sum of days of reported drug use for all individuals (person-days), and the distribution of anxiolytic-hypnotic polypharmacy for all claims for ambulatory, pharmacy, and hospital care. Annual prevalence of any anxiolytic-hypnotic use in Taiwan was higher than 20%. The number of person-days greatly increased from 2002 (4.0%) to 2009 (6.6%). The increases in use between 2002 and 2009 were greatest for clonazepam (prevalence, 7% versus 1.8%; person-days, .2% versus .6%) and zolpidem (prevalence, 2.4% versus 4.2%; person-days, .5% versus 1.5%). Polypharmacy accounted for almost 70% of all person-days of anxiolytic-hypnotic use. This nationwide, population-based survey presents real-world epidemiological evidence about anxiolytic-hypnotic use. The adverse effects of the long-term use of anxiolytics-hypnotics have been established, and unnecessary use of these drugs, particularly in polypharmacy regimens, should be avoided.

Risk of refracture associated with compliance and persistence with bisphosphonate therapy in Taiwan

Bisphosphonates have been used for the treatment of postmenopausal osteoporosis since the early 1990s and studies show that compliant patients experience a lower fracture rate. This cohort study showed that the compliance of Taiwanese patients was poor and the refracture risk was related to compliance with bisphosphonate therapy. Bisphosphonates are potent inhibitors of osteoclast activity, and reduce bone turnover by inhibiting bone resorption. According to Taiwanese reimbursement guidelines, patients with osteoporosis-related fractures are eligible for bisphosphonate treatment. This study aimed to elucidate the relationship of refracture risk with compliance/persistence with bisphosphonate therapy in Taiwan. This was a retrospective, administrative, database analysis measuring the adherence status and impact of poor adherence to bisphosphonate therapy in Taiwan. Study data derived from the National Health Insurance Research Database (NHIRD) were used to assemble a cohort of all osteoporosis patients who initiated bisphosphonate treatment between January 1, 2004, and December 31, 2005. Patients were followed until death, end of registration in NHIRD, or end of study period (December 31, 2006), whichever occurred first. Compliance was calculated as medication possession ratio (MPR; sum of days of supply of osteoporosis medications divided by follow-up duration). The refracture rates for osteoporosis patients were 5.15 %, 7.36 %, and 8.49 % in the first, second, and third year, respectively, and were significantly lower for patients with >80 % compliance than with <80 % compliance (p < 0.05). Nearly 50 % patients were noncompliant (MPR < 80 %) at 3 months, and only around 30 % patients were adherent at 1 year. Refracture risk increased with MPR < 80 %, age, and co-morbidities like diabetes mellitus or dementia. Patients with concomitant statin medication had significantly lower refracture risk. The compliance of Taiwanese patients with osteoporosis medication is poor, and refracture risk is related to compliance with bisphosphonate therapy.

Medication adherence and fracture risk among patients on bisphosphonate therapy in a large United States health plan

The association between bisphosphonate adherence in the first 12months after therapy initiation and subsequent fracture risk was examined. Patients were identified from a large, commercially-insured population with integrated pharmacy and medical claims. Eligible patients were aged ≥45years, were new to osteoporosis therapy (no osteoporosis medication claims in prior year) with first (index) bisphosphonate claim between 1/1/2005 and 4/30/2008, and had continuous insurance coverage for ≥12months pre- and post-index. Patients with fracture claims≤12-months post-index were excluded. Adherence was assessed using the medication possession ratio (MPR) over 12-months post-index (i.e., sum of days' supply dispensed divided by 365days). Patients with a MPR>0.8 were considered adherent. The follow-up period to assess incident fracture began at month 13. The analysis included 33,558 new bisphosphonate users with mean age (SD) 59.5 (9.3) years; 94.0% were female. Median MPR at 12months was 0.61 for alendronate and risedronate; 0.58 for ibandronate. Proportionally more nonfracture patients (39.3%) had a MPR>0.8 compared with fracture patients (34.9%, p<0.001). In multivariate modeling of bisphosphonate users' experience, those with a MPR>0.8 had a 14% lower risk of subsequent fracture than those with MPR<0.5, after controlling for demographics, insurance type, select comorbidities, and other potential confounders (p=0.0459). In a large, commercially-insured population, suboptimal adherence with bisphosphonate treatment was associated with increased fracture risk even after controlling for potential confounders.

Comparison of Adherence Between Nilotinib and Dasatinib As Second-Line Therapies in Chronic Myeloid Leukemia

Abstract 2754 Background:According to the NCCN guidelines, the recommended treatment option for patients diagnosed with Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) in chronic or accelerated phases who are resistant or develop intolerance to first-line imatinib is to switch to one of the two second-generation BCR-ABL tyrosine kinase inhibitors, nilotinib or dasatinib. There is limited information on their comparative adherence. Analysis of adherence may reveal whether these two drugs are being used as intended and how adherence issues may potentially affect clinical outcomes. Nonadherence to imatinib has been associated with loss of cytogenetic response, imatinib failure, and higher rates of inpatient visits. A prior study covering the period up to 6/2009 has revealed a better adherence profile for nilotinib versus dasatinib. Since dasatinib was approved for once daily use in addition to twice daily use in 05/2009, this study replicated the analysis using more recent data to compare adherence between nilotinib and dasatinib as second-line therapies in CML. Methods:Medical and pharmacy records from two databases from January 1997 to April 2010 were combined to identify adult patients diagnosed with CML (ICD-9 code 205.1x) with ≥1 prescription for either nilotinib or dasatinib. Patients were required to have continuous enrollment ≥1 month prior to and after the index date, defined as the first prescription for nilotinib or dasatinib, and to continue their treatment ≥1 month before discontinuing or switching to another TKI. Adherence over an up-to 180-day period was evaluated based on the proportion of days covered (PDC; sum of days of medication on hand for nilotinib or dasatinib divided by the number of calendar days in the study period). Medication possession ratio (MPR) was also evaluated in a sensitivity analysis. PDC and MPR were compared between cohorts using linear regression models. Discontinuation was defined as a treatment gap ≥30 days, and rates were compared between cohorts using Kaplan-Meier survival analyses and Cox proportional hazard regression models. In a sensitivity analysis, discontinuation was defined as a treatment gap ≥90 days. All multivariate regression models were controlled for age, gender, CML complexity, adverse events at baseline, number of inpatient days, emergency room (ER) visits and outpatient visits during baseline, medical costs during baseline, CML year of diagnosis, Charlson Comorbidity Index, and bone marrow or stem cell transplant before the index date. Results:Adherence and discontinuation were analyzed for a total of 558 CML patients receiving a second-line TKI (473 dasatinib and 85 nilotinib). Patient characteristics were generally similar. Patients in the dasatinib cohort had a longer mean follow-up period compared with those in the nilotinib cohort (162 days vs. 146 days; P = 0.0007) and greater utilization and costs associated with inpatient and ER services. The mean PDC over the study period for nilotinib was higher compared with dasatinib (0.81 vs 0.68). After adjusting for confounding factors, the nilotinib group had a 0.115 higher PDC (approximately 17% higher) compared to the dasatinib group (P = 0.0004). Additionally, patients in the nilotinib group had a significantly higher MPR compared to patients in the dasatinib group (0.90 vs. 0.77 P = 0.0043). Discontinuation rates (gap ≥30 days) were significantly higher for dasatinib users than for nilotinib users, with an adjusted hazard ratio of 2.15 (P = 0.0013). Dasatinib-treated patients had higher discontinuation rates than nilotinib-treated patients after 3 months (40% vs 22%) and 6 months (50% vs 28%). These unadjusted differences were robust in the sensitivity analysis with discontinuation defined as a treatment gap ≥90 days, but the difference between the cohorts was no longer significant after adjusting for confounding factors (HR 1.76, P = 0.1328). Conclusions:This retrospective study showed that CML patients treated with nilotinib for second-line treatment were significantly more adherent to therapy, based on PDC and MPR, and had a lower discontinuation rate than did patients receiving dasatinib in this analysis. Further studies are needed to better understand treatment-specific factors affecting adherence and persistence (e.g., treatment cost, tolerability profile, dosing convenience). Disclosures:Guerin:Novartis Pharmaceutical Corporation: Annie Guerin is an employee of Analysis Group, Inc, which has received research funds from Novartis Pharmaceuticals. Bollu:Novartis Pharmaceutical Corporation: Employment, Vamsi K. Bollu worked for the Novartis Pharmaceuticals Corporation while performing this analysis but is currently employed by Sunovion Pharmaceuticals Inc. Sunovion Pharmaceuticals Inc. was not in any way associated with this study. Guo:Novartis Pharmaceutical Corporation: Employment. Stepner:Novartis Pharmaceutical Corporation: Michael Stepner is an employee of Analysis Group, Inc, which has received research funds from Novartis Pharmaceuticals. Griffin:Novartis Pharmaceutical Corporation: James D. Griffin is an employee of the Dana Farber Institute which has received consultancy fees from Analysis Group, Inc, which has received research funds from Novartis Pharmaceuticals Corporation. Wu:Novartis Pharmaceutical Corporation: Eric Q. Wu is an employee of Analysis Group, Inc, which has received consultancy funds from Novartis Pharmaceutical Corporation.

Long-term Compliance with Mesalamine Therapy in Patients with Quiescent Ulcerative Colitis: Results from a Long-term Phase IV Study of MMX® Mesalamine

Purpose: Patients with quiescent ulcerative colitis (UC) are often required to remain on long-term maintenance therapy to prevent recurrence of active disease. However, patients frequently report forgetting to take their medication, particularly in the absence of symptoms. This may be made worse by the requirement for multiple tablets, with multiple times daily administration. MMX® mesalamine (Shire Pharmaceuticals Inc., USA; MMX, Cosmo Technologies Ltd., Ireland) features a low pill burden and once-daily (QD) dosing. In this analysis of a long-term phase IV maintenance study using MMX mesalamine, we examine compliance over time with a once-daily mesalamine formulation. Methods: The Strategies in Maintenance for Patients Receiving Long-term Therapy (SIMPLE) study was a phase IV, multicenter, open-label trial conducted in 51 centers across the USA. Patients with quiescent UC (defined as no rectal bleeding and 0-1 more bowel movements than normal per day, either at enrollment or following 8 weeks' treatment with MMX mesalamine [2.4-4.8g/day; acute phase]) received MMX mesalamine 2.4g/day QD for 12 months (maintenance phase). We examined compliance at 6 months, and 12 months after entry to the maintenance phase. Compliance was assessed via prescription refill data using the formula: [sum of days' supply dispensed]/[sum of days in all refill intervals] x 100. Patients who took ≥80% of study medication were considered to be compliant. Results: In total, 208 patients were enrolled to the 12-month maintenance phase, and 207 were included in the maintenance phase efficacy population. During the maintenance phase, 79.2 and 77.3% of patients remained compliant with their prescribed treatment at 6 and 12 months, respectively. Considering all patients, average compliance with MMX mesalamine in was 86.7% by month 12. Compliance was similar in patients who entered the maintenance phase directly (87.3%) and those who first required acute treatment with MMX mesalamine to achieve disease quiescence (84.8%). Examination of patient outcomes according to some predefined patient and disease characteristics did not identify any significant differences. Conclusion: In this study, the majority of patients were compliant with MMX mesalamine after 6 months treatment, and a similar proportion were also complaint after 12 months. Additionally, compliance was maintained regardless of previous treatment and was equally high in patients who entered the maintenance phase directly, and those who required additional acute phase treatment with MMX mesalamine to achieve disease quiescence. This research was funded by Shire Pharmaceuticals Inc. Disclosure: Sunanda Kane - Research Funding from Shire Pharmaceuticals Inc. Dory Solomon - Employee, Shire Pharmaceuticals Inc. Mary Palmen - Employee, Shire Pharmaceuticals Inc. Karen Barrett - - Employee, Shire Pharmaceuticals Inc. This study was funded by Shire Pharmaceuticals Inc.

Utilization patterns of extended-release niacin in Canada: Analysis of an administrative claims database

To evaluate utilization patterns with extended-release niacin (ERN) compared with those observed with other lipid-modifying drugs (LMDs). A random sample of 17% of patients who had at least one LMD dispensation between January 2004 and February 2007 was obtained from the administrative databases of the Régie de l'assurance maladie du Quebec. Primary outcomes included drug adherence, persistence and discontinuation with ERN and other LMDs, and daily maintenance dose attainment (1500 mg and 2000 mg) with ERN at one-year follow-up. Adherence was defined as the sum of days of all dispensations divided by the total number of days of follow-up. Persistence was defined as renewal of prescription before the end of dispensation plus a grace period (50% prescription duration). Among 26,862 patients, the majority received statins (73.4%), whereas 867 (3.2%) received ERN. The mean age of ERN patients was 62 years and 75% were male. After one year, adherence with ERN was below that of statins (62.0% versus 74.9%), as was persistence (36.1% versus 46.7%), while discontinuation rates were higher (64.0% versus 53.3%). The median time until discontinuation for ERN was shorter than for statins (66 days versus 99 days). After one year, 5.8% of patients were taking 1500 mg or more and 3.2% were on 2000 mg. In the present cohort of patients from regular clinical practice in Quebec, ERN use was associated with low prescription rates, inferior adherence and persistence compared with other LMDs, high discontinuation rates, and very low 2000 mg dose attainment.

Hydroxyurea Adherence and Associated Outcomes in Medicaid Enrollees with Sickle Cell Disease.

Abstract 2483Poster Board II-460 Background:Laboratory and clinical benefits of hydroxyurea (HU) for patients with sickle cell disease (SCD) are well-established in the literature, with data drawn primarily from a few randomized trials and several single site observational studies. However, there is a paucity of data on the use of HU in real-world settings among SCD populations. Further, little research exists on the extent and implications of HU non-adherence among SCD patients. This study sought to assess the extent to which children and adults diagnosed with SCD (HbSS and HbSC) are adherent with prescribed HU therapy and potential associations between HU adherence and clinical and economic outcomes. Methods:Retrospective claims of enrollees in the North Carolina Medicaid program (6/1999-8/2008) were analyzed. Inclusion criteria were ≥1 claim with a diagnosis for SCD (i.e., ICD-9-CM 282.6, 282.6x), continuous health plan enrollment for ≥12 months prior to and following HU initiation, and ≥2 HU prescriptions in the 12 months following HU initiation. Adherence was measured using the medication possession ratio (MPR), defined as the sum of days supplied with HU during the 12 months following HU initiation, divided by the number of days in the follow-up period (365), less the number of days hospitalized. Consistent with other studies of adherence, we considered MPR≥0.8 to be adherent. Multivariate regression analyses were used to estimate the association between HU adherence and economic and clinical outcomes (e.g., costs, likelihood of event) in the first year of therapy. In addition to the adherence indicator, covariates included age, gender, race, Charlson Comorbidity Index (CCI) score, and the number of SCD-related office visits in the year prior to HU initiation. Results:312 subjects (51% male, mean age [SD] 21 [12.2] years) met all inclusion criteria; 51% were '18 years old. The mean MPR was 0.60 (median=0.55), and only 35% of subjects were deemed adherent. Age, race and gender were similar across the adherent and nonadherent groups, while the nonadherent had a slightly higher (though low overall) CCI (0.68 vs. 0.35, p=0.0166) and more SCD-related office visits prior to HU initiation (18.0 vs. 10.6, p=0.0303). Multivariate regression models revealed that in the 12-months following HU initiation, treatment adherence was associated with a significant reduction in both all-cause and SCD-related inpatient (-$4,922, p=0.0010; -$4,383, p<0.0001, respectively) and ER costs (-$564, p=0.0010; -$420, p=0.0010, respectively), as well as SCD-related total costs (-$5,243, p=0.0010). Adherence was associated with an increase in SCD-related pharmacy costs (+$192, p<0.0001) and all-cause office visit costs (+$1,879, p=0.0370). Adherence was also associated with a reduced risk of SCD-related inpatient stay (hazard ratio [HR]=0.65, p=0.0343), ER visit, both all cause and SCD-related (HR=0.72, p=0.0447; HR=0.58, p=0.0080, respectively), and vaso-occlusive event (HR=0.66, p=0.0130). As a sensitivity analysis, we lowered the adherence threshold to ≥0.6; 48% would then be considered adherent. Significant economic benefits (i.e., all-cause and SCD-related inpatient and ER costs; SCD-related total costs) of adherence at the '0.8 threshold were no longer statistically significant using the ≥0.6 definition, but adherence at the lower threshold was still associated with a significant reduced risk of SCD-related ER visits and vaso-occlusive events. Conclusions:Adherence to HU in patients with SCD may be suboptimal. Adherence to HU is associated with improved outcomes, both clinical and economic. Disclosures:Off Label Use: Hydroxyurea is approved for adults with sickle cell disease. We will be discussing its use in pediatric and adult patients..

Employment Outcomes of Persons With a Mental Disorder and Comorbid Chronic Pain

Employment Outcomes of Persons With a Mental Disorder and Comorbid Chronic Pain

Prescriptions for vitamin Damong patients taking antiresorptive agents in Canada

ABSTRACTBackground: Data on the rate of concomitant vitamin D use with antiresorptive medications are limited. Such information is important because vitamin D is indicated in patients with osteoporosis, including those receiving bisphosphonates, and there is evidence of inadequate use by these patients.Objective: To examine prescription vitamin D utilization patterns.Research design and methods: A retrospective analysis of patients aged ≥ 65 years was conducted in a Canadian pharmacy-insurance organization (RAMQ) who received at least one prescription for an antiresorptive agent (i.e., alendronate, risedronate, raloxifene) from January 1, 1996, through December 31, 2003, and did not switch to any other agent during the 1-year post period. Data on prescriptions of vitamin D formulations on the RAMQ formulary (e.g., alfacalcidol, calcitriol, cholecalciferol, doxercalciferol, ergocalciferol) were also captured. No data on generic or over-the-counter vitamin D preparations were available. A vitamin D and antiresorptive agent possession ratio (RP) was computed as:where ∑DSPVD = the sum of the days of supply with prescription vitamin D and ∑DSARR = the sum of days of supply with alendronate, risedronate, or raloxifeneA vitamin D and antiresorptive agent overlap ratio (RO) was computed as:where ∑DSPVDOARR = the sum of days of supply of prescription vitamin D overlapping with alendronate, risedronate, or raloxifene, and ∑DSARR = the sum of the days of supply with alendronate, risedronate, or raloxifene.Results: A total of 46 226 antiresorptive treatment users were identified, > 90% of whom were women. A total of 17 151 (37.1%) had concomitant vitamin D prescriptions. The average duration of prescription therapy with alendronate, risedronate, or raloxifene was 247 days; and the mean duration of prescription vitamin D therapy was 83 days. Patients had a supply of vitamin D for 55% of days of antiresorptive agents therapy (RP = 0.55) and a vitamin D supply overlapping with 24% of their days on antiresorptive agents (RO = 0.24). Possession and overlap ratios were significantly higher in patients receiving once-weekly bisphosphonate prescriptions compared with once-daily regimens (bisphosphonates or raloxifene). Vitamin D prescriptions were also significantly more likely in patients receiving prescriptions for once-weekly bisphosphonates (odds ratio (OR) = 4.65; 95% CI = 4.29–5.05; p < 0.0001) and once-daily bisphosphonates (OR = 1.91; 95% CI = 1.76–2.07; p < 0.0001) compared with once-daily raloxifene.Conclusions: Despite the benefits of vitamin D for osteoporosis, most patients (≈63%) receiving prescriptions for antiresorptive agents were not taking vitamin D, indicating a substantial treatment gap. The study is limited by including data only on (1) pharmacy claims, which do not equate to patient behaviors, such as filling or refilling prescriptions and/or taking the medications; and (2) prescription (but not generic or over-the-counter) vitamin D formulations.

Apnea is associated with neurodevelopmental impairment in very low birth weight infants.

To determine whether apnea in preterm infants is associated with abnormal neurodevelopmental outcome. We determined the number of days that apnea and bradycardia spells were noted by the nursing staff, during the initial hospitalization of 175 preterm infants of less than <1250 g birth weight or <32 weeks gestation who had been enrolled in the follow-up program of the Royal Victoria Hospital. Multiple logistic and multiple linear regression models were constructed to determine the relationships between apnea days and neurodevelopmental impairment at 3 years of age, after correcting for gestation, sex, intrauterine growth restriction, intraventricular hemorrhage, periventricular leukomalacia, pre- and postnatal steroids, and maternal education. A total of 41 infants had neurodevelopmental impairment (Bayley MDI or PDI <70, cerebral palsy or blindness). By multiple logistic regression, an increasing number of days on which at least one apnea occurred, "total apnea days", and male sex were significantly associated with increasing probability of neurodevelopmental impairment, p<0.01, the sum of days of assisted ventilation and apnea days occurring after extubation was also associated with impairment in a separate regression model, p<0.001. Lower MDI at 3 years was significantly associated with postnatal steroid use, p=0.004. Lower PDI was associated with increasing apnea days, male sex, and postnatal steroid use, p<0.001. Functional impairment (a score on any one of the four dimensions of the Vineland scale <70), found in 17% of the infants, was associated with increasing apnea days, p<0.05. Caffeine treatment was not independently associated with any outcome. An increasing number of days that apnea was recorded during hospitalization was associated with a worse outcome. Among the potential explanations for this finding is the possibility that multiple recurrent hypoxic and bradycardic spells may cause brain injury.