Assessment of potential risk factors associated with ischaemic colitis.

Ischaemic colitis (IC) has been associated with a number of diverse disorders and risk factors, including irritable bowel syndrome (IBS) and constipation. We sought to assess, through a large-scale population study, the potential risk factors associated with IC. Patients with IC and matched controls without IC were identified using the medical and pharmacy claims data from the HealthCore Managed Care Database from 1st January 2000 to 31st May 2005. A multivariate conditional logistic regression model was developed to identify significant risk factors of IC. Interactions of age, sex, prior IBS diagnosis, and prior constipation diagnosis were further evaluated. We identified 1754 patients with IC and 6970 non-IC controls; 64% were women, and mean ages were 63 and 62 years respectively. The final parsimonious model comprised 19 independent variables associated with increased risk for IC including shock, dysentery, bloating, IBS, colon carcinoma, constipation, cardiovascular disease, dyspepsia, abdominal, aortic, or cardiovascular surgery, 12-month laxative, H(2) receptor blocker and oral contraceptive use. A significant interaction was observed between age and prior IBS on risk for IC. In conclusion, multiple risk factors for IC were identified and we confirmed that patients with IBS or constipation are at greater risk for IC.

Patients with irritable bowel syndrome or constipation have an increased risk for ischaemic colitis.

AIMS: To estimate the relative risk for ischaemic colitis in patients with and without irritable bowel syndrome or constipation, and to evaluate the role of irritable bowel syndrome and constipation as confounders in the relationship between commonly used gastrointestinal medications and ischaemic colitis. METHODS: Patient cohorts were identified with the use of longitudinal MarketScan research databases from 1 January 1999 to 31 December 2002. Patients in each study cohort were matched 1:1 with comparable control patients using a propensity score. A Cox proportional hazards models were used to estimate relative risk for ischaemic colitis. RESULTS: The relative risk for ischaemic colitis was 3.17 and 2.78 times higher for patients with irritable bowel syndrome and constipation, respectively, than for those without these disorders. Patients who were taking an antispasmodic, a proton pump inhibitor, or an H2-antagonist were at increased risk for ischaemic colitis [relative risk with 95% CI 2.73 (1.41-5.39), 2.00 (1.05-3.79), 2.75 (1.22-6.17) respectively]; however, when these results were adjusted for irritable bowel syndrome or constipation, the relative risks were attenuated and no longer statistically significant. CONCLUSIONS: Patients with irritable bowel syndrome or constipation demonstrated a two- to threefold increased risk for ischaemic colitis. Moreover, irritable bowel syndrome and constipation strongly confounded the relationship between gastrointestinal drug use and the risk for ischaemic colitis, suggesting that etiologic studies of ischaemic colitis risk must account for the presence of irritable bowel syndrome or constipation.

Comparison of amlodipine/valsartan/hydrochlorothiazide single pill combination and free combination: adherence, persistence, healthcare utilization and costs.

OBJECTIVES: To determine whether amlodipine/valsartan/hydrochlorothiazide single pill combination (SPC) is associated with improved persistence, adherence and reduced healthcare utilization and costs compared to the corresponding free combination (FC). METHODS: Adult (≥18 years) patients covered by commercial and Medicare Supplemental insurance in the Truven MarketScan database with hypertension (HTN) diagnosis between October 2009 and December 2011 were included. At least two filled prescriptions for the SPC cohort or two periods of minimum 15 days of concurrent use of amlodipine, valsartan and hydrochlorothiazide (HCT) for the FC cohort were required. Cohorts were propensity score matched (PSM) to balance on important confounders. Outcomes included: 1) adherence (proportion of days covered [PDC] and medication possession ratio [MPR]); 2) persistence (treatment gap >30 days); 3) all-cause and HTN-specific healthcare utilization and costs at 12 months. RESULTS: After cohort matching with PSM, patients taking SPC (N = 9221) exhibited better outcomes than FC (N = 1884): higher mean adherence (85.7% vs. 77.0%), mean PDC (73.8% vs. 60.6%) and persistence (46.8% vs. 23.6%) (all p < 0.0001). Patients taking SPC were associated with higher odds of persistence (OR: 3.51; 95% CI: 3.08-4.02), MPR ≥80% (OR: 2.72; 95% CI: 2.40-3.08) and PDC ≥80% (OR: 2.88; 95% CI: 2.55-3.26). After PSM, the SPC cohort exhibited statistically significantly lower mean number of resource utilization events compared to FC. Patients in the SPC cohort also had a statistically significantly (p < 0.05) lower percentage of patients with ≥1 all-cause hospitalization (15.0% vs. 18.2%), ≥1 all-cause emergency room (ER) visits (25.7 vs. 31.4%), and ≥1 ER HTN-specific visits (9.7% vs. 14.1%). The costs incurred by SPC cohort patients were 2.8% to 41.7% numerically lower than the FC cohort, statistically significant for all-cause ER costs ($430.6 vs. $549.5, p < 0.05). CONCLUSIONS: Real-world data indicate an association of the amlodipine/valsartan/HCT SPC with improved adherence and persistence vs. FC with no difference in overall healthcare or hypertension specific costs between the cohorts.

Economic impact of switching from valsartan to other angiotensin receptor blockers in patients with hypertension.

BACKGROUND: The approaching availability of lower-cost generic angiotensin receptor blockers (ARBs) may affect formulary policies for patients maintained on the ARB valsartan. OBJECTIVE: Estimate the economic impact of switching from valsartan (including valsartan-based single-pill combinations) to other ARBs without apparent medical reasons. RESEARCH DESIGN AND METHODS: Patients with essential hypertension and at least 6 months of continuous valsartan treatment free of hospitalization, cardiovascular events, renal events or ARB-associated adverse events were identified from the MarketScan administrative claims database from January 1, 2004 to March 31, 2008. Those who subsequently switched to a different ARB with at least a 5% copayment decrease (switchers) were matched to those who did not switch (maintainers) according to propensity score quintiles and selected baseline characteristics. Refills were not required after the index fill for the switched-to ARB or maintained valsartan. Matched switchers and maintainers were compared in terms of medication discontinuation, healthcare resource use and costs during the 6 months following the index fill. RESULTS: A total of 99,926 valsartan maintainers and 2150 switchers (with a mean copayment decrease of $16.5 per month) were identified and matched. After matching, switching from versus maintaining valsartan was associated with an 8% higher risk of medication discontinuation (p < 0.008), 19.1 additional outpatient visits/100 patients (p = 0.002) and 9.3 additional hypertension-related inpatient days/100 patients (p = 0.030). Concurrently, switching from versus maintaining valsartan was associated with higher total medical costs by $748/patient (p < 0.001), driven largely by higher costs for hypertension-related medical services by $492/patient (p = 0.004). LIMITATIONS: Exact reasons for switching were not available and the study assessed only the short-term impacts of switching. CONCLUSIONS: Hypertension patients maintained on valsartan who switched to a different ARB with a lower copayment experienced substantial increases in medication discontinuation, healthcare resource use and costs compared to those who maintained valsartan treatment.

Controlled outgrowth of dissociated neurons on patterned substrates.

The cytoarchitecture of nervous tissue is lost during the dissociation procedures used to form primary cell cultures. As a first step toward reestablishing an ordered arrangement of these cells in vitro, we developed a set of procedures for patterning the outgrowth of cells cultured on 2-dimensional substrates. These procedures used a combination of surface chemistry and photolithographic techniques. The adhesive properties of either silicon or silicon dioxide (quartz) surfaces were controlled by covalently binding small organic molecules to the surface with silane coupling agents. The attachment and growth of either embryonic mouse spinal cells or perinatal rat cerebellar cells were found to be promoted by binding certain amine derivatives to the surface. In particular, cells grown on surfaces bound with diamines and triamines, but not with monoamines, formed cultures whose morphology was similar to that of cells cultured on conventional substrates, i.e., glass coated with poly(D-lysine). The attachment of cells to a substrate was inhibited by binding alkane chains (e.g., n-tetradecane) to the surface and plating the cells in media containing 5-10% (vol/vol) serum. Patterns of selected adhesivity were formed using photochemical resist materials and lithographic masking techniques compatible with the silane chemistry. Cultures of either spinal cord cells or cerebellar cells could be confined to square regions on the scale of 50 micron. Cerebellar cells could be confined to grow on lines with widths less than 10 micron. This width is comparable to the diameter of granule cell somata. The patterned growth of cerebellar cells was maintained up to 12 d in vitro. Over this time period the granule cells were observed to develop electrical excitability and immunoreactivity for neuron-specific enolase. Purkinje neurons also developed electrical excitability when grown on the chemically modified surfaces. Immunochemical reactivity of the patterned cultures for glial fibrillary acid protein (GFAP) showed that glia are patterned along with the associated granule cells. Interestingly, the GFAP-positive glia that proliferated on surfaces bound with amine derivatives attained primarily a tile-shaped, fibroblast-like morphology, while those proliferating on glass coated with poly(D-lysine) developed primarily a spindle-shaped, process-bearing morphology. Granule cells preferentially associated with the spindle-shaped glia.

Drug switching patterns among patients taking non-steroidal anti-inflammatory drugs: a retrospective cohort study of a general practitioners database in the United Kingdom.

OBJECTIVE: To examine the frequency and determinants of switching between different non-steroidal anti-inflammatory drugs (NSAIDs) and the relationship with co-prescription of gastro-protective drugs (GPDs). DESIGN: This was an analysis of 30,654 patients receiving a total of 209,140 NSAID prescriptions in the UK from 1 January 1997 to 31 December 1998 identified through the MediPlus database. Analyses examined switching, repeat, termination and GPD co-prescription rates in new and continuing takers according to age and sex. RESULTS: Each patient received an average of 6.8 prescriptions in the year of study. Of the prescriptions 72.2% were for one of three NSAIDs, ibuprofen, diclofenac, or naproxen, and 7.2% of prescriptions were for fixed combination products of an NSAID plus a gastroprotective drug. At least 16.0% of continuing takers, and 28.5% of new takers switched to another NSAID in the review period. On average, new patients switched more frequently than continuing patients (0.39 switches/patient/year versus 0.23 switches/patient/year, p < 0.001). Switching between NSAIDs decreased with age and was less common in women (p < 0.05). Switching was associated with a 24% and 33% increased probability of GPD prescription in new and continuing takers, respectively. DISCUSSION: The frequency of switching, and of GPD co-prescription at switching, suggest that dissatisfaction with NSAIDs is frequent, and that gastrointestinal intolerance is a common feature of this dissatisfaction.