Mean Absolute Reduction Research Articles

Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt

Topical therapy is usually of limited benefit in the treatment of severe atopic dermatitis (AD), and the need for a safe and effective systemic treatment may be required in certain cases especially in children. We evaluated the efficacy and safety of methotrexate and cyclosporine in the treatment of 40 children with severe AD. Patients were divided into two groups (each consisting of 20 patients); group A was treated with methotrexate (7.5 mg/week) while group B was treated with cyclosporine (2.5 mg/kg/day). The severity scoring for atopic dermatitis (SCORAD) was used to indicate efficacy of treatment. In group A, the mean SCORAD score at the beginning of the study was 57.90 ± 3.21 that was reduced at the end of the treatment period to reach 29.35 ± 6.32 with a mean absolute reduction of 26.25 ± 7.03. In group B, the mean SCORAD score was 56.54 ± 4.82 at the start of treatment and was 31.35 ± 8.89 at the end of 12 weeks of treatment. The mean absolute reduction was 25.02 ± 8.21. There was no statistically significant difference in the reduction of SCORAD score between both groups (P ± 0.93). Mild and temporary adverse effects were reported in some patients in both groups. Methotrexate or cyclosporine in low doses can be considered as effective, relatively safe, and well-tolerated treatments for severe AD in children.

HIV infection and glycemic response to newly initiated diabetic medical therapy

Type 2 diabetes (DM2) is increasingly common in HIV-infected individuals. Antiretroviral agents and chronic inflammation may adversely affect glycemic control. However, little is known about the effectiveness of diabetic medical therapy in HIV-infected patients. The objective of this study was to compare the effectiveness of initial diabetic medical therapy in patients with and without HIV infection. A retrospective cohort study was conducted among adults with DM2 initiating diabetic medications within the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Generalized estimating equations were used to compare changes in hemoglobin A1c (HbA1c) through the year after initiation of therapy, controlling for baseline HbA1c and demographic and clinical covariates. Two hundred and eighty-six HIV-infected patients and 858 age and sex-matched HIV-uninfected patients initiated diabetic medications during the study period. Overall, patients had an adjusted absolute mean reduction in HbA1c of 1.04% [95% confidence interval (CI) -0.87 to -1.22] during the first year of therapy. HIV-infected patients achieved significantly smaller reductions in HbA1c, with an absolute mean difference of -0.17% (95% CI -0.28 to -0.06; P = 0.003). On subanalyses, HIV-infected patients on a protease inhibitor-based regimen had significantly smaller reductions in HbA1c compared to HIV-uninfected patients (adjusted absolute difference -0.21%, 95% CI -0.35 to -0.08; P = 0.002). Patients with HIV infection who initiate diabetic medical therapy achieve smaller reductions in HbA1c than patients without HIV infection in the course of routine clinical care. This less robust response may in part be related to use of antiretrovirals that exacerbate insulin resistance, specifically protease inhibitors.

Inter-Individual Differences in Baseline Coagulation Activities and Their Implications for International Normalized Ratio Control During Warfarin Initiation Therapy

Genetic polymorphisms of cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) and patient demographic characteristics are responsible for inter-individual differences in warfarin maintenance dosage requirements. At present, however, the factors associated with over-anticoagulation responses, especially before achieving the maintenance phase, have not been completely clarified. In this study, we investigated the effects of baseline coagulation activity assessed in terms of the level of fully carboxylated plasma normal prothrombin (NPT) on international normalized ratio (INR) control during the induction phase of warfarin therapy. Our objectives were to (1) identify factors associated with inter-patient variability in baseline NPT (NPT(0)); (2) estimate the therapeutic NPT (NPT(tx)) levels that can achieve an INR of 2-3; and (3) investigate the influence of NPT(0) on the INR response to warfarin by employing modelling and simulation techniques. We measured NPT before (NPT(0)) and during the introduction of warfarin therapy for up to 3 months and analysed functional single nucleotide polymorphisms (SNPs) of VKORC1 and CYP4F2 in 179 Chinese patients. The patients were classified into tertile groups according to NPT(0) values (i.e. high, intermediate and low groups), and in each group the NPT(tx) achieving therapeutic INR, the absolute reduction of NPT from NPT(0) to NPT(tx), and the percentage inhibition of NPT(0) [{(NPT(0) - NPT(tx))/NPT(0)} × 100] were obtained. The nonlinear relationship between NPT and INR was modelled on the basis of the INR value before warfarin treatment (INR(0)) added by the nonlinear increase in INR after warfarin initiation, which was predicted using the percentage inhibition of NPT(0) and a nonlinear coefficient (λ). The population parameter λ and its inter-individual variability and intra-individual variability in INR in the NPT-INR model were estimated by nonlinear mixed-effect modelling software NONMEM(®). Multivariate analysis identified age and liver disease as covariates of NPT(0), but none of the SNPs had a significant influence. Although the mean absolute NPT reduction necessary to achieve NPT(tx) was dependent on NPT(0) (i.e. the higher the NPT(0), the larger the reduction in NPT), the percentage inhibition was within the narrow range of 67-72 % of NPT(0), irrespective of NPT(0). However, a significantly higher percentage inhibition (80 % on average) was observed in patients with INR values exceeding 4.0. As the nonlinear coefficient λ in the developed model was dependent on NPT(0) (i.e. the higher the NPT(0), the larger the nonlinear λ value), the simulated nonlinear NPT-INR curves were superimposable in the three respective NPT(0) groups, and the only difference was the starting median NPT(0) level. As a result, a steeper increase in the slope of the nonlinear NPT-INR curve might be expected in patients with a lower NPT(0) after initiation of warfarin. The present study suggests that INR may be prolonged by warfarin nonlinearly as a function of the percentage inhibition of NPT(0). Furthermore, these results indicate that NPT(0) may contribute to inter-individual variability in the INR response, and that patients with low NPT(0) may have the potential to show a sharp increase in INR during initiation therapy with warfarin.

Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial

The cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown. Women with resected node-positive or intermediate-risk node-negative HER2 overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF)≥55% were randomized (1:2) to doxorubicin 60 mg/m2 (A)+cyclophosphamide 600 mg/m2 (C) every 21 days (q21d) for four cycles or PLD 35 mg/m2+C q21d+trastuzumab 2 mg/kg weekly (H) for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m2 with H for 12 weeks followed by H to complete 1 year. The primary end point was cardiac event rate or inability to administer 1 year of trastuzumab. Of 181 randomized patients, 179 underwent cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to cardiotoxicity was 18.6% [n=11; 95% confidence interval (CI) 9.7% to 30.9%] with A+C→T+H and 4.2% (n=5; 95% CI 1.4% to 9.5%) with PLD+C+H→T+H (P=0.0036). All events, except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P=0.0014). PLD+C+H→T+H is feasible and results in lower early cardiotoxicity rates compared with A+C→T+H.

Analysis of molecular mechanisms of response and resistance to vemurafenib (vem) in BRAFV600E melanoma.

8503^ Background: Vem induces frequent clinical responses (RR >50%) and improved survival in patients (pts) with BRAF-mutated metastatic melanoma. Multiple mechanisms of escape from vem have been proposed. We performed a centralized analysis of pretreatment, cycle 1, day 15 (D15), and progression (DP) tumor samples collected during the phase II BRIM-2 trial (Sosman et al, NEJM 2012). Methods: Of 132 pts enrolled, archival tumor samples, biopsies taken at baseline (BL), D15, and DP were obtained from 84, 38, 26, and 22 pts, respectively, and analyzed by immunohistochemistry (IHC) for signaling molecules in the MAPK, PI3K/AKT, and cell cycle pathways. Genetic analyses of signaling genes were performed using Sequenom MASSarray and direct DNA sequencing. Results: High levels of ERK phosphorylation were seen at BL indicating constitutive MAPK signaling due to the BRAF mutation. In 19/22 paired samples, pERK levels were reduced following vem (BL vs D15). Mean absolute pERK reduction in pts with clinical response (RECIST criteria) to vem (n=14) was significantly greater than in non-responders (n=8; p=0.013). Baseline cytoplasmic PTEN H-score was higher in responders vs non-responders (H-score=88 vs 68; p=0.042). At progression, upregulation of pERK (H-score=181) was frequently, but not uniformly found vs D15 tumors (H-score=48.5). At progression, increases in Cyclin D1 and Ki67 were seen, without obvious changes in PTEN or pAKT. NRAS mutations occurred in 3/13 DP; 2 had paired BL samples without NRAS mutations. Only 1/82 pts had a concomitant NRAS and BRAF mutation at BL, and did not respond to vem. MAP2K1 (MEK1) codon 124 mutations occurred in 7/92 BL and 1/20 DP samples. 2 pts with BL MEK1 mutations had partial responses. Conclusions: MAPK signaling was effectively inhibited by vem early in treatment, and in the subset of patients with matched tumor samples the degree of pathway inhibition correlated with clinical response. MAPK signaling is upregulated in many lesions at progression. NRAS mutations appear to be a mechanism of acquired resistance in a few tumors (3/13), while the role of MEK1 mutations in resistance is less clear.

Modeling frailty-correlated defaults using many macroeconomic covariates

We propose a novel time series panel data framework for estimating and forecasting time-varying corporate default rates subject to observed and unobserved risk factors. In an empirical application for a U.S. dataset, we find a large and significant role for a dynamic frailty component even after controlling for more than 80% of the variation in more than 100 macro-financial covariates and other standard risk factors. We emphasize the need for a latent component to prevent a downward bias in estimated default rate volatility and in estimated probabilities of extreme default losses on portfolios of U.S. debt. The latent factor does not substitute for a single omitted macroeconomic variable. We argue that it captures different omitted effects at different times. We also provide empirical evidence that default and business cycle conditions partly depend on different processes. In an out-of-sample forecasting study for point-in-time default probabilities, we obtain mean absolute error reductions of more than forty percent when compared to models with observed risk factors only. The forecasts are relatively more accurate when default conditions diverge from aggregate macroeconomic conditions.

Once‐daily administration of trospium chloride extended release provides 24‐hr coverage of nocturnal and diurnal symptoms of overactive bladder: An integrated analysis of two phase III trials

Once-daily extended release (XR) trospium chloride, which provides therapeutic trospium plasma concentrations over 24 hours, has demonstrated efficacy in treating overactive bladder (OAB) symptoms as evaluated over a 24-hr period. This analysis examined the effects of trospium XR on diurnal and nocturnal OAB symptoms. Pooled data were analyzed from two identically designed Phase III trials in which patients with OAB were randomized to receive trospium XR 60 mg or placebo once daily in the morning for 12 weeks. Efficacy was assessed using 3-day urinary diaries. Diurnal events were those occurring from arising from bed in the morning until retiring in the evening; nocturnal events were those occurring from retiring until arising. In total, 1,165 patients received trospium XR (N = 578) or placebo (N = 587). At Week 12 comparison of trospium XR versus placebo, a significantly greater mean reduction from baseline in nocturnal voids (-0.8 vs. -0.6; P = 0.006) and diurnal voids (-1.9 vs. -1.4; P < 0.0001) was noted. At Week 12, the mean percent reduction from baseline with trospium XR versus placebo in nocturnal urge urinary incontinence (UUI) episodes (-60.2% vs. -48.3%; P = 0.003) and mean absolute reduction in diurnal UUI episodes (-2.0 vs. -1.5; P < 0.0001) was significantly greater. Predictors of nocturnal response were duration (weeks) and type of therapy (trospium XR vs. placebo). Reductions in nocturnal toilet voids were accompanied by significant improvements in sleep-related quality of life (QoL) domains. Trospium XR significantly improved both nocturnal and diurnal OAB symptoms. Nocturnal improvements were associated with sleep-related QoL benefits. These results indicate that the XR formulation of trospium chloride provides effective 24-hr coverage of OAB symptoms.

Inflammatory Abdominal Aortic Aneurysm Endovascular Repair into the Long-Term Follow-Up

To investigate long-term outcomes for inflammatory abdominal aortic aneurysms (IAAA) after endovascular treatment (EVAR). Between May 1997 and January 2009, 9 male patients (Mean 67 years, range 54-75 years) with IAAA were treated with EVAR using commercially available endografts. Results were assessed using contrast-enhanced computed tomography (CT) at 3 months, 12 months, and biannually thereafter. Echo-color duplex scanning was also recommended at 3, 6, and 12 months after discharge, and annually thereafter. Primary endpoints were aneurysm-related mortality, aneurysm sac evolution, perianeurysmal fibrosis (PAF) thickness, and hydronephrosis progression. No aneurysm-related deaths were observed during the long-term follow-up of eight patients (one patient death unknown). Maximum aneurysm sac diameter progressively reduced in eight patients (89%) and remained unchanged in one (11%). The absolute mean reduction of the aneurysm size was 26.2%. PAF regressed in two patients (22%), reduced in five (56%), and remained unchanged in two (22%). The absolute median reduction of the PAF thickness was 55.1%. No endoleak was observed during the follow-up period. Hydronephrosis persisted in all three patients who were preoperatively diagnosed with this pathology. Survival rates were 89%, 66.7%, and 66.7% at 12, 36, and 60 months, respectively. This series suggests that EVAR for IAAA into the long-term is associated with a positive trend for both PAF and aneurysm diameter reduction. EVAR does not seem to offer any benefits for hydronephrosis, but seems to effectively exclude the aneurysm sac in anatomically suitable patients.

Adherence to a Fixed-Dose Combination of Rosiglitazone/Glimepiride in Subjects Switching from Monotherapy or Dual Therapy with a Thiazolidinedione and/or a Sulfonylurea

In 2005, a fixed-dose combination therapy (FDCT) of rosiglitazone maleate and glimepiride became available for treatment of type 2 diabetes mellitus. It is hypothesized that FDCTs increase adherence by decreasing the number of required tablets. To assess changes in medication adherence and hemoglobin A(1c) (A1C) values in subjects switching from monotherapy with either a sulfonylurea or rosiglitazone or dual therapy with both to rosiglitazone/glimepiride FDCT. This retrospective database analysis included subjects with 1 or more prescription fills for rosiglitazone, a sulfonylurea, or rosiglitazone/glimepiride FDCT during the identification period of January 1, 2006, to September 30, 2006. Subjects were grouped according to baseline and follow-up period treatment regimens: sulfonylurea or rosiglitazone monotherapy switched to sulfonylurea and rosiglitazone dual therapy (Mono/Dual), monotherapy to rosiglitazone/glimepiride FDCT (Mono/FDCT), sulfonylurea and rosiglitazone dual therapy in both periods (Dual/Dual), and dual therapy to rosiglitazone/glimepiride FDCT (Dual/FDCT). The medication possession ratio (MPR) was calculated as a measure of adherence. The change in A1C from the baseline period to the follow-up period was assessed for each cohort. The study included 16,490 subjects. From baseline to follow-up, MPR decreased for both the Mono/FDCT cohort and the Mono/Dual cohort, but the magnitude of this decrease was less for the Mono/FDCT cohort (-0.02 vs -0.10; p < 0.001). Mean MPR significantly improved for the Dual/FDCT cohort compared with the Dual/Dual cohort (+0.10 vs +0.05; p < 0.001). The mean absolute A1C reduction did not differ significantly between the Mono/FDCT cohort (-1.08%) and the Mono/Dual cohort (-0.77%). Compared with the Dual/Dual cohort, the Dual/FDCT cohort experienced a greater absolute reduction in A1C (-0.06% vs -0.51%; p = 0.004). The results remained statistically significant in the multivariate model. Switching to rosiglitazone/glimepiride FDCT, in comparison with switching to dual therapy, was associated with improvements in medication adherence and glycemic control.

Comparison of model forms for estimating stem taper and volume in the primary conifer species of the North American Acadian Region

• The performance of ten commonly used taper equations for predicting both stem form and volume in balsam fir [ Abies balsamea (L.) Mill], red spruce[ Picea rubens (Sarg.)], and white pine[ Pinus strobus (L.)] in the Acadian Region of North America was investigated.• Results show that the Kozak () and Bi () equations were superior to the other equations in predicting diameter inside bark for red spruce and white pine, while the Valentine and Gregoire () equation performed slightly better for balsam fir.• For stem volume, the Clark et al. () equation provided the best predictions across all species when upper stem diameter measurements were available, while the Kozak () and compatible taper equation of Fang et al. () performed well when those measurements were unavailable.• The incorporation of crown variables substantially improved stem volume predictions (mean absolute bias reduction of 7–15%; root mean square error reduction of 10–15%) for all three species, but had little impact on stem form predictions.• The best taper equation reduced the predicted root mean square error by 16, 39, and 45% compared to estimates from the widely used Honer (1965) regional stem volume equations for balsam fir, red spruce, and white pine, respectively.• When multiple taper equations exist for a certain species, the use of the geometric mean of all predictions is an attractive alternative to selecting the “best”equation.

A systematic review of school-based marijuana and alcohol prevention programs targeting adolescents aged 10–15

Aims: The purpose of this systematic review was to determine if school-based marijuana and alcohol prevention programs are effective in preventing marijuana and alcohol use in adolescents between the ages of 10–15 years. In particular, we examined knowledge versus comprehensive type prevention programs in order to better understand the inconsistency of results in school-based marijuana and alcohol prevention programs found in the literature. Methods: We performed a systematic literature review to identify published or unpublished papers between January 01, 1980 and December 02, 2007 that reviewed the long-term effectiveness (1 year or longer) of school-based marijuana and alcohol primary prevention programs targeting adolescents aged 10–15 years. Results: Long-term marijuana and alcohol prevention programs that utilized a “comprehensive” program content resulted in: (a) a mean absolute reduction of 12 days of alcohol usage per month and (b) a mean absolute reduction of 7 days of marijuana usage per month among adolescents aged 10–15 years old. In comparison, school-based marijuana and alcohol prevention programs that utilized “knowledge only” program content resulted in a mean absolute decrease of 2 days of alcohol usage per month among adolescents aged 10–15 years old. Only one study used knowledge-based content and marijuana use as an outcome measure and as such statistical pooling was not possible. Conclusions: The most effective primary prevention programs for reducing marijuana and alcohol use among adolescents aged 10–15 years in the long-term were comprehensive programs that included anti-drug information combined with refusal skills, self-management skills and social-skills training.

Topical Silver for Infected Wounds

Abstract Reference/Citation: Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev. 2007(1);CD005486. Clinical Question: ...

Modeling Frailty-Correlated Defaults Using Many Macroeconomic Covariates

We propose a new econometric framework for estimating and forecasting the default intensities of corporate credit subject to observed and unobserved risk factors. The model combines common factors from macroeconomic and financial covariates with an unobserved latent (frailty) component for discrete default counts, observed contagion factors at the industry level, and standard risk measures such as ratings, equity returns, and volatilities. In an empirical application, we find a large and significant role for a dynamic frailty component even after controlling for more than eighty percent of the variation in more than hundred macroeconomic and financial covariates, as well as industry level contagion dynamics and equity information. We emphasize the need for a latent component to prevent the downward bias in estimated default rate volatility at the rating and industry levels and in estimated probabilities of extreme default losses on portfolios of U.S. debt. The latent factor does not substitute for a single omitted macroeconomic variable. We argue that it captures different omitted effects at different times. We also provide empirical evidence that default and business cycle conditions depend on different processes. In an out-of-sample forecasting study for point-in-time default probabilities, we obtain mean absolute error reductions of more than forty percent when compared to models with observed risk factors only. The forecasts are relatively more accurate when default conditions diverge from aggregate macroeconomic conditions.

A weighted linear spectral mixture analysis approach to address endmember variability in agricultural production systems

The least squares error (LSE) technique is frequently used to estimate abundance fractions in linear spectral mixture analysis (LSMA). The LSE is typically equally weighted for all wavebands, assuming equally important effects. This is, however, not always the case and therefore traditional LSMA often results in suboptimal fraction estimates. This study presents a weighted LSMA approach that prioritises wavebands with minor or no negative effects on fraction estimates. Synthetic mixed pixel spectra compiled from in situ measured spectra of bare soil, citrus tree and weed canopies were used for validation. The results show markedly improved fraction estimates obtained for the weighted approach, with a mean absolute gain of 0.24 in R 2 and a mean absolute reduction in fraction abundance error of 0.06.

Effects of a plyometric program on vertical landing force and jumping performance in college women

Objectives To examine the effects of a plyometric program on peak vertical ground reaction force as well as kinetic jumping characteristics in recreationally athletic college women. Design Six week prospective exercise intervention. Setting Division I university campus. Participants Twenty college females who competed recreationally in basketball were randomly assigned to a training ( n=10) or control ( n=10) group. Main outcome measures The absolute change values for vertical ground reaction force, countermovement jump height, peak and average jump power, and peak jump velocity. Comparisons were made using Mann–Whitney U tests. Results Vertical ground reaction force decreased in the intervention group (−222.8±610.9 N), but was not statistically different ( p=0.122) compared to the change observed in the control group (54.6±257.6 N). There was no difference in the absolute change values between groups for countermovement jump height (1.0±2.8 cm vs. −0.2±1.5 cm, p=0.696) or any of the associated kinetic variables following the 6-week intervention. Conclusions Although not statistically significant, the mean absolute reduction in vertical ground reaction force in the training group is clinically meaningful. Eight of the 10 women in the training group reduced vertical ground reaction force by 17–18%; however, improvements in jumping performance were not observed. This indicates that programs aimed at enhancing performance must be designed differently from those aimed at reducing landing forces in recreationally athletic women.

Predicting intraocular pressure change before initiating therapy: timolol versus latanoprost

To study intraocular pressure (IOP) reductions with timolol and latanoprost reached in clinical practice, taking into account data that are routinely collected by the ophthalmologist; to predict IOP reduction from these variables. A cohort of patients with primary open-angle glaucoma (suspect) or ocular hypertension was recruited from nine Dutch centres. Mean absolute and relative IOP reduction was calculated in order to compare timolol to latanoprost. IOP reduction was calculated by comparing patients with certain characteristics to those who had none. One hundred and fifty-six persons started on timolol and 76 started on latanoprost monotherapy. Mean [95% confidence interval (CI)] absolute reduction was 7.2 mmHg (7.9; 6.5) for timolol and 6.9 mmHg (8.0; 5.8) for latanoprost. Mean relative reduction (95% CI) was 27.2% (29.3; 25.1) for timolol and 26.6% (30.2; 22.9) for latanoprost. No significant difference in IOP reduction between timolol and latanoprost was found when adjusting for data that are routinely collected by the ophthalmologist. At the time of starting treatment, none of these items normally used for the management of glaucoma, except IOP at baseline, could predict change in IOP. In clinical practice, timolol and latanoprost achieve similar IOP reductions that are comparable to those achieved in randomized trials. No clinically relevant information for glaucoma management can be used to predict IOP reduction accurately.

Early goal-directed therapy in severe sepsis and septic shock: a contemporary review of the literature

Aggressive approaches to acute diseases such as acute myocardial infarction, trauma, and stroke have improved outcomes. Early goal-directed therapy for severe sepsis and septic shock represents a similar approach. An analysis of the literature assessing external validity and generalizability of this intervention is lacking. Eleven peer-reviewed publications (1569 patients) and 28 abstracts (4429 patients) after the original early goal-directed therapy study were identified from academic, community and international settings. These publications total 5998 patients (3042 before and 2956 after early goal-directed therapy). The mean age, sex, APACHE II scores and mortality were similar across all studies. The mean relative and absolute risk reduction was 0.46 +/- 26% and 20.3 +/- 12.7%, respectively. These findings are superior to the original early goal-directed therapy trial which showed figures of 34% and 16%, respectively. A consistent and similar decrease in healthcare resource consumption was also found. Early goal-directed therapy modulates systemic inflammation and results in significant reductions in morbidity, mortality, and healthcare resource consumption. Early goal-directed therapy has been externally validated and is generalizable across multiple healthcare settings. Because of these robust findings, further emphasis should be placed on overcoming logistical, institutional, and professional barriers to implementation which can save the life of one of every six patients presenting with severe sepsis and septic shock.

Analysis of Recent Papers in Hypertension

Analysis of Recent Papers in Hypertension

A Comparison of the Analgesic Efficacy of Tramadol Contramid OAD Versus Placebo in Patients with Pain Due to Osteoarthritis

One thousand twenty-eight (1,028) patients with pain due to osteoarthritis (OA) of the knee were enrolled in this multicenter, randomized, double-blind, parallel study designed to assess the analgesic efficacy and safety of Tramadol Contramid ® OAD compared to placebo. An open-label phase was followed by a double-blind phase, in which a total of 646 patients were randomized to double-blind treatment with placebo or Tramadol Contramid OAD. Patients were titrated to their optimal dose (200 mg or 300 mg), which was maintained for 12 weeks. An absolute mean reduction of 3.0 ± 2.1 on a Pain Intensity Numerical Rating Scale (PI-NRS) was noted in the Tramadol Contramid OAD treatment group. The difference between active and placebo groups regarding this absolute mean reduction was statistically significant ( P < 0.001) throughout the study. The responder analysis demonstrated that a significantly greater percentage of patients in the active treatment arm achieved a reduction of ≥1 and ≥2 points on the PI-NRS score by the end of the study ( P = 0.035). A significantly greater percentage of respondents in the Tramadol Contramid OAD group indicated improvement on both the Patient and Physician Global Impressions of Change ( P = 0.0002). Both the 200 mg and 300 mg doses contributed to the overall superiority of Tramadol Contramid OAD. The most frequent adverse events were consistent with the known side effects of tramadol and were generally mild to moderate in intensity. These results confirm that Tramadol Contramid OAD given once daily is an efficacious and safe treatment for pain due to OA.

An Adaptation of the Diabetes Prevention Program for Use With High-Risk, Minority Patients With Type 2 Diabetes

The purpose of this pilot study was to determine the effectiveness of an edited Diabetes Prevention Program (DPP) Lifestyle Resources Core Teaching Plan for managing patients with type 2 diabetes in an urban underserved setting. Modifications were made to attempt to cut to the bare essentials to work within the constrained budgets of safety net providers. The primary aim was to achieve a mean absolute reduction in HbA1c level of 1 percentage point. The authors conducted a randomized controlled trial of 9 months' duration for patients with type 2 diabetes with an HbA1c>or=8.0%. A total of 67 patients randomized into usual-care and case management groups were evaluated with an intention-to-treat analysis. A modified DPP workbook was used during 7 monthly visits with a nurse case manager. As compared with the usual-care group, those in the case management group experienced a greater reduction in HbA1c level (-1.87 vs -0.54; P=.011) and weight (-2.47 kg vs +0.88 kg; P=.011). Use of an edited version of the DPP workbook in an urban, low-income, minority population with type 2 diabetesproduced a significant absolute reduction in HbA1c percentage and weight.