Significant Difference In Treatment Effect Research Articles

The Impact of Expanding Insurers' Duty to Settle: Evidence from the Royal Globe Doctrine

The historic 1979 California Supreme Court decision in Royal Globe Insurance Company v. Superior Court unexpectedly extended to injured-third-parties the right to sue the injurer’s insurer for bad faith in claim settlement, expanding the set of eligible plaintiffs to those with the greatest incentive to sue. Using data on automobile bodily injury liability claims, we make use of the quasi-experimental nature of this decision and employ synthetic control methods to examine resulting changes in observed insurance settlements. Estimates indicate a significant increase in compensation amounts with little evidence of an increase in fraud indications or a decrease in insurers’ fraud monitoring, among paid claims. Effects are modest, but significant differences in treatment effects are found for claims of different sizes and characters, with small claims and claims without fraud suspicion indicators receiving more beneficial treatment under expanded bad faith liability.

Pulmonary rehabilitation for chronic obstructive pulmonary disease.

Pulmonary rehabilitation for chronic obstructive pulmonary disease.

Amlodipine+benazepril is superior to hydrochlorothiazide+benazepril irrespective of baseline pulse pressure: subanalysis of the ACCOMPLISH trial.

Pulse pressure (PP) is an independent risk factor for cardiovascular (CV) disease and death but few studies have investigated the effect of antihypertensive treatments in relation to PP levels before treatment. The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial showed that the combination of benazepril+amlodipine (B+A) is superior to benazepril+hydrochlorothiazide (B+H) in reducing CV events. We aimed to investigate whether the treatment effects in the ACCOMPLISH trial were dependent on baseline PP. High-risk hypertensive patients (n=11,499) were randomized to double-blinded treatment with single-pill combinations of either B+A or B+H and followed for 36 months. Patients were divided into tertiles according to their baseline PP and events (CV mortality/myocardial infarction or stroke) were compared. Hazard ratios (HRs) for the treatment effect (B+A over B+H) were calculated in a Cox regression model with age, coronary artery disease, and diabetes mellitus as covariates and were compared across the tertiles. The event rate was increased in the high tertile of PP compared with the low tertile (7.2% vs 4.4% P<.01). In the high and medium PP tertiles, HRs were 0.75 (95% confidence interval [CI], 0.60-0.95; P=.018) and 0.74 (CI, 0.56-0.98, P=.034), respectively, in favor of B+A. There was no significant difference between the treatments in the low tertile and no significant differences in treatment effect when comparing the HRs between tertiles of PP. B+A has superior CV protection over B+H in high-risk hypertensive patients independent of baseline PP although the absolute treatment effect is enhanced in the higher tertiles of PP where event rates are higher.

Sex-specific differences in diabetes prevention: a systematic review and meta-analysis.

In people with prediabetes, lifestyle interventions and glucose-lowering medications are effective in preventing the progression to type 2 diabetes. It is unclear whether differences in treatment effects between men and women need to be taken into consideration when choosing a preventive strategy for an individual person. We systematically searched PubMed, the Cochrane Library, EMBASE, CINAHL, Web of Science, and reference lists of pertinent review articles from 1980 to June 2013. We conducted random effects meta-analyses of published and unpublished data to determine differences of treatment effects between men and women. Twelve randomised control trials (RCTs) provided sex-specific information on treatment effects. Compared with usual care, men and women who received lifestyle interventions had a lower rate of progression to type 2 diabetes (RR 0.60 [95% CI 0.35, 1.05] after 1 year; RR 0.63 [95% CI 0.51, 0.79] after 3 years); greater weight reduction (-2.45 kg; [95% CI -3.56, -1.33 kg] after 3 years); and greater reductions of fasting plasma glucose (-0.31 mmol/l [95% CI -0.48, -0.15] after 3 years) and 2 h post-challenge-glucose (-0.68 mmol/l [95% CI -1.03, -0.34] after 3 years). No statistically significant differences in treatment effects between men and women were apparent for any outcomes (p values of all comparisons ≥ 0.09). Our study emphasises the importance of preventive interventions in people with prediabetes and indicates no differences of beneficial preventive effects on the incidence of type 2 diabetes and weight gain between men and women.

Measuring treatment response in psychotic depression: The Psychotic Depression Assessment Scale (PDAS) takes both depressive and psychotic symptoms into account

BackgroundThere is no established psychometric instrument dedicated to the measurement of severity in psychotic depression (PD). The aim of this study was to investigate whether a new composite rating scale, the Psychotic Depression Assessment Scale (PDAS), covering both the psychotic and the depressive domains of PD, could detect differences in effect between two psychopharmacological treatment regimens. MethodsWe reanalyzed the data from the Study of Pharmacotherapy of Psychotic Depression (STOP-PD), which compared the effect of Olanzapine+Sertraline (n=129) versus Olanzapine+Placebo (n=130). The response to the two regimens was compared using both a mixed effects model and effect size statistics on the total scores of three rating scales: the 17-item Hamilton Depression Rating Scale (HAM-D17), its 6-item melancholia subscale (HAM-D6), and the 11-item PDAS consisting of the HAM-D6 plus five items from the Brief Psychiatric Rating Scale covering psychotic symptoms. ResultsAccording to both statistical approaches, the PDAS, the HAM-D17 and the HAM-D6 were all able to detect significant differences in treatment effect between Olanzapine+Sertraline and Olanzapine+Placebo (Olanzapine+Sertraline being superior). Notably, 45% of the trial participants were at least “probable psychotic” at their last assessment in the trial. LimitationsThe STOP-PD was not designed specifically to answer the research questions of the present study. ConclusionsThe Psychotic Depression Assessment Scale (PDAS) is a sensitive measure of treatment response in PD. The fact that 45% of the patients still experienced psychotic symptoms at their last trial assessment emphasizes the need to include items pertaining to psychotic symptoms in rating scales for PD.

Comparison of Treatment Effect Estimates From Prospective Nonrandomized Studies With Propensity Score Analysis and Randomized Controlled Trials of Surgical Procedures

We aimed to compare treatment effect estimates from NRSs with PS analysis and RCTs of surgery. Evaluating a surgical procedure in randomized controlled trials (RCTs) is challenging. Nonrandomized studies (NRSs) involving use of propensity score (PS) analysis to limit bias are of increasing interest. Meta-epidemiological study. We systematically searched MEDLINE via PubMed for all prospective NRSs with PS analysis evaluating a surgical procedure. Related RCTs, addressing the same clinical questions, were systematically retrieved. Our primary outcome of interest was all-cause mortality. We also selected 1 subjective outcome. We calculated the summary odds ratios (OR) for each study design, the ratio of OR (ROR) between the designs and the summary ROR across clinical questions. An ROR<1 indicated that the experimental intervention is more favorable in NRSs with PS analysis than RCTs. We retrieved 70 reports of NRSs with PS analysis and 94 related RCTs evaluating 31 clinical questions, of which 22 assessed all-cause mortality and 26 a subjective outcome. The combined ROR for all-cause mortality was 0.83 (95% confidence interval: 0.65-1.04). For subjective outcomes, the combined ROR was 1.07 (0.87-1.33). There was no statistically significant difference in treatment effect between NRSs with PS analysis and RCTs. Prospective NRSs with suitable and careful PS analysis can be relied upon as evidence when RCTs are not possible.

Differences in Treatment Effect Among Clinical Subgroups in a Randomized Clinical Trial of Long-Acting Injectable Risperidone and Oral Antipsychotics in Unstable Chronic Schizophrenia

A long-term randomized trial of unstable patients with schizophrenia found no benefit of long-acting injectable (LAI) risperidone over oral treatment in preventing or delaying time to psychiatric hospitalizations or on clinical outcomes. The initial analyses did not examine whether benefits of LAI emerged in selected subgroups.Patients with schizophrenia or schizoaffective disorder who had been hospitalized within the past 2 years or judged to be at risk for hospitalization because of increasing psychiatric service use were randomly assigned to LAI risperidone 12.5 to 50 mg per injection biweekly or to the psychiatrist's choice of oral antipsychotics and followed for up to 2 years. The primary endpoint was psychiatric rehospitalization. Symptoms, quality of life, and global functioning were assessed through blinded videoconference interviews. Cox's regression and mixed effects models were used to assess difference in treatment effect within 12 subgroups defined by hospitalization at study entry, substance abuse, race, symptom severity, quality of life, body mass index, age, race or sex, or reported medication compliance.Mixed models and Cox's regression using up to 24 months of follow-up data showed no significant differences in treatment effect in 10 of 12 subgroups on psychiatric symptoms, quality of life, or time to hospitalization. With adjustment for multiple comparisons, treatment effect differed by race on substance use outcomes, with white participants showing more benefit from LAI than other groups.LAI risperidone showed no superiority to psychiatrist's choice of oral treatment in most clinically defined subgroups, although the white patients benefited more than the other groups on substance abuse outcomes.

Fluoxetine combined with clorazepate dipotassium and behaviour modification for treatment of anxiety-related disorders in dogs

The effectiveness of clorazepate dipotassium combined with fluoxetine and a behaviour modification programme for the treatment of anxiety disorders in dogs was investigated. Forty dogs with anxiety disorders were initially enrolled and 36 dogs completed the trial. Dogs were classified into two behavioural categories (anxious dogs with aggression and anxious dogs without aggression) according to their presenting complaints, and were also subdivided into males, females, juveniles and adults. The dog owners were provided with a behaviour modification plan for their dogs to be commenced in the first week of therapy. Clorazepate dipotassium was administered PO at 1.0mg/kg every 24h for 4weeks, and fluoxetine was administered PO at 1.0mg/kg every 24h for 10weeks. Therapy with both drugs was initiated simultaneously. Improvement was reported in 25/36 dogs. Significant differences in treatment effects were observed between anxious dogs with aggression and anxious dogs without aggression (P<0.05). Positive correlations between owner compliance with the treatment plan and reported improvement achieved during three periods of study were also noted.

Relationships of peripheral blood lymphocyte counts (PBLC) with antitumor activity of NGR-hTNF given in combination with chemotherapy (CT).

3038 Background: Antitumor effects of NGR-hTNF (N), a tumor-targeted antivascular agent, are driven at low dose by an early vessel stabilization that greatly enhances both intratumoral CT uptake and T-cell infiltration. Synergism with CT was shown in immunocompetent mice, but not in nude mice lacking functional T cells. Methods: By an individual patient pooled analysis of 396 patients (pts) from 7 ph II trials in 6 tumor types, we estimated the effects of baseline PBLC on the antitumor activity of N (with or without CT) and CT alone. Low dose N (0.8 μg/m2) was given in combination with CT in 171 pts. Control groups of 140 and 85 pts receiving N and CT alone, respectively, were also analyzed. CT was doxorubicin or a platinum-based regimen. In all trials, response to therapy was assessed every 6 weeks by RECIST. Endpoints of interest were response rate (RR, complete plus partial response), disease control rate (DCR, RR plus stable disease), duration of response (DOR) and progression-free survival (PFS). In logistic and Cox regression analyses, PBLC data were dichotomized in high or low levels by the median cutpoint (1.5/mL; 95% CI, 1.4-1.6). Multivariate models included age, sex, PS and tumor type as covariates. Results: In both N-alone and CT-alone groups, there was no statistically significant difference in treatment effect according to baseline PBLC. Conversely, high PBLC were related to better treatment outcome in the N plus CT group, compared to low PBLC. In this N plus CT group, high PBLC (vs low) were associated with higher RR (OR=2.8; 95% CI, 1.2-6.3; p=.01) and DCR (OR=2.6; 1.3-4.9; p=.004), and with longer DOR (HR=0.39; 0.16-0.96; p=.04) and PFS (HR=0.60; 0.43-0.85; p=.004). For high vs low PBLC, RR was 29% vs 14%, DCR 76% vs 57%, median DOR 8.2 vs 6.3 months, and median PFS 5.0 vs 3.0 months, respectively. On multivariate analyses, high PBLC remained an independent predictor of increased RR (OR=2.7; p=.01) and DCR (OR=2.6; p=.005), and improved DOR (HR=0.36; p=.04) and PFS (HR=0.60; p=.005). Conclusions: Consistently with preclinical data, these results highlight the potential value of PBLC in predicting tumor response to NGR-hTNF in combination with CT, which merits further clinical validation Clinical trial information: NCT00994097-NCT00484432-NCT00484276-NCT00484211-NCT00483509-NCT00483080-NCT01358071.

Impact of Treatments for Depression on Comorbid Anxiety, Attentional, and Behavioral Symptoms in Adolescents With Selective Serotonin Reuptake Inhibitor–Resistant Depression

To assess the relative efficacy of antidepressant medication, alone and in combination with cognitive behavioral therapy (CBT), on comorbid symptoms of anxiety, attention, and disruptive behavior disorders in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial. Adolescents with selective serotonin reuptake inhibitor (SSRI)-resistant depression (N = 334) were randomly assigned to a medication switch alone (to another SSRI or to venlafaxine) or to a medication switch plus CBT. Anxiety, attention-deficit/hyperactivity disorder (ADHD), and disruptive behavior disorder (DBD) symptoms were assessed by psychiatric interview and self-report at regular intervals between baseline and 24 weeks. The differential effects of medication and of CBT, and the impact of remission on the course of comorbid symptoms and diagnoses, were assessed using generalized linear mixed models. Remission was associated with a greater reduction in scalar measures of anxiety, ADHD, and DBDs, and a greater decrease in the rate of diagnosed anxiety disorders. The correlations between the changes in symptoms of depression on the CDRS-R and anxiety, ADHD, and oppositional symptoms were modest, ranging from r = 0.12 to r = 0.28. There were no significant differential treatment effects on diagnoses, or corresponding symptoms. The achievement of remission had a beneficial effect on anxiety, ADHD, and DBD symptoms, regardless of the type of treatment received. There were no differential effects of medication or CBT on outcome, except for a nonsignificant trend that those adolescents treated with SSRIs showed a greater decrease in rates of comorbid DBDs relative to those treated with venlafaxine. Clinical trial registration information-Treatment of SSRI-Resistant Depression In Adolescents (TORDIA); http://clinicaltrials.gov/; NCT00018902.

Effects of Combined Prednisone + Fluvastatin on Cholesterol and Bilirubin in Pediatric Patients With Minimal Change Nephropathy

BackgroundNephrotic syndrome is associated with hyperlipidemia and low serum bilirubin. Corticosteroids and statins are routinely administered to patients with this syndrome. However, knowledge of the mechanisms that underlie hyperlipidemia is incomplete. ObjectivesThe aim of this study was to compare the effects of prednisone monotherapy with those of prednisone + fluvastatin on lipid, albumin, and bilirubin levels in patients with nephrotic syndrome. MethodsPediatric patients (4–12 years of age) with minimal change nephropathy were consecutively assigned to receive prednisone monotherapy (1–2 mg/kg/d; maximal total dose, ≤60 mg) or prednisone at the same dosage plus fluvastatin (5 mg/d if aged <5 years; 10 mg/d if aged ≥5 years), for 6 weeks. A control group comprised healthy children without evidence of renal, hepatobiliary, cardiovascular, or hematologic disease. Total and direct bilirubin, albumin, triglycerides (TG), total cholesterol (TC), and 24-hour urinary protein (Upr) were determined at baseline (week 0) and at weeks 4 and 6 after the start of therapy. ResultsSixty evaluable patients were assigned active treatment (monotherapy: 16 male, 14 female; mean age, 7.6 [3.6] years [range, 6–12 years]; combination therapy: 15 male, 15 female; mean age, 7.1 [4.9] years [range, 4–12 years]); the control group comprised 50 healthy children (26 male, 24 female). With both prednisone monotherapy and prednisone + fluvastatin, total and direct bilirubin, and albumin were significantly increased from baseline, and TG, TC, and Upr were significantly decreased (all, P < 0.01). There was no significant difference in treatment effect between the 2 treatment groups. Pretreatment total and direct bilirubin levels were significantly lower in the active-treatment groups than in the control group (n = 50) (all, P < 0.01); after treatment, total and direct bilirubin concentrations were increased to levels reported in the control group. Pre- and posttreatment levels of total bilirubin were positively correlated with albumin but negatively correlated with TC. ConclusionsLow blood bilirubin levels appeared to have reduced resistance to oxidative stress and to have contributed to disturbances in lipid metabolism in these pediatric patients with nephrotic syndrome. Prednisone with or without fluvastatin apparently corrected bilirubin levels and reduced blood lipids. There was no apparent additive effect of fluvastatin on lipids. Clinical Trial Registration: ChiCTR-TQR-12002602.

Abstract 9654: Dipeptidyl Peptidase-4 Inhibitors May Reduce the Risk of Major Adverse Cardiovascular Events and All-cause Mortality In Patients With Type 2 Diabetes: Meta-analyses Oof Randomized Controlled Trials

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists, both of which have an incretin effect, represent novel, effective therapeutic approaches to treating hyperglycemia in type 2 diabetes mellitus (T2DM). Their impact on cardiovascular (CV) outcomes, however, is still under investigation. Hypotheses: We assessed the impact of DPP-4 inhibitors and GLP-1 agonists on the risk of a composite of cardiovascular death, myocardial infarction, and stroke (MACE), and on all-cause mortality (ACM) in T2DM. Methods: We searched Medline, EMBASE, and Cochrane Library for randomized controlled trials (RCTs) published up to February 2010 that compared an incretin agent versus usual care, placebo, or other active agents for patients with T2DM, and reported a pre-specified CV outcome. We also searched a major trial registry, FDA and EMEA databases, and contacted authors about unclear CV outcome information. We undertook Der-Simonian and Laird random effect meta-analyses of MACE and all-cause mortality, using inverse-variance weights and continuity correction of 0.005. We excluded total-zero-event trials. We conducted subgroup analyses using a small number of pre-specified hypotheses, including study duration, type of control, treatment mode, and risk of bias. Results: Of 61 eligible trials, data on MACE was available in 33 trials of DPP-4 inhibitors (107 events /24341 patients), and 9 of GLP-1 agonists (12/3745), and ACM in 20 trials of DPP-4 inhibitors (45/17317), and 3 of GLP-1 (3/1404). There was a significant reduction in MACE (RR 0.53, 95% CI 0.33 to 0.85) between DPP-4 inhibitors and control, and a non-significant reduction in ACM (RR 0.46, 95% CI 0.19 to 1.07). No significant differences were found between GLP-1 agonists and control in MACE (RR 0.77, 95% CI 0.13 to 4.61) or ACM (RR 3.53,0 to &gt;999). There was no significant heterogeneity detected in all analyses (p&gt;0.1). Subgroup analyses did not show any significant differences in treatment effect, except that the effect on all-cause mortality differs by treatment mode (monotherapy vs. combination/add-on therapy, interaction p=0.04). Conclusion: DPP-4 inhibitors may reduce the risk of MACE and ACM. The effect of GLP-1 agonists on CV outcomes remains uncertain.

A randomised trial of honey barrier cream versus zinc oxide ointment

In this single-blind multicentre, intervention study, 31 patients with symmetrical intertrigo in large skin folds were included to study the clinical effect of two topical treatments, i.e. standard therapy with zinc oxide ointment versus honey barrier cream. Patients were treated twice daily for 21 days, and the severity of intertrigo was scored in an observation period of 21 days. Patients were used as their own controls by treating symmetrical skin folds, on the left and right side. There was no significant difference in treatment effect between intervention groups. For the majority of patients, both treatments were effective. However, the use of honey barrier cream showed lower pruritus complaints (12.9% versus 29.0%). Honey barrier cream is a suitable alternative in the treatment of intertrigo, and promotes patient comfort.

Effects of rapid maxillary expansion in hyperdivergent patients

This retrospective cohort study was performed to evaluate the skeletal and dental changes in the short and long terms in hyperdivergent patients treated with rapid maxillary expansion and fixed appliances. The sample consisted of 143 patients who had rapid maxillary expansion with a Haas-type expander followed by edgewise therapy. Two groups were established: a normal vertical dimension group (mandibular plane angle >20° and <27°; n = 52) and a hyperdivergent group (mandibular plane angle ≥27°; n = 91). Lateral cephalograms were taken before treatment (average age, 11.5 years in both groups) and after fixed appliance therapy (average age, 14.3 years in both groups). Subjects who exhibited opening or closing in the mandibular plane angle during treatment greater than 1.5° (opening group, n = 23; closing group, n = 26) were followed in the long term (average age, 20.3 years). Longitudinal changes in the different groups were evaluated statistically as well as the prevalence rates of hyperdivergent patients in the opening and closing groups. No significant differences in treatment effects were found in any sagittal or vertical dentoskeletal variables examined. The long-term evaluation of the patients at 5 or more years posttreatment showed no significant skeletal changes. The prevalence rate of hyperdivergent patients in the opening group was not significant. The results of this study indicate that rapid maxillary expansion can be carried out successfully in patients with increased vertical dimensions without detrimental effects on the vertical skeletal relationships. Thus, an increased mandibular plane angle is not a contraindication for rapid maxillary expansion therapy.

PROTOCOL: Nutrition interventions and programs for reducing mortality and morbidity in pregnant and lactating women and women of reproductive age: a systematic review

PROTOCOL: Nutrition interventions and programs for reducing mortality and morbidity in pregnant and lactating women and women of reproductive age: a systematic review

S1-4: Retrospective Analysis of Study EGF30008 by Mass-Spectrometry Based Serum Assay (VeriStrat®).

Abstract Background: In EGF30008 the addition of lapatinib (La) to first-line treatment with letrozole (Le) significantly improved progression-free survival (PFS) in patients (pts) with hormone receptor positive (HR+), HER2 positive (HER2+) metastatic breast cancer (hazard ratio (HR) = 0.71; p=0.019), but not in HR+, HER2 negative (HER2−) pts. This study assessed the ability of VeriStrat (VS), a mass-spectrometry blood-based pretreatment assay correlating with clinical outcome from EGFR-TKI therapy, to stratify pt outcome in EGF30008. The VS assay assigns VS Good (Good), VS Poor (Poor), or Indeterminate labels to a serum sample based on a specific 8-peak signature in the mass-spectra (Taguchi F et al., JNCI 2007). Methods: Blinded to clinical data, pretreatment serum was analyzed using standard VS procedurei. Statistical analyses were performed using Mantel-Haenszel and Cox proportional hazards methods; correlations were evaluated using Fisher's exact and χ2 tests. Results: Of the 1286 pts randomized (HER2+=219; HER2−=952; HER2 unknown=115), 1163 pts had serum available; a VS label was assigned to 1046 pts (961 Good; 80 Poor; 5 Indeterminate); 117 were not evaluable (hemolyzed). In the overall population there was no significant difference in PFS between Good and Poor groups within the Le+La arm (p=0.53). In contrast, PFS of the Good group was longer than that of the Poor group within the Le only arm (HR=0.36, p&amp;lt;0.001) and comparable with that of Good pts within the Le+La arm (median PFS 10.8 mo vs 11.0 mo). An interaction test showed significantly different HRs for PFS in Good vs Poor between treatment arms (p=0.002). In the HER2+ population both Good (n= 169) and Poor (n= 13) groups received significant PFS benefit from addition of La to Le: in Good HR=0.71, p=0.046, medians 3.0 mo (Le) vs 8.0 mo (Le+La); in Poor HR=0.17, p=0.02, medians 2.3 mo (Le) vs 8.6 mo (Le+La). In the HER2− population median PFS for the Poor group (n=58) increased from 3.1 to 11.0 mo (HR=0.57, p=0.068) with addition of La to Le, whereas the Good group (n=702) received no significant benefit, median 13.6 mo on Le and 13.8 mo on Le+La (PFS HR= 0.85, p=0.09). In multivariate analysis VS remained independently significant and predictive of differential treatment effect in the overall population. No significant correlation of VS classification with HER2 status (p=0.35) or prior adjuvant hormonal therapy (p=0.33) was found. VeriStrat was also not significantly correlated with baseline HER2 ECD levels (low &amp;lt;15 ng/ml vs. high ≥15 ng/ml), p = 0.23, or ER expression (H-score:lower quartile:&amp;lt;160 vs. rest), p=0.18. Conclusions: In the overall population VeriStrat predicted PFS in Le alone but not in the Le+La combination, with a significant differential treatment effect. VeriStrat identified a subset of pts with inferior PFS on Le therapy. Adding La to Le improved outcome in HER2+ pts, and interestingly suggested an improvement in the VS Poor subset of HER2− pts. HER2− VS Good pts do not gain benefit with the addition of La. No correlation between VS and investigated predictors of benefit from the addition of La to Le in HER2− pts was observed. If these results can be validated in a prospective study, the addition of La to Le may be a potential treatment option for HER2− HR+ VS poor pts. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S1-4.

Safety and Efficacy of Milk and Molasses Enemas Compared With Sodium Phosphate Enemas for the Treatment of Constipation in a Pediatric Emergency Department

The purpose of this study was to determine the safety and efficacy of routine milk and molasses enemas (MME) compared with sodium phosphate enemas for the treatment of constipation in the pediatric emergency department (ED). A secondary objective included the identification of factors associated with enema selection in the pediatric ED. This study was approved by the University of Texas Southwestern Medical Center Institutional Review Board. The study design was a retrospective comparative chart review. Medical records of patients who presented to the ED and received either MME or sodium phosphate enema for constipation between November 1, 2007, and November 1, 2008, were identified and reviewed for data collection. The following data were collected to determine safety and efficacy: baseline demographics, chief complaint, medical history, radiographic imaging, enema type, treatment dose, adverse effects, improvement in symptoms, time until defecation, failure of initial therapy requiring additional intervention, and time from treatment until disposition. Both treatment groups had similar baseline characteristics. No statistically significant differences in treatment effect were noted between MME and sodium phosphate enemas. Several clinically significant trends were noted including the need for additional rectal treatment after administration of sodium phosphate enemas versus oral therapy after MME. In addition, there were 6 cases of treatment failure with sodium phosphate enemas versus 1 case with MME. No statistically significant differences were found between MME and sodium phosphate enemas. Based on our results, the 2 treatment options were found to be equally safe and effective.

Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk patients with and without metabolic syndrome

Metabolic syndrome (MetS) is a clustering of atherosclerotic coronary heart disease risk factors. This post-hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg in a cohort of 618 high-risk hypercholesterolaemic patients with (n=368) and without (n=217) MetS who had previously been on statin monotherapy. Patients were randomised 1:1 to double-blind ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg for 6 weeks. Least squares mean percent change from baseline and 95% confidence intervals in lipid efficacy parameters were calculated for the population and within subgroups. Treatment with ezetimibe/simvastatin was significantly more effective than rosuvastatin at lowering low-density lipoprotein cholesterol, total cholesterol, non- high-density lipoprotein cholesterol, and apolipoprotein B (all p<0.001). No significant differences in treatment effects were seen between the presence and absence of MetS. In this post-hoc analysis of high-risk hypercholesterolaemic patients the lipid-reducing effects of ezetimibe/simvastatin or rosuvastatin were not altered significantly by the presence of MetS.

Long acting injection versus oral risperidone in first-episode schizophrenia: Differential impact on white matter myelination trajectory

ContextImaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations. ObjectivesExamine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects. DesignTwo groups of SZ subjects (RLAI, N=11; and RisO, N=13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study. Main outcome measureWM volume change scores. ResultsWM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function. ConclusionsThe results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions.

Randomised comparison of the effects of Sprinkles and Foodlets with the currently recommended supplement (Drops) on micronutrient status and growth in Iranian children

Multiple micronutrient supplementation with Sprinkles powder and crushable Foodlets tablets may be effective means of controlling micronutrient deficiencies in infants. Their efficacy has not been tested in countries like Iran where wheat as the staple food may affect nutrient bioavailability. This study aimed to compare the efficacy of Sprinkles, Foodlets and the current supplement (Drops) for improving micronutrient status and growth among Iranian infants. Infants of 6-18 months of age, living in an urban district of Iran were randomised to receive daily Sprinkles (n=120), Foodlets (n=121) or Drops (n=121) for 4 months. Haemoglobin (Hb), serum ferritin, serum retinol, serum zinc, 25(OH) D concentration and anthropometry were assessed at baseline and at 4 months. Iron status improved with all treatments. Drops showed significantly greater changes in Hb and serum ferritin, though changes in anaemia prevalence were not different across groups. Infants having Foodlets and Sprinkles had significantly greater reductions in proportion of children with zinc deficiency compared with Drops. No significant differences in treatment effects were observed for mean serum 25(OH) D and retinol, or for growth of infants across groups. The study was the first efficacy trial with Sprinkles and Foodlets in the Middle East where wheat or rice is the principal complementary foods. Differences across treatment groups were largely consistent with supplement micronutrient composition for iron and zinc, with no benefit in this population for serum retinol, 25(OH) D, growth or anthropometric status. The trial identified trade-offs in combining multiple micronutrients in a single delivery mechanism.