Impact of soluble CD26 on treatment outcome and hepatitis C virus-specific T cells in chronic hepatitis C virus genotype 1 infection.

BACKGROUND: Interferon and ribavirin therapy for chronic hepatitis C virus (HCV) infection yields sustained virological response (SVR) rates of 50-80%. Several factors such as non-1 genotype, beneficial IL28B genetic variants, low baseline IP-10, and the functionality of HCV-specific T cells predict SVR. With the pending introduction of new therapies for HCV entailing very rapid clearance of plasma HCV RNA, the importance of baseline biomarkers likely will increase in order to tailor therapy. CD26 (DPPIV) truncates the chemokine IP-10 into a shorter antagonistic form, and this truncation of IP-10 has been suggested to influence treatment outcome in patients with chronic HCV infection patients. In addition, previous reports have shown CD26 to be a co-stimulator for T cells. The aim of the present study was to assess the utility of CD26 as a biomarker for treatment outcome in chronic hepatitis C and to define its association with HCV-specific T cells. METHODS: Baseline plasma from 153 genotype 1 and 58 genotype 2/3 infected patients enrolled in an international multicenter phase III trial (DITTO-HCV) and 36 genotype 1 infected patients participating in a Swedish trial (TTG1) were evaluated regarding baseline soluble CD26 (sCD26) and the functionality of HCV-specific CD8(+) T cells. RESULTS: Genotype 1 infected patients achieving SVR in the DITTO (P = 0.002) and the TTG1 (P = 0.02) studies had lower pretreatment sCD26 concentrations compared with non-SVR patients. Sixty-five percent of patients with sCD26 concentrations below 600 ng/mL achieved SVR compared with 39% of the patients with sCD26 exceeding 600 ng/mL (P = 0.01). Patients with sCD26 concentrations below 600 ng/mL had significantly higher frequencies of HCV-specific CD8(+) T cells (P = 0.02). CONCLUSIONS: Low baseline systemic concentrations of sCD26 predict favorable treatment outcome in chronic HCV infection and may be associated with higher blood counts of HCV-specific CD8(+) T cells.

Management of Pharyngeal Fistulas After Anterior Cervical Spine Surgery: A Treatment Algorithm for Severe Complications.

STUDY DESIGN:: Retrospective database- query to identify all anterior spinal approaches. OBJECTIVES:: To assess all patients with pharyngo-cutaneous fistulas after anterior cervical spine surgery. SUMMARY OF BACKGROUND DATA:: Patients treated in University of Heidelberg Spine Medical Center, Spinal Cord Injury Unit and Department of Otolaryngology (Germany), between 2005 and 2011 with the diagnosis of pharyngo-cutaneous fistulas. METHODS:: We conducted a retrospective study on 5 patients between 2005 and 2011 with PCF after ACSS, their therapy management and outcome according to radiologic data and patient charts. RESULTS:: Upon presentation 4 patients were paraplegic. 2 had PCF arising from one piriform sinus, two patients from the posterior pharyngeal wall and piriform sinus combined and one patient only from the posterior pharyngeal wall. 2 had previous unsuccessful surgical repair elsewhere and 1 had prior radiation therapy. In 3 patients speech and swallowing could be completely restored, 2 patients died. Both were paraplegic. The patients needed an average of 2-3 procedures for complete functional recovery consisting of primary closure with various vascularised regional flaps and refining laser procedures supplemented with negative pressure wound therapy where needed. CONCLUSION:: Based on our experience we are able to provide a treatment algorithm that indicates that chronic as opposed to acute fistulas require a primary surgical closure combined with a vascularised flap that should be accompanied by the immediate application of a negative pressure wound therapy. We also conclude that particularly in paraplegic patients suffering this complication the risk for a fatal outcome is substantial.

A new poly(ortho ester)-based drug delivery system as an adjunct treatment in filtering surgery.

PURPOSE: Pharmacologic modulation of wound healing after glaucoma filtering surgery remains a major clinical challenge in ophthalmology. Poly(ortho ester) (POE) is a bioerodible and biocompatible viscous polymer potentially useful as a sustained drug delivery system that allows the frequency of intraocular injections to be reduced. The purpose of this study was to determine the efficacy of POE containing a precise amount of 5-fluorouracil (5-FU) in an experimental model of filtering surgery in the rabbit. METHODS: Trabeculectomy was performed in pigmented rabbit eyes. An ointmentlike formulation of POE containing 1% wt/wt 5-FU was injected subconjunctivally at the site of surgery, during the procedure. Intraocular pressure (IOP), bleb persistence, and ocular inflammatory reaction were monitored until postoperative day 30. Quantitative analysis of 5-FU was performed in the anterior chamber. Histologic analysis was used to assess the appearance of the filtering fistula and the polymer's biocompatibility. RESULTS: The decrease in IOP from baseline and the persistence of the filtering bleb were significantly more marked in the 5-FU-treated eyes during postoperative days 9 through 28. Corneal toxicity triggered by 5-FU was significantly lower in the group that received 5-FU in POE compared with a 5-FU tamponade. Histopathologic evaluation showed that POE was well tolerated, and no fibrosis occurred in eyes treated with POE containing 5-FU. CONCLUSIONS: In this rabbit model of trabeculectomy, the formulation based on POE and containing a precise amount of 5-FU reduced IOP and prolonged bleb persistence in a way similar to the conventional method of a 5-FU tamponade, while significantly reducing 5-FU toxicity.

Study of the impact of tissue density heterogeneities on 3-dimensional abdominal dosimetry: comparison between dose kernel convolution and direct monte carlo methods.

Dose kernel convolution (DK) methods have been proposed to speed up absorbed dose calculations in molecular radionuclide therapy. Our aim was to evaluate the impact of tissue density heterogeneities (TDH) on dosimetry when using a DK method and to propose a simple density-correction method. METHODS: This study has been conducted on 3 clinical cases: case 1, non-Hodgkin lymphoma treated with (131)I-tositumomab; case 2, a neuroendocrine tumor treatment simulated with (177)Lu-peptides; and case 3, hepatocellular carcinoma treated with (90)Y-microspheres. Absorbed dose calculations were performed using a direct Monte Carlo approach accounting for TDH (3D-RD), and a DK approach (VoxelDose, or VD). For each individual voxel, the VD absorbed dose, D(VD), calculated assuming uniform density, was corrected for density, giving D(VDd). The average 3D-RD absorbed dose values, D(3DRD), were compared with D(VD) and D(VDd), using the relative difference Δ(VD/3DRD). At the voxel level, density-binned Δ(VD/3DRD) and Δ(VDd/3DRD) were plotted against ρ and fitted with a linear regression. RESULTS: The D(VD) calculations showed a good agreement with D(3DRD). Δ(VD/3DRD) was less than 3.5%, except for the tumor of case 1 (5.9%) and the renal cortex of case 2 (5.6%). At the voxel level, the Δ(VD/3DRD) range was 0%-14% for cases 1 and 2, and -3% to 7% for case 3. All 3 cases showed a linear relationship between voxel bin-averaged Δ(VD/3DRD) and density, ρ: case 1 (Δ = -0.56ρ + 0.62, R(2) = 0.93), case 2 (Δ = -0.91ρ + 0.96, R(2) = 0.99), and case 3 (Δ = -0.69ρ + 0.72, R(2) = 0.91). The density correction improved the agreement of the DK method with the Monte Carlo approach (Δ(VDd/3DRD) < 1.1%), but with a lesser extent for the tumor of case 1 (3.1%). At the voxel level, the Δ(VDd/3DRD) range decreased for the 3 clinical cases (case 1, -1% to 4%; case 2, -0.5% to 1.5%, and -1.5% to 2%). No more linear regression existed for cases 2 and 3, contrary to case 1 (Δ = 0.41ρ - 0.38, R(2) = 0.88) although the slope in case 1 was less pronounced. CONCLUSION: This study shows a small influence of TDH in the abdominal region for 3 representative clinical cases. A simple density-correction method was proposed and improved the comparison in the absorbed dose calculations when using our voxel S value implementation.

Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial.

BACKGROUND: The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18-59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. METHODS: We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18-59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. FINDINGS: One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75-86) in the R-ACVBP group and 67% (59-73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38-0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81-91] vs 73% [66-79]; HR 0·48 [0·30-0·76]; p=0·0015) and overall survival (92% [87-95] vs 84% [77-89]; HR 0·44 [0·28-0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3-4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). INTERPRETATION: Compared with standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18-59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic effects of the intensive regimen were raised but manageable. FUNDING: Groupe d'Etudes des Lymphomes de l'Adulte and Amgen.

Addressing current treatment challenges in Crohn's disease in real life: A physician's survey.

BACKGROUND: In recent years several trials have addressed treatment challenges in Crohn's disease. Clinical trials however, represent a very special situation. AIMS: To perform a cross-sectional survey among gastroenterologists on the current clinical real life therapeutic approach focussing on the use of biologics. METHODS: A survey including six main questions on clinical management of loss of response, diagnostic evaluation prior to major treatment changes, preference for anti-tumour necrosis factor (TNF) agent, (de-)escalation strategies as well as a basic section regarding personal information was sent by mail to all gastroenterologists in Switzerland (n=318). RESULTS: In total, 120 questionnaires were analysed (response rate 37.7%). 90% of gastroenterologists in Switzerland use a thiopurine as the first step-up strategy (anti-TNF alone 7.5%, combination 2.5%). To address loss of response, most physicians prefer shortening the interval of anti-TNF administration followed by dose increase, switching the biologic and adding a thiopurine. In case of prolonged remission on combination therapy, the thiopurine is stopped first (52.6%) after a mean treatment duration of 15.7 months (biologic first in 41.4%). CONCLUSIONS: Everyday clinical practice in Crohn's disease patients appears to be incongruent with clinical data derived from major trials. Studies investigating reasons underlying these discrepancies are of need to optimize and harmonize treatment.

Anticonvulsants in the treatment of aggression in the demented elderly: an update

Complex psychopathological and behavioral symptoms, such as delusions and aggression against care providers, are often the primary cause of acute hospital admissions of elderly patients to emergency units and psychiatric departments. This issue resembles an interdisciplinary clinically highly relevant diagnostic and therapeutic challenge across many medical subjects and general practice. At least 50% of the dramatically growing number of patients with dementia exerts aggressive and agitated symptoms during the course of clinical progression, particularly at moderate clinical severity. METHODS: Commonly used rating scales for agitation and aggression are reviewed and discussed. Furthermore, we focus in this article on benefits and limitations of all available data of anticonvulsants published in this specific indication, such as valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin and topiramate. RESULTS: To date, most positive and robust data are available for carbamazepine, however, pharmacokinetic interactions with secondary enzyme induction limit its use. Controlled data of valproate do not seem to support the use in this population. For oxcarbazepine only one controlled but negative trial is available. Positive small series and case reports have been reported for lamotrigine, gabapentin and topiramate. CONCLUSION: So far, data of anticonvulsants in demented patients with behavioral disturbances are not convincing. Controlled clinical trials using specific, valid and psychometrically sound instruments of newer anticonvulsants with a better tolerability profile are mandatory to verify whether they can contribute as treatment option in this indication.

Longer term clinical and virological outcome of sub-Saharan African participants on antiretroviral treatment in the Swiss HIV Cohort Study.

OBJECTIVES: Persons from sub-Saharan Africa (SSA) are increasingly enrolled in the Swiss HIV Cohort Study (SHCS). Cohorts from other European countries showed higher rates of viral failure among their SSA participants. We analyzed long-term outcomes of SSA versus North Western European participants. DESIGN: We analyzed data of the SHCS, a nation-wide prospective cohort study of HIV-infected adults at 7 sites in Switzerland. METHODS: SSA and North Western European participants were included if their first treatment combination consisted of at least 3 antiretroviral drugs (cART), if they had at least 1 follow-up visit, did not report active injecting drug use, and did not start cART with CD4 counts >200 cells per microliter during pregnancy. Early viral response, CD4 cell recovery, viral failure, adherence, discontinuation from SHCS, new AIDS-defining events, and survival were analyzed using linear regression and Cox proportional hazard models. RESULTS: The proportion of participants from SSA within the SHCS increased from 2.6% (<1995) to 20.8% (2005-2009). Of 4656 included participants, 808 (17.4%) were from SSA. Early viral response (6 months) and rate of viral failure in an intent-to-stay-on-cART approach were similar. However, SSA participants had a higher risk of viral failure on cART (adjusted hazard ratio: 2.03, 95% confidence interval: 1.50 to 2.75). Self-reported adherence was inferior for SSA. There was no increase of AIDS-defining events or mortality in SSA participants. CONCLUSIONS: Increased attention must be given to factors negatively influencing adherence to cART in participants from SSA to guarantee equal longer-term results on cART.

Involuntary treatment of alcohol-dependent patients: a study of 17 consecutive cases of civil commitment.

AIM: To investigate the baseline and follow-up characteristics of a group of alcohol-dependent patients being treated under civil commitment. METHODS: This study involved a cross-sectional comparative analysis of baseline characteristics and a follow-up survey of a group of committed alcoholic patients. The study was undertaken in the Alcohol Unit of a 1,000-bed general and university hospital. The study included 17 consecutive cases of civil commitment (representing 15 patients, of whom 2 were committed twice) and a comparative group of 34 randomly selected age- and sex-matched patients. Baseline characteristics of the cases (at the time of commitment) and of patients from the comparative group were collected from medical records, including sociodemographic data, medical condition, patterns of drinking and number and dates of previous treatments for alcohol-related problems. A structured follow-up interview of the cases provided information on their medical condition, social status, patterns of alcohol use, type and duration of residential treatment as well as their perceptions of commitment. RESULTS: During a 4-year period, our Unit referred 23 cases of alcohol-dependent patients (out of 367) to the Guardianship Authority, requesting civil commitment. On 17 occasions, patients were committed to residential treatment, including 2 patients who underwent commitment on two separate occasions, thus representing a total of 15 different patients. In comparison with age- and sex-matched patients seen at the Unit, the cases were characterized by multiple medical, social and psychological alcohol-related impairments. At the time of follow-up, 14 out of 15 patients were alive, among whom 10 agreed to be interviewed. Eight of these reported complete abstinence, whereas 9 considered their alcohol problem as less severe than before. The average duration of commitment was 29 weeks. The majority of patients retrospectively considered the measure as having been justified and useful. The patients' satisfaction with the decision to commit was higher among women than among men. Health-related quality of life at the time of follow-up, as assessed by the MOS 36-Item Short Form Health Survey questionnaire, was good on average and better than that usually reported by other cohorts of alcoholics undergoing treatment. CONCLUSIONS: The usefulness of residential civil commitment of certain severely impaired alcohol-dependent patients is underscored. This study suggests that civil commitment not only may save the lives of endangered patients but could also be a health-promoting measure that may sometimes allow for recovery from dependence. Unexpectedly, this measure was retrospectively well accepted by many patients, who considered the commitment decision as having been justified and useful.

Treatment of brain metastases from non-small cell lung cancer with whole-brain radiotherapy (wbrt) in combination with gefitinib (gft) or temozolomide (tmz): a randomized multicenter phase ii trial of the swiss group of clinical cancer research (sakk #70/03)

BACKGROUND: Patients with BM rarely survive .6 months and are commonly excluded from clinical trials. We aimed at improving outcome by exploring 2 combined modality regimens with at the time novel agents for which single-agent activity had been shown. METHODS: NSCLC patients with multiple BM were randomized to WBRT (10 × 3 Gy) and either GFT 250 mg p.o. daily or TMZ 75 mg/m2 p.o. daily ×21/28 days, starting on Day 1 of RT and to be continued until PD. Primary endpoint was overall survival, a Simon's optimal 2-stage design was based on assumptions for the 3-month survival rate. Cognitive functioning and quality of life were also evaluated. RESULTS: Fifty-nine patients (36 M, 23 F; 9 after prior chemo) were included. Median age was 61 years (range 46-82), WHO PS was 0 in 18 patients, 1 in 31 patients, and 2 in 10 patients. All but 1 patients had extracranial disease; 33 of 43 (TMZ) and 15 of 16 (GFT) had adenocarcinoma histology. GFT arm was closed early after stage 1 analysis when the prespecified 3-mo survival rate threshold (66%) was not reached, causes of death were not GFT related. Main causes of death were PD in the CNS 24%, systemic 41%, both 8%, and toxicity 10% [intestinal perforation (2 patients), pneumonia (2), pulmonary emboli (1), pneumonitis NOS (1), seizure (1)]. We summarize here other patients' characteristics for the 2 trial arms: TMZ (n ¼ 43)/GFT (n ¼ 16); median treatment duration: 1.6 /1.8 mo; Grade 3-4 toxicity: lymphopenia 5 patients (12%)/0; fatigue 8 patients (19%)/2 patients (13%). Survival data for TMZ/GFT arms: 3-month survival rate: 58.1% (95% CI 42.1-73)/62.5% (95% CI 35- 85); median OS: 4.9 months (95% CI 2.5-5.6)/6.3 months (95% CI 2.2- 14.6); median PFS: 1.8 months (95% CI 1.5-1.8)/1.8 (95% CI 1.1-3.9); median time to neurol. progr.: 8.0 months (95% CI 2.2-X)/4.8 (95% CI 3.9-10.5). In a model to predict survival time including the variables' age, PS, number of BM, global QL, total MMSE score, and subjective cognitive function, none of the variables accounted for a significant improvement in survival time. CONCLUSIONS: The combinations of WBRT with GFT or TMZ were feasible. However, in this unselected patient population, survival remains poor and a high rate of complication was observed. Four patients died as a result of high-dose corticosteroids. Preliminary evaluation of cognitive function andQL failed to show significant improvement. Indications and patient selection for palliative treatment should be revisited and careful monitoring and supportive care is required. Research and progress for this frequent clinical situation is urgently needed. Trial partly supported by AstraZeneca (Switzerland), Essex Chemie (Switzerland) and Swiss Federal Government.

Predictors of the Indefinite-Duration Anticoagulation Treatment Strategy In Patients with Cancer Associated Thrombosis

Background: In patients with cancer and acute venous thromboembolism (VTE), current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Methods and results: Among 1'247 patients with acute VTE enrolled in the Swiss Venous Thromboembolism Registry (SWIVTER) from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, and 83 (26%) tumor surgery within 6 months. Patients with cancer were older (66±14 vs. 60±19 years, p<0.001), more often hospitalized at the time of VTE diagnosis (46% vs. 36%, p=0.001), immobile for >3 days (25% vs. 16%, p<0.001), and more often had thrombocytopenia (6% vs. 1%, p<0.001) than patients without cancer. The 30-day rate of VTE-related death or recurrent VTE was 9% in cancer patients vs. 4% in patients without cancer (p<0.001), and the rates of bleeding requiring medical attention were 5% in both groups (p=0.57). Cancer patients received indefinite-duration anticoagulation treatment more often than patients without cancer (47% vs. 19%, p<0.001), and LMWH mono-therapy during the initial 3 months was prescribed to 45% vs. 8%, p<0.001, respectively. Among patients with cancer, prior VTE (OR 4.0, 95%CI 2.0-8.0), metastatic disease (OR 3.0, 95%CI 1.7-5.2), outpatient status at the time of VTE diagnosis (OR 3.8, 95%CI 1.9-7.6), and inpatient treatment (OR 4.4, 95%CI 2.1-9.2) were independently associated with the prescription of indefinite-duration anticoagulation treatment. Conclusions: Less than half of the cancer patients with acute VTE received a prescription for indefinite-duration anticoagulation treatment. Recurrent VTE, metastatic cancer, outpatient VTE diagnosis, and VTE requiring hospitalization were associated with an increased use of this strategy.

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. METHODS: We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). FINDINGS: 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. INTERPRETATION: Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease.

Protective effect and economic impact of insecticide application methods on barley

The objective of this work was to evaluate the protective effect of different forms of insecticide application on the transmission of yellow dwarf disease in barley cultivars, as well as to determine the production costs and the net profit of these managements. The experiments were carried out during 2011 and 2012 growing seasons, using the following managements at main plots: T1, seed treatment with insecticide (ST) + insecticide on shoots at 15-day interval; T2, just ST; T3, insecticide applied on shoots, when aphid control level (CL) was reached; T4, without insecticide; and T5, ST + insecticide on shoots when CL was reached. Different barley cultivars - BRS Cauê, BRS Brau and MN 6021 - were arranged in the subplots. Insecticides lambda cyhalothrin (pyrethroid) and thiamethoxam (neonicotinoid) were used. There were differences on yellow dwarf disease index in both seasons for the different treatments, while damage to grain yield was influenced by year and aphid population. Production costs and net profit were different among treatments. Seed treatment with insecticide is sufficient to reduce the transmission of yellow dwarf disease in years with low aphid population pressure, while in years with larger populations, the application of insecticide on shoots is also required.

Treatment intensification and risk factor control: toward more clinically relevant quality measures.

BACKGROUND: Intensification of pharmacotherapy in persons with poorly controlled chronic conditions has been proposed as a clinically meaningful process measure of quality. OBJECTIVE: To validate measures of treatment intensification by evaluating their associations with subsequent control in hypertension, hyperlipidemia, and diabetes mellitus across 35 medical facility populations in Kaiser Permanente, Northern California. DESIGN: Hierarchical analyses of associations of improvements in facility-level treatment intensification rates from 2001 to 2003 with patient-level risk factor levels at the end of 2003. PATIENTS: Members (515,072 and 626,130; age >20 years) with hypertension, hyperlipidemia, and/or diabetes mellitus in 2001 and 2003, respectively. MEASUREMENTS: Treatment intensification for each risk factor defined as an increase in number of drug classes prescribed, of dosage for at least 1 drug, or switching to a drug from another class within 3 months of observed poor risk factor control. RESULTS: Facility-level improvements in treatment intensification rates between 2001 and 2003 were strongly associated with greater likelihood of being in control at the end of 2003 (P < or = 0.05 for each risk factor) after adjustment for patient- and facility-level covariates. Compared with facility rankings based solely on control, addition of percentages of poorly controlled patients who received treatment intensification changed 2003 rankings substantially: 14%, 51%, and 29% of the facilities changed ranks by 5 or more positions for hypertension, hyperlipidemia, and diabetes, respectively. CONCLUSIONS: Treatment intensification is tightly linked to improved control. Thus, it deserves consideration as a process measure for motivating quality improvement and possibly for measuring clinical performance.