Economic analysis of a multicentre,randomised, phase III trial comparing FOLFOXIRI with FOLFIRI in patients with metastatic colorectal cancer in Greece

ABSTRACT

Introduction: An economic evaluation of the irinotecan, leucovorin, 5-fluorouracil (FOLFIRI) combination versus the irinotecan, oxaliplatin, leucovorin, 5-fluorouracil (FOLFOXIRI) regimen in patients with metastatic colorectal cancer was performed in the context of a randomised phase III study.

Methods: The trial did not find any differences in efficacy and, therefore, a cost-minimisation analysis was undertaken. Treatment cost accounts for the administration of first and second line chemotherapy, for concomitant medications, for laboratory and other examinations and hospitalisations due to treatment side effects. Unit prices used reflect 2006 and are common among NHS hospitals in Greece.

Results: The mean total cost of therapy in the FOLFOXIRI group (€18?344, 95% CI: €16?951–€19?776), was significantly higher than the FOLFIRI group (€12?201, 95% CI: €11?011–€13?427). Mean chemotherapy cost of the FOLFOXIRI group (€9016; 95% CI: €8338–€9669) was significantly higher than that of the FOLFIRI group (€4830; 95% CI: €4435–€5231). The next largest component of cost involves second line drugs, where the average cost per patient was €3306 (95% CI: €2479–€4237) in the FOLFIRI group and €3996 (95% CI: €3196–€4892) in the FOLFOXIRI group. The cost of hospitalisations was €1814 (95% CI: €1672–€1954) in the first group and €2663 (95% CI: €2469–€2859) in the second. The rest of the components represent a small part of the total cost and there are no differences in the two groups.

Conclusion: The combination of irinotecan, leucovorin, 5-fluorouracil has the same effectiveness as the combination of irinotecan, oxaliplatin, leucovorin, 5-fluorouracil in patients with metastatic colorectal cancer, nonetheless it is associated with a much lower overall treatment cost and it should be the preferred treatment regimen in this context.     

Economic implications of using pegfilgrastim rather than conventional G-CSF to prevent neutropenia during small-cell lung cancer chemotherapy

ABSTRACT

Background: For the prevention of chemotherapy-induced febrile aplasia, a single injection of pegfilgrastim per cycle has the same efficacy as six to ten injections of conventional granulocyte colony-stimulating factor (G-CSF). However, there are few data on the economic impact of pegfilgrastim use, especially in the context of small-cell lung cancer.

Methods: This retrospective study involved 31 patients and 129 treatment cycles (32 with pegfilgrastim and 97 with granulocyte colony-stimulating factor (G-CSF)). We estimated the direct costs for preventing and managing febrile aplasia from the payer's perspective and also conducted a willingness-to-pay study with 100 healthy subjects, in order to estimate how highly a single-jab strategy was valued relative to multiple injections.

Results: The costs per cycle were respectively €1743?±?837 and €1466?±?836 for the pegfilgrastim and G-CSF strategies (p?<?0.001). The excess cost of the pegfilgrastim strategy was partly compensated for by the perceived value of the single-jab strategy: 88% of interviewees would prefer the pegfilgrastim strategy; 16% would be willing to pay all the excess cost (€277) and 67% would be willing to pay half the excess cost.

Conclusion: In this willingness-to-pay survey, the excess cost associated with pegfilgrastim relative to other G-CSF-based prophylactic strategies is partly offset by the perceived convenience of a single injection.     

Projected economic impact of clinical findings of generic entry of topiramate on G4 European countries

ABSTRACT

Objectives: To explore the effects of generic substitution of the antiepileptic drug (AED) topiramate (Topamax in Canada; to convert observed Canadian costs into the settings of France, Germany, Italy, and the United Kingdom (UK); and to forecast the economic impact of generic topiramate entry in these four European countries.

Research design and methods: Health claims from Régie de l'assurance maladie du Québec (RAMQ) plan (1/2006–9/2008) and IMS Health data (1998–2008) were used. Patients with epilepsy and ≥2 topiramate dispensings were selected. An open-cohort design was used to classify observation into mutually-exclusive periods of branded versus generic use of topiramate. Canadian healthcare utilization and costs (2007 CAN$/person-year) were compared between periods using multivariate models. Annualized per-patient costs (2007€ or 2007£/person-year) were converted using Canadian utilization rates, European prices and service-use ratios. Non-parametric bootstrap served to assess statistical significance of cost differences. Topiramate market was forecasted following generic entry (09/2009–09/2010) using autoregressive models based on the European experience. The economic impact of generic topiramate entry was estimated for each country.

Results: A total of 1164 patients (mean age: 39.8 years, 61.7% female) were observed for 2.6 years on average. After covariates adjustment, generic-use periods were associated with increased pharmacy dispensings (other AEDs: +0.95/person-year, non-AEDs: +12.28/person-year, p?<?0.001), hospitalizations (?+?0.08/person-year, p?=?0.015), and lengths of hospital stays (+0.51 days/person-year, p?<?0.001). Adjusted costs, excluding topiramate, were CAN$1060/person-year higher during generic use (p?=?0.005). Converted per-patient costs excluding topiramate were significantly higher for generic relative to brand periods in all European countries (adjusted cost differences per person-year: €706–815, p?<?0.001 for all comparisons). System-wide costs would increase from 3.5 to 24.4% one year after generic entry.

Limitations: Study limitations include the absence of indirect costs, possible claim inaccuracies, and IMS data limitations.

Conclusions: Higher health costs were projected for G4 European countries from the Canadian experience following the generic entry of topiramate.     

Patient characteristics,drug adherence patterns,and hypoglycemia costs for patients with type 2 diabetes mellitus newly initiated on exenatide or insulin glargine

ABSTRACT

Objective: Examine real-world effectiveness and hypoglycemia cost burden in patients with type?2 diabetes newly initiated on exenatide or insulin glargine.

Design and methods: Retrospective cohort study describing patient characteristics, drug adherence patterns, and 1-year hypoglycemia rates with associated costs using an administrative claims database. Adult subjects with type?2 diabetes had an initial claim for exenatide or insulin glargine between May?1, 2005 and June?30, 2007, and had continuous eligibility for ≥?6 months pre- and ≥?12 months post-initiation.

Results: The exenatide cohort (n?=?3262) was 53?±?10?years (±SD); 54% female. The insulin glargine cohort (n?=?3038) was 56?±?12?years; 41% female. The mean Deyo-Charlson comorbidity index score was 1.45 for exenatide versus 1.82 for insulin glargine (p?<?0.001). Baseline OAD use rates for exenatide and insulin glargine, respectively, were 77% versus 69% metformin; 47% versus 65% sulfonylurea; 50% versus 49% thiazolidinedione; 56% versus 60% multiple OAD. For patients with two or more pharmacy claims for exenatide or insulin glargine, the 12-month medication possession ratio (MPR) was 68?±?29% for exenatide and 58?±?28% for insulin glargine (p?<?0.001). MPR ≥?80% was higher for exenatide (p?<?0.001) and fewer patients discontinued therapy (p?<?0.001). The probability of a hypoglycemic event was significantly lower for exenatide (p?<?0.005), resulting in lower associated annual costs.

Conclusions: This study provides the first real-world observational comparison of type?2 diabetes patients newly initiated on exenatide or insulin glargine. Exenatide patients had a lower comorbidity burden, better drug adherence, and a lower rate of hypoglycemic events with associated costs. Retrospective database analyses examine medical care utilization in large populations using a relatively inexpensive and expedient approach. However, data are only representative of a commercial health-care plan with limited information on multiple variables usually collected during clinical trials.     

Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway

Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia.

Objective This study examined pretreatment with metformin and activation of AMPK in molecular and behavioral levels associated with memory.

Materials and methods Rats were pretreated with metformin (200?mg/kg) for 2 weeks and 4-vessels occlusion global cerebral ischaemia was induced. Three days after ischaemia, memory improvement was done by passive avoidance task and neurological scores were evaluated. The amount of Brain-Derived Neurotropic Factor (BDNF) and phosphorylated and total P70S6 kinase (P70S6K) were measured.

Results Pretreatment with metformin (met) in the met?+?ischaemia/reperfusion (I/R) group reduced latency time for enter to dark chamber compared with the sham group (p?<?0.001) and increased latency time compared with the I/R group (p?<?0.001). Injection of Compound C (CC) (as an AMPK inhibitor) concomitant with metformin reduced latency time in I/R rats compared with the I/R?+?met group (p?<?0.05). Neurological scores were reduced in met treated rats compared with the sham group. Pretreatment with metformin in I/R animals reduced levels of pro-BDNF compared with the I/R group (p?<?0.001) but increased that compared with the sham group (p?<?0.001). The level of pro-BDNF decreased in the met?+?CC?+?I/R group compared with the met?+?I/R group (p?<?0.01). Pretreatment with metformin in I/R animals significantly increased P70S6K compared with the I/R group (p?<?0.001).

Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.     

Smoking Status and Cost of Illness in Patients with Depressive Disorder Based on the National Health Survey in Spain

Background: Twenty-one percent of subjects with depressive disorder (DD) smoke. This prevalence is expected to be related to healthcare resources utilization (HRU) and sick leave, thereby accounting for substantial costs to the National Health System (NHS) and to society that still need to be characterized. The objective was to estimate cost of illness in patients with DD according to their smoking status. Methods: We used the 2011/2012 National Health Survey to document HRU and lost-workday equivalents (LWDE). Men and women 18+ years old with a DD self-reported to a physician in the past 12?months were categorized into: smokers (daily smokers), former smokers, and never smokers. HRU and LWDE were computed on an annualized basis. Multivariate general linear models adjusted for sex, age, and comorbidities were applied. Results: Data from 1,816 subjects (381 smokers, 290 former smokers, and 1,145 never smokers) were analyzed. Smokers had higher total per patient annual costs (thousands, €3.14), and higher annual healthcare costs (€2.53) than former smokers (€2.35, p?<?.1; and €1.93, p?<?.05) and never smokers (€2.42, p?<?.05; and €2.06, p?<?.1): with excess costs of €0.79 and €0.72 for total annual costs and €0.60 and €0.47 for annual healthcare costs (p?=?.029 and p?=?.056, respectively). Conclusions: Smoking DD subjects were associated with higher HRU and costs from both the societal and healthcare perspectives, when compared with former and never smokers in the Spanish general population. Supporting people with DD to quit smoking might therefore be a value-for-money health policy in Spain.     

Artemisia pallens alleviates acetaminophen induced toxicity via modulation of endogenous biomarkers

Abstract

Context: Acetaminophen (APAP) leads to severe hepatic and renal necrosis and thus causes significant clinical problems. Artemisia pallens Walls ex D.C. (Asteraceae) possesses various pharmacological properties such as antidiabetic, antioxidant, analgesic, and anti-inflammatory activity.

Objective: The objective was to evaluate the protective effects of Artemisia pallens methanol extract (APME) in APAP-induced hepatic and nephro-toxicity.

Materials and methods: The methanolic extract of aerial parts of Artemisia pallens (APME) was prepared. Toxicity was induced in male Wistar rats (180–220?g) by administration of APAP (700?mg/kg, p.o., 14?d). APME (100, 200, and 400?mg/kg, p.o.) was administered to rats 2?h before APAP oral administration. Various biochemical and molecular parameters along with histopathological aberration were studied in the kidney and liver of rats.

Results: Pretreatment with APME (200 and 400?mg/kg, p.o.) significantly (p?<?0.01 and p?<?0.001) decreased aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, blood urea nitrogen (BUN), and serum creatinine as compared with APAP-treated rat. Decreased level of serum albumin, serum uric acid, and HDL were significantly (p?<?0.01 and p?<?0.001) restored by APME (200 and 400?mg/kg, p.o.) pre-treatment. Administration of APME (200 and 400?mg/kg, p.o.) significantly (p?<?0.01 and p?<?0.001) reduced the elevated level of cholesterol, LDL, LDH, triglyceride, and VLDL. It also significantly (p?<?0.01 and p?<?0.001) restored the altered level of hepatic and renal antioxidant enzymes (superoxide dismutase (SOD) and glutathione (GSH)). The increased level of malondialdehyde (MDA) and nitric oxide (NO) in hepatic as well as renal tissue was significantly (p?<?0.01 and p?<?0.001) decreased by APME (200 and 400?mg/kg, p.o.) administration. Histological alternation induced by APAP in liver and kidney was also reduced by the APME (200 and 400?mg/kg, p.o.) pre-treatment.

Conclusion: It is concluded that the methanol extract of Artemisia pallens alleviates APAP induced in rats toxicity through its antioxidative and anti-inflammatory actions.     

Effect of curcumin in mice model of vincristine-induced neuropathy

Abstract

Context: Curcumin exhibits a wide spectrum of biological activities which include neuroprotective, antinociceptive, anti-inflammatory, and antioxidant activity.

Objective: The present study evaluates the effect of curcumin in vincristine-induced neuropathy in a mice model.

Materials and methods: Vincristine sulfate (0.1?mg/kg, i.p. for 10 consecutive days) was administered to mice to induce neuropathy. Pain behavior was assessed at different days, i.e., 0, 7, 10, and 14?d. Sciatic nerve total calcium, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), nitric oxide (NO), and lipid peroxidation (LPO) were also estimated after the 14th day of study. Pregabalin (10?mg/kg, p.o.) and curcumin (15, 30, and 60?mg/kg, p.o.) were administered for 14 consecutive days.

Results: Curcumin at 60?mg/kg significantly attenuated the vincristine-induced neuropathic pain manifestations in terms of thermal hyperalgesia (p?<?0.001) and allodynia (p?<?0.001); mechanical hyperalgesia (p?<?0.001); functional loss (p?<?0.001); and in the delayed phase of formalin test (p?<?0.001). Curcumin at 30 and 60?mg/kg exhibited significant changes (p?<?0.001) in antioxidant levels and in total calcium levels in vincristine-injected mice.

Conclusion: Curcumin at 30 and 60?mg/kg dose levels significantly attenuated vincristine-induced neuropathy which may be due to its multiple actions including antinociceptive, calcium inhibitory, and antioxidant effect.     

Epidemiology,clinical and economic outcomes of admission hyponatremia among hospitalized patients

ABSTRACT

Background: Hyponatremia, the most frequent electrolyte derangement identified among hospitalized patients, is associated with worsened outcomes in patients with pneumonia, heart failure and other disorders.

Research design and methods: We performed a retrospective cohort study of hospitalized patients to quantify the attributable influence of admission hyponatremia on hospital costs and outcomes. Data were derived from a large administrative database with laboratory components, representing 198,281 discharges from 39 US hospitals from January 2004 to December 2005. Hyponatremia was defined as admission serum [Na⁺]?<?135?mEq/L.

Results: The incidence of hyponatremia at admission was 5.5?%?(n?=?10,899). Patients with hyponatremia were older (65.7?±?19.6 vs. 61.5?±?21.8, p?<?0.001) and had a higher Deyo-Charlson Comorbidity Index score (1.8?±?2.1 vs. 1.3?±?1.8, p?<?0.001) than those with normal [Na⁺]. A higher proportion of hyponatremic patients required intensive care unit (ICU) (17.3?%?vs. 10.9?%?, p?<?0.001) and mechanical ventilation (MV) (5.0?%?vs. 2.8?%?, p?<?0.001) within 48?hours of hospitalization. Hospital mortality (5.9?%?vs. 3.0?%?, p?<?0.001), mean length of stay (HLOS, 8.6?±?8.0 vs. 7.2?±?8.2 days, p?<?0.001) and costs ($16,502?±?$28,984 vs. $13,558?±?$24,640, p?<?0.001) were significantly greater among patients with hyponatremia than those without. After adjusting for confounders, hyponatremia was independently associated with an increased need for ICU (OR 1.64, 95?%?CI 1.56–1.73) and MV (OR 1.68, 95?%?CI 1.53–1.84), and higher hospital mortality (OR 1.55, 95?%?CI 1.42–1.69). Hyponatremia also contributed an increase in HLOS of 1.0 day and total hospital costs of $2,289.

Conclusions: Hyponatremia is common at admission among hospitalized patients and is independently associated with a 55?%?increase in the risk of death, substantial hospital resource utilization and costs. Potential for bias inherent in the retrospective cohort design is the main limitation of our study. Studies are warranted to explore how prompt normalization of [Na⁺] may impact these outcomes.     

The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines

Abstract

Context: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment.

Objective: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action.

Materials and methods: Mice treated acutely with PC (25, 50, or 100?mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30–180?min), carrageenan-induced pleurisy (4?h), and tail-flick test (1–8?h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence.

Results: PC reduced (p?<?0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE₂. PC decrease total leukocyte migration (100?mg/kg: p?<?0.01), neutrophils (50 and 100?mg/kg: p?<?0.05 and 0.001), and TNF-α (25, 50, and 100?mg/kg: p?<?0.01, 0.05, and 0.001, respectively), besides reducing NO production (p?<?0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p?<?0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p?<?0.001) the number of c-Fos-immunoreactive neurons in PAG.

Discussion and conclusion: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.     

FOLFOX与XELOX方案治疗晚期结直肠癌毒性表现的系统评价

目的 系统评价氟尿嘧啶/亚叶酸钙联合奥沙利铂（FOLFOX方案）与卡培他滨联合奥沙利铂（XELOX方案）治疗晚期结直肠癌毒性差异,为晚期结直肠癌＂个体化＂药物治疗方案选择提供依据。方法 检索PubMed、Embase、Cochrane、CNKI等数据库和ASCO会议文献,采用系统评价的方法进行系统评价。结果共10个研究4084例患者纳入毒性的系统评价,结果 表明XELOX方案在手足综合症（RR=3.60,95%CI：2.27~5.72,P〈0.0001）、血小板减少（RR=1.83,95%CI：1.36~2.48,P〈0.0001）发生率高于FOLFOX方案,在中性粒细胞减少（RR=0.24,95%CI：0.14~0.41,P〈0.0001）发生率低于FOLFOX方案;恶心、呕吐、腹泻以及神经毒性发生率两方案无统计学差异。结论 在晚期结直肠癌治疗中,FOLFOX方案与XELOX方案在毒性反应方面各有特点,应结合患者具体情况,选择最宜治疗方案。     

Effects of pioglitazone on metabolic control and blood pressure: a randomised study in patients with type 2 diabetes mellitus

SUMMARY

Aim: This Swiss multicentre study examined the efficacy and safety of oral pioglitazone in patients with type 2 diabetes.

Methods: Patients were randomised to pioglitazone at once-daily doses of 30mg for 20 weeks (n?=?76), 30?mg for 12 weeks followed by 45?mg for 8 weeks (n?=?74), or 45?mg for 20 weeks (n?=?84); 94.9% of patients completed 12 weeks and 88.9% completed all 20 weeks. Almost all (96.6%) patients received pioglitazone in combination with other anti-diabetic treatments.

Results: Mean HbA1c at baseline was 8.8?±?1.2%, and changes to endpoint were ?1.1?±?1.1%, ?1.1?±?1.4% and ?0.9?±?1.6%, respectively for the three dose groups (p?<?0.001 for each group). Triglyceride concentrations decreased in each group and the overall mean change during the study was ?0.58?mmol/l (p?<?0.001 versus baseline). HDL-cholesterol increased, with an overall mean change of 0.10?mmol?l^?1 (p?<?0.001 versus baseline). Blood pressure decreased from baseline, particularly for hypertensive patients with mean changes: systolic -10mmHg, p?<?0.001, diastolic-8mmHg, p?<?0.001 versus baseline. Serum alanine aminotransferase and γ-glutamyl transferase concentrations were significantly (p?<?0.001 for each) reduced during the study.

Conclusions: The study demonstrates the efficacy of pioglitazone 30?mg?day^?1 and 45?mg?day^?1 in the treatment of type 2 diabetes, with an improved lipid profile and decreased blood pressure in addition to improved glycaemic control.     

Prevention of arsenic-mediated reproductive toxicity in adult female rats by high protein diet

Abstract

Context: The detrimental effects of arsenic on female reproductive functions may involve overt oxidative stress. Casein and pea [Pisum sativum Linn. (Fabaceae)] proteins have antioxidant properties.

Objective: To investigate the role of casein- and pea-supplemented high-protein diet (HPD) in utero-ovarian protection from arsenic toxicity.

Materials and methods: Adult female Wistar rats were orally gavaged with vehicle (Gr-I) or arsenic at 3?ppm/rat/d (Gr-II and Gr-III) for 30 consecutive days, when they were maintained on either regular diet containing 18% protein (Gr-I and Gr-II), or HPD containing 27% protein in the form of casein (20%) and pea (7%) (Gr-III). Reproductive functions were evaluated using a battery of biochemical and histological techniques.

Results: As compared to Gr-I, the Gr-II rats suffered from loss of estrous cyclicity, reduction in weight (mg/100?g body weight) of ovary (Gr-I: 54.3?±?4.2 versus Gr-II: 35.8?±?1.6; p?<?0.001) and uterus (Gr-I: 161.7?±?24.6 versus Gr-II: 94.44?±?13.2; p?<?0.05), utero-ovarian degeneration, attenuated ovarian activities (unit/mg tissue/h) of Δ⁵, 3β-hydroxysteroid dehydrogenase (Gr-I: 3.41?±?0.12 versus Gr-II: 2.31?±?0.09; p?<?0.01) and 17β-hydroxysteroid dehydrogenase (Gr-I: 3.82?±?0.57 versus Gr-II: 1.24?±?0.19; p?<?0.001), and decreased serum estradiol level (pg/ml) (Gr-I: 61.5?±?2.06 versus 34.1?±?2.34; p?<?0.001). Ovarian DNA damage was preponderant with blatant generation of malondialdehyde (nM/mg tissue; Gr-I: 15.10?±?2.45 versus Gr-II: 29.51?±?3.44; p?<?0.01) and attenuated superoxide dismutase activity (unit/mg tissue) (Gr-I: 2.18?±?0.19 versus Gr-II: 1.33?±?0.18; p?<?0.05). The Gr-III rats were significantly protected from these ill effects of arsenic.

Discussion and conclusion: HPD, by way of antioxidant properties, may find prospective role in the protection of reproductive damage caused by arsenic.     

A cost-minimisation analysis comparing moxifloxacin with levofloxacin plus ceftriaxone for the treatment of patients with community-acquired pneumonia in Germany: results from the MOTIV trial

ABSTRACT

Objective: This study presents a cost-minimisation analysis of moxifloxacin compared to combination treatment with levofloxacin and ceftriaxone in patients hospitalised with community-acquired pneumonia (CAP) in Germany.

Research design and methods: In the MOTIV study, 738 adult patients with CAP requiring hospitalisation and initial parenteral antibiotic therapy were randomised to sequential IV/oral therapy with either moxifloxacin (n?=?368), or levofloxacin and ceftriaxone (n?=?365). The primary effectiveness endpoint was the proportion of patients demonstrating clinical improvement 5–7 days after the completion of study treatment. Subgroup analysis considered patients with severe CAP according to pneumonia severity index (PSI) risk class IV and V, microbiologically proven infection, a history of chronic obstructive pulmonary disease, and a history of cardiovascular disease. The analysis included the cost of study medication, hospital stay, readmission and inpatient procedures and diagnostics. Event frequency in the study was multiplied by German unit costs to estimate per-patient expenditure. The analysis was conducted from a hospital perspective. Sensitivity analysis investigated the effect of costing from an insurer perspective.

Results: No significant difference was found in the percentage of successfully treated patients. Average per patient cost was €2190 for the moxifloxacin group, and €2619 for the levofloxacin + ceftriaxone group (difference –€430, 95% CI: –€138, –€740; p?<?0.05). Variability in total costs was wide, with some patients accruing up to €18?000. Medication cost was significantly lower with moxifloxacin than levofloxacin + ceftriaxone (–€470, 95% CI: –€522, –€421), and accounted for between 15 and 30% of total costs.

Conclusions: In this analysis of patients hospitalised with CAP in Germany, treatment with moxifloxacin was significantly less costly than treatment with levofloxacin and ceftriaxone.     

24-hour bronchodilator efficacy of single doses of indacaterol in subjects with COPD: comparison with placebo and formoterol

ABSTRACT

Objective: To assess the bronchodilator efficacy, safety and tolerability of indacaterol, a novel, once-daily inhaled β₂-agonist bronchodilator, in patients with chronic obstructive pulmonary disease (COPD).

Methods: This crossover, double-blind, double-dummy study was conducted to evaluate the 24-h bronchodilator effect of a range of single doses of indacaterol (150?µg, 300?µg and 600?µg), given in the morning via single-dose dry powder inhaler (SDDPI) in subjects with COPD, compared with placebo and with the daily therapeutic dose of formoterol (two 12?µg doses 12?h apart, via an SDDPI). Tolerability and safety were also assessed.

Results: Fifty-one subjects with moderate-to-severe COPD received each of the five treatments on separate study days in randomised sequence. The 24-h trough FEV₁ (primary endpoint; mean [95%?CI]) was 1.46 (1.43, 1.49)?L with indacaterol 600?µg (p?<?0.001 vs. placebo, p?<?0.01 vs. formoterol, p?<?0.05 vs. indacaterol 150?µg), 1.45 (1.42, 1.48)?L with indacaterol 300?µg (p?<?0.001 vs. placebo, p?<?0.05 vs. formoterol), 1.42 (1.39, 1.45)?L with indacaterol 150?µg (p?<?0.001 vs. placebo), 1.41 (1.38, 1.43)?L with formoterol (p?<?0.001 vs. placebo) and 1.28 (1.25, 1.31)?L with placebo. All treatments were well tolerated and there was little effect on serum potassium, blood glucose or QTc interval.

Conclusion: All doses of indacaterol were effective in providing 24-h bronchodilation and were well-tolerated in subjects with COPD. The bronchodilator efficacy of indacaterol (150, 300 and 600?μg) at 24?h post-dose was at least as efficacious as formoterol 12?µg twice daily.     

The impact of a worksite migraine intervention program on work productivity,productivity costs,and non-workplace impairment among Spanish postal service employees from an employer perspective

SUMMARY

Background: Migraine is associated with a significant productivity loss to employers, who may benefit from making a migraine intervention available to their employees.

Objective: To evaluate changes in migraine-related productivity and non-workplace impairment associated with a migraine intervention program from the employer perspective.

Methods: This was a pre-test post-test study of Spanish Postal Service employees with migraine. The intervention consisted of counseling from occupational health physicians and rizatriptan 10?mg for symptomatic treatment of two subsequent migraine headaches. Physicians also prescribed additional medications for migraine prophylaxis, treatment of tension headaches, and rescue medications. Migraine-related work loss and non-workplace impairment (interference with daily and social activities) were self-reported at baseline (pre-intervention) and separately following each migraine headache (post-intervention) with the aid of a diary. Migraine-related work loss was reported as work loss due to absenteeism, reduced productivity while at work, and the sum of the two (total lost work day equivalents [LWDE]). An employer perspective was taken for the cost analysis, and thus productivity costs were the only costs considered.

Results: A total of 436 patients comprised the population for analysis. The number of migraine-related LWDE per migraine attack were 0.48 days per migraine headache in the month before the intervention, decreasing to 0.20 days and 0.07 days per migraine headache during the first and second migraine headaches following the intervention (^?p?<?0.0001 vs. baseline). Total migraine-related productivity costs per migraine headache were €34/patient before the intervention, decreasing to €14/patient and €5/patient during the first and second headaches following the intervention (?p < 0.0001).

Non-workplace activity impairment was also significantly reduced (?p < 0.0001) following the intervention. The main limitations of the study were the lack of a parallel control group and the potential for differential recall bias between the usual care and the intervention periods. In addition, the results may not be generalizable to other employers or other countries.

Conclusion: This study documents the value of a workplace migraine intervention program, which focused on migraine prevention and rizatriptan-based symptomatic treatment. It also highlights the important role occupational health clinics can play in helping employers and employees reduce the burden of migraine.     

Association between cigarette consumption and academic achievement in Korean adolescents

Aims: The purpose of this study was to examine whether smoking frequency and cigarette consumption are related to academic achievement in Korean adolescents. Method: Data from the Seventh Korea Youth Risk Behavior Web-based Survey (KYRBWS-VII) administered in 2011 were analyzed; 75,643 adolescents from the first year of middle school through the third year of high school participated in the survey. We used multivariate logistic regression analysis to investigate the association in question after adjusting for variables such as age, body mass index, frequency of drinking, frequency of breakfast consumption, parents’ education level, family economic status, mental stress and the frequency of vigorous physical activity (PA), moderate PA and muscular strength exercises. Results: The odds ratios (ORs) for achieving average or higher academic achievement in boys compared with those who never smoked and stratified by the frequency of smoking were as follows: 1–2 day(s) per month, 0.594 (p?<?0.001); 3–5 days per month, 0.571 (p?<?0.001); 6–9 days per month, 0.529 (p?<?0.001); 10–19 days per month, 0.472 (p?<?0.001); 20–29 days per month, 0.491 (p?<?0.001) and every day, 0.342 (p?<?0.001). For girls, the ORs for achieving average or higher academic achievement compared with those who never smoked and stratified by the frequency of smoking were as follows: 1–2 day(s) per month, 0.482 (p?<?0.001); 3–5 days per month, 0.409 (p?<?0.001); 6–9 days per month, 0.648 (p?=?0.037); 10–19 days per month, 0.723 (p?=?0.032); 20–29 days per month, 0.543 (p?<?0.001) and every day, 0.433 (p?<?0.001). The ORs in boys for achieving average or higher academic achievement compared with those who never smoked and stratified by cigarette consumption were as follows: <1 cigarette per day, 0.656 (p?<?0.001); 1 cigarette per day, 0.541 (p?<?0.001); 2–5 cigarettes per day, 0.446 (p?<?0.001); 6–9 cigarettes per day, 0.375 (p?<?0.001); 10–19 cigarettes per day, 0.281 (p?<?0.001) and ≥20 cigarettes per day, 0.340 (p?<?0.001). For girls, the ORs for achieving average or higher academic achievement compared with those who never smoked and stratified by cigarette consumption were as follows: <1 cigarette per day, 0.550 (p?<?0.001); 1 cigarette per day, 0.507 (p?<?0.001); 2–5 cigarettes per day, 0.549 (p?<?0.001); 6–9 cigarettes per day, 0.356 (p?<?0.001); 10–19 cigarettes per day, 0.353 (p?<?0.001) and ≥20 cigarettes per day, 0.729 (p?=?0.242). Conclusion: There are certain indicators that smoking negatively influences educational achievement in Korean adolescents. To improve academic achievement, it is recommended that adolescents do not smoke.     

Antiallergic effect of piperine on ovalbumin-induced allergic rhinitis in mice

Abstract

Context: Allergic rhinitis (AR) is a global health problem that affects a large number of population. Piperine (PIP) has been reported to exhibit anti-inflammatory, anti-histaminic, and immunomodulatory activities; however, its antiallergic profile has not been studied.

Objective: The objective of the study was to investigate the antiallergic potential of PIP in ova-albumin (OVA)-induced AR, mast cell degranulation (MSD), and OVA-induced paw edema.

Materials and methods: Mice were sensitized with OVA alternately on 1, 3, 5, 7, 9, 11, and 13th day. They were treated with either vehicle, PIP (10, 20, and 40?mg/kg, p.o.), or montelukast (10?mg/kg, p.o.) from the 14th to 20th day. On the 21st day, intranasal (OVA: 5% µl) challenge was done. Animals were evaluated for physiological parameters, biochemical parameters, spleen weight, expression of interleukins (IL-6 and IL-1β), and immunoglobin-E (IgE). Histopathology of nasal mucosa, lungs, and spleen was carried out. MSD and paw edema studies were made to understand the mechanism of action.

Results: PIP (10, 20, and 40?mg/kg, p.o.) showed a significant dose-dependent protection with respect to nasal rubbing, redness of nose, and sneezing (p?<?0.001) following nasal challenge. PIP dose dependently reduced histamine, NO concentration (p?<?0.001), as well as reduced expression of IL-6, IL-1β, and IgE (p?<?0.001) as compared with the control group. Histopathology showed inhibition of infiltration of eosinophils and hyperplasia. It dose dependently reduced MSD and paw edema (p?<?0.001).

Discussion and conclusion: PIP acts by mast cell-stabilizing activity, exhibits immunomodulatory and anti-inflammatory activity, thereby providing an effective treatment for AR.     

Possible involvement of nitric oxide in antidepressant-like effect of silymarin in male mice

Abstract

Context: Silymarin (SM) is extracted from milk thistle Silybum marianum L. [Asteraceae (Compositae)] and known for antioxidative and anti-inflammatory effects.

Objective: The potential antidepressant-like effect of acute SM and possible involvement of nitric oxide (NO) were determined in male mice.

Material and methods: SM was administered orally (5, 10, 20, 50, 100, and 200?mg/kg; p.o.) 60?min before the tests. After assessment of locomotor activity, the immobility time was measured in forced swimming test (FST) and tail suspension test (TST). To assess the possible involvement of NO, a non-specific NO synthase inhibitor, l-NAME (10?mg/kg, i.p.), and a specific iNOS inhibitor, aminoguanidine (AG) (50?mg/kg, i.p.), were administered separately 30?min before SM (20 and 100?mg/kg).

Results: SM at its effective doses 10, 20, 50, and 100?mg/kg decreased the immobility time in a dose-dependent manner (p?<?0.01, p?<?0.05, p?<?0.05, and p?<?0.001, respectively) in FST. SM (10, 20, 50, and 100?mg/kg) also lowered the immobility measure dose dependently in TST (p?<?0.01, p?<?0.05, p?<?0.01, and p?<?0.001, respectively). In addition, 50% of maximum response (ED₅₀) of SM was around 10?mg/kg. The dose 100?mg/kg proved the most effective dose in both the tests. Further, this effect was not related to changes in locomotor activity. Moreover, l-NAME reversed the effect of SM (20 and 100?mg/kg) in FST and SM (100?mg/kg) in TST. However, AG did not influence this impact.

Conclusion: The antidepressant-like effect of SM is probably mediated at least in part through NO and SM may increase NO tune.