Statistical Difference In Efficacy Research Articles

Sequential therapy with crizotinib and a second-generation ALK inhibitor versus direct therapy of a second-generation ALK inhibitor in ALK-positive advanced lung cancer: a real-world study.

There are few real-world studies in which the efficacy of sequential crizotinib and second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are compared with direct therapy of second-generation ALK TKI in ALK-positive advanced lung cancer. Between May 2014 and October 2022, 211 patients from the Zhejiang Cancer Hospital who harbored ALK rearrangement were analyzed. Of these patients, 115 received crizotinib with sequential second-generation ALK TKIs, and 96 patients received a second-generation ALK TKI directly. The survival analysis of median progression-free survival (PFS), overall survival (OS), and central nervous system time to progression (CNS TTP) in the various groups were calculated using the Kaplan-Meier method and compared by the log-rank test. Of the 211 lung cancer patients with ALK rearrangement, there were no statistical differences in PFS (25.27 vs. 20.47 months, P=0.644) and OS (70.27 months vs. not reached, P=0.991) between the 115 patients in the sequential therapy group and the 96 patients in the direct second-generation group. In the patients with baseline brain metastases at study entry (n=54), the sequential therapy group had a significantly shorter median CNS TTP than the direct second-generation group (10.40 vs. 22.40 months, P=0.040). Multivariate analyses revealed that the prognostic factors for PFS included performance status (PS, P=0.047) and brain metastases (P=0.010). For OS, the prognostic factors included PS (P=0.047) and liver metastases (P=0.021). There was no statistical difference in efficacy between first-generation sequential second-generation ALK TKIs and direct therapy of second-generation ALK TKI regimens. The CNS efficacy of the direct second-generation group was better than that of the sequential therapy group. The prognostic factors for PFS included PS and brain metastases, while the prognostic factors for OS, PS and liver metastases were included.

Comparison of Corneal Densitometry and Visual Quality after Small Incision Lenticule Extraction (SMILE) and Laser Epithelial Keratomileusis (LASEK): One-Year Comparative Study.

To investigate changes in corneal densitometry (CD) and visual quality following small incision lenticule extraction (SMILE) and laser epithelial keratomileusis (LASEK) in patients with mild-to-moderate myopia. A retrospective analysis was performed on 24 and 25 patients (46 eyes each) who underwent SMILE and LASEK, respectively, for mild-to-moderate myopia. The visual quality and CD values were recorded. Using the Pentacam Scheimpflug system, CD values were collected in three concentric optical zones at the depths of the anterior, central, and posterior layers. Efficacy, safety, predictability, corneal wavefront aberrations, and QoV scores were measured to evaluate visual quality. A correlation analysis was performed between changes in CD and clinical characteristics. There were no statistical differences in efficacy and safety indices between the two groups. At 3 months postoperatively, a pronounced reduction in several zones was observed in the LASEK group (p < 0.05), whereas no obvious change was observed in the SMILE group. There were obvious changes in the CD values in several zones in the SMILE and LASEK groups (p < 0.05) after 1 year. The magnitude of the CD changes in the anterior and central corneal layers was smaller in the SMILE group than in the LASEK group (all p < 0.05). Lower HOAs, spherical aberration, and horizontal comas of the anterior and whole corneal surfaces were observed in the SMILE group. QoV scores were similar between the two groups. CD decreased in the SMILE and LASEK groups after 1 year; there was a smaller reduction in SMILE than in LASEK. SMILE and LASEK did not differ significantly in terms of safety and effectiveness in correcting mild-to-moderate myopia.

Outpatient Treatment of Confirmed COVID-19: A Living, Rapid Review for the American College of Physicians.

Clinicians and patients want to know the benefits and harms of outpatient treatment options for SARS-CoV-2 infection. To assess the benefits and harms of 12 different COVID-19 treatments in the outpatient setting. Epistemonikos COVID-19 L·OVE Platform, searched on 4 April 2022. Two reviewers independently screened abstracts and full texts against a priori-defined criteria. Randomized controlled trials (RCTs) that compared COVID-19 treatments in adult outpatients with confirmed SARS-CoV-2 infection were included. One reviewer extracted data and assessed risk of bias and certainty of evidence (COE). A second reviewer verified data abstraction and assessments. The 26 included studies collected data before the emergence of the Omicron variant. Nirmatrelvir-ritonavir and casirivimab-imdevimab probably reduced hospitalizations (1% vs. 6% [1 RCT] and 1% vs. 4% [1 RCT], respectively; moderate COE). Nirmatrelvir-ritonavir probably reduced all-cause mortality (0% vs. 1% [1 RCT]; moderate COE), and regdanvimab probably improved recovery (87% vs. 72% [1 RCT]; moderate COE). Casirivimab-imdevimab reduced time to recovery by a median difference of 4 days (10 vs. 14 median days [1 RCT]; high COE). Molnupiravir may reduce all-cause mortality, sotrovimab may reduce hospitalization, and remdesivir may improve recovery (low COE). Lopinavir-ritonavir and azithromycin may have increased harms, and hydroxychloroquine may result in lower recovery rates (low COE). Other treatments had insufficient evidence or no statistical difference in efficacy and safety versus placebo. Many outcomes had few events and small samples. Some antiviral medications and monoclonal antibodies may improve outcomes for outpatients with mild to moderate COVID-19. However, the generalizability of the findings to the currently dominant Omicron variant is limited. American College of Physicians. (PROSPERO: CRD42022323440).

Efficacy and safety of rituximab biosimilars or reference product as first-line treatment in patients with low-tumour-burden follicular lymphoma: A systematic review and meta-analysis.

The role of rituximab in the first-line treatment of low-tumour-burden follicular lymphoma (LTB-FL) has been supported by a large number of data. However, whether rituximab biosimilars have the same efficacy and safety as the reference drug (MabThera) is still controversial. Electronic databases and the ClinicalTrail.gov website were extensively searched using relevant search criteria. The risk of bias of the included studies was assessed using the RoB 2 assessment scale, and the RevMan 5.4 statistical software was used for meta-analysis. A total of 1223 patients were included in four clinical randomized controlled trials. There was no statistical difference in efficacy between biosimilars and MabThera groups (the objective response rate: RR=1.00, 95% CI: 0.93-1.08, p=0.92; the progression-free survival: RR=1.04, 95% CI: 0.96-1.12, p=0.30; the overall survival: RR=1.00, 95% CI: 0.98-1.03, p=0.76; the serious adverse events: RR=1.15, 95% CI: 0.69-1.89, p=0.59; the infusion-related reaction: RR=0.91, 95% CI: 0.77-1.09, p=0.32). In terms of safety, there was also no significant difference between two groups. Our study concluded that the efficacy and safety of rituximab biosimilars in the treatment of LTB-FL are highly similar to those of the original drug.

Randomised clinical trial: comparison of efficacy and adverse effects of a standard triple clarithromycin-containing regimen with high-dose amoxicillin and bismuth therapy in Helicobacter pylori eradication

The clarithromycin-based triple therapy is the most prescribed Helicobacter pylori eradication regimen in Europe; it causes adverse effects in a significant proportion of subjects, leading to discontinuation. Alternative therapies are required because of increasing clarithromycin resistance or to decrease the adverse effects. We compared the efficacy and spectrum of adverse effects of clarithromycin-based triple therapy with the high-dose amoxicillin/bismuth regimen. A randomised clinical trial enrolled healthy individuals aged 40-64 years. H. pylori was assessed with a 13C-urea breath test. In total 579 H. pylori-positive subjects were randomly allocated in two groups: group 1: clarithromycin 500 mg, amoxicillin 1000 mg, esomeprazole 40 mg, all twice daily; group 2: bismuth subcitrate 240 mg twice daily, amoxicillin 1000 mg three times daily, esomeprazole 40 mg twice daily. Regimens were administered for 14 days.Information on treatment completion and adverse effects were collected via a telephone interview at 21-28 days after medication delivery. The efficacy was assessed by UBT 6 months after the treatment. We analysed 483 subjects for adverse effects (248 vs. 235 respectively). Furthermore, 316 subjects were analysed for efficacy. In per-protocol analysis, a higher efficacy was seen in group 1 (88.4 vs. 77.0%; P < 0.001); no difference was observed in compliance (90.3 and 91.2%). Therapy-related adverse effects were more common in group 1 (56.9 vs. 40.0%; P < 0.01). In intention-to-treat analysis no statistical difference in efficacy was revealed. Bismuth-based high-dose amoxicillin therapy showed a lower efficacy but was less frequently associated with adverse effects. Further research is required to examine the high-dose amoxicillin and bismuth-containing regimens in various populations to maximise eradication efficacy.

Certolizumab pegol in the treatment of psoriasis: Real-life data.

Certolizumab pegol (CZP), the only Fc-free, PEGylated anti-tumor necrosis factor biologic agent. This study aims to investigate the effect and safety of CZP in moderate-to-severe chronic plaque psoriasis. We performed a retrospective observational analysis of the moderate-to-severe psoriasis patients under ceratolizumab pegol therapy. Primer endpoints were efficacy of CZP, defined as statistically significant improvement of Psoriasis Area and Severity Index (PASI), Physician's Global Assessment (PGA), and clinical Disease Activity index for Psoriatic Arthritis (cDAPSA) in the 24 week of therapy. Secondary endpoints were safety of CZP especially during COVID-19 pandemic. Fifty-six moderate-to-severe psoriasis patients treated with CZP were evaluated retrospectively. We observed a rapid and significant reduction of PASI, PGA, and cDAPSA scores in W4. After loading dose, we observed loss of clinical efficacy of CZP in eight patients and optimized therapy by increasing the dosing of CZP. Dose escalation of CZP permitted the achievement and long-term maintenance of clinical improvement in these patients. We compare the clinical efficacy of CZP between naive and patients who has been treated with other biologic agents. There were no statistical differences in efficacy between these two groups. No side effects were observed during CZP treatment. There were no cases of death from COVID-related disease in our study population or patients hospitalized for COVID-19 related disease. Our results demonstrate that CZP is an effective and safe therapeutic option for patients with moderate-to-severe chronic plaque psoriasis.

Effect of CO₂ fractional laser on the early control of scar post-secondary repair in patients with a cleft lip

To observe and compare the clinical efficacy of CO₂ fractional laser in the early control of scar post-secondary repair in patients with a cleft lip. In the treatment group, 43 patients with secondary repair of cleft lip were treated via CO₂ fractional laser. The control group covered 70 patients post-cheiloplasty. The effect in the two groups after six months was compared. The duration from the beginning of the laser treatment to surgery and patient gender were analyzed to determine if they affected the efficacy of the laser treatment for scars. 1) The curative effect in the treatment group was better than that in the control group (P<0.000 1), the total effectiveness rate was 90.7% in the treatment group. 2) No significant statistical difference in efficacy was observed between men and women (P=0.487). Moreover, no significant statistical difference in efficacy (P=0.055) was observed among patients one year after surgery, within the duration of <3 months, and within the duration of ≥3 months. CO₂ fractional laser had a definite effect on the treatment of scar post-secondary repair in patients with a cleft lip. No significant correlation was observed between treatment effect and patient gender, and no difference was noted among patients one year after surgery. In the beginning of the laser treatment, no difference was observed between the durations of <3 months and ≥3 months after the reconstruction, Therefore, early intervention of scars a year after secondary repair of a cleft lip can achieve good results.

Inactivation of Bacillus anthracis and Bacillus atrophaeus spores on different surfaces with ultraviolet light produced with a low‐pressure mercury vapor lamp or light emitting diodes

To obtain quantitative efficacy data of two ultraviolet light (UVC) technologies for surface inactivation of Bacillus anthracis Ames and Bacillus atrophaeus spores. Spores were deposited onto test coupons and controls of four different materials, via liquid suspension or aerosol deposition. The test coupons were then exposed to UVC light from either a low-pressure mercury vapor lamp or a system comprised of light emitting diodes, with a range of dosages. Positive controls were held at ambient conditions and not exposed to UVC light. Following exposure to UVC, spores were recovered from the coupons and efficacy was quantified in terms of log10 reduction (LR) in the number of viable spores compared to that from positive controls. Decontamination efficacy varied by material and UVC dosage (efficacy up to 5·7 LR was demonstrated). There was no statistical difference in efficacy between the two species or between inoculation methods. Efficacy improved for the LED lamp at lower relative humidity, but this effect was not observed with the mercury vapor lamp. This study will be useful in determining whether UVC could be used for the inactivation of B. anthracis spores on different surface types.

P3841Real world outcomes for clopidogrel versus ticagrelor treated patients with acute coronary syndrome: a systematic literature review and meta-analysis

Abstract Introduction The ischemic benefit of ticagrelor over clopidogrel seen in randomized trials has not been fully reproduced in real world cohorts. The discrepancy between these two treatments may be influenced by differences in prescribing. Purpose To provide insights in patient care for patients with high levels of comorbidities. Methods A systematic literature review and meta-analysis were conducted to compare clinical outcomes for clopidogrel vs. ticagrelor in real-world populations with acute coronary syndrome. MEDLINE and Embase were searched from inception to January 2018. Pairwise meta-analyses were performed using unadjusted random-effects models for both outcomes and patient characteristics to test for differences. Heterogeneity was assessed using the I2 statistic. Results The search identified 17 studies for analysis from 1,771 publications (TOTAL N=66,198; CLO N=54,175; TIC N=12,023). Clopidogrel-treated patients were more likely to have diabetes (33% vs. 24%), hypertension (59% vs. 47%), hyperlipidaemia/dyslipidaemia (45% vs. 39%), and prior stroke/transient ischemic attack (TIA) (8% vs. 5%). A slightly higher risk of myocardial infarction (MI) was observed for clopidogrel (4.5% vs. 3.5%; OR 1.29 [1.15–1.46]) and included clopidogrel patients had significantly more comorbidities (Figure 1). No statistical difference between clopidogrel and ticagrelor was found for risk of MACE, defined as the composite of cardiovascular (CV) death, MI or stroke, (13.6% vs. 10.1%; OR 1.41 [95% confidence interval 0.93–2.14]), despite clopidogrel patients having significantly more diabetes and hypertension (p≤0.01). Similarly, the risks of CV death (2.3% vs. 2.1%; OR 1.11 [0.58–2.13]), stroke (1.2% vs. 1.1%; OR 1.11 [0.56–2.17]), and stent thrombosis (1.3% vs. 1.0%; OR 1.34 [0.88–2.06]) were not statistically differentiable, despite clopidogrel patients having significantly more hyperlipidaemia in studies analysed for CV death (p&lt;0.05); significantly more diabetes, hypertension, peripheral arterial disease (PAD), hyperlipidaemia, and prior stroke/TIA in studies analysed for stroke (p&lt;0.05); and significantly more hyperlipidaemia and prior stroke/TIA in studies analysed for stent thrombosis (p&lt;0.01). There were no significant differences in all bleeding events (major or minor, as defined by study) (2.0% vs. 2.7%; OR 0.74 [0.54–1.00]) or major bleeding (2.9% vs. 2.7%; OR 1.07 [0.85–1.33]). Included clopidogrel patients had significantly more diabetes, hypertension, PAD, and prior stroke/TIA (p&lt;0.05). Significant heterogeneity (I2 &gt;60%) was observed for MACE, CV death, stroke and bleeding. Figure 1. Comorbidities in MI Conclusion This analysis suggests clopidogrel-treated patients had more comorbidities than ticagrelor-treated patients, which may introduce a bias with negative impact on their outcomes. Despite this circumstance, with the exception of MI, this analysis showed no statistical difference in efficacy and safety between clopidogrel and ticagrelor. Acknowledgement/Funding This analysis was funded by Sanofi.

Comparison of Induction Chemotherapy Versus Adjuvant Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma Treated with IMRT and Concurrent Cisplatin

To compare the efficacy and toxicities of concurrent chemoradiation (CCRT) with adjuvant chemotherapy (ACT) (CCRT+ACT) versus induction chemotherapy (ICT) plus CCRT (ICT+CCRT) in locally advanced nasopharyngeal cancer (LANPC). Patients with stage III-IVB NPC (7th ed AJCC staging) treated from January 2011 to January 2017 at 3 centers in China were retrospectively reviewed. All patients were treated with IMRT with concurrent cisplatin (80 mg/m2 on day 1, 22, and 43). Three chemo regimens were used in ICT or ACT. They are PF (5 FU 500-750 mg/m2, continuous infusion 1-5 days, cisplatin 25 mg/m2, day 1-3), TP (docetaxel 75 mg/m2, day 1, and cisplatin 25 mg/m2, day 1-3), or TPF (docetaxel 60-75 mg/m2, day 1, cisplatin 20-25 mg/m2, day 1-3, and 5 FU 500-750 mg/m2, continuous infusion 1-5 days). Two to three cycles of chemo were delivered every 21 days. The primary endpoint was overall survival (OS). Secondary endpoints included locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and toxicities. Survivals were calculated with Kaplan-Meier method. The differences between survivals were calculated by Log-rank test. Toxic effects were analyzed using the χ2 test. All statistical tests were two-side. A total of 350 patients were identified and 301 were eligible for analysis. 155 patients were treated with ICT+CCRT and 146 with CCRT+ACT. With a median follow-up of 61.5 months (range:5.81-89.70 months), there was no significant difference between the ICT+CCRT group and CCRT+ACT group in 5-year OS (83.2% vs. 79.5%, p=0.190 ), LRFS (84.7% vs. 83.2%, p=0.486 ) or DMFS (78.9% vs. 74.3%, p=0.119 ). However, in patients with early T-stage and advanced N-stage disease (stage T1-2N2-3), ICT+CCRT significantly improved 5-year OS (84.1% vs. 74.6%, p=0.043) and DMFS (71.4% vs. 60.3%, p=0.039), but not LRFS (93.2% vs. 92.4%, p=0.624). There was no statistical difference in OS, LRFS, and DMFS between two groups in patients with advanced T-stage and early N-stage disease (stageT3-4N0-1) (81.7% vs.76.7%, p=0.535; 77.5% vs.73.3%, p=0.463; 84.0% vs. 79.4%, p=0.452, respectively). In the ICT+CCRT group, 43 patients received PF, 54 TP, and 58 TPF. There were no statistical differences in survivals between different chemo regimens. In the CCRT+ACT group, 83 patients received PF, 61 TP, and 2 TPF. Again, there were no statistical differences in survivals between different chemo regimens. In addition, there were no statistical differences in survivals with the same chemo regimen either it was given before or after CCRT. The grade 3 or 4 adverse events of two groups had no statistical difference in both hematologic and non-hematologic toxicities (P>0.05). There was no statistical difference in efficacy and toxicities between ICT+CCRT versus CCRT+ACT in LANPC. However, ICT+CCRT may be superior in patients with early T-stage and advanced N-stage disease (T1-2N2-3). Randomized trial may be warranted in this patient population.

Efficacy and toxicity of CDK 4/6 inhibitors in breast cancer: Systematic review and meta-analysis of the phase III clinical trials.

e14591 Background: Selective CDK4/6 inhibitors such as palbociclib, abemaciclib, and ribociclib have demonstrated efficacy in advanced HR+/HER2- breast cancer. Drug-related toxicity has been manageable, but variable amongst the drugs. This meta-analysis was conducted to guide CDK inhibitor choice based on efficacy and toxicity. Methods: A systematic literature review of Pubmed, Cochrane Library, and EMBASE was performed in December 2018. Efficacy was evaluated via reported progression free survival (PFS) and pooled hazard ratios (HR). Overall response rate (ORR), treatment discontinuation, and treatment-related adverse events (AEs) were measured via pooled odds ratios (OR). Meta-analyses were performed using random effects modeling and 95% confidence intervals (CI). Results: A pooled analysis of 7 phase III clinical trials (n = 4415) demonstrated a HR of 0.55 (CI: 0.51-0.60) for PFS and an OR of 1.93 (CI: 1.54-2.42) for ORR. First-line treatment trials (n = 3020) pairing CDK 4/6 inhibitors with NSAI/tamoxifen had a HR of 0.56 (CI: 0.51-0.60) for prolonged PFS and an OR of 1.64 (CI: 1.39-1.95) for ORR. Second-line treatment trials (n = 1916) pairing CDK 4/6 inhibitors with fulvestrant had an HR of 0.54 (CI: 0.48-0.61) for prolonged PFS and an OR of 2.48 (CI: 1.57-3.90) for ORR. Palbociclib and ribociclib had similar rates of grade 3/4 AEs, neutropenia, and treatment discontinuation. Abemaciclib had lower rates of grade 3/4 AEs overall, but significantly increased rates of diarrhea and treatment discontinuation due to AEs. Conclusions: Each drug demonstrated a significant improvement in PFS. However, there is no statistical difference in efficacy among the three CDK inhibitors. Treatment decisions can be guided by the tolerability of AEs amongst the medications. Further patient follow-up will illuminate whether there is an OS advantage in this novel drug class. [Table: see text]

Cryoneurolysis in facet joint syndrome management

Objective To assess the clinical usefulness of facet joint cryoneurolysis in patients suffering from back pain of facet origin. Material and methods Twenty nine patients suffering from chronic low back pain > 3 months were consecutively included in this single centre between 2015 and 2018 and 45 cryoneurolysis were performed. The decision to perform cryoneurolysis was made by the operator and based on multiple criteria : clinical history of pain in favour of facet joint pain, imaging data and a positive response to at least one medial block test. The following criteria were noted prior to the procedure : pain location, mean duration of pain prior to denervation, laterality of the pain, and intensity (visual analogic scale (VAS) score 1–10). All cryoneurolysis were performed ambulatory under local anaesthesia and computed tomography (CT) guidance. Sensory and motor stimulation were performed at each treated level and correlated to pain outcome. Follow-up clinical examination was performed at 1, 3, 6 and 12 months after procedure and clinical effectiveness was defined as a 50 % pain decrease on VAS scores. Results A total of 29 patients with a mean age of 60, y.o were included in our study, including 11 men and 18 women. Prior to the procedure, mean VAS score was 7,31/10. A total of 45 procedures were performed and an average of 2 cycles were performed per localisation and per intervention. Thirty out of the 45 procedures performed were considered a success, that is, a global success rate of 66 % percent with a mean pain relief period of 6,8 months. There was no statistical difference in efficacy depending on the sensory stimulation threshold, no correlation was found between threshold evolution during the procedure and procedure success. Conclusion Cryoneurolysis of the medial branch is effective in patient presenting with facet joint pain in 66 % of cases. It should be considered as an alternate tool to alleviate facet joint mediated pain, in accurately selected patients.

Clinical Impact of Pharmacogenetic-Guided Treatment for Patients Exhibiting Neuropsychiatric Disorders: A Randomized Controlled Trial.

Pharmacogenetic testing holds promise as a personalized medicine tool by permitting individualization of pharmacotherapy in accordance with genes influencing therapeutic response, side effects, and adverse events. The authors evaluated the effect on outcomes for patients diagnosed with neuropsychiatric disorders of pharmacogenetics (PGx)-guided treatment compared to usual standard of care. This was a prospective, randomized study of 237 patients at an outpatient community-based psychiatric practice conducted between April 2015 and October 2015. Baseline patient assessments and a buccal swab were collected for pharmacogenetic testing at study initiation. For the experimental group, PGx results were provided to the clinicians as guides to treatment. Control subjects were treated according to the usual standard of care with no clinician reference to their PGx results. Neuropsychiatric Questionnaire (NPQ) and Symbol Digit Coding Test (SDC) scores and adverse drug events, hospitalizations, and medication information were collected at 30, 60, and 90 days. More than half (53%) of patients in the control group reported at least 1 adverse drug event compared to 28% of patients with PGx-guided medication management (P = .001). NPQ and SDC scores improved for both groups, but no statistical difference in efficacy as measured by these assessments was observed within the 90-day observation period. Pharmacogenetic testing may facilitate psychiatric drug therapy with greater tolerability and similar efficacy compared to standard of care. ClinicalTrials.gov Identifier: NCT02411123​​.

Efficacy and tolerability of ADHD medications in a clinical practice

Randomized controlled trials have shown that stimulants reduce symptoms of impulsivity and hyperactivity in children with attention deficit/hyperactivity disorder (ADHD); however, these rigid protocols show no advantage of one medication over another. Our study examined the question of differential efficacy and tolerability of five medications used for ADHD, in the open-label setting of our outpatient child neurology clinic. This retrospective study identified 137 children and adolescents (109 boys and 28 girls), with a mean age of 10 years (range 4 to 19 years) treated for ADHD. Treatment options were amphetamine/dextroamphetamine extended release (adderall XR) in 19.0%, amphetamine/dextroamphetamine (adderall), osmotic controlled-released (OROS) formulation of methylphenidate (OROS-MPH, concerta) in 29.2%, atomoxetine (strattera) in 21.9% and methylphenidate standard release (MPH) in 16.8%. Global effectiveness was assessed for each medication. Overall, 78% of patients improved with medication, with no significant statistical difference in efficacy among the five medications. Side effects included decreased appetite (14.6%), insomnia (10.2%), headaches (7.3%), and tics (3.7%). The only difference in side effects was with atomoxetine showing a significantly lower incidence of headaches than amphetamine/dextroamphetamine XR, amphetamine/dextroamphetamine or OROS-MPH. In conclusion, our results in the open-label setting were comparable to those found in randomized controlled trials; the medications we examined were equally effective with minimal differences in side effect profiles.

One-Year Outcomes of the SAVE Study: Sirolimus as a Therapeutic Approach for UVEitis.

To determine the efficacy and safety of repeated intravitreal and subconjunctival administrations of sirolimus in patients with noninfectious uveitis at 1 year in the Sirolimus as a Therapeutic Approach UVEitis (SAVE) Study. Open-label, prospective, and randomized interventional clinical trial in which 30 patients with noninfectious intermediate, posterior, or panuveitis were randomized 1:1 to receive sirolimus 352-μg intravitreal or 1320-μg subconjunctival. Sirolimus was administered at days 0, 60, and 120. At month 6, all subjects were allowed to receive sirolimus at intervals greater than or equal to 2 months and until month 12. Changes in vitreous haze (VH), visual acuity (VA), and retinal thickness at month 12 were compared with baseline. Of patients with active uveitis at baseline (n = 20), 70% showed greater than or equal to 2 steps reduction of VH at month 12 (P < 0.05), 88% (n = 7) of patients with inactive uveitis at baseline showed either no change or reduction of VH to no haze, 36% (n = 10) of all patients (n = 28) gained greater than or equal to one line of VA, 21% (n = 6) lost greater than or equal to 1 line, and 43% (n = 12) showed no change. At the end of 1 year, no statistical differences in efficacy were found between intravitreal and subconjunctival groups. No serious adverse events were determined to be secondary to sirolimus. Repeated subconjunctival/intravitreal injections of sirolimus appear to be tolerated by patients with noninfectious uveitis over 12 months. Results from the index study suggest that sirolimus may provide benefits to patients with uveitis. Both intravitreal and subconjunctival routes demonstrate similar bioactivity/efficacy. The intravitreal route, however, was better tolerated. The SAVE Study illustrates for the first time the application of local formulations of sirolimus in non-infectious intermediate, posterior, and pan-uveitis. Subconjunctival/Intravitreal sirolimus may help to control inflammation while offering better tolerability/safety profiles than systemic therapies, including immunosuppressants and corticosteroids.

Reply to E.J. Moylan et al

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-38 study was designed to determine whether gemcitabine (G) added to dose-dense paclitaxel (P) following dose-dense doxorubicin and cyclophosphamide (dose-dense AC followed by PG) would improve outcomes in women with node-positive breast cancer relative to both dose-dense AC followed by P and docetaxel (T) AC (TAC).1 Dose-dense AC followed by P had been defined as an optimal adjuvant chemotherapy regimen with a toxicity profile that allowed for the addition of G and represented the conventional control arm for B-38. However, it was recognized that if dose-dense AC followed by PG improved outcomes over dose-dense AC followed by P, questions about the activity of the regimen relative to an optimal T-based regimen would persist, so B-38 included TAC as a second control arm. Inclusion of what were perceived as two optimal adjuvant chemotherapy regimens as controls also provided the opportunity for direct comparison of the two regimens in a large phase III trial. Results showed no benefit with the addition of G and no statistical differences in efficacy between the control regimens. However, toxicity profiles differed; thus, physicians and patients can now choose an anthracycline and taxane regimen based on considerations of schedule and toxicity, not relative efficacy. As Moylan et al2 point out, there was no statistically significant difference between dose-dense therapy and TAC in the estrogen receptor (ER) –positive cohort, which supports our statement regarding these findings. The results from B-38 were analyzed and submitted for publication before results from the referenced Southwest Oncology Group (SWOG) study were reported. Clearly, the use of weekly paclitaxel is an acceptable alternative to the dose-dense schedule of four cycles of paclitaxel, but it may be associated with more neurotoxicity. The meta-analysis by Bonilla et al is not based on data from trials but from a literature review. In fact, the authors stated in the conclusion, “However, additional data from randomized controlled trials are needed before dose-dense therapy can be considered as the standard of care.”3 NSABP B-38 is one such trial, with almost 5,000 patients randomly assigned. Moylan et al express “grave concerns” about the characterization in our study of the control regimens with equivalent efficacy as optimal, inferring that we were advocating for indiscriminant use of these regimens in all patients with node-positive, ER-positive breast cancer. This was clearly not the theme of our discussion. B-38 was designed in 2002, was activated in 2004, and completed accrual in 2007. Perou et al4 first described their intrinsic breast cancer types by unsupervised hierarchical clustering analysis in 2000. The apparent utility of the Oncotype DX recurrence score assay to identify subgroups of patients with ER-positive breast cancer who did not derive benefit from chemotherapy was reported in 2006 by the NSABP in node-negative patients5,6 and by SWOG in 2009 in node-positive patients.7 As a result of these and other studies, it has been increasingly recognized that the degree of benefit a patient receives from chemotherapy depends on the molecular subtype of the tumor. As stated in our discussion, biology must be the most important consideration for the development of future trials. The era of large adjuvant trials that do not consider molecular subtypes has run its course. We agree that many patients with node-positive, ER-positive breast cancer may not require a third-generation adjuvant regimen or need chemotherapy at all. Trials such as RxSPONDER ({type:clinical-trial,attrs:{text:NCT01272037,term_id:NCT01272037}}NCT01272037), which is evaluating the role of chemotherapy in node-positive patients with low Oncotype DX recurrence scores, are needed to determine whether promising predictive markers will be able to define groups of ER-positive patients who will not benefit from chemotherapy. Conversely, we should be recruiting patients with high-risk ER-positive tumors to trials such as SWOG 1207/NSABP B-53 ({type:clinical-trial,attrs:{text:NCT01674140,term_id:NCT01674140}}NCT01674140), which is evaluating the addition of a mammalian target of rapamycin inhibitor to endocrine therapy, rather than continuing to address nuances of chemotherapy.

In vitro activity of ethanolic and water extract of guava leaves at various concentrations against Lactobacillus acidophilus

Introduction: Chemical substances used for prevention of dental caries are known to have many side-effects. Thus, natural products should be explored for their anticaries action. Objectives: To prepare 5% and 20% concentrations of ethanolic and water extracts of guava leaves and to assess their activity against Lactobacillus acidophilus. Materials and Methods: In vitro experimental study was conducted in Department of Biosciences. Ethanolic and water extracts of guava leaves were prepared using Soxhlet extractor. Two concentrations 5% and 20% weight/volume of both extracts were prepared. Test organism L. acidophilus Microbial Type Culture Collection 447 was obtained in lyophillized form. After revival in nutrient broth, bacteria were grown on Lactobacilli de Man, Rogosa, Sharpe agar for further experiment. Antimicrobial testing of extracts was done using Agar well-diffusion method. Ten plates each were prepared for both extracts. Chlorhexidine (0.2%) served as a positive control and distilled water as a negative control. Results: Mean zone of inhibition produced by 5% and 20% ethanolic extract was 11.2 mm and 14.1 mm respectively and by 5% and 20% water extract was 1.6 mm and 5.1 mm respectively. Statistical analysis of results using one-way ANOVA and post-hoc Tukey's test revealed that activity of 5% ethanolic extract and 5%, 20% water extract was significantly less than that of 0.2% chlorhexidine. There was no statistical difference in efficacy of 20% ethanolic extract of guava and 0.2% chlorhexidine (P = 0.270). Conclusion: Ethanolic and water extracts of guava leaves possess antibacterial activity against L. acidophilus with 20% ethanolic extract being as efficacious as 0.2% chlorhexidine.

A Retrospective Study of the Safety and Efficacy of a First-Line Treatment with Modified FOLFOX-4 in Unresectable Advanced or Recurrent Gastric Cancer Patients

Aim: Dismal clinical results in patients with unresectable advanced or recurrent gastric cancer highlight the need for effective systemic chemotherapy. An increase in adverse events associated with systemic chemotherapy is shown in elderly patients, but it remains controversial whether they should receive the same chemotherapy used for younger patients. We retrospectively studied 73 patients with unresectable advanced or recurrent gastric cancer, including 48 nonelderly patients (<65 years old) and 25 elderly patients (≥65 years old) who received a combination of oxaliplatin, 5-fluorouracil and leucovorin (modified FOLFOX-4, mFOLFOX-4 regimen). Patients and Methods: From January 2006 to June 2011, 73 patients with histologically confirmed unresectable advanced or recurrent gastric cancer were enrolled in this study. All patients were treated with an mFOLFOX-4 regimen of 85 mg/m² of oxaliplatin and 200 mg/m² of leucovorin on the first day, followed by a 24-hour continuous infusion of 1,000 mg/m² of 5-fluorouracil in 2 days with a 2-week interval. Treatment continued until disease progression or intolerable adverse events occurred. Results: Overall response rates show clinical efficacy (41.1%, 30/73 patients), stable cancer (26.0%, 19/73 patients) and progressive cancer (32.9%, 24/73 patients). The response rate was 36.0% in the elderly group and 43.8% in the nonelderly group (p = 0.891). In elderly patients, the overall time to progression was 8.1 months and the median overall survival was 11.9 months. On the other hand, in nonelderly patients, the overall time to progression was 7.9 months (p = 0.483) and the median overall survival was 11.2 months (p = 0.953). The results show no statistical differences in efficacy and adverse events between elderly and nonelderly groups (all p > 0.05). Conclusion: The mFOLFOX-4 therapy is an effective and safe first-line treatment for unresectable advanced or recurrent gastric cancer patients. Moreover, mFOLFOX-4 was well tolerated and effective in both nonelderly and elderly patients.

Safety and Efficacy of On-demand Versus Continuous Use of Nonsteroidal Antiinflammatory Drugs in Patients with Inflammatory Arthritis: A Systematic Literature Review

To systematically review the efficacy and safety of on-demand versus continuous use of nonsteroidal antiinflammatory drugs (NSAID) in patients with inflammatory arthritis and to assess if longterm continuous treatment with NSAID in comparison with NSAID treatment on-demand reduces radiographic progression. A systematic literature review was performed in Medline, Embase, the Cochrane Library, and American College of Rheumatology/European League Against Rheumatism 2008-2009 meeting abstracts as part of the multinational 3e (Evidence, Expertise, Exchange) Initiative for generating practical recommendations about Pain Management by Pharmacotherapy in Inflammatory Arthritis. Articles fulfilling predefined inclusion criteria were reviewed and quality appraisal was performed. The search yielded a total of 1410 articles from Medline and Embase, 73 from Cochrane Central, and 3 meeting abstracts. After review, only one study fulfilled the defined inclusion criteria, which indicated that longterm continuous treatment with NSAID versus NSAID treatment on-demand reduced radiographic progression in patients with ankylosing spondylitis. Secondary measured endpoints were disease activity measures including pain and the frequency of observed adverse events in both groups. Relevant adverse events tended to occur more frequently in the continuous treatment group with odds ratios of 2.79 for hypertension, 1.67 for abdominal pain, 1.35 for diarrhea, 0.95 for dyspepsia, and 3.2 for depression. None of these differences were statistically significant, with the exception of depression, which could not be explained. Based on a single study, there does not seem to be a statistical difference in efficacy between the on-demand versus continuous use of NSAID in the context of ankylosing spondylitis. There were no studies in patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. Research is needed to study the risk-benefit ratio of continuous versus on-demand use of NSAID.

SELECT: Randomized phase III study of docetaxel (D) or pemetrexed (P) with or without cetuximab (C) in recurrent or progressive non-small cell lung cancer (NSCLC) after platinum-based therapy.

7502 Background: SELECT investigated whether the addition of C to standard chemotherapy improved progression-free survival (PFS) in patients (pts) with recurrent or progressive NSCLC after failure of platinum-based therapy. Methods: SELECT was a multicenter, open label, randomized phase III trial. Per investigator choice, pts received either P (500 mg/m2) or D (75 mg/m2) on day 1 and then were randomized within each group to chemotherapy plus C (400/250 mg/m2) (initial/weekly) or chemotherapy alone. Therapy was given for up to six 3-week cycles; pts randomized to C continued weekly monotherapy until disease progression or unacceptable toxicity. The primary objective was PFS for PC vs. P as determined by an Independent Review Committee (IRC). Secondary endpoints included overall survival (OS), objective response rate (ORR) and duration of response (DOR) by IRC, and safety. Preplanned subgroup analyses for epidermal growth factor receptor (EGFR) staining intensity by immunohistochemistry and histology were performed. Results for PC vs. P only are presented. Results: Between Jan 2005 and Feb 2010, 938 total pts were randomized. Baseline demographics were comparable between PC (n=301) and P (n=304): median age 64 years; male 60%; Caucasian 88%; KPS 80-100/60-70 84%/16%; squamous/non-squamous 24%/76%. Median PFS (months) PC: 2.89 and P: 2.76 (hazard ratio [HR] =1.03 [95% confidence interval (CI)=0.87-1.21]; p=0.76). Median OS (months) PC: 6.93 and P: 7.79 (HR=1.01 [95% CI=0.86-1.20]; p=0.86). ORR PC: 6.6% and P: 4.3% (odds ratio =1.59 [95% CI=0.78-3.26]; p=0.20). Median DOR (months) PC: 4.17 and P: 6.93 (HR=1.58 [95% CI=0.74-3.36]; p=0.24). There were no statistical differences in efficacy based on histology or EGFR staining intensity. More drug-related AEs/SAEs were observed in the PC arm, with differences mainly attributable to skin toxicities, GI (diarrhea/stomatitis), and hypomagnesemia. Conclusions: The addition of C to P did not improve efficacy in this pt population. Further biomarker analyses are planned. The safety profiles for C and P were consistent with existing data and no new safety signals were observed.