Add-on perceptual learning on refractive amblyopia in children

AIM:To evaluate the visual outcomes of standard amblyopic treatment add-on training via perceptual learning in refractive amblyopic children and to identify the risk factors for treatment failure.METHODS:Retrospective charts were reviewed in children with refractive amblyopia who received standard treatment and add-on Cambridge Visual Stimulator(CAM)training.The add-on CAM group that was enrolled had worn full-corrected glasses for at least 2mo before training.A control group received only the standard treatment.Treatment success was defined as best-corrected visual acuity(BCVA)≥20/25.The age,sex,initial BCVA,refractive errors,sessions and duration of training,and final BCVA were recorded.RESULTS:A total of 209 children(129 children in add-on CAM group and 80 children in control group)were enrolled.Seventy-six percent of unilateral and 87%of bilateral amblyopic children achieved treatment success.In children with unilateral or bilateral moderate amblyopia,the duration to reach BCVA≥20/25 was significantly shorter in add-on CAM group than in control group.Poor initial BCVA(P<0.001)and high astigmatism(P=0.007)were risk factors for treatment failure after add-on CAM training.Age,sex,and types of refractive error were not associated with treatment success.CONCLUSION:Add-on CAM training is an effective strategy for visual improvement and can shorten the treatment course when the effect of standard treatment is limited in amblyopic children.

Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

Allicin as add-on therapy for Helicobacter pylori infection: A systematic review and meta-analysis

BACKGROUND Allicin(2-propene-1-sulfinothioic acid S-2-propenyl ester,diallyl thiosulfinate)extracted from garlic,has proven activity against Helicobacter pylori(H.Pylori)infection.In recent years,clinical trials have explored its utility as an add-on therapy with variable outcomes reported.AIM To perform a systemic review of allicin as an add-on treatment for H.Pylori infection and assess its efficacy in randomized controlled trials(RCTs).METHODS Electronic databases including MEDLINE,EMBASE,the Web of Science,the Cochrane Database,the China National Knowledge Infrastructure Database,Chinese VIP Information Databases,Chinese Medical Databases,and the Wan-Fang Database were searched for keywords including“allicin”,“Helicobacter pylori”,“randomized clinical trials”,and their synonyms.A meta-analysis was performed using the fixed-effects model for low heterogeneity and the randomeffects model for high heterogeneity with sensitivity analysis.Bias was evaluated using Egger’s tests.Trial sequential analysis(TSA)was used to evaluate information size and treatment benefits.The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to assess the level of quality,and studies were classed as“high quality”,“moderate quality”,“low quality”,and“very low quality”.RESULTS A total of eight RCTs consisting of 867 participants(435 from the allicin group and 432 from the control group)were included.Eradication rate in the allicin group(93.33%,406/435)was significantly higher than that of the control group(83.56%,361/432)[I2=0%,odds ratio(OR)=2.75,95%confidence interval(CI):1.74-4.35,P<0.001].The healing rate of ulcers following H.pylori therapy in the allicin group(86.17%,349/405)was significantly higher than that of the control group(75.87%,305/402)[I2=0%,OR=2.05,95%CI:1.39-3.03,P<0.001].The total remission rate of peptic ulcers across all allicin groups was 95.99%,which was significantly higher than that of controls[95.99%(359/374)vs 89.25%(332/372),I2=0,heterogeneity P=0.84,OR=3.13,95%CI:1.51-6.51,P=0.002].No significant differences in side effects were observed.TSA suggested that the trials were of sufficient standard to draw reliable conclusions.The quality of outcomes including eradication rates and side effects was graded as“very low”due to downgrades for“risk of bias”and“indirectness”.Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as"low"due to downgrades for“risk of bias”.CONCLUSION Allicin as an add-on therapy improves H.pylori eradication,healing of ulcers,and remission of symptoms.These results are suggested to be treated with caution due to limited quality.

Add-on therapy of herbal formulation rich in standardized fenugreek seed extract in type 2 diabetes mellitus patients with insulin therapy: An efficacy and safety study

Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract(IND-2) add-on therapy in type 2 diabetes mellitus(T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial.Methods: T2DM patients(n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar(FBS) level between 100-140 mg/dL received IND-2 capsules(700 mg, thrice a day) for 16 weeks.The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16.Secondary end-points include post-prandial blood sugar level, glycosylated Hb(HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks.Safety and adverse events(AEs) were also assessed during the study.Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after addon therapy of IND-2.However, add-on therapy of IND-2 significantly reduced(P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline.Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoproteincholesterol levels were significantly increased(P<0.01) after IND-2 add-on therapy.Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16.Additionally, add-on therapy of IND-2 did not produce any serious adverse events.Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia.Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM.

New endoscopes and add-on devices to improve colonoscopy performance

Colonoscopy is the gold standard for colorectal cancer prevention; however, it is still an imperfect modality. Precancerous lesions can be lost during screening examinations, thus increasing the risk of interval cancer. A variety of factors either patient-, or endoscopist dependent or even the procedure itself may contribute to loss of lesions. Sophisticated modalities including advanced technology endoscopes and add-on devices have been developed in an effort to eliminate colonoscopy's drawbacks and maximize its ability to detect potentially culprit polyps. Novel colonoscopes aim to widen the field of view. They incorporate more than one cameras enabling simultaneous image transmission. In that way the field of view can expand up to 330°. On the other hand a plethora of add-on devices attachable on the standard colonoscope promise to detect lesions in the proximal aspect of colonic folds either by offering a retrograde view of the lumen or by straightening the haustral folds during withdrawal. In this minireview we discuss how these recent advances affect colonoscopy performance by improving its quality indicators(cecal intubation rate, adenoma detection rate) and other metrics(polyp detection rate, adenomas per colonoscopy, polyp/adenoma miss rate) associated with examination's outcomes.

Follow-Up Study of a Multiple Myeloma Patient Successfully Treated with Clarithromycin (CAM), Low-Dose Lenalidomide and Low-Dose Dexamethasone: Significance and Possible Mechanism of Action of CAM as an Add-On Therapy

Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied;but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.

Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets

Schizophrenia is a severe psychiatric disorder characterized by emotional,behavioral and cognitive disturbances, and the treatment of schizophrenia is oftencomplicated by noncompliance and pharmacoresistance. The search for thepathophysiological mechanisms underlying schizophrenia has resulted in theproposal of several hypotheses to explain the impacts of environmental, genetic,neurodevelopmental, immune and inflammatory factors on disease onset andprogression. This review discusses the newest insights into the pathophysiologyof and risk factors for schizophrenia and notes novel approaches in antipsychotictreatment and potential diagnostic and theranostic biomarkers. The currenthypotheses focusing on neuromediators (dopamine, glutamate, and serotonin),neuroinflammation, the cannabinoid hypothesis, the gut-brain axis model, andoxidative stress are summarized. Key genetic features, including small nucleotidepolymorphisms, copy number variations, microdeletions, mutations andepigenetic changes, are highlighted. Current pharmacotherapy of schizophreniarelies mostly on dopaminergic and serotonergic antagonists/partial agonists, butnew findings in the pathophysiology of schizophrenia have allowed theexpansion of novel approaches in pharmacotherapy and the establishment ofmore reliable biomarkers. Substances with promising results in preclinical andclinical studies include lumateperone, pimavanserin, xanomeline, roluperidone,agonists of trace amine-associated receptor 1, inhibitors of glycine transporters,AMPA allosteric modulators, mGLUR2-3 agonists, D-amino acid oxidase inhibitorsand cannabidiol. The use of anti-inflammatory agents as an add-on therapy ismentioned.

Effect of Second-generation Antiepileptic Drugs on Diplopia:A Metaanalysis of Placebo-controlled Studies

Different antiepileptic drugs(AEDs) may cause similar adverse effects,one of which is diplopia.However,the AEDs causing diplopia and the dose-response effect of each drug remains uncertain.In this study,we compared several second-generation AEDs to find out whether they would contribute to the risk of diplopia and their effect-causing dose.A meta-analysis was performed on 19 studies in agreement with our inclusion criteria.The results showed that eight commonly used second-generation AEDs(gabapentin,levetiracetam,oxcarbazepine,lamotrigine,pregabalin,topiramate,vigabatrin and zonisamide) could cause diplopia.The reported odds ratios(ORs) ranged from 1.406 to 7.996.Ranking risks from the highest to the lowest ORs of the eight AEDs of any dose resulted in the following order:use of oxcarbazepine(7.996),levetiracetam(7.472),lamotrigine(5.258),vigabatrin(3.562),pregabalin(3.048),topiramate(2.660),gabapentin(1.966),zonisamide(1.406).Taking into account the ORs above,we can conclude that second-generation AEDs of any dose may cause diplopia.However,the levetiracetam-caused diplopia needs to be further studied according to the data(OR,7.472;95% confidence interval,0.375-148.772).These findings ask for better concerns about patients’ quality of life when giving antiepileptic treatments.

揭开MSN Messenger 5.0糖衣陷阱

随着MSN 8正式登场,Microsoft日前也继而推出MSN Messenger 5.0。或者一些MSN Messenger用户已经急不及待升级了MSN Messenger 5.0。相信用过MSN Messenger 5.0的人,评语就是觉得新版本外观不错,但新功能未见突出。不过,在这个美丽的外表背后,MSN Messenger 5.0原来隐藏了一些“玄机”,甚至会“不利”于用户,就让笔者亲自为大家解剖这套软件,好让大家考虑清楚才决定应否升级吧!

A follow-up study on newer anti-epileptic drugs as add-on and monotherapy for partial epilepsy in China

Background Recently,new anti-epileptic drugs （AEDs） have been more frequently selected to treat epilepsy.In the present study,we evaluated the dynamic changes of efficacy and safety of three newer AEDs for treating partial epilepsy in China.Methods Patients were collected sequentially and were divided into three groups which accepted oxcarbazepine （OXC）,lamotrigine （LTG） or topiramate （TPM） therapy.Each group included monotherapy and add-on therapy subgroups.We followed all patients for one year and recorded the indexes of efficacy and safety in detail.Results A total of 909 patients finished the follow-up observation.No significant difference was found in proportion of patients with 〉 or =50% reduction,〉 or =75% reduction and 100% seizure reduction in the LTG and OXC groups between the first and the second six months.In the TPM group there was a statistical difference between the first and the second six months in proportion of patients with 〉 or =50% reduction （P=-0.002）,〉 or =75% reduction （P 〈0.0001） and 100% seizure reduction （P=0.009） in the monotherapy subgroup,and about 〉 or =75% reduction and 100% seizure reduction in the add-on therapy subgroup （P 〈0.0001）.The efficacy between the add-on and monotherapy subgroups showed a statistical difference.The safety of the three newer AEDs was good.Conclusions The three newer AEDs all showed good efficacy and tolerability for partial epilepsy.And the efficacy can be maintained for at least one year.

SLAP BASH

Wu Zhengqiang walked into a salon in Hangzhou with a free facial care offer-and walked out with a bill for 40,000RMB (5,851USD),after being charged various add-on services A video of his dismayed pout created a meme that would garner over 42 million views,70,000forwards,and comments on Weibo.