Add-on Group Research Articles

Demographic and clinical characteristics of patients with type 1 diabetes mellitus initiating sodium-glucose cotransporter 2 inhibitors in Japan: A real-world administrative database analysis

AimsTo investigate the baseline demographic and clinical characteristics of patients with type 1 diabetes mellitus (T1DM) newly treated with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) as an add-on to insulin, or treated with insulin alone or in combination with oral anti-diabetic drugs other than an SGLT2i. MethodsRetrospective study using data from the JMDC database (December 21, 2018, to October 31, 2020). Included patients with T1DM treated with an SGLT2i (add-on to insulin) (n = 1027) or with insulin (n = 4320). Baseline demographic and clinical characteristics were summarized, and change in insulin dose and efficacy outcomes, including hemoglobin A1c (HbA1c) and body mass index (BMI), before and after the first SGLT2i or insulin prescription were evaluated. ResultsThe SGLT2i add-on group had higher HbA1c and BMI than the insulin group. Daily insulin doses decreased from immediately before to after the first SGLT2i prescription. HbA1c and BMI improved from baseline to after the first SGLT2i prescription. ConclusionsThis large real-world study reported the baseline demographic and clinical characteristics of patients with T1DM newly treated with an SGLT2i in Japan. The findings may guide the appropriate use of SGLT2i and support large-scale database studies in T1DM research.

MO972: Impact of Inhibition of Pcsk-9 Among Renal Transplant Recipients with High Cardiovascular Risk

Abstract BACKGROUND AND AIMS Monoclonal antibodies inhibiting proprotein convertase subtilisin/Kexin type A(PCSK-9) have emerged as one of the new cholesterol-lowering agents. It is not evaluated among renal transplant recipients despite its favorable safety profile. We aimed to evaluate the safety and efficacy of evolocumab in reducing lipids and cardiovascular events among risky renal transplant recipients. METHOD About 195 kidney transplant recipients—with high cardiovascular risk (>20)—were enrolled in this randomized controlled study during the period between 6.2017 and 6.2018. Patients who received statin and evolocumab (140 mg/2 weeks, group 1, n = 97) while those who were maintained on statin alone comprised group 2 (n = 98). They were followed up for 24 months. RESULTS The two groups were comparable regarding their demographics (P > 0.05). Before enrollment in the study, post-transplant complications were comparable apart from a higher prevalence of NODAT in group 2 (P = 0.033). Smokers were significantly more prevalent in group 1. Basal graft function was significantly higher in group 1 despite equivalent regimen of immunosuppression in both groups (P > 0.05). Clinically two groups were comparable concerning cardiovascular events and both graft and patient outcomes (P > 0.05). Basal cholesterol was significantly higher in group 1 (5.5 versus 4.7, P < 0.001) which dropped significantly after 3 months (versus12 months in group 2) and thereafter (P = 0.031). We observed that triglycerides in the two groups were comparable (P > 0.05) till the end of the study. CONCLUSION Evolocumab is a promising add on lipid-lowering agent. In high risk renal transplant, earlier reduction of cholesterol was observed in the add-on evolocumab group but without significant positive cardiovascular impact.

The Post-COVID 19 long term surveillance study sequel to an add-on Ayurveda regimen

It has been 18 months now since the world-wide outbreak of COVID 19 (Corona Virus Disease 19) and still the ongoing research is being done for disease specific medicines. During June 2020 to August 2020, an attempt was made to explore if an add-on Ayurveda regimen comprising of Dasamoolkadutrayadi Kashayam and Guluchyadi Kwatham in tablet forms can be prescribed along with standard of care; which has established the clinical evidence that there is advantage of accelerated symptomatic recovery, early discharge from hospital, reducing the duration of hospital stay. After informed consent the patients were followed up over 9 months after discharged from hospital. The purpose of the present extended study was to find the impact of disease even though patients were discharged after appropriate treatment and if there were any late effects in the add-on Ayurveda treatment group after 9 months as it was one of the first few formal studies world-wide; since there was no long term follow up data available.The study concluded that no additional late effects or symptoms or complications which were known in Post COVID phase; were observed in study group who received the add-on Ayurveda regimen as compared to the control group with conventional standard of care.

Risk Assessment in Pulmonary Arterial Hypertension (PAH): Insights from the Inspire Study with LIQ861

<h3>Purpose</h3> The objective of this analysis was to assess for risk status improvement in PAH patients receiving inhaled dry powder treprostinil (LIQ 861) in the INSPIRE study. <h3>Methods</h3> INSPIRE was a Phase 3, open-label, multicenter study of WHO Group I PAH patients to evaluate the long-term safety and tolerability of LIQ861. Patients with New York Heart Association functional class (NYHA FC) II or III were transitioned to LIQ861 after receiving a stable dose of Tyvaso® for ≥3 months (Transition) or were started on LIQ861 as prostacyclin-naïve patients in addition to background therapy with an ERA and/or PDE5i. Transition patients received an initial dose of LIQ861 that was comparable to their Tyvaso® dose. Add-On patients initiated LIQ861 at a dose of 26.5 mcg 4 times/day. Dose increments in both groups were by 26.5 mcg as tolerated and as per the treating physicians' discretion. Three risk variables (NYHA FC, 6MWD and NT-pro BNP) were measured at baseline and during LIQ861 treatment. The percent of patients who achieved low-risk (NYHA FC: I-II; 6-minute walk distance (6MWD) >440m; N-terminal pro-brain natriuretic peptide (NT-pro BNP) <300ng/liter) were assessed at Baseline, Month 2, Month 4, and Month 8 in Transition, Add-On, and Overall Groups. <h3>Results</h3> A total of 121 patients were enrolled (55 Transition; 66 Add-On) in the trial. Overall, 51% of patients met 2 or 3 low risk variables at Baseline (n=120). At Month 2 (n=103), Month 4 (n=99) and Month 8 (n=91) there were 65%, 63% and 76% of patients who met 2 or 3 low risk variables respectively (Figure 1). Overall, a larger percentage of patients met 2 or 3 PAH low-risk variables at Month 8 than at Baseline. The percentage of patients increased from 51% at Baseline to 76% overall, and the shift was more pronounced in the Add-On Group (from 42% to 73%) than the Transition Group (62% to 79%). <h3>Conclusion</h3> In WHO group 1 PAH patients, LIQ861 was shown to improve risk stratification using the French non-invasive criteria.

An open labeled, randomized, controlled clinical study to evaluate the efficacy of Torchnil capsules and Febcin tablet as add-on therapy for Covid-19 patients

ObjectivesThis study was conducted to evaluate the efficacy and safety of Cap. Torchnil & Tab. Febcin when given as add-on therapy to Covid19 positive patients with moderate disease. Material and methodsFollowing written informed consent, patients were randomized to receive Cap. Torchnil & Tab. Febcin in addition to standard of care (SOC) [Add-on Group] or only SOC [SOC Group] for 14 days. Effect on clinical symptoms, WHO Clinical Assessment scale, hospital stay duration, time to Covid negative report, Sp02 levels and biomarkers was assessed during admission and relapse rate, if any, post discharge for 3 months. Results193 patients were screened and 150 completed the study, 77 in Add-on Group and 73 in SOC Group. Improvement in Covid related symptoms, WHO Assessment scale, time to covid negative report and duration of hospital stay was observed earlier in Add-on Group. Statistically significant fall in biomarker levels viz. CPK, D-dimer and IL-6 values at Day 14 and LDH levels at Days 7 & 14 was observed in Add-on Group. Improvement in Sp02 levels was also seen earlier in Add-on Group. Only 2 patients complained of acidity. Post discharge, 91 patients (49 from Add-on group and 42 from SOC group) came for physical visits. All these patients were clinically stable with no evidence of relapse. ConclusionThe study results thus showed that Cap. Torchnil and Tab. Febcin were effective and safe when given as add-on therapy to SOC in the clinical management of patients with moderate Covid-19 disease.

AYUSH-64 as an adjunct to standard care in mild to moderate COVID-19: An open-label randomized controlled trial in Chandigarh, India

ObjectiveTo determine the therapeutic efficacy and safety of AYUSH-64 as an add-on to standard care in mild to moderate COVID-19. Design setting, and interventionsThis open-label randomized controlled parallel-group trial was conducted at a designated COVID care centre in India in 80 patients diagnosed with mild to moderate COVID-19 and randomized into two groups. Participants in the AYUSH-64 add-on group (AG) received AYUSH-64 two tablets (500 mg each) three times a day for 30 days along with standard conventional care. The control group (CG) received standard care alone. Main outcome measuresProportion of participants who attained clinical recovery on day 7, 15, 23 and 30, proportion of participants with negative RT-PCR assay for COVID-19 at each weekly time point, change in pro-inflammatory markers, metabolic functions, HRCT chest (CO-RADS category) and incidence of Adverse Drug Reaction (ADR)/Adverse Event (AE). ResultsOut of 80 participants, 74 (37 in each group) contributed to the final analysis. Significant difference was observed in clinical recovery in the AG (p < 0.001 ) compared to CG. Mean duration for clinical recovery in AG (5.8 ± 2.67 days) was significantly less compared to CG (10.0 ± 4.06 days). Significant improvement in HRCT chest was observed in AG (p = 0.031) unlike in CG (p = 0.210). No ADR/SAE was observed or reported in AG. ConclusionsAYUSH-64 as adjunct to standard care is safe and effective in hastening clinical recovery in mild to moderate COVID-19. The efficacy may be further validated by larger multi-center double-blind trials.

Effect of Dapagliflozin in Combination with Lobeglitazone and Metformin in Korean Patients with Type 2 Diabetes in Real-World Clinical Practice.

PurposeThis study aimed to evaluate the efficacy and tolerability of dapagliflozin as an add-on or a switch therapy to lobeglitazone plus metformin (MFM) in Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice.Materials and MethodsThe study included 109 patients who started dapagliflozin as add-on or switch therapy to lobeglitazone plus MFM. The primary outcome was a change in glycated hemoglobin (HbA1c) level from baseline after 12 months of treatment. Secondary outcomes included changes in fasting plasma glucose (FPG), lipid profiles, body weight, visceral fat area (VFA), and blood pressure after 12 months of treatment.ResultsThe baseline HbA1c was 8.3±1.3% (8.7±1.5% in the add-on group and 8.1±1.0% in the switch group). After 12 months, mean HbA1c decreased (-0.91%) in all patients (p<0.05) (-1.39% in the add-on group and -0.63% in the switch group). Significant reductions in FPG were also observed in both the add-on and switch groups (-54.37 mg/dL and -24.68 mg/dL, respectively). Overall, there was a significant improvement in serum triglyceride (-24.74 mg/dL), low density lipoprotein cholesterol (-7.92 mg/dL), body weight (-2.98 kg), VFA (-9.00 cm2), and systolic blood pressure (-8.67 mm Hg). Approximately 35.8% of patients achieved HbA1c <7.0% after 12 months.ConclusionDapagliflozin, as an add-on or a switch therapy to lobeglitazone plus MFM, can be a suitable alternative for Korean patients with inadequately controlled T2DM. The combination therapy resulted in significant reductions in HbA1c levels, body weight, and blood pressure.

Home training with or without joint mobilization compared to no treatment: a randomized controlled trial.

[Purpose] To investigate if joint mobilization in patients with subacromial pain syndrome has additional benefits to a home training program on shoulder function and pain, and to compare home training to no physical therapy. [Participants and Methods] Eighty-nine primary care patients (mean age 45 years) with subacromial pain syndrome during an average of 23 weeks. Home training was performed twice a day during a 12 week period. One of the intervention groups received add-on shoulder joint mobilization to the home training. A third group did not receive any physical therapy. Constant-Murley score, pain and active range of motion was evaluated at baseline, 6 weeks, 12 weeks and 6 months. [Results] The total Constant-Murley score revealed no significant differences between groups at any time point. All groups improved over time. The add-on joint mobilization group reached clinical important change at 12 weeks. The subscale pain showed that both intervention groups reported less pain after 12 weeks compared to the reference group. [Conclusion] Home training is not superior to no treatment evaluated with the total Constant-Murley score. However, home training with or without add-on joint mobilization may decrease pain compared to no treatment.

Efficacy of omarigliptin, once-weekly dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes.

BACKGROUNDOmarigliptin is one of several once-weekly dipeptidyl peptidase-4 inhibitors (DPP-4is). Despite the high frequency of switching from various daily DPP-4is to omarigliptin in actual clinical practice, data regarding its efficacy in patients with type 2 diabetes (T2D) after switching are limited.AIMTo analyze the efficacy of omarigliptin in Japanese patients with T2D who had previously received treatment with other glucose-lowering agents.METHODSForty-nine T2D patients treated for the first time with omarigliptin were recruited retrospectively and divided into four groups defined as either add-on or switched from daily DPP-4is: switched from linagliptin, switched from sitagliptin, and switched from vildagliptin. During a 3-mo follow-up, the clinical parameters among these groups were assessed and compared, with the impact of the switch on glycemic variability as measured by continuous glucose monitoring also being evaluated in the switched groups.RESULTSHemoglobin A1c levels saw a significant decrease of -0.32% ± 0.41% in the add-on group (P = 0.002). However, the other groups’ variables depended on the pre-switch daily DPP-4i: switched from linagliptin, -0.05% ± 0.22%; switched from sitagliptin, -0.17% ± 0.33%; and switched from vildagliptin, 0.45% ± 0.42%, which saw significant worsening (P = 0.0007). Multivariate logistic regression analysis revealed that switching from vildagliptin to omarigliptin was independently associated with worsening glycemic control (P = 0.0013). The mean and standard deviation of sensor glucose value, the mean amplitude of glycemic excursions, and the mean of daily difference significantly improved when switching the patient from either linagliptin or sitagliptin to omarigliptin. However, in patients switched from vildagliptin, not only did the glucose variability indices see no improvements, the mean of daily difference even underwent significant worsening.CONCLUSIONAdministering omarigliptin as add-on therapy or switching to it from sitagliptin and linagliptin, but not vildagliptin, improves glycemic control and thus should help in decision making when selecting DPP-4is for T2D patients.

Efficacy of vibegron in patients with overactive bladder: Multicenter prospective study of real-world clinical practice in Japan, SCCOP study 19-01.

To evaluate the efficacy and safety of vibegron in patients with overactive bladder (OAB) in real-world clinical practice in Japan. This multicenter, prospective, non-controlled study consecutively enrolled patients with OAB determined by an OAB symptom score (OABSS) of three points or more and a question 3 (urgency) score of two points or more. A total of 212 patients from 43 institutions were recruited from January 2019 through March 2020. Vibegron, 50 mg, was administrated daily for 8 weeks as first-line monotherapy (first-line group, FL), monotherapy switching from antimuscarinics (post-antimuscarinic group, PA) or mirabegron (post-mirabegron group, PM) and combination therapy with antimuscarinics (add-on group). The OABSS was collected at baseline and every 2 weeks. Adverse events were recorded at every visit. Of the 212 patients registered, 188 (male 76, female 112) were eligible for analysis (124 in the FL group, 27 in PA, 29 in PM, and eight in the add-on group). The add-on group was excluded from further analysis due to its small number. The OABSS (mean ± SD) showed significant improvement in all groups (FL; 8.8± 2.5, 3.8± 2.8, PM; 9.4± 2.2, 4.5± 4.0, PM; 8.9± 2.5, 4.7± 3.3 at 0 and 8 weeks, respectively). The overall incidence of adverse events was 25%. No grade 3 or higher adverse events were observed. In the real-world clinical setting, vibegron is effective and well-tolerated by OAB patients, including those switching therapy from antimuscarinics and mirabegron.

Effect of valproate and add-on levetiracetam on inflammatory biomarkers in children with epilepsy

BackgroundContemporary research indicates the role of neuroinflammation/inflammatory markers in epilepsy. In addition, comorbidities such as anxiety and poor health-related quality of life are vital concerns in clinical care of pediatric patients with epilepsy. This open-label, prospective, observational study evaluated the effect of valproate and add-on levetiracetam on serum levels of C–C motif ligand 2 (CCL2) and Interleukin-1 beta (IL-1β) in pediatric patients with epilepsy. We also studied effect of valproate and add-on levetiracetam on anxiety and health-related quality of life (HRQoL) in specified age subgroups. MethodsChildren aged 1 to 12 years, diagnosed with epilepsy (generalized or focal seizures), treated with valproate (n = 40) and valproate with add-on levetiracetam (n = 40) were included. All patients were followed up for 16 weeks and assessed for changes in serum CCL2 and IL-1β levels. Spence Children Anxiety Scale short version (SCAS-S) and QOLCE-16 scales were used to measure anxiety and HRQoL, respectively, in specific age groups. ResultsThe serum CCL2 level decreased significantly (p < .001) from 327.95 ± 59.07 pg/ml to 207.02 ± 41.50 pg/ml in the valproate group and from 420.65 ± 83.72 pg/ml to 250.06 ± 46.05 pg/ml in the add-on levetiracetam group. Serum IL-1β level did not change significantly in both groups. Spence Children Anxiety Scale short version scores were decreased and QOLCE-16 scores were increased significantly (p < .001) in both valproate and add-on levetiracetam groups. ConclusionsThe results of our study suggest that valproate and levetiracetam led to decrease serum CCL2 levels without any change in serum IL-1β levels in children with epilepsy. Anti-inflammatory property of valproate and levetiracetam might underlie their antiepileptic effect and CCL2 could be a potential marker of drug efficacy in epilepsy. Also, valproate and levetiracetam reduced anxiety and improved quality of life in children with epilepsy in the age groups evaluated.

Effect of febuxostat on left ventricular diastolic function in patients with asymptomatic hyperuricemia: a sub analysis of the PRIZE Study

Hyperuricemia is related to an increased risk of cardiovascular events from a meta-analysis and antihyperuricemia agents may influence to cardiac function. We evaluated the effect of febuxostat on echocardiographic parameters of diastolic function in patients with asymptomatic hyperuricemia as a prespecified endpoint in the subanalysis of the PRIZE study. Patients in the PRIZE study were assigned randomly to either add-on febuxostat treatment group or control group with only appropriate lifestyle modification. Of the 514 patients in the overall study, 65 patients (31 in the febuxostat group and 34 in the control group) who had complete follow-up echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e′) at baseline and after 12 and 24 months were included. The primary endpoint was a comparison of the changes in the E/e′ between the two groups from baseline to 24 months. Interestingly, e′ was slightly decreased in the control group compared with in the febuxostat group (treatment p = 0.068, time, p = 0.337, treatment × Time, p = 0.217). As a result, there were significant increases in E/e′ (treatment p = 0.045, time, p = 0.177, treatment × time, p = 0.137) after 24 months in the control group compared with the febuxostat group. There was no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive troponin I between the two groups during the study period. In conclusions, additional febuxostat treatment in patients with asymptomatic hyperuricemia for 24 months might have a potential of preventable effects on the impaired diastolic dysfunction.

A randomised controlled trial of effectiveness and safety of Niclosamide as add on therapy to the standard of care measures in COVID-19 management

BackgroundCOVID-19 pandemic has ignited the urge for repurposing old drugs as candidate antiviral medicines to treat novel challenges of viral infections. Niclosamide (NCS) is an anti-parasitic drug of known antiviral potential. Therefore, this study attempts to investigate the antiviral effect and safety of NCS on SARS-CoV-2 caused COVID-19 patients. MethodsRandomized controlled open label clinical trial encompassed 75 COVID-19 patients treated with standard of care plus NCS were included as experimental group and 75 COVID-19 patients treated with only standard of care therapy as control group. Survival rate, time to recovery, and side effects were the main endpoints for the assessment of the therapeutic effect and safety of NCS. ResultsNo significant difference between the two study groups in the incidence of death Vs recovery within 30 days of follow up(p = 1).Median survival time to cure in the NCS addon group was significantly less than controls (5 Vs 7days, Log rank p = 0.005).All the recoveries took place within 20 days in the NCS add on group, which is 10 days shorter than that in the controls (30 days), NCS add on treatment increased the risk of cure by 60% per day compared to control group (adjusted HR = 1.6,p = 0,007) after adjusting for the count of comorbidities. Additionally, two or more comorbidities reduced the risk of cure to 33% (p < 0.001).Male gender increased the risk of cure by 42% (p = 0.046). Older age group decreased the risk of recovery per day to 0.58 and 0.53 for 50–59 and 60+ years of age. Hyypertension (HT) and diabetes mellitus (DM) significantly reduced the risk of being cured per day to 0.56 (p = 0.003)and 0.65 (p = 0.039) respectively. No significant signals of safety in NCS add on therapy compared to control group. Conclusionadding NCS to the standards of care measures increased the risk of the cure and had shorter time to stay in the hospital compared with controls., male gender increased the risk of cure, while older patients>40 years, HT, and DM decreased the risk of cure. Also, NCS add on therapy was relatively safe; hence, NCS is of clinical benefit for freeing hospital beds for more patients in pandemic crisis.

P82. Limited bend out of proximal thoracic curve is associated with add on phenomenon following posterior surgery for Lenke 1A curves

<h3>BACKGROUND CONTEXT</h3> Add-on phenomenon following posterior surgery for Lenke 1A curves has been studied and lowest instrumented vertebra (LIV) selection, skeletal immaturity, and L4 right vertebral tilt have been identified as risk factors. To minimize the risk, LIV has been recommended to be set at the last substantially touched vertebra (LSTV); however, add-on phenomenon has been observed even when LIV was set at LSTV and immediate postop X-rays showed minimal residual curve. To study the possible causes in this scenario, we can keep LIV consistently at or immediately adjacent to LSTV and compare characteristics between curves with and curves without add-on phenomenon. <h3>PURPOSE</h3> To study risk factors for add-on phenomenon while keeping LIV consistently at or immediately adjacent to LSTV. <h3>STUDY DESIGN/SETTING</h3> Case control study, single institution. <h3>PATIENT SAMPLE</h3> We identified 21 consecutive patients who had Lenke 1A curves, preop upper thoracic bending X-rays, and minimum of 2 year follow-up from patients who underwent posterior scoliosis surgery at a single institution from 2006 to 2017. <h3>METHODS</h3> We used billing records to identify patients who underwent posterior scoliosis surgery from 2006 to 2017 at a single institution. From the 21 patients who met our criteria, we obtained age at presentation and at time of surgery from medical records. The main thoracic curve (MT), proximal thoracic curve (PT), and PT bend out Cobb angle, % PT correction on bend out = (PT - PT on bend out)/PT, Risser stage, and L4 tilt were determined from preop X-rays. Upper instrumented vertebra (UIV) was either T3 or T4. LIV was at or immediately adjacent LSTV such that if LSTV was: a) T12, LIV was primarily L1 (LSTV+1); b) L1, LIV was L1; c) L2, LIV was L1 if L1 was neutral on bending xrays (LSTV-1) and L2 if not (LSTV); d) L3, LIV was L2 (LSTV -1). Residual curve, lowest instrumented vertebra adjacent disc angle (LIVDA), and lumbar curve were measured in first (avg 2 months) and last follow-up (avg. 40 months). Add-on phenomenon was defined as (1) an increase in the residual Cobb angle of at least 10°, (2) an increase in the lumbar curve of 5 ° (3) increase in LIVDA of greater than 5 °. <h3>RESULTS</h3> The residual curve progressed more than 10 ° in 3 patients between two follow-ups, 1/3 of whom had progression of LIVDA of greater than 5 ° and 2/3 of whom had progression of the lumbar curve of more than 5 °. These 3 patients were the add-on group (AG). None of the other 18 patients met any of the criteria for add-on phenomenon and were the non-add-on group (nAG). There were no significant differences between the two groups in the age at the time of presentation or surgery, Risser stage, preoperative MT and PT. One out of 3 patients in AG and 10/18 patients in nAG had L4 tilt to the right (p=0.59). LIV=LSTV-1 did not appear to be a risk factor (p=0.38); all 8 of those patients were in the nAG while 3 patients in AG had LIV either at LSTV or LSTV+1. PT bend out Cobb angles were statistically larger (25.7o +/- 2.1o, range 24 to 28, versus 10.8o +/- 5.5 °, range 0 to 21, p=0.0002) and the % PT correction with bend out was statistically lower (5.0 +/- 2.7%, range 3 to 8, versus 53 +/- 19%, range 25 to 100, p=0.0004) in the AG compared to the nAG. <h3>CONCLUSIONS</h3> We demonstrated an association between add-on phenomenon and limited correction of PT on bend out in Lenke 1A curves where the LIV was primarily at or immediately adjacent to LSTV. If % PT correction with bend out is less than 10%, the surgeon may consider treating the curve as a Lenke 2A curve and set UIV at T1 or T2. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Efficacy of Peginterferon alfa-2b in Nucleoside Analogue Experienced Patients with Negative HBeAg and Low HBsAg: A Non-Randomized Clinical Trial.

IntroductionHepatitis B surface antigen (HBsAg) clearance is the treatment goal for hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB). However, its rate is extremely low with nucleoside (acid) analogues (NAs) monotherapy. Peginterferon could enhance HBsAg clearance. This study aimed to evaluate the efficacy of peginterferon alfa-2b (PegIFNα-2b) in NAs-experienced patients with CHB with negative HBeAg and low HBsAg level.MethodsHBeAg-negative patients with CHB who had received NAs therapy over 24 weeks with HBsAg < 1500 IU/mL and HBV DNA < 100 IU/mL were enrolled. Patients received either PegIFNα-2b add-on therapy (n = 108) or continuous NAs monotherapy (n = 75). The primary endpoint was HBsAg clearance rate at week 48.ResultsAt week 48, serum HBV DNA was undetectable among all PegIFNα-2b add-on therapy patients. Almost all patients maintained HBV DNA suppression in the PegIFNα-2b add-on group (100%, 108/108) and NAs monotherapy group (97.33%, 73/75). Only patients with PegIFNα-2b add-on therapy achieved HBsAg clearance (50.93%, 55/108) and HBsAg seroconversion (48.15%, 52/108) at week 48. Patients with baseline HBsAg < 100 IU/mL achieved the highest HBsAg clearance rate and HBsAg seroconversion rate at week 48 (60.87%, 28/46 and 58.70%, 27/46 respectively). HBsAg clearance and HBsAg seroconversion at week 72 had no significant difference with continuing or discontinuing PegIFNα-2b therapy after 48 weeks of treatment. PegIFNα-2b add-on therapy was well tolerated.ConclusionsPegIFNα-2b add-on therapy increases HBsAg clearance rate and seroconversion rate for HBeAg-negative patients with CHB, particularly for those with lower HBsAg level. It would be unnecessary to prolong PegIFNα-2b duration after 48 weeks of PegIFNα-2b treatment.

Peg-interferon alpha add-on Tenofovir disoproxil fumarate achieved more HBsAg loss in HBeAg-positive chronic hepatitis B naïve patients.

Several studies have showed that combining peg-interferon alpha (Peg-IFNα) with nucleotide analogues has complementary effects in chronic hepatitis B (CHB), but the optimal regimen and potential mechanisms remain unclear. This was a prospective, longitudinal and multicentre clinical trial (NCT03013556). HBeAg-positive CHB naïve patients were randomly assigned to three groups: tenofovir disoproxil fumarate (TDF) monotherapy for 96weeks, TDF alone for 48weeks and sequentially Peg-IFNα added for 48weeks, TDF de novo combination with Peg-IFNα for 48weeks then TDF alone for 48weeks. The primary endpoint was HBeAg seroconversion at week 96 and HBsAg loss as the secondary endpoint. Furthermore, the levels of 12 cytokines in serum were assessed at different time points. A total of 133 patients were included in the analysis. The rates of HBeAg seroconversion at 96weeks were not significant different among the three groups (p=0.157). Interestingly, patients in the Peg-IFNα add-on group showed markedly lower HBsAg level compared with the other two groups at week 96. In addition, only three patients in the Peg-IFNα add-on group achieved HBsAg loss. For the following 24weeks from week 96, no HBsAg reappearance in the three patients and no new patients with HBsAg loss were observed in the three groups. Serum cytokine analysis showed that the baseline level of interferon-inducible protein-10 (IP-10) was strongly higher in HBeAg conversion patients and HBsAg loss patients. Compared with de novo combination and TDF alone, the addition of Peg-IFNα in TDF-treated group might be an effective strategy for HBsAg loss in HBeAg-positive CHB naïve patients.

Effect of Colchicine in Reducing Inflammatory Biomarkers and Cardiovascular Risk in Coronary Artery Disease: A Meta-analysis of Clinical Trials.

Colchicine's role in reducing inflammation and cardiovascular adverse events despite standard care in coronary artery disease (CAD) is controversial. Can colchicine reduce inflammation [high-sensitivity C-reactive protein (hs-CRP)] in CAD? PubMed, Cochrane Library, and Trial registries. The meta-analysis included 15 studies using add-on colchicine in patients with CAD. The outcomes evaluated were hs-CRP, white blood cell and neutrophil count, a composite end point of major cardiovascular events, myocardial infarction (MI), cardiovascular and all-cause mortality, and gastrointestinal adverse events. The analysis was performed using a random-effects model to calculate pooled mean difference and odds ratio (OR). The meta-analysis revealed a mean reduction of 0.36 mg/L in hs-CRP levels [95% confidence interval (CI): -0.51 to -0.20] with add-on colchicine. The mean white blood cell reduction of 371.75 per µL (95% CI: -544.27 to -199.24) and the mean neutrophil reduction also favored the add-on colchicine group. There was a reduction in composite end point of major cardiovascular events [OR, 0.65 (95% CI: 0.51-0.83)] and MI [OR, 0.77 (95% CI: 0.63-0.95)] with add-on colchicine therapy. There was no reduction in cardiovascular/overall mortality. Gastrointestinal adverse events were less with low-dose colchicine than those with high dose. Add-on colchicine has reduced the inflammation in CAD as implicated by a decrease in inflammatory markers. It has also lowered the incidence of MI but not mortality. With this present trend, the authors recommend further trials to validate the effectiveness of add-on colchicine in the secondary prevention of CAD.

A pilot clinical study of an add-on Ayurvedic formulation containing Tinospora cordifolia and Piper longum in mild to moderate COVID-19

BackgroundAfter declaration of COVID- 19 as pandemic by WHO, countries adopted several measures to contain the spread as well as test and treat the patients. Further, as no effective management protocols to address this pandemic were available, a need was felt to explore the integration of modern and traditional medicines to treat COVID- 19 cases. ObjectiveTo undertake a study with Ayurveda formulation as add on to existing standard of care (SOC) and to compare the outcomes in terms of patient acceptability, the time to clinical recovery, hospital stay as well as any signs of drug-herb interaction between the Ayurveda formulation and the SOC. Material and methodsAn exploratory nonrandomized prospective study has been undertaken for comparing the outcomes of traditional Ayurvedic classical formulation of Tinospora cordifolia (Guduchi) and Piper longum (Pippali) as an add on to standard of care (SOC) using modern medicine with SOC alone. This has been done in mild and moderate COVID- 19 cases, at a tertiary care integrative Medicine hospital in the National Capital Region, Gurgaon, India. The outcomes have been evaluated in terms of the duration of hospital stay, the time to clinical recovery, safety and non- interference/interaction of Ayurvedic and Further, long term impact of COVID- 19 treatment has been evaluated using quality of life questionnaire after 3 months of discharge. ResultsFindings of present study reveals that the Ayurveda add-on formulation of T. cordifolia (Guduchi) and P. longum (Pippali) has reduced the length of hospital stay and improve the recovery time. General feeling of wellbeing and activity levels were better in the 3 month follow-up post discharge in the Ayurveda add-on group. ConclusionAddition of Ayurveda formulation has reduced the time of recovery and duration of hospital stay. However, this formulation needs further investigated to provide more information on effective and safe herbal add-on to SOC for better outcomes to treatment of COVID-19 disease.

Add on yoga treatment for negative symptoms of schizophrenia: A multi-centric, randomized controlled trial

The efficacy of antipsychotic medications in the treatment of negative symptoms of schizophrenia is modest at best. Preliminary studies suggest the beneficial effects of add on Yoga, a traditional Indian practice, in the treatment of schizophrenia. Hence, in this study, we examined the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia in a randomized, wait-list controlled design from two clinical institutes in south India. 89 patients (age – 34.20 ± 8.06 years; education – 14.22 ± 2.69 years; 28 females) were randomized into the add-on yoga or treatment as usual (TAU - wait-list control) group. Patients had a mean illness duration of 10.97 ± 7.24 years with an age at onset of 23.34 ± 5.81 years. Central block randomization was followed to ensure concealed allocation. Participants randomized to the yoga treatment group attended 12 supervised yoga training sessions over two weeks and practiced yoga sessions at home for the subsequent 10 weeks. 64 patients completed the trial. An intent to treat analysis was conducted with 89 participants using a linear mixed model. Improvement in negative symptoms was our primary outcome measure. The two groups were matched on demographic variables and baseline psychopathology severity. Participants in the add-on yoga group had significantly greater improvement in negative symptoms (SANS baseline: 49.13 ± 2.30; 12-weeks follow up: 31.55 ± 2.53) compared to the TAU group (SANS baseline: 51.22 ± 2.40; 12-weeks follow up: 45.30 ± 2.93; t = 3.36; p = 0.006; Cohen's d-0.65). The current study findings suggest the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia. The effectiveness of yoga practice as a regular clinical intervention for patients needs to be explored in future studies by integrating yoga services along with other clinical services.

BLOOD PRESSURE LOWERING EFFECTS AND SAFETY OF ESEXERENONE, NEWLY AVAILABLE MINERALOCORTICOID RECEPTOR BLOCKER

Objective: Esaxerenone (CS-3150) is a novel, highly potent, selective and long acting non-steroidal mineralocorticoid receptor (MR) blocker with MR blocking action of IC50 3.7 nM, other steroid hormone receptors blocking action of IC50 &gt;5000 nM and half life loss of 18.6 hours. The authors aimed to investigate blood pressure (BP)-lowering ability and safety of esaxerenone in resistant hypertensive patients by add-on or by replacement from spironolactone or eplerenone. Design and method: This study was designed as a prospective observational study in 230 patients, approved by the local ethical committee and followed for 12 weeks. In add-on group, 52 resistant hypertensive patients, whose office BP was &gt; 130/80 (&lt;75 years old) or 140/90 (&gt;75 years old) treated with at least three hypertensive agents (CCBs, RAS inhibitors and diuretics) according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019), were treated by the add-on use of esaxerenone. In replacement group, 208 resistant hypertensive patients, whose BP was controlled by at least 4 antihypertensive drugs including spironolactone or eplerenone, were medicated with esaxerenone by replacement from spironolactone or eplerenone. Results: In add-on group, both systolic and diastolic BP were significantly lowered from 139 ± 16 / 82 ± 14 mmHg (means ± SD) to 129 ± 16 / 79 ± 12 mmHg (p &lt; 0.0001 and p = 0.0185, respectively) with mean esaxerenone dose of 1.44 mg. In replacement group, systolic BP was significantly lowered from 126 ± 16 mmHg (means ± SD) to 120 ± 14 mmHg (p &lt; 0.0001), but diastolic BP was not, with mean esaxerenone dose of 1.58 mg once a day, which was changed from mean spironolactone and eplerenone doses of 34 and 58 mg, respectively. In add-on group, serum potassium concentration was significantly increased from 4.18 ± 0.46 to 4.40 ± 0.58 mmol/L and eGFR was decreased from 74.2 ± 23.9 to 66.9 ± 24.0, but those in replacement group were not significantly changed. Conclusions: This study suggested that esaxerenone has more potent BP lowering ability than spironolactone or eplerenone especially in systolic BP and has the equivalent safety.