Oral Combination Therapy Research Articles

Melanonychia and subungual papule in a middle-aged man

Melanonychia and subungual papule in a middle-aged man

P490 MANAGEMENT OF SEVERE HYPERCHOLESTEROLEMIA IN ITALY: EVIDENCE FROM SANTORINI STUDY

Abstract The management of severe hypercholesterolemia (sHC) (LDL–C >160 mg/dL) represents a clinical challenge in routine practice, mainly in the setting of high cardiovascular (CV) risk. The aim of the present analysis was to assess the characteristics and management at baseline examination of patients with sHC enrolled in the Italian cohort of SANTORINI study. The SANTORINI study (NCT04271280) is a multinational, observational, prospective study evaluating the use of lipid–lowering therapies (LLTs) in 9044 adult patients with high– and very–high CV risk enrolled from 14 European countries between March 2020 and February 2021, with a 12–month follow–up period per patient. The Italian cohort comprised 1977 patients, 229 (11.6%) of whom were classified with sHC. Their mean age was 59.4 years, 56% were male, BMI was 27.2 kg/m2 and mean LDL–C levels were 196.7 mg/dL. In 7% of cases sHC was reported to be associated with a clinical diagnosis of familial hypercholesterolemia. By investigators, 150 (65.5%) patients were classified at very–high and 79 (34.5%) at high CV risk, mainly (74.2%) based upon ESC/EAS European guidelines criteria. Atherosclerotic cardiovascular disease was actually present in 68.4% of patients, while 40.6% were on primary prevention. Despite sHC was associated with high CV risk, 64.6% of patients had no documented LLTs at baseline, 15.3% was receiving lipid–lowering monotherapy including 9.2% on statins (6.1 % moderate and 2.6% high–intensity), 1.7% were on ezetimibe, 1.6% on PCSK9i and 0.5% on other oral LLTs, and 20.1% was receiving combination therapy (10.9% were on statin + ezetimibe, 4.8% on PCSK9i + oral LLT, and 4.4% other oral combination therapy). Based on present findings, it is therefore concluded that, although the clinicians mostly follow current guidelines to determine CV risk in hypercholesterolemia, there is a low utilisation of LLTs, especially combination therapies, in the subgroup of patients with sHC at high and very–high CV risk. This means that further measures are needed to improve the therapeutic management of these patients in order to minimise the risk of adverse cardiovascular events.

OA43 Peri-procedural management and incidence of bleeding events following musculoskeletal injections and aspirations in people on anticoagulation and antiplatelet therapy

Abstract Background/Aims Corticosteroid injections and aspirations are common interventions for managing musculoskeletal conditions and inflammatory arthritis. However, there remains limited safety evidence to support safe practice for injection decisions in people on anticoagulant therapy, particularly direct oral anticoagulant (DOAC) medications regarding incidence of bleeding events or complications. Although there is increasing evidence for warfarin continuation, there is considerable variation in published guidance, manufacturer recommendations and specialty approaches to peri-procedural management of DOACs. This study reports on peri-procedural practice regarding continuation or discontinuation, bleeding events and complication rates in people on anticoagulant and antiplatelet medication undergoing musculoskeletal injections. Methods A prospective observational study was undertaken (October 2018- December 2020) using weekly electronic database searches to identify musculoskeletal injection and aspiration procedures undertaken in orthopaedics, rheumatology and radiology in two large NHS providers. Reply-paid questionnaires were sent to all consecutive adults within two weeks of procedures. Information was collected on bleeding events/complications, anticoagulant/antiplatelet use, products, doses, indications, INR levels and checking, discontinuation/re-initiation, comorbidities, and other medications. Concurrent electronic searches were also undertaken for emergency attendance or admissions within 30 days following procedures to identify unreported serious bleeding events or complications. Results Electronic searching identified 5,080 musculoskeletal procedures with 1,338 (26.3%) respondents (ages 20-99 years) returning questionnaires. 356 received >1 procedure over the timeframe and 49 bilateral procedures. There were 45 reports of bleeding events and all non-clinically significant localised bruising of the skin: 25/1106 (0.2%) without anticoagulation or antiplatelet therapy; 20/232 (8.6%) with anticoagulant/antiplatelet therapy, occurring only with continued medications. Incidences included: warfarin with unknown INR levels (n= 2/36, 5.5%); DOACs (n=9/72, 12.5%) [apixaban (5/24, 21%), rivaroxaban (4/45, 8.8%)]; antiplatelets [clopidogrel (4/28, 14.2%), clopidogrel & NSAID (1/4, 25%), aspirin (1/72, 1.3%), aspirin & NSAID (2/11, 18.1%), NSAID (1/3, 33.3%)]. Localised bruising was more common with DOAC continuation, aspirin with NSAID use, clopidogrel use and older age. Only 3/72 respondents on DOACs reported instructions to interrupt medications (orthopaedics). There were no serious bleeding or thromboembolic events identified through electronic searches for any recipient within 30 days following procedures. Conclusion This observational study found no significant bleeding events resulting from musculoskeletal injections or aspirations with continuation of warfarin (INR < 3.80), direct oral anticoagulant use, antiplatelet or combination therapy. The only consequence reported was some occurrence of localised bruising, also reported without medication use. It was not universal practice to determine INR levels prior to procedures with warfarin use and common practice to continue DOACs and antiplatelet medications. This research adds to evidence that musculoskeletal injections and aspirations appear to be very low risk procedures for bleeding complications with continuation of anticoagulant and antiplatelet therapy. Further research on intra-articular or intra-tissue iatrogenic consequences with anticoagulant/antiplatelet use is needed to add to procedural risk/benefit evaluations. Disclosure C. McCrum: Grants/research support; Funding grant to provide professional education workshops-Novartis, Janssen. S. Grainger: None.

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation.

Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years). Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74.

A Water-Soluble Polymer-Lumefantrine Conjugate for the Intravenous Treatment of Severe Malaria.

Uncomplicated malaria is effectively treated with oral artemisinin-based combination therapy (ACT). Yet, there is an unmet clinical need for the intravenous treatment of the more fatal severe malaria. There is no combination intravenous therapy for uncomplicated due to the nonavailability of a water-soluble partner drug for the artemisinin, artesunate. The currently available treatment is a two-part regimen split into an intravenous artesunate followed by the conventional oral ACT . In a novel application of polymer therapeutics, the aqueous insoluble antimalarial lumefantrine is conjugated to a carrier polymer to create a new water-soluble chemical entity suitable for intravenous administration in a clinically relevant formulation . The conjugate is characterized by spectroscopic and analytical techniques, and the aqueous solubility of lumefantrine is determined to have increased by three orders of magnitude. Pharmacokinetic studies in mice indicate that there is a significant plasma release of lumefantrine and production its metabolite desbutyl-lumefantrine (area under the curve of metabolite is ≈10% that of the parent). In a Plasmodium falciparum malaria mouse model, parasitemia clearance is 50% higher than that of reference unconjugated lumefantrine. The polymer-lumefantrine shows potential for entering the clinic to meet the need for a one-course combination treatment for severe malaria.

Abstract 5091: Potentiating immunogenicity of PD1 blockage with metronomic Oral CAPOX for local and liver metastasized colorectal cancer

Abstract Since the appearance of oxaliplatin, FOLFOX therapy is positioned as the standard of care for colorectal cancer (CRC). And after the advent of capecitabine, an oral prodrug of 5-FU, both FOLFOX and CAPOX remain the first-line treatment for local and advanced CRC. Even though oral 5-FU prodrug has approved more than two decades ago, orally available oxaliplatin has not been developed yet. Oral chemotherapy has garnered attention in the era of cancer immunotherapy because oral form of the therapy makes metronomic therapy feasible. In this regard, we invented orally absorbable oxaliplatin exploiting complexation with bile acid moiety. The invention encouraged to expand the dosing of combination treatment of 5-FU and oxaliplatin, the most established chemotherapy combination of CRC, into metronomic scheduling. Oral CAPOX therapy is developed to administrate 5-FU and oxaliplatin combination (FOX) metronomically for chemo-immunotherapy. Metronomic dosage successfully induced immunogenic cancer cell death in colorectal cancer xenograft mouse model not exerting toxicity to other organs abolishing immune suppressive effect of chemotherapy. Oral CAPOX boosted tumor immunity translating immune microenvironment. Immune cell population and activation was analyzed using flow cytometry. Suppressive immune cell population decreased after Oral CAPOX treatment. Especially, immune-suppressive macrophage population diminished. Macrophages became immunogenic and presented antigen more frequently. Improved tumor microenvironment combined with anti-PD1 treatment activated and proliferated T cells locally and systemically. Oral CAPOX and anti-PD1 combination therapy activated cytotoxic T cell in tumor tissue and tumor draining lymph node. This therapy also activated NK cells systemically. Oral CAPOX and anti-PD1 combination treatment regressed established tumor completely in more than 90% of the mouse showing its capacity for clinical usage. Liver is the region which makes CRC least immunogenic among metastatic site and the organ CRC is metastasized most abundantly. Immuno-suppresive macrophage in liver is known for the factor discriminating liver metastasized CRC from other organs metastasized one suppressing T cells. Because Oral CAPOX therapy converts macrophage more immunogenic, Oral CAPOX therapy could reverse immunosuppressive tumor microenvironment of liver metastasized colorectal cancer. Oral CAPOX and anti-PD1 combination is treated liver metastasized CRC model and showed standing out antitumor efficacy, and T cell activation. Citation Format: Seong Jin Park, Seho Kweon, Moyo Knowledge Mudhibadhi, Ha Rin Kim, Youngro Byun. Potentiating immunogenicity of PD1 blockage with metronomic Oral CAPOX for local and liver metastasized colorectal cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5091.

Retrospective Study of the Efficacy and Safety of Laser and Oral Combination Therapy for Non-responders to Neodymium-doped Yttrium Aluminum Garnet Laser: A Review of 20 Patients with Onychomycosis

Background: Oral antifungal drugs are the primary treatment for onychomycosis. However, there are few studies on the effectiveness and safety of oral combination therapy after laser treatment. Objective: We sought to contrast the efficacy and safety of laser and oral combination therapy with that of oral monotherapy for non-responders to laser treatment. Methods: We retrospectively evaluated the medical charts and photographs of 20 patients who received four sessions of Nd:YAG laser. Among these patients, 11 were "laser non-responders" and 9 were "laser partial responders". Afterward, 10 patients received oral drugs in addition to laser treatment (combination therapy) and the other 10 were completely altered to oral drugs, with no laser treatment (oral monotherapy). Clinical evaluation was conducted at baseline and 3 months after treatment. Recurrence was evaluated 3 months after the final evaluation. Results: Clinical evaluation revealed that combining or switching to oral antifungal drugs was substantially effective in the laser non-responder group (Z = -2.481, p = 0.013). Combination therapy was more effective than oral monotherapy (Z = -1.324, p = 0.247). Furthermore, positive baseline mycological results demonstrated a higher possibility of laser monotherapy failure (χ2 = -5.089, p = 0.024). There were two cases of recurrence in the oral monotherapy group and no adverse effect was discovered in any patient. Conclusion: This study highlighted that the combination of oral drugs with laser therapy could be beneficial regarding efficacy, recurrence, and safety in the treatment of patients who are refractory to laser therapy.

Safety and efficacy of combination of oral iron chelators in thalassemia major patients

Background: To assess the safety and efficacy of combination of oral iron chelation therapy in transfusion dependent thalassemia patients and to compare it with other regimes. Method: 150 transfusion dependent thalassemia patients with iron overload were recruited for a prospective, case control study. They were divided into 4 groups based on their chelation regime. The drugs used were deferasirox (DFX) alone, deferiprone (DFP) alone, DFP+DFX in combination, parenteral desferrioxamine (DFO) with either DFX or DFP with 50, 15, 70 and 15 in each group respectively. Doses used were DFX-30 mg/kg, DFP- 75 mg/kg/day, DFP+DFX-50 +30 mg/kg/day, DFO+DFP-25 mg/kg/d+50 mg/kg/day and DFO+DFX-25 mg/kg/d +30 mg/kg/d daily. Base line haematological, hepatic and renal profile and S. ferritin samples were collected and analyzed. Patients were monitored monthly for compliance and side effects. 30 patients were excluded during the course of study. Tests were repeated after 18 months period and the results of 120 patients were compared between the groups and statistically analyzed. Results: There was statistically significant reduction of S. ferritin in both groups taking oral combination therapy and parenteral therapy (p<0.0001). There were no serious hematological, renal/hepatic side effects in any groups. Conclusions: The oral combination therapy of iron chelators is safer and was well tolerated by all the patients and is similarly efficacious to the parenteral therapy in lowering S. ferritin.

Antithrombotic therapies in Canadian atrial fibrillation patients with concomitant coronary artery disease: Insights from the CONNECT AF + PCI-II program

BackgroundSelecting the appropriate antithrombotic regimen for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) or have had medically managed acute coronary syndrome (ACS) remains complex. This multi-centre observational study evaluated patterns of antithrombotic therapies utilized among Canadian patients with AF post-PCI or ACS. Methods and resultsBy retrospective chart audit, 611 non-valvular AF patients [median (interquartile range) age 76 (69–83) years, CHADS2 score 2 (1–3)] who underwent PCI or had medically managed ACS between August 2018 and December 2020 were identified by 68 cardiologists across eight provinces in Canada. Overall, triple antithrombotic therapy [TAT: combined oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT)] was the most common initial antithrombotic strategy, with use in 53.8 % of patients, followed by dual pathway therapy (32.7 % received OAC and a P2Y12 inhibitor, and 4.1 % received OAC and aspirin) and DAPT (9.3 %). Median duration of TAT was 30 (7, 30) days. Compared to the previous CONNECT AF + PCI-I program, there was an increased use of dual pathway therapy relative to TAT over time (P-value <.0001). DOACs (direct oral anticoagulants) represented 90.3 % of all OACs used overall, with apixaban being the most utilized (50.5 %). Proton pump inhibitors were used in 57.0 % of all patients, and 70.1 % of patients on ASA. Planned antithrombotic therapies at 1 year were: 76.2 % OAC monotherapy, 8.3 % OAC + ASA, 7.9 % OAC + P2Y12 inhibitor, 4.3 % DAPT, 1.3 % ASA alone, and <1 % triple therapy. ConclusionIn accordance with recent Canadian Cardiovascular Society guideline recommendations, we observed an increased use of dual pathway therapy relative to TAT over time in both AF patients post-PCI (elective and emergent) and in those with medically managed ACS. Additionally, DOACs have become the prevailing form of anticoagulation across all antithrombotic regimens. Our findings suggest that Canadian physicians are integrating evidence-based approaches to optimally manage the bleeding and thrombotic risks of AF patients post-PCI and/or ACS.

Prevention of stricture after semi-circumferential and whole circumferential esophageal endoscopic resection

: Stricture formation after esophageal endoscopic resection (ER) worsens a patient’s quality of life because it causes dysphagia and requires multiple endoscopic dilations. Numerous methods are available to prevent esophageal stricture formation after ER. For noncircumferential resections, much evidence indicates local steroid injection is the best choice and is therefore widely used in clinical practice. However, local steroid injection alone is insufficient to prevent stricture of whole circumferential resections. Accordingly, we should select oral steroid administration or combination therapy (oral steroid administration + local steroid injection) for such extensive resections. However, the stricture rate is significantly higher compared with noncircumferential resections despite these prevention methods. Steroid therapies, including local injection and oral administration, have the advantages of high effectiveness and low cost. However, concerns include the risk of steroid-related complications such as immunosuppression, diabetes onset/exacerbation, and fragility of the esophageal wall. Also, favorable outcomes of modified steroid methods such as local triamcinolone acetonide (TA) injection together with a polyglycolic acid sheet (PGA), TA-soaked PGA sheet together with a fully covered metal stent, and TA filling method have been reported. Innovative methods include tissue engineering approaches such as cell sheet transplantation and autologous mucosal transplantation. Despite the promise of these methods, further studies are required to establish their efficacies before widespread use in clinical practice.

Brief Review on Diabetes Mellitus

Abstract: Approximately 422 million people (8.5% of the world's population) have been diagnosed with diabetes, making it one of the top causes of death worldwide. Despite significant efforts being made to find effective treatment options, the prevalence is expected to keep rising. An overview of diabetes mellitus, its management, and the role of various healthcare experts is provided in this article. The incidence is predicted to continue expanding despite great efforts on the means of treatments are exerted. This article provides an overview on diabetes mellitus, its treatment and the role of different healthcare professionals in its management. Diabetes has a direct impact on the development of particular retinopathy, nephropathy, neuropathy, heart vascular, and cerebrovascular illnesses. For many disorders, combination therapy is preferable to monotherapy. For chronic disorders, oral hypoglycemic medication combination therapy is best. Important components of combination therapy include sulfonyl urea, alpha glucosidase inhibitors, biguanides, meglitinides, and thiazolidinediones.

What is the role of autoantibodies in post-artesunate delayed hemolysis?

We read with great interest the recent publication by Kurth et al.1 that highlights an interesting aspect of post-artesunate delayed hemolysis (PADH) among uncomplicated malaria patients treated with oral artemisinin-based combination therapy (ACT). Post-treatment delayed hemolysis has increasingly been observed, especially among travellers from non-endemic areas.2 Besides the well-known ‘pitting’ mechanism, the article discussed that ACT might produce drug-autoantibodies that contribute to post-treatment hemolysis. We would like to discuss the possible role of autoantibodies against red blood cells (RBC) as a pathophysiologic mechanism of PADH and the clinical implication of corticosteroid therapy for patients with PADH. Camprubí et al. (2019) reported a case of PADH in a splenectomized patient with a positive direct antiglobulin test (DAT); this raised a critical discussion as the ‘pitting’ mechanism cannot explain the hemolysis in this patient.3 The phenomenon may be explained by three hypotheses involving drug-induced immune hemolytic anaemia. First, the drug, acting as a hapten, attaches to the RBC membrane and induces autoantibody reactions. Second, the immune complex mechanism involves anti-drug antibodies produced during artesunate treatment in previous infections. Once artesunate is administered in subsequent infections, a drug-anti-drug immune complex is formed and randomly binds to the RBC surface, which activates complement fixation and opsonization, leading to cell lysis. Lastly, it assumes that the drug may act as a coating for the RBCs. If IgG antibodies against the drug are present, the reaction to the drug-coated RBCs can cause hemolysis. The immune complex mechanism may explain the high levels of autoantibodies found among ‘semi-immune’ patients of African descent who developed PADH in the recent study by Kurth et al.

Tolerability, safety and survival in patients with severe pulmonary arterial hypertension treated with intravenous epoprostenol (Veletri®): a prospective, 6-months, open label, observational, non-interventional study

BackgroundEpoprostenol AS (Veletri®), a thermostable epoprostenol formulation, provides better drug stability and improved clinical use compared to previous epoprostenol formulations. This study aims to expand clinical experience in the use of Veletri®, especially regarding tolerability, safety and survival.MethodsPulmonary arterial hypertension (PAH) patients at high risk despite pretreatment with at least double oral combination therapy and with clinical indication for epoprostenol (Veletri®) treatment were consecutively included in this prospective, open label, observational, non-interventional study. Clinical data were assessed at baseline, after 3 and 6 months. Adverse events (AEs) and serious adverse events (SAEs) were documented. Survival from initiation of Veletri® was assessed at last patient out.ResultsFifteen patients (60 ± 13.7 years, WHO functional class III (n = 10) or IV (n = 5), severely impaired right ventricular function, mean pulmonary arterial pressure 54.8 ± 8.9 mmHg, mean pulmonary vascular resistance 4.4 ± 0.7 (median 3.8) Wood Units) were enrolled and treated with a mean dosage of 7.9 ± 3.9 (median 7.5) ng/kg/min. Eleven patients completed the study (treatment withdrawal n = 1, death n = 3). After a mean follow-up of 19.1 ± 13.5 (median 18.0) months, seven patients died and three were listed for lung transplantation. Seven AEs (nausea n = 3, diarrhea n = 1, flushing n = 2, headaches n = 1) and three SAEs (catheter infection n = 2, catheter occlusion n = 1) were related to Veletri®. The 1- and 2-year survival rates were 73.3% and 52.4%, respectively.ConclusionsThe study showed that safety and tolerability of epoprostenol AS (Veletri®) was comparable to previous prostacyclin formulations and was feasible for most patients. The maximum tolerable dosage was lower than dosages reported in the literature. In future applications/trials the up-titration process should be pushing for higher dosages of epoprostenol in the occurrence of side effects, as the achievement of a high and effective dosage is crucial for the clinical benefit of the patients. Survival was as expected in these prevalent severely impaired patients.Trial registration The study was registered in the EUPAS registry (EUPAS32492).

Reversible cardiomyopathy in a patient with chronic myelomonocytic leukemia treated with decitabine/cedazuridine: a case report

BackgroundHypomethylating agents (HMAs) have shown efficacy in the treatment of hematological malignancies and are indicated for the treatment of chronic myelomonocytic leukemia (CMML). While the HMA decitabine, in its intravenous formulation, has been used since 2006 for the treatment of CMML, use of its oral formulation has been limited by poor bioavailability due to first-pass metabolism by the enzyme cytidine deaminase. The dose of intravenous decitabine is limited by toxicities such as cardiomyopathy and heart failure. Therefore, cedazuridine was developed as an inhibitor of cytidine deaminase. Cedazuridine decreases the first-pass metabolism of oral decitabine allowing therapeutic levels to be achieved at lower doses, and thus, the novel oral combination of cedazuridine with decitabine was developed. While cardiomyopathy and heart failure are well-established adverse effects associated with intravenous decitabine alone, there to our knowledge there have been no documented incidences of reversible cardiomyopathy in the literature or in patients who participated in the phase 2 and phase 3 clinical trials of oral decitabine-cedazuridine.CaseThis case study presents an 85 year-old Caucasian female with CMML who developed cardiomyopathy and heart failure with reduced ejection fraction after completing 5 cycles of therapy with decitabine/cedazuridine. Furthermore, her symptoms and cardiac function recovered upon discontinuation of the drug.ConclusionsWe present an occurrence of reversible cardiomyopathy in a patient who completed 5 cycles of decitabine/cedazuridine, an oral combination therapy developed to enhance oral bioavailability of decitabine thereby limiting its adverse effects. As the decitabine/cedazuridine combination therapy rises in popularity due to its convenient oral formulation, more trials are needed to understand the prevalence of cardiomyopathy with this drug and to discover preventative strategies for cardiotoxic effects.

Efficacy and Safety Comparison of Basic Fibroblast Growth Factor-Related Decapeptide 0.1% Solution (bFGFrP) Plus Oral PUVA Combination Therapy with Oral PUVA Monotherapy in the Treatment of Vitiligo.

Phototherapy in its different forms, is mainstay of vitiligo management. Combining treatment modalities like topical calcipotriol (for quicker, more intense repigmentation), Low dose azathioprine with PUVA have proven to be beneficial in management of vitiligo due to different mechanisms of repigmentation and their synergistic effects. Topical bFGF-related decapeptide (bFGFrP) application followed by sun exposure/ UVA phototherapy yields effective repigmentation. bFGFrP has shown to aid the targeted phototherapy in smaller lesions and its combinations with other treatment modalities have been very promising. However, there is paucity of studies on combination treatments; especially oral PUVA along with bFGFrP. This study was aimed at evaluating safety and efficacy of combination of bFGFrP with Oral PUVA in vitiligo (larger body surface area 20% or more). Phase IV, randomized, multicentre study (N = 120) in adult patients with stable vitiligo of 6 months treatment period with monthly follow up visits. Psoralen (Tab. Melanocyl) dosage 0.6 mg/kg orally 2 h before exposure to UVA phototherapy. Oral PUVA therapy, initially, at an irradiation dose 4 J/cm2 (PUVA group), followed by increments 0.5 J/cm2 every four sittings if tolerated for twice weekly. Primary end point was improvement in extent of repigmentation (EOR) in target lesion (at least 2 cm × 2 cm in greatest dimension, without leukotrichia), while secondary endpoints were improvement in patient global assessment (PGA) and safety at end of 6 months of treatment period in bFGFrP + oral PUVA combination group and Oral PUVA monotherapy group. End of 6 months, significantly greater EOR >50%) was achieved in 61.8% (34 patients, n = 55) from combination group while 30.2% (16 patients, n = 53) from the oral PUVA monotherapy group (n = 53). Regarding Grade of repigmentation (GOR), complete repigmentation was observed 5.5% (3 patients, n = 55) in combination group whereas no patient showed complete repigmentation in monotherapy group (p ≤ 0.05), PGA showed significant overall improvement in combination group (p ≤ 0.05); 6 patients (10.9%) from combination group Vs one (1.9%) showed complete improvement. During treatment period, there were no reported adverse events. Addition of bFGFrP to oral PUVA therapy resulted in intense and faster induction of repigmentation than oral PUVA monotherapy with favorable safety profile.

The role of inflammation in the development of diabetic polyneuropathy and the possibility of its correction

To study the effect of the combined drug Cytoflavin on the mechanisms of nonspecific inflammation in the treatment of diabetic polyneuropathy (DPN) with an assessment of the dynamics of the TNF-α index. An open comparative prospective observation of patients with a history of DPN for more than 5 years and a high level of TNF-α was carried out. All patients underwent basic oral combined hypoglycemic therapy, the main group used the combined drug Cytoflavin 10 ml (per 200 ml 0.9% NaCl) for 10 days, followed by the transition to the enteral form of the drug, 2 tablets 2 times a day for 1 months The main indication for the appointment of Cytoflavin was the presence of comorbid pathology in the form of cerebrovascular disease in all studied patients. The severity of clinical symptoms of DPN, the quality of life (QOL) of patients, as well as the dynamics of the level of TNF-α as an indicator reflecting the process of inflammation were assessed. As a result of the treatment in the study group, there was an improvement in QoL, a decrease in the severity of sensory complaints and a decrease in the level of TNF-α, which may indicate a possible anti-inflammatory mechanism of the combined drug Cytoflavin. Cytoflavin can inhibit inflammation and reduce the severity of sensitive disorders in patients with DPN.

Implementation of the Revised National Malaria Control Guidelines: Compliance and Challenges in Public Health Facilities in a Southern Nigerian State.

There has been a concerted effort to reduce malaria burden and bring malaria related mortality to zero. The objectives of this survey were to assess the level of adherence to the current revised malaria control guidelines in the public health facilities in Cross River State of Nigeria and to identify the challenges as well as suggest ways for improvement in treatment outcomes. This was a mixed observational and qualitative survey conducted in 32 public health facilities from 21st to 25th June 2022. Treatment records on malaria were assessed for adherence to the National guidelines. In-depth interviews were conducted with 36 key informants and 4 purposefully selected stakeholders to identify the successes and challenges. Quantitative data were summarized and presented in simple proportions and percentages while qualitative information was recorded, the transcripts thematically coded, analyzed and presented using NVivo 11 software. The survey revealed that vector control program was poorly implemented across the state. For case management, presumptive treatment was frequently practiced especially at secondary health facilities for uncomplicated malaria. More than 60% of uncomplicated malaria were being treated with parenteral artemether instead of oral artemisinin combination therapy (ACTs) as recommended. Severe malaria were not treated with Intravenous (IV) Artesunate as first line drug in about 40% of the secondary health facilities. Key successes were noted in malaria management in pregnancy. Major challenges identified include: stock out of commodities, shortage of clinical man power, and low trust in parasitological diagnosis. The survey showed that adherence to the key recommendations in various categories of malaria control among health care providers in the public health facilities was below expectation. Malaria preventive treatment in pregnancy with SP fared better perhaps because of its inclusion in ANC packages.

Rationale of Cross-Sectional Descriptive Study on Clinical Effectiveness of Oral Combination Therapy Based on Secnidazole, Azithromycin and Fluconazole in Syndromic Treatment of Abnormal Vaginal Discharge in Kinshasa/DR Congo

Rationale of Cross-Sectional Descriptive Study on Clinical Effectiveness of Oral Combination Therapy Based on Secnidazole, Azithromycin and Fluconazole in Syndromic Treatment of Abnormal Vaginal Discharge in Kinshasa/DR Congo

121 RELEVANCE OF COMORBIDITIES ON INITIAL COMBINATION THERAPY IN PULMONARY ARTERIAL HYPERTENSION

Abstract Rationale Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. Methods The study enrolled 181 treatment-naive PAH patients with a 6- months (IQR 144-363 days) right heart catheterization and risk assessment after initial oral combination therapy. Results Group-A, 96 (53.0%) patients without cardiac comorbidities; Group-B, 54 (29.8%) patients with one cardiac comorbidity; Group-C, 31 (17.1%) patients with ≥2 cardiac comorbidities. Group-C patients were older with a balanced gender distribution. There was a significant difference in PVR reduction moving from the absence to one or ≥2 cardiac comorbidities, respectively, median -45.0%, -30.3%, -24.3%. A ERS/ESC low-risk status was present at first follow-up in 50 (52.0%) patients in Group-A, 19 (35.1%) in Group-B, and 9 (29.0%) in Group-C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group-A, 15 (27.7%) in Group-B, and 7 (22.6%) in Group-C. Group-A patients were 2.3 times more likely to achieve/maintain a low risk status compared with Group-B and -C (OR 2.27, 95% C.I. 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Conclusion Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment- induced decrease in PVR.

986. Pseudomonas Prosthetic Joint Infections: Is there a role for monotherapy?

Abstract Background Pseudomonas species are a less common but devastating pathogen family in prosthetic joint infections (PJI). Despite advancements in management, Pseudomonas PJI remains particularly difficult to treat due to fewer antibiotic options and robust biofilm formation. The purpose of this study was to better evaluate outcomes after Pseudomonas PJI treatment. Methods All hip or knee PJIs, at a single institution, with positive Pseudomonas culture were analyzed. 51 patients (29 hips and 22 knees) meeting inclusion criteria were identified. The primary outcome of interest was infection clearance at 1-year after surgical treatment, defined as reassuring aspirate without ongoing antibiotic treatment or death within one year post-operatively. Monomicrobial and polymicrobial infections were evaluated separately. Results Among monomicrobial PJIs, ten (50.0%) patients were clear of infection at one year post-operatively. Patients treated with 2-stage exchange (n=11) had a 1-year clearance rate of 54.5% compared to 60.0% with DAIR (n=5) and 25.0% with resection or amputation (n=4). Two of six patients treated with fluoroquinolone monotherapy met 1-year infection clearance, despite fluoroquinolone sensitivity, compared to four of five patients meeting 1-year clearance when treated with combined intravenous and oral therapy for at least 6 weeks. Resistance to anti-pseudomonal agents was infrequent (20%, n=4/20), and three of ten mono- and polymicrobial PJI patients with recurrent Pseudomonas PJI developed resistance to anti-pseudomonal therapy. Polymicrobial infections were the most common presentation (54.9%) of Pseudomonas positive PJI with a mortality rate of 46.4% (n=13/28) at a median follow-up of 4.2 years [IQR: 3.4-5.7]. Conclusion Despite surgical and antibiotic treatment regimens consistent with traditional treatment algorithms, our data portrays poor clearance rate of Pseudomonas PJI with relatively poor outcomes in patients treated with oral or intravenous monotherapy. Pseudomonas infections are difficult to eradicate and likely require deviations from classical therapeutic protocols to improve treatment success. Disclosures William A. Jiranek, MD, Biomech Holdings LLC: Stocks/Bonds|DePuy, A Johnson &amp; Johnson Company: IP royalties Thorsten M. Seyler, MD, PhD, Heraeus: Paid consultant|Pattern Health: IP royalties|Restor3d: IP royalties|Smith &amp; Nephew: Paid consultant|Total Joint Orthopedics: Paid consultant|Zimmer: research.