Single Drug Therapy Research Articles

Single Drug Therapy of PD-1/PD-L1 Checkpoint Inhibitors for Advanced Urothelial Bladder Cancer

Since the first approval of Atezolizumab in May 2016, immunotherapy, PD-1/PD-L has completely changed the way bladder cancer is treated, as chemotherapy was the sole available choice as a treatment for bladder cancer, and the results still was not optimistic, with five licensed drugs treating bladder cancer. Despite the generally poor prognosis of advanced bladder cancer, some patients show persistent responses to immune checkpoint inhibitors. This review summarizes the efficacies and safety of the five drugs: Durvalumab, Atezolizumab, Avelumab and other drugs - from different studies respectively for treating advanced bladder cancer and mentions the side effects and future perspectives. For the treatment, all inhibitors that was licensed have akin efficacy and safety traits, but they differ in terms of dosage, frequency, and financial burden. Only Pembrolizumab, to date, has revealed advantage over conventional chemotherapy in a stochastic Phase III scenario. Pembrolizumab and Atezolizumab are also well tolerated and approved for patients who are unable to receive cisplatin treatment. Patients with bladder cancer now have some hope, thanks to immunotherapy. The current environment is continuously evolving, and new immunotherapy-combination trials are being conducted to further enhance results.

Real-world data for lenalidomide maintenance in responding patients of diffuse large B-cell lymphoma.

Approximately 40% patients of diffuse large B-cell lymphoma (DLBCL) would develop disease recurrence/progression after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy, with highly poor prognosis. An effective strategy to prolong the survival of this patient population is the additional single-drug maintenance therapy. lenalidomide, an immunomodulatory drug with oral activity, has direct anti-tumor activity and indirect effects mediated by multiple immune cells in the tumor microenvironment, such as B, T, natural killer (NK), and dendritic cells. Combining its controllable toxicity, it is promising in long-term maintenance therapy. This study aims at evaluating the clinical effect of lenalidomide maintenance therapy in responding DLBCL patients with R-CHOP treatment. This retrospective study was devised in DLBCL cases who obtained complete response (CR) or partial response (PR) following 6-8cycles of R-CHOP treatment between January 1, 2015 and July 31, 2019. Patients (n=141) included were respectively assigned to receive lenalidomide maintenance treatment (lenalidomide, n=50) and drug-free maintenance treatment (control, n=91) after CR/PR. lenalidomide was provided orally at 25 mg/day for 10 days, with a cycle of 21 days and a treatment course of 2 years. Progression-free survival (PFS) was taken as the primary outcome. Of the total 141 subjects, the median follow-up time was 30.9months (range, 5.7-68.9months). The 2-year PFS was 84% (95% CI: 74%-94%) in the lenalidomide group and 53% (95% CI: 43%-63%) in the control group. The median PFS of the lenalidomide group was not reached, and that of the control group was 42.9months (HR=0.32; 95% CI: 0.16-0.63; p=0.001). No remarkable difference in overall survival (OS) between the two groups was indicated (HR=0.42; 95% CI: 0.16-1.12; p=0.08). Central nervous system (CNS) recurrence happened in 5 patients (5.5%) of the control group, while none of the patients with lenalidomide had CNS recurrence. Additionally, neutropenia and cutaneous reactions were the most common Grade 1-2 adverse reactions after lenalidomide treatment, and neutropenia was the most frequent Grade 3-4 adverse reaction. Two-year lenalidomide maintenance treatment can significantly prolong the PFS of DLBCL patients who obtained CR/PR to first-line R-CHOP treatment.

ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs

Single-cell RNA sequencing technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potential for precision medicine has yet to be reached. Towards this, we propose A Single-cell Guided Pipeline to Aid Repurposing of Drugs (ASGARD) that defines a drug score to recommend drugs by considering all cell clusters to address the intercellular heterogeneity within each patient. ASGARD shows significantly better average accuracy on single-drug therapy compared to two bulk-cell-based drug repurposing methods. We also demonstrated that it performs considerably better than other cell cluster-level predicting methods. In addition, we validate ASGARD using the drug response prediction method TRANSACT with Triple-Negative-Breast-Cancer patient samples. We find that many top-ranked drugs are either approved by the Food and Drug Administration or in clinical trials treating corresponding diseases. In conclusion, ASGARD is a promising drug repurposing recommendation tool guided by single-cell RNA-seq for personalized medicine. ASGARD is free for educational use at https://github.com/lanagarmire/ASGARD.

Importance and Utility of the Principle of Ayurveda for Community Health

A nation is built by its citizens and these citizens with their good health, hard work determines the future of a nation. To ensure a bright and prosperous future we need to focus on the health of a community. Community health is defined as simple services that are delivered by common men outside hospitals and clinics. Community health services can be classified into Preventive Health Services, Promotive Health Services, Curative Health Services, and Rehabilitative Health Services. Preventive health services include measures by which we can avoid the disease before its occurrence Dincharya, Ritucharya, Sadvrit, Tryoupstham, and Vegdharan can be included in this category. Similarly, promotive heath care services include Rasayan, Vaajikaran, Ashtaaharvidhi vishesh ayatan, Sadvrit, Tryoupstham. Curative health services include single-drug therapy for the different diseases called Ekal dravya and treatment of Kaas, Swash, Atisaar, Amlapita which are very common. Rehabilitative health services such as physical therapy, counseling, and other mental health services can be provided by Ashwashan chikitsa, Medhya rasaayan, Yoga, Pathya palan, Padansikkarm palan.

Posaconazole as single or adjunctive antifungal in mucormycosis of the maxilla: systematic review and meta-analysis

Introduction: The aim of this systematic review was to analyse the benefits of utilizing posaconazole as a single drug therapy or in combination with other antifungals for the treatment of maxillary mucormycosis as opposed to sole use of amphotericin B. Materials and methods: Databases (MEDLINE via PubMed, Cochrane, EBSCO-host, Scopus, Science Direct, Clinical Trial Registry- India (CTRI) and Google scholar), review articles were searched from 1997 to 2022, using various MeSH terms. Results: After application of the inclusion and exclusion criteria, four articles were finally selected. Three-month survival rate and duration of hospital stay were analysed as primary outcomes. There was no difference in survival among cases of maxillary mucormycosis treated with either drug alone. Death reported after treatment with combination treatment was less as compared to that with amphotericin B alone; however, there was non-significant difference in survival among cases treated with posaconazole in addition to amphotericin B or amphotericin B alone. Conclusion: Posaconazole can be used a single drug therapy for the treatment of maxillary mucormycosis due to its benefits outweighing its risks. The limitations of this study are the paucity of studies and Randomized Controlled Trials available in the literature in this field of study.

Recent advances in the progress of immune checkpoint inhibitors in the treatment of advanced gastric cancer: A review.

Most patients with advanced gastric cancer were treated with palliative therapy, which had a poor curative effect and a short survival time. In recent years, the clinical research of immune checkpoint inhibitors in advanced gastric cancer has made a breakthrough and has become an important treatment for advanced gastric cancer. The modes of immune checkpoint inhibitors in the treatment of advanced gastric cancer include single drug, combined chemotherapy, radiotherapy, and multiple immune drug combination therapy, among which combination therapy shows better clinical efficacy, and a large number of trials are currently exploring more effective combination therapy programs. In this paper, the new clinical research progress of immune checkpoint inhibitors in the treatment of advanced gastric cancer is reviewed, with an emphasis on combination therapy.

Abstract 14860: Quantitative Whole Blood Platelet Aggregation Predicts Occurrence of Subacute Thrombosis in Patients After Percutaneous Coronary Intervention

Introduction: The risk of subacute thrombosis (SAT) after percutaneous coronary intervention (PCI) is high if patients show high whole blood platelet aggregation. Hypothesis: For such high-risk patients, even though dual antiplatelet therapy is performed, whole platelet aggregation should be quantitated and if high, the indication for additional antiplatelet therapy determined. Methods: This is a retrospective analysis of 26,314 stents from 26,314 patients (20,028 males; mean age 70±11 years). The whole blood platelet aggregatory threshold index (PATI; WBA-Neo; ISK, Osaka, Japan) was calculated. PATI was used to determine the minimum concentration of adenosine 5'-diphosphate causing a non-reversible aggregation of platelets and indicated platelet aggregation (range 0-8 μM). The higher the PATI, the lower the platelet aggregation. All patients received single or double antiplatelet drug therapy according to physician choice. Results: SAT occurred in 35 (0.13%) of 26,314 patients after PCI. Total blood PATI was 5.25±2.46 in 35 patients with SAT and 7.14±1.75 in 26,279 patients without SAT (P<0.001). Receiver operating characteristic (ROC) curves of the PATI for detection of occurrence of SAT showed an area under the curve (AUC) of 0.721. Best cutoff point of PATI was 6.435μM (sensitivity of 81% and specificity of 66%) for detection of occurrence of SAT (Youden index=0.464, P<0.001). No significant differences existed in the percentage of each coronary risk factor between patients with and without SAT after PCI (63% vs 47% for diabetes mellitus, P=0.054, 66% vs 75% for hypertension, P=0.209, 46% vs 57% for hyperlipidemia, P=0.190, and 34% vs 28% for smoking habits, P=0.381). Conclusions: In patients after PCI, despite single or double antiplatelet drug therapy, the whole blood platelet aggregation should be checked, and if PATI is <6.435 the indication for additional antiplatelet therapy should be considered.

Abstract 14681: Quantitative Whole Blood Platelet Aggregation Predicts Occurrence of Subacute Thrombosis in Patients After Percutaneous Coronary or Peripheral Intervention

Introduction: The risk of subacute thrombosis (SAT) after percutaneous coronary intervention (PCI) or percutaneous peripheral intervention (PPI) is high if patients show high whole blood platelet aggregation. Hypothesis: For such high-risk patients, even though dual antiplatelet therapy is performed, whole platelet aggregation should be quantitated and if high, the indication for additional antiplatelet therapy determined. Methods: This is a retrospective analysis of 12095 stents from 12095 patients (9173 males; mean age 69±11 years; 9470 PCI, 2625 PPI). The whole blood platelet aggregatory threshold index (PATI; WBA-Neo; ISK, Osaka, Japan) was calculated. PATI was used to determine the minimum concentration of adenosine 5'-diphosphate causing a non-reversible aggregation of platelets and indicated platelet aggregation (range 0-8 μM). The higher the PATI, the lower the platelet aggregation. All patients received single or double antiplatelet drug therapy according to physician choice. Results: SAT occurred in 18 (0.19%) of 9470 patients after PCI and in 9 patients (0.34%) of 2625 patients after PPI. Of 9470 patients after PCI, total blood PATI was 4.40 in 18 patients with SAT and 7.00 in 9452 patients without SAT (P<0.001). Of 2625 patients after PPI, the total blood PATI was 4.97 in nine patients with SAT and 6.39 in 2616 patients without SAT; the former was significantly lower than the latter (P<0.001). We combined patients with PCI and PPI. PATI was divided into nine grades: 0-0.99, 1-1.99, 2-2.99. 3-3.99, 4-4.99. 5-5.99, 6-6.99, 7-7.99, and >7.99. Of 12095 patients, if PATI was 0-0.99, the incidence of SAT was greatest at 1.89%. If PATI was >7.99, the incidence of SAT was lowest at 0.09%. We divided 12095 patients into two groups: PATI of 0-4.99 (N=2229) and PATI of >4.99(N=9866); the incidence of SAT was greater in the former (0.72%) than latter (0.11%; P<0.001). No significant differences existed in the percentage of each coronary risk factor between patients with and without SAT after PCI, PPI, and PCI or PPI. Conclusions: In patients after PCI and/or PPI, despite single or double antiplatelet drug therapy, the whole blood platelet aggregation should be checked, and if PATI is 0-4.99 the indication for additional antiplatelet therapy should be considered.

PCSK9 inhibitors: effectiveness of treatment and changes in background lipid-lowering therapy in a real world Italian population. The AT-TARGET-IT study

Abstract Introduction PCSK9 inhibitors (PCSK9i) significantly decrease LDL cholesterol (LDL-C), either as monotherapy or in addition to the maximally tolerated dose of statin and/or ezetimibe. Yet, few data are available on efficacy and background lipid-lowering therapy (LLT) adjustment in patients treated with PCSK9i in real-world observations. Purpose AT-TARGET-IT is an Italian multicenter registry involving 9 Italian centers, designed to assess efficacy, adherence, and persistence of PCSK9i, as well as prescribing doctors' behavior in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH). The aim of the present analysis was to assess efficacy and changes in background LLT therapy in patients on PCSK9i in a real-world single country observation. Methods From June through November 2021, we enrolled patients with PCSK9i first prescription from 6 months before inclusion through starting of PCSK9i use. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at the latest observation preceding inclusion in the study. Background therapy was assessed at baseline and during follow-up, evaluating treatment withdrawal, reduction of doses, or changes from statin-ezetimibe association to single drug therapy. Results We enrolled 798 patients (27% with FH) receiving either alirocumab or evolocumab and followed for a median time of 19.3 months. At the time of PCSK9i first prescription LDL-C was 147.6 mg/dl and reached 51.5 mg/dl at the time of latest observation (64% reduction), and 129 patients (16%) were not receiving any LLT, 669 patients received background LLT, of them 246 (31%) were taking ezetimibe alone and 423 (53%) were taking statins with or without ezetimibe. At the end of the observation period, 785 patients (98%) were still receiving PCSK9i and 550 (69%) did not change background LLT. Of 248 patients changing background LLT, 116 (47%) withdrew therapy, 132 (53%) changed dose or type of LLT. After stratification by achievement of LDL-C target according CV risk class, 483 patients achieved the target (60%). Target was achieved at the end of the observation period in 63% of patients taking triple therapy, 65% patients receiving PCSK9i plus statins, 62% of patients receiving PCSK9i plus ezetimibe and 55% receiving PCSK9i alone (Figure 1). No significant differences in terms of percentage of patients changing background LLT during PCSK9i treatment were found between patients at target for LDL-C and those not at target. Conclusion AT-TARGET-IT study shows that PCSK9i therapy is effective in reaching LDL-C target in the majority of patients, yet a sizable number of them (40%) remains undertreated. LLT background therapy is either reduced or withdrawn in 31% of patients, being responsible for not reaching target. Reasons for inappropriate LLT changes in patients receiving PCSK9i should be identified and removed to optimize lipid control. Funding Acknowledgement Type of funding sources: None.

Comparison of Single vs Combination Drug Therapy in Extensively Drug Resistant Salmonella typhi: An Observational Study from Pakistan.

IntroductionAntibiotic resistance has become a significant problem in typhoid fever due to the emergence of extensively drug resistant (XDR) Salmonella enterica serovar typhi. In Pakistan, an outbreak of ceftriaxone-resistant typhoid was first reported in November 2016.MethodsA retrospective chart review was conducted at Liaquat National Hospital and Medical University, in Karachi, Pakistan. Patient records were identified from the microbiology laboratory data of all admitted patients who had blood culture positive for XDR Salmonella typhi from January 2017 to December 2019.ResultsOut of 254 patients, 179 (70%) were male with an average age of 11.7 ± 10.9 years. Around 190 (74%) patients were treated with combination therapy, 126 (49%) were given azithromycin and meropenem and 61 (24%) received azithromycin and imipenem. A total of 64 (25%) patients received single drug therapy, 33 (12%) were given azithromycin, 23 (9%) meropenem, and 8 (3%) imipenem. Analysis indicated that single drug therapy resulted in an earlier onset of defervescence compared with combination therapy (5.03±2.98 days vs 3.45±2.48 days; P <0.001), with a decreased occurrence of pancytopenia (P <0.001).ConclusionSingle antimicrobial therapy achieved defervescence earlier than combination therapy, with carbapenems performing better than azithromycin.

A Real-World Study of Optimal Treatment with Anlotinib First-Line Therapy in Advanced Hepatocellular Carcinoma.

PurposeTo observe the efficacy and safety of anlotinib as a first-line treatment for patients with advanced hepatocellular carcinoma (aHCC) in a real-word environment, explore the optimal treatment regimen for patients with aHCC using anlotinib as a first-line treatment.Patients and MethodsData from 62 patients with aHCC who received anlotinib single-drug first-line therapy between February 2019 and November 2021. Patients received anlotinib monotherapy, which may be interrupted or discontinued or changed in the event of unacceptable or severe adverse events (AEs) or failure to inhibit tumor progression. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate(ORR), disease control rate (DCR), overall survival (OS), and safety.ResultsAmong the 62 patients, in the best overall response assessment, there were 12 with complete response (CR; 19.4%), 17 with partial response (PR; 27.4%), 25 with stable disease (SD; 40.3%), and 8 with progressive disease (PD; 14.5%). The ORR and DCR were 46.8% and 87.1%, respectively. Among the 11 patients who received tyrosine kinase inhibitors (TKIs) combined with programmed death 1 (PD-1) inhibitors after disease progression, three (27.3%) had CR, one (9.1%) had PR, three (27.3%) had SD, and four (36.4%) had PD. Therefore, the ORR and DCR were 36.4% and 63.6%, respectively. The median PFS for anlotinib monotherapy was 7.37 months (95% confidence interval [CI]: 5.88–8.86) and the median OS did not reach. AEs occurred in 95.2% of patients during anlotinib monotherapy, with the most common being thrombocytopenia (51.6%). The incidence of grade ≥3 AEs was 38.7%.ConclusionAnlotinib is effective and well-tolerated as a first-line treatment for patients with aHCC. Treatment with TKIs and PD-1 inhibitors after disease progression has also shown preliminary efficacy and safety; therefore, sequential therapy with anlotinib-TKIs and PD-1 inhibitors may be an effective treatment for patients with aHCC.

Ayurveda single drug therapy for Prameha in Nighantu Sahitya: A review

Diabetes is one of the most rapidly increasing diseases in the contemporary context. Its swift global raise indicates that its causes are possibly closely associated with lifestyle and eating habits in the general population. The handling of Diabetes is majorly management and not curative in nature. Understanding the management of diabetes, so far, has not been very promising either in the prevention of its incidence or its complications. The science of Ayurveda provides a huge repertoire of anti-diabetic drugs which needs further exploration. The descriptions of Prameha vis-à-vis Diabetes mellitus and its treatment are scattered in different classics of Ayurveda. This is an attempt to compile the information available from Nighantu Sahitya (the section of Ayurveda literature that predominantly deals with drugs, their morphology, properties, and actions) for documenting single drugs mentioned for Prameha Roga (mostly correlated to Diabetes Mellitus) and their potential in handling the disease. A total of 142 plant sourced drugs with Pramehahara activity enlisted from 12 Nighantus are included here. The paper accentuates the recognized sources of those single drugs, the botanical classification and their anti-diabetic potential. On observation, the members of Fabaceae were found to be most frequent in occurrence and hence has been a prime focus in this paper. A primary glance showed many drugs that are not in wide use for Prameha are enlisted here thus opening newer arenas for Diabetic research and clinical practice.

Application of Immune Checkpoint Inhibitors in EGFR Mutant Advanced Non-small Cell Lung Cancer

近年来，免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）极大地提高了无驱动基因突变的非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的生存率。与野生型肿瘤相比，表皮生长因子受体（epidermal growth factor receptor, EGFR）突变的肿瘤在程序性细胞死亡配体1（programmed cell death ligand 1, PD-L1）、肿瘤突变负荷（tumor mutational burden, TMB）等免疫微环境特征上具有更大的异质性。ICIs是否适用于EGFR突变的NSCLC患者一直存在争议。临床研究显示免疫单药对于EGFR突变的NSCLC患者无显著疗效，ICIs联合化疗和抗血管生成药物则显示了良好的生存获益。本文就EGFR突变晚期NSCLC患者ICIs单药或联合治疗的临床研究及相关机制进行综述。

Combined PARP and Dual Topoisomerase Inhibition Potentiates Genome Instability and Cell Death in Ovarian Cancer

Although ovarian cancer is a rare disease, it constitutes the fifth leading cause of cancer death among women. It is of major importance to develop new therapeutic strategies to improve survival. Combining P8-D6, a novel dual topoisomerase inhibitor with exceptional anti-tumoral properties in ovarian cancer and compounds in preclinical research, and olaparib, a PARP inhibitor targeting DNA damage repair, is a promising approach. P8-D6 induces DNA damage that can be repaired by base excision repair or homologous recombination in which PARP plays a major role. This study analyzed benefits of combining P8-D6 and olaparib treatment in 2D and 3D cultures with ovarian cancer cells. Measurement of viability, cytotoxicity and caspase activity were used to assess therapy efficacy and to calculate the combination index (CI). Further DNA damage was quantified using the biomarkers RAD51 and γH2A.X. The combinational treatment led to an increased caspase activity and reduced viability. CI values partially show synergisms in combinations at 100 nM and 500 nM P8-D6. More DNA damage accumulated, and spheroids lost their membrane integrity due to the combinational treatment. While maintaining the same therapy efficacy as single-drug therapy, doses of P8-D6 and olaparib can be reduced in combinational treatments. Synergisms can be seen in some tested combinations. In summary, the combination therapy indicates benefits and acts synergistic at 100 nM and 500 nM P8-D6.

NEXGB: A Network Embedding Framework for Anticancer Drug Combination Prediction.

Compared to single-drug therapy, drug combinations have shown great potential in cancer treatment. Most of the current methods employ genomic data and chemical information to construct drug–cancer cell line features, but there is still a need to explore methods to combine topological information in the protein interaction network (PPI). Therefore, we propose a network-embedding-based prediction model, NEXGB, which integrates the corresponding protein modules of drug–cancer cell lines with PPI network information. NEXGB extracts the topological features of each protein node in a PPI network by struc2vec. Then, we combine the topological features with the target protein information of drug–cancer cell lines, to generate drug features and cancer cell line features, and utilize extreme gradient boosting (XGBoost) to predict the synergistic relationship between drug combinations and cancer cell lines. We apply our model on two recently developed datasets, the Oncology-Screen dataset (Oncology-Screen) and the large drug combination dataset (DrugCombDB). The experimental results show that NEXGB outperforms five current methods, and it effectively improves the predictive power in discovering relationships between drug combinations and cancer cell lines. This further demonstrates that the network information is valid for detecting combination therapies for cancer and other complex diseases.

The MEK1/2 Inhibitor ATR-002 (Zapnometinib) Synergistically Potentiates the Antiviral Effect of Direct-Acting Anti-SARS-CoV-2 Drugs.

The coronavirus disease 2019 (COVID-19) represents a global public health burden. In addition to vaccination, safe and efficient antiviral treatment strategies to restrict the viral spread within the patient are urgently needed. An alternative approach to a single-drug therapy is the combinatory use of virus- and host-targeted antivirals, leading to a synergistic boost of the drugs’ impact. In this study, we investigated the property of the MEK1/2 inhibitor ATR-002’s (zapnometinib) ability to potentiate the effect of direct-acting antivirals (DAA) against SARS-CoV-2 on viral replication. Treatment combinations of ATR-002 with nucleoside inhibitors Molnupiravir and Remdesivir or 3C-like protease inhibitors Nirmatrelvir and Ritonavir, the ingredients of the drug Paxlovid, were examined in Calu-3 cells to evaluate the advantage of their combinatory use against a SARS-CoV-2 infection. Synergistic effects could be observed for all tested combinations of ATR-002 with DAAs, as calculated by four different reference models in a concentration range that was very well-tolerated by the cells. Our results show that ATR-002 has the potential to act synergistically in combination with direct-acting antivirals, allowing for a reduction in the effective concentrations of the individual drugs and reducing side effects.

HIV protease inhibitor nelfinavir is a potent drug candidate against echinococcosis by targeting Ddi1-like protein.

SummaryBackgroundAlveolar echinococcosis (AE), which is caused by larval Echinococcus multilocularis, is one of the world's most dangerous neglected diseases. Currently, no fully effective treatments are available to cure this disease.MethodsIn vitro protoscolicidal assay along with in vivo murine models was applied in repurposing drugs against AE. Genome-wide identification and homology-based modeling were used for predicting drug targets. RNAi, enzyme assay, and RNA-Seq analyses were utilized for investigating the roles in parasite survival and validations for the drug target.FindingsWe identified nelfinavir as the most effective HIV protease inhibitor against larval E. multilocularis. Once-daily oral administration of nelfinavir for 28 days resulted in a remarkable reduction in parasite infection in either immune-competent or immunocompromised mice. E. multilocularis DNA damage-inducible 1 protein (EmuDdi1) is predicted as a target candidate for nelfinavir. We proved that EmuDdi1 is essential for parasite survival and protein excretion and acts as a functionally active protease for this helminth. We found nelfinavir is able to inhibit the proteolytic activity of recombinant EmuDdi1 and block the EmuDdi1-related pathways for protein export. With other evidence of drug efficacy comparison, our results suggest that inhibition of EmuDdi1 is a mechanism by which this HIV proteinase inhibitor mediates its antiparasitic action on echinococcosis.InterpretationThis study demonstrates that nelfinavir is a promising candidate for treating echinococcosis. This drug repurposing study proves that the widely prescribed drug for AIDS treatment is potent in combating E. multilocularis infection and thus provides valuable insights into the development of single-drug therapy for highly prevalent co-infection between HIV and helminth diseases.FundingThis work was supported by the National Natural Science Foundation of China (31802179), the Natural Science Foundation of Gansu Province, China (No. 21JR7RA027), and the State Key Laboratory of Veterinary Etiological Biology (No. SKLVEB2021YQRC01).

Prevalence and Associated Risk Factors of African Animal Trypanosomiasis in Cattle in Lambwe, Kenya.

Background African animal trypanosomiasis (AAT) affects livestock productivity in sub-Saharan Africa. This study aimed to determine cattle AAT's prevalence and associated risk factors in Lambwe Valley, Kenya. Methods In a cross-sectional survey, livestock owners were recruited from four villages of Lambwe in Homa Bay, Kenya. Blood samples were collected from the jugular veins of cattle, and buffy coat smears were examined under a microscope. Parasites were further detected using polymerase chain reaction (PCR). Using a semistructured questionnaire, livestock owners were interviewed on their knowledge of AAT and control practices. Chi-square and multilevel models were used for the analysis. Results The overall prevalence was 15.63% (71/454). Trypanosoma vivax 10.31% and T. congolense Savannah 6.01% were the common species and subspecies. A total of 61 livestock keepers were involved in the study. Of these, 91.80% (56/61) knew AAT, and 90.16% (55/61) could describe the symptoms well and knew tsetse fly bite as transmission mode. Self-treatment (54.09%; 33/61) was common, with up to 50.00% of the farmers using drugs frequently. Isometamidium (72.13%; 44/61) and diminazene (54.09%; 33/61) were drugs frequently used. Although 16.39% (10/61) of the farmers claimed to use chemoprophylactic treatment, 6/10 did not use the right drugs. Animals (92.1%; 58/63) with clinical signs had positive infections. Villages closer to the national park recorded a higher prevalence. Infections were higher in cattle owned by those self-treating (27.23%; 58/213), those using drug treatment without vector control (27.62%; 50/181), those using single-drug therapy, and those practicing communal grazing (20.00%; 59/295). Clinical signs strongly associate with positive infections under multilevel modeling. Conclusion Cattle trypanosomiasis is prevalent in the Lambwe region of Kenya. This is influenced by inappropriate control practices, communal grazing, and the proximity of farms to the national park. In addition, clinical signs of the disease have a strong association with infections.

Detection Rate and Influencing Factors of Microalbuminuria in Hypertensive Patients

Abstract Background To investigate the detection rate and relevant influencing factors of microalbuminuria (MAU) in hypertensive patients in China. Methods A cross-sectional survey was conducted in 181,053 hypertensives from 600 hospitals across China. A questionnaire was used to collect information including patients’ risk factors, disease conditions, and antihypertensive drug treatment. Blood pressure was measured, and urine albumin to creatinine ratio was determined by urine strips. Patients were divided into the following subgroups: hypertension only, hypertension with and without MAU, cardiovascular risk factors, atherosclerotic cardiovascular disease (ASCVD), and single or combination drug therapy. Results A total of 136,483 patients with hypertension were enrolled. Patients with MAU, risk factors, and ASCVD or treated with combination drug therapy had significantly higher blood pressure compared with their corresponding counterparts (all P &amp;lt; 0.001). The detection rate of MAU was 27.8%, 25.7%, 29.1%, and 33.4% in hypertension only, hypertension with cardiovascular risk factors, hypertension with ASCVD, and hypertension with cardiovascular risk factors and ASCVD, respectively. Multivariate logistic regression analysis showed that age &amp;lt; 45 years, female, body mass index ≥ 28 kg/m2, living in Western China, living in Northeastern China, hypertension with risk factors and ASCVD, and combination drug therapy were positively correlated with MAU. Conclusions The detection rate of MAU is the highest in hypertensive patients with cardiovascular risk factors and ASCVD, and their blood pressure control is poor. Risk factor control and better blood pressure management are recommended.

Cost variation analysis of various brands of anti-retroviral agents currently available in Indian market: an economic perspective study

Background: The aim was to analyze the percentage cost variations among different brands of the commonly prescribed anti-retroviral agents in the treatment of human immunodeficiency virus.Methods: The cost of different brands of commonly used Anti-Retroviral agents was sorted out by referring latest Indian drug index online, drug today, current index of medical specialties, Indian drug review.Results: The percentage variation in the cost was above 100% with most of the commonly used anti-retroviral agents. Overall sequinafir 500 mg shows maximum cost variation of 1490.3%, while nelfinavir (625 mg) shows minimum cost variation of 6.1% in single drug therapy. Lamivudine 300 mg and tenofovir 300 mg combination shows maximum cost variation of 14055% whereas, lamivudine 150 mg, zidovudine 300 mg and efavirenz 600 mg shows minimum cost variation of 10% in combination drug therapy.Conclusions: HIV is the most common infectious, life-threatening disease and drugs are to be prescribed for life-long period. If a costly brand is prescribed, the patients cannot afford to pay more money for their treatment. This also leads to poor patient compliance, dissatisfaction and failure of the treatment. Ideally, therefore, the drugs should be prescribed in such a way, to save the patient's economic burden and enhance the compliance of the treatment.