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Quantifying and documenting prior beliefs in clinical trials.

Collecting and documenting subjective prior beliefs from knowledgeable clinicians about the potential results of a clinical trial has many advantages. Two large trials of prophylactic treatments in an HIV-positive population are used as examples. The trials recruited patients of primary care physicians and compared treatments which were in use in clinical practice. Opinions about these trials were elicited from 58 practising HIV clinicians. It is shown how the documented opinions can be used to augment the monitoring process; the prior opinions are updated with interim data using approximate B

UK malaria treatment guidelines 2016.

1.Malaria is the tropical disease most commonly imported into the UK, with 1300-1800 cases reported each year, and 2-11 deaths. 2. Approxima … choice (Grade 2C) and dihydroartemisinin-piperaquine (Eurartesim(®)) is an alternative. Quinine or atovaquone-proguanil (Malarone(®)) can be used if an ACT is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline. 11. Severe falciparum malari …

Pneumocystis carinii pneumonia incidence and chemoprophylaxis failure in ambulatory HIV-infected patients. HIV Outpatient Study (HOPS) Investigators.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) remains the most frequently reported serious opportunistic infection in AIDS patients and the second highest cause of mortality among persons with AIDS in the United States, despite the availability of effective chemoprophylaxis. METHODS: To evaluate incidence of PCP and determinants of PCP chemoprophylaxis failure, we analyzed data from 2842 patients visits to infectious diseases physicians at 10 HIV clinics (eight private and two public) in eight U.S. cities from January 1992 through June 1996 as part of the HIV Outpatient Study (HOPS). We pe

Immune-related diagnostic indicators and targeted therapies for COPD combined with NASH were identified and verified via WGCNA and LASSO.

INTRODUCTION: The incidence of chronic obstructive pulmonary disease (COPD) and non-alcoholic fatty liver disease (NAFLD) has increased sign … rugs associated with COPD and NASH were identified through cMAP analysis, including ansoprazole and atovaquone. In addition, we further identified the hub genes S100A9 and MYH2 for NAFLD and COPD by machine learning methods. The immune infiltration indicated that these two core genes might be involved in the immunomodulatory process of NASH by regulating the …

Low-dose intravenous and subcutaneous CIS43LS monoclonal antibody for protection against malaria (VRC 612 Part C): a phase 1, adaptive trial.

BACKGROUND: Human monoclonal antibodies might offer an important new approach to reduce malaria morbidity and mortality. In the first two pa … sed for P falciparum detection. Participants who tested positive for P falciparum were treated with atovaquone-proguanil and those who remained negative were treated at day 21. Participants were followed-up until 24 weeks after dosing. The primary outcome was safety and tolerability of CIS43LS at each dose level, assessed in the as-treated population. Second …

The Therapeutic Potential of Imidazole or Quinone-Based Compounds as Radiosensitisers in Combination with Radiotherapy for the Treatment of Head and Neck Squamous Cell Carcinoma.

The addition of platinum chemotherapy to primary radiotherapy (chemoradiation) improves survival outcomes for patients with head and neck squamous cell carcinoma (HNSCC), but it carries a high incidence of acute and long-term treatment-related complications, resulting in a poor quality of life. In addition, patients with significant co-morbidities, or older patients, cannot tolerate or do not benefit from concurrent chemoradiation. These patients are often treated with radiotherapy alone resulting in poor locoregional control and worse survival outcomes. Thus, there is an urgent need to assess

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… Quinone-Based Compound in the Treatment of HNSCC: Atovaquone Atovaquone is a chemical compound that belongs to the class of naphthoquinone analogues of ubiquinone. … In addition, atovaquone showed anti-cancer activity in cancer stem cells [ 57 ]. Moreover, it has been shown that atovaquone can also induce apoptosis in hepatocellular carcinoma (HCC) by a mechanism of DNA double-stranded breaks both in vitro and in vivo [ 58 ]. …

Drug susceptibility of Plasmodium falciparum in eastern Uganda: a longitudinal phenotypic and genotypic study.

BACKGROUND: Treatment and control of malaria depends on artemisinin-based combination therapies (ACTs) and is challenged by drug resistance, … rine (5·1 nM [3·2-7·7]), mefloquine (9·5 nM [6·6-13·0]), dihydroartemisinin (1·5 nM [1·0-2·0]), and atovaquone (0·3 nM [0·2-0·4]). Compared with results from our study in 2010-13, significant improvements in susceptibility were seen for chloroquine (median IC50 288·0 nM [IQR 122·0-607·0]; p<0·0001), monodesethylamodiaquine (76·0 nM [44·0-137]; p<0·0001), and …

Experience of SARS-CoV-2 infection in two kidney transplant recipients living with HIV-1 infection.

There is still no consensus on the optimal management of COVID-19 within the general population due to the emerging evidence base. High-risk groups, including kidney transplant recipients living with HIV present unique additional challenges. Here we discuss two kidney transplant recipients living with HIV with SARS-CoV-2 infection and their clinical course, and review the existing literature for this subset of challenging patients.

Prophylaxis for opportunistic infections among HIV-infected patients receiving medical care.

In 1995 and 1997, the United States Public Health Service (USPHS) and the Infectious Disease Society of America (IDSA) published recommendations for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), and toxoplasmosis in HIV-infected adults. We evaluated their implementation at four hospital-based HIV clinics in New York City in patients who initially met the CD4+ criterion for prophylaxis between January, 1995 and April, 1997. Medical records were reviewed at 6-month intervals to determine drugs prescribed. We identified 149 patients for the PCP sa

Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO).

Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology

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… We therefore recommend atovaquone as first alternative to TMP-SMX as PcP prophylaxis in patients with underlying hematologic or oncologic malignancies. … Low-dose atovaquone has been described to be less effective in PcP prophylaxis [ 164 ]; thus, 1500 mg atovaquone should be administered once daily (off-label use) (A-II t ). To increase bioavailability of atovaquone, it should be taken during a fatty meal [ 165 , 166 ]. …

Human monoclonal antibody MAM01 for protection against malaria in adults in the USA: a first-in-human, phase 1, dose-escalation, double-blind, placebo-controlled, adaptive trial.

BACKGROUND: Malaria remains a leading cause of mortality among children in Africa, and recent advances in control have stagnated. Although n … remaining aparasitaemic on days 20, 23, and 27. Participants who tested positive were treated with atovaquone-proguanil or artemether-lumefantrine; those who remained negative were empirically treated at day 27. A second dose of 5 mg/kg subcutaneously was administered to the cohorts that received 5 mg/kg subcutaneously or intravenously 2-4 weeks after compl …

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.

Purpose of reviewAcute myeloid leukemia (AML) in children remains a challenging disease to cure with suboptimal outcomes particularly when compared to the more common lymphoid leukemias. Recent advances in the genetic characterization of AML have enhanced understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. Here, we review key cytogenetic and molecular features of pediatric AML and how new therapies are being used to improve outcomes.Recent findingsRecent studies have revealed an increasing number of mutations, including WT1, CBFA2T

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… Recent studies have shown that atovaquone has effects on AML cells by inhibiting STAT3 phosphorylation and subsequent expression of STAT3 target genes [ 99 ]. … In adults, atovaquone is commonly used in post-SCT for PJP prophylaxis, and one retrospective study demonstrated that adults with AML who underwent SCT with prolonged atovaquone use had lower relapse rates than those with shorter atovaquone exposure, providing further rationale for clinical use of atovaquone …

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital.

Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients.

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… Safety and tolerability of atovaquone prophylaxis (1500 mg daily) has been demonstrated in autologous stem cell transplant recipients ( Colby et al , 1999 ), but studies of efficacy in non-HIV-infected patients are lacking. … Nebulised pentamidine may also be used, and atovaquone may be considered in patients unable to tolerate TMP–SMX or dapsone. …

Critically Ill Immunosuppressed Host

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… (leucovorin); or ▪ Atovaquone 1500 mg PO BID with meals (or nutritional supplement) and sulfadiazine 1000-1,500 mg PO q6h; or ▪ Atovaquone 1500 mg PO BID with meals; or ▪ Pyrimethamine (leucovorin) and azithromycin 900-1200 mg PO QD For severely iII patients who cannot take oral medications TMP-SMX … pyrimethamine (leucovorin); or ▪ Atovaquone 1500 mg PO BID with meals (or nutritional supplement) and sulfadiazine 1000-1,500 mg PO q6h; or ▪ Atovaquone 1500 mg PO BID with meals; or ▪ Pyrimethamine (leucovorin) and azithromycin 900-1200 mg PO QD For severely iII patients who cannot take oral medications …

Incidence of Pneumocystis jirovecii pneumonia utilizing a polymerase chain reaction-based diagnosis in patients receiving bendamustine.

BackgroundPneumocystis jirovecii pneumonia (PJP) is a life-threatening infection occurring in patients receiving bendamustine. The poorly defined incidence, particularly when utilizing polymerase chain reaction (PCR)-based diagnostic techniques, precipitates unclear prophylaxis recommendations. Our objective was to determine the cumulative incidence of PJP diagnosed by single copy target, non-nested PCR in patients receiving bendamustine.MethodsPatients were evaluated for PJP from initiation of bendamustine through 9 months after the last administration. The cumulative incidence of PJP was est

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… The patient was switched to atovaquone therapy for PJP and transferred to a medical floor within 48 hours of ICU admission. Patient #8 was diagnosed with PJP and started on intravenous clindamycin and oral primaquine due to a severe sulfa allergy while hospitalized. … She was successfully treated with atovaquone without any complications. A month later, the patient underwent allogeneic SCT. Prophylaxis was not significantly associated with a reduction in the development of PJP when compared no prophylaxis (HR 0.37, 95% CI (0.05, 3.04), p = 0.36). …

Targeting the nuclear export receptor exportin-1 in acute myeloid leukaemia: From biology to clinical translation.

BACKGROUND: Exportin-1 (XPO1), a key regulator of nucleocytoplasmic transport, is frequently dysregulated in acute myeloid leukemia (AML) and contributes to leukemogenesis, disease progression and therapeutic resistance. Selective inhibitors of nuclear export (SINEs), especially selinexor and eltanexor, have shown promising antileukemic potential. However, their clinical value, optimal therapeutic positioning and rational use in AML remain to be fully clarified. METHODS: We collected and reviewed relevant literature to summarize the biological roles of XPO1 in AML and the therapeutic potentia

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… In xenograft models, atovaquone plus selinexor reduced bone marrow leukaemic infiltration and prolonged survival, and higher CD62L expression was associated with improved outcomes. … Atovaquone and selinexor as a novel combination treatment option in acute myeloid leukemia. Cancer Lett. 2025;613:217501. 73. Kojima K, Kornblau SM, Ruvolo V, et al. Prognostic impact and targeting of CRM1 in acute myeloid leukemia. Blood. 2013;121(20):4166–4174. 74. …

Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016.

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial

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… A prospective randomized trial comparing the toxicity and safety of atovaquone with trimethoprim/sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation. … Atovaquone as long-term suppressive therapy for toxoplasmic encephalitis in patients with AIDS and multiple drug intolerance. Atovaquone Expand Access Group AIDS. 1996;10(10):1107–1112. 207. Garcia Garrido HM et al. (2015) Response to hepatitis A vaccination in immunocompromised travelers. …

Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review.

Babesia microti is an obligate intra-erythrocytic parasite transmitted by infected ticks. B. microti is a eukaryote much larger than prokaryotic microbes and more similar to human hosts in their biochemistry and metabolism. Moreover, Babesia spp. possess various immune evasion mechanisms leading to persistent and sometimes life-threatening diseases in immunocompromised hosts. Chronic lymphocytic leukemia (CLL) is the most prevalent adult B-cell malignancy, and a small percentage of CLL transforms into aggressive lymphomas. CLL also causes immune dysfunction due to the over-expansion of immatur

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… He completed the 10-day course of atovaquone and azithromycin treatment at home. The patient was able to do all his normal physical activities for the next 2 months. … Clinical and molecular evidence of atovaquone and azithromycin resistance in relapsed babesia microti infection associated with rituximab and chronic lymphocytic leukemia. …