Transfusion Challenges in Patients with Hematological Malignancies in Sub-Saharan Africa: A Prospective Observational Study from the Uganda Cancer Institute.
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ABSTRACT:
SUBMITTER: Ddungu H
PROVIDER: S-EPMC7028934 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To summarize recent developments for HIV-associated malignancies (HIVAM) in low-income and middle-income countries (LMIC) with particular focus on sub-Saharan Africa (SSA).Antiretroviral therapy (ART) scale-up is leading to epidemiologic transitions in LMIC similar to high-income countries, with aging and growth of HIV-infected populations, declining infectious deaths, increasing cancer deaths, and transitions from AIDS-defining cancers to non-AIDS defining cancers. Despite ART scale-up, the HIVAM burden remains high including an enormous AIDS-defining cancers burden in SSA. For Kaposi sarcoma, patients treated with ART and chemotherapy can experience good outcomes even in rural SSA, but Kaposi sarcoma heterogeneity remains insufficiently understood including virologic, immunologic, and inflammatory features that may be unique to LMIC. For cervical cancer, scale-up of prevention efforts including vaccination and screening is underway, with benefits already apparent despite continuing high disease burden. For non-Hodgkin lymphoma, curative treatment is possible in the ART era even in SSA, and multifaceted approaches can improve outcomes further. For many other prevalent HIVAM, care and research efforts are being established to guide treatment and prevention specifically in LMIC.Sustained investment for HIVAM in LMIC can help catalyze a cancer care and research agenda that benefits HIV-positive and HIV-negative patients worldwide.
| S-EPMC5241291 | biostudies-other
Project description:The transfusion support of hematological malignancies considers 2 dimensions: the quantity of what we order (in terms of triggers, doses, targets, and intervals), and the special qualities thereof (with respect to depths of matching and appropriate product modifications). Meanwhile, transfusion-related enhancements in the quantity and quality of life may not be dose dependent but rather tempered by unintended patient harms and system strains from overexposure. Evidence and guidelines concur in endorsing clinically noninferior conservative red blood cell (RBC) transfusion care strategies (eg, triggering at hemoglobin <7-8 g/dL and in single-unit doses for stable, nonbleeding inpatients). However, the unique subpopulation of patients with hematological malignancies who are increasingly managed on an outpatient basis, and striving at least as much for quality of life as quantity of life, is left on the edges of these recommendations, with more questions than answers. If a sufficiently specific future wave of evidence can satisfy the concerns (and contest the assumptions) of the remaining proponents of liberalism, and if conservatism is broadly adopted, savings may be potentially immense. These savings can then be reinvested to address other gaps and inconsistencies in RBC transfusion care, such as the best achievable degrees of prophylactic antigen matching that can minimize alloimmunization-related service delays and reactions.
| S-EPMC6246005 | biostudies-literature
Project description:BackgroundPatients with suspected tuberculosis are often overtreated with antituberculosis drugs. We evaluated the diagnostic value of the focused assessment with sonography for HIV-associated tuberculosis (FASH) in rural Tanzania.MethodsIn a prospective cohort study, the frequency of FASH signs was compared between patients with confirmed tuberculosis and those without tuberculosis. Clinical and laboratory examination, chest x-ray, Xpert MTB/RIF assay, and culture from sputum, sterile body fluids, lymph node aspirates, and Xpert MTB/RIF urine assay was done.ResultsOf 191 analyzed patients with a 6-month follow-up, 52.4% tested positive for human immunodeficiency virus, 21.5% had clinically suspected pulmonary tuberculosis, 3.7% had extrapulmonary tuberculosis, and 74.9% had extrapulmonary and pulmonary tuberculosis. Tuberculosis was microbiologically confirmed in 57.6%, probable in 13.1%, and excluded in 29.3%. Ten of eleven patients with splenic or hepatic hypoechogenic lesions had confirmed tuberculosis. In a univariate model, abdominal lymphadenopathy was significantly associated with confirmed tuberculosis. Pleural- and pericardial effusion, ascites, and thickened ileum wall lacked significant association. In a multiple regression model, abnormal chest x-ray (odds ratio [OR] = 6.19; 95% confidence interval [CI], 1.96-19.6; P < .002), ≥1 FASH-sign (OR = 3.33; 95% CI, 1.21-9.12; P = .019), and body temperature (OR = 2.48; 95% CI, 1.52-5.03; P = .001 per °C increase) remained associated with tuberculosis. A combination of ≥1 FASH sign, abnormal chest x-ray, and temperature ≥37.5°C had 99.1% sensitivity (95% CI, 94.9-99.9), 35.2% specificity (95% CI, 22.7-49.4), and a positive and negative predictive value of 75.2% (95% CI, 71.3-78.7) and 95.0% (95% CI, 72.3-99.3).ConclusionsThe absence of FASH signs combined with a normal chest x-ray and body temperature <37.5°C might exclude tuberculosis.
| S-EPMC6483805 | biostudies-literature
Project description:BackgroundNosocomial infection (NI) causes prolonged hospital stays, increased healthcare costs, and higher mortality among patients with hematological malignancies (HM). However, few studies have compared the incidence of NI according to the HM lineage.ObjectiveTo compare the incidence of NI according to the type of HM lineage, and identify the risk factors for NI.MethodsThis prospective observational study monitored adult patients with HM admitted for >48 hours to the General Hospital of the People's Liberation Army during 2010-2013. Attack rates and incidences of NI were compared, and multivariable logistic regression was used to control for confounding effects.ResultsThis study included 6,613 admissions from 1,922 patients. During these admissions, 1,023 acquired 1,136 NI episodes, with an attack rate of 15.47% and incidence of 9.6‰ (95% CI: 9.1-10.2). Higher rates and densities of NIs were observed among myeloid neoplasm (MN) admissions, compared to lymphoid neoplasm (LN) admissions (28.42% vs. 11.00%, P<0.001 and 11.4% vs. 8.4‰, P<0.001). NI attack rates in acute myeloid leukemia (AML) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) were higher than those in MDS (30.69% vs. 20.19%, P<0.001; 38.89% vs. 20.19%, P = 0.003). Attack rates in T/NK-cell neoplasm and B-cell neoplasm were higher than those in Hodgkin lymphoma (15.04% vs. 3.65%; 10.94% vs. 3.65%, P<0.001). Multivariable regression analysis indicated prolonged hospitalization, presence of central venous catheterization, neutropenia, current stem cell transplant, infection on admission, and old age were independently associated with higher NI incidence. After adjusting for these factors, MN admissions still had a higher risk of infection (odds ratio 1.34, 95% CI: 1.13-1.59, P<0.001).ConclusionDifferent NI attack rates were observed for HM from different lineages, with MN lineages having a higher attack rate and incidence than LN lineages. Special attention should be paid to MN admissions, especially AML and MDS/MPN admissions, to control NI incidence.
| S-EPMC4240653 | biostudies-literature
Project description:CD47 is a cell-surface ligand that is overexpressed in various malignancies and that binds to SIRPα on macrophages to promote tumor cell evasion of phagocytosis. Blocking the CD47-SIRPα axis can increase the phagocytosis of macrophages to exert antitumor effects. CD47-based immunotherapy is a current research focus. The combination of anti-CD47 antibodies with other drugs has shown encouraging response rates in patients with hematological tumors, but side effects also occur. Bispecific antibodies and SIRPα/Fc fusion proteins appear to balance the efficacy and safety of treatment. We review the latest clinical research advances and discuss the opportunities and challenges associated with CD47-based immunotherapy for hematological malignancies.
| S-EPMC10920290 | biostudies-literature
Project description:BACKGROUND:Every year, an estimated 2.6 million stillbirths occur worldwide, with up to 98% occurring in low- and middle-income countries (LMIC). There is a paucity of primary data on cause of stillbirth from LMIC, and particularly from sub-Saharan Africa to inform effective interventions. This study aimed to identify the cause of stillbirths in low- and middle-income settings and compare methods of assessment. METHODS:This was a prospective, observational study in 12 hospitals in Kenya, Malawi, Sierra Leone and Zimbabwe. Stillbirths (28 weeks or more) were reviewed to assign the cause of death by healthcare providers, an expert panel and by using computer-based algorithms. Agreement between the three methods was compared using Kappa (κ) analysis. Cause of stillbirth and level of agreement between the methods used to assign cause of death. RESULTS:One thousand five hundred sixty-three stillbirths were studied. The stillbirth rate (per 1000 births) was 20.3 in Malawi, 34.7 in Zimbabwe, 38.8 in Kenya and 118.1 in Sierra Leone. Half (50.7%) of all stillbirths occurred during the intrapartum period. Cause of death (range) overall varied by method of assessment and included: asphyxia (18.5-37.4%), placental disorders (8.4-15.1%), maternal hypertensive disorders (5.1-13.6%), infections (4.3-9.0%), cord problems (3.3-6.5%), and ruptured uterus due to obstructed labour (2.6-6.1%). Cause of stillbirth was unknown in 17.9-26.0% of cases. Moderate agreement was observed for cause of stillbirth as assigned by the expert panel and by hospital-based healthcare providers who conducted perinatal death review (κ = 0.69; p < 0.0005). There was only minimal agreement between expert panel review or healthcare provider review and computer-based algorithms (κ = 0.34; 0.31 respectively p < 0.0005). CONCLUSIONS:For the majority of stillbirths, an underlying likely cause of death could be determined despite limited diagnostic capacity. In these settings, more diagnostic information is, however, needed to establish a more specific cause of death for the majority of stillbirths. Existing computer-based algorithms used to assign cause of death require revision.
| S-EPMC6894270 | biostudies-literature
Project description:AbstractRemarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.
| S-EPMC10106177 | biostudies-literature
Project description:IntroductionCytomegalovirus (CMV) predisposes to several clinical complications and is a major cause of morbidity and mortality in immunocompromised patients, including patients with hematological malignancies (HM). The present study was carried out to determine the distribution of CMV glycoprotein B, N, and O (gB, gN, and gO) genotypes and their potential effect on its viral load and on clinical outcomes in a cohort of Tunisian non-hematopoietic stem cell transplant (HSCT) patients with HM undergoing chemotherapy.MethodsCMV viral load was evaluated by real-time quantitative PCR. The gB, gN, and gO genotypes of the CMV strains were analyzed by multiplex nested PCR and sequencing.ResultsThis prospective study involved 60 clinical isolates obtained from 60 non-HSCT patients with HM undergoing chemotherapy. Mixed CMV gB, gN, and gO genotypes were the predominant glycoprotein genotypes in 31%, 41.4%, and 46.4% of patients, respectively. Mixed gB genotypes were associated with higher initial levels of CMV load (p = 0.001), increased rate of fever (0.025), and co-infection with other herpesviruses (HHVs) (p = 0.024) more frequently than in single gB genotype. Mixed gN genotypes were more associated with severe lymphopenia (ALC < 500/µL) (p = 0.01) and increased risk of death (p = 0.042) than single gN genotype. Single gO2b genotype had also a more unfavorable outcome (p = 0.009) than the other single gO genotype. Mixed gO genotypes were associated with female gender (p = 0.015), acute leukemia disease (p = 0.036), initial high level of CMV viral load (at least 1000 copies/mL) (p = 0.029), skin rash (p = 0.01) more frequently than in single gO genotype. The gO1a/gN3b linkage was associated with an increased initial viral load (p = 0.012).ConclusionInfection with mixed CMV genotypes was common and multiple gB, gN, and gO genotypes were associated with clinical manifestation and higher viral load.
| S-EPMC8322362 | biostudies-literature
Project description:BackgroundImproving breast cancer survival in sub-Saharan Africa (SSA) is urgently needed, requiring early diagnosis and improved access to treatment. However, data on the types of and barriers to receiving breast cancer therapy in this region are limited and have not been compared between different SSA countries and treatment settings.MethodsIn different health care settings across Uganda, Nigeria and Namibian sites of the prospective African Breast Cancer - Disparities in Outcomes cohort study, we assessed the percentage of newly diagnosed breast cancer patients who received treatment (systemic, surgery and/or radiotherapy) for cancer and their socio-demographic and clinical determinants. Treatment data were systematically extracted from medical records, as well as self-reported by women during 6-month follow-up interviews, and were used to generate a binary indicator of treatment received within 12 months of diagnosis (yes/no), which was analysed via logistic regression.ResultsOf 1325 women, cancer treatment had not been initiated treatment within 1 year of diagnosis for 227 (17%) women and 185 (14%) of women with stage I-III disease. Untreated percentages were highest in two Nigerian regional hospitals where 38% of 314 women were not treated (32% among stage I-III). At a national referral hospital in Uganda, 18% of 430 women were not treated (15% among stage I-III). In contrast, at a cancer care centre in Windhoek, Namibia, where treatment is provided free to the patient, all non-black (100%) and almost all (98.7%) black women had initiated treatment. Percentages of untreated women were higher in women from lower socio-economic groups, women who believed in traditional medicine and, in Uganda, in HIV+ women. Self-reported treatment barriers confirmed treatment costs and treatment refusal as contributors to not receiving treatment.ConclusionsFinancial support to ensure treatment access and education of treatment benefits are needed to improve treatment access for breast cancer patients across sub-Saharan Africa, especially at regional treatment centres, for lower socio-economic groups, and for the HIV-positive woman with breast cancer.
| S-EPMC6691541 | biostudies-literature
Project description:BackgroundChildren in Sub-Saharan Africa (SSA) comprise half of the total regional population, yet existing mental health services are severely under-equipped to meet their needs. Although effective interventions for the treatment of disruptive behavioral disorders (DBDs) in youth have been tested in high-poverty and high-stress communities in developed countries, and are relevant for widespread dissemination in low- and middle-income countries (LMICs), most of these evidence-based practices (EBPs) have not been utilized in SSA, a region heavily impacted by poverty, diseases including HIV/AIDS, and violence. Thus, this paper presents a protocol for a scale-up longitudinal experimental study that uses a mixed-methods, hybrid type II, effectiveness implementation design to test the effectiveness of an EBP, called Multiple Family Group (MFG) aimed at improving child behavioral challenges in Uganda while concurrently examining the multi-level factors that influence uptake, implementation, sustainment, and youth outcomes.MethodsThe MFG intervention will be implemented and tested via a longitudinal experimental study conducted across 30 public primary schools located in both semi-urban and rural communities. The schools will be randomly assigned to three study conditions (n = 10 per study condition): (1) MFG delivered by trained family peers; (2) MFG delivered by community health workers; or; (3) comparison: usual care comprising mental health care support materials, bolstered with school support materials. A total of 3000 children (ages 8 to 13 years; grades 2 to 7) and their caregivers (N = 3000 dyads); 60 parent peers, and 60 community health workers will be recruited. Each study condition will comprise of 1000 child-caregiver dyads. Data will be collected at baseline, 8 and 16 weeks, and 6-month follow-up.DiscussionThis project is the first to test the effectiveness of the MFG intervention while concurrently examining multi-level factors that influence overall implementation of a family-based intervention provided in schools and aimed at reaching the large child population with mental health service needs in Uganda. Moreover, the study draws upon an EBP that has already been tested for delivery by parent peers and community facilitators, and hence will take advantage of the advancing science behind task-shifting. If successful, the project has great potential to address global child mental health needs.Trial registrationClinicalTrials.gov, ID: NCT03081195 . Registered on 16 March 2017.
| S-EPMC6080393 | biostudies-literature