RESUMEN
BACKGROUND: Cancer-related stigma impacts patients' emotional health, care engagement, and cancer outcomes, but few measures of cancer stigma exist. We culturally adapted and assessed psychometric properties of the Cataldo Cancer Stigma Scale (CCSS) in Tanzania. METHODS: We administered the CCSS short version (21 items), plus 12 locally-derived items, to 146 adult cancer patients. We conducted exploratory factor analysis, examined internal consistency/reliability, and assessed convergent validity with relevant measures. RESULTS: We identified a 17-item cancer stigma scale with strong psychometric properties and four subscales: enacted stigma, shame and blame, internalized stigma, and disclosure concerns. Stigma was rare except for disclosure concerns. Stigma was positively associated with depression and anxiety and negatively associated with social support, quality of life, and illness acceptance. CONCLUSIONS: The scale provides valid, culturally-informed measurement of cancer stigma in Tanzania. Future studies should assess associations with care engagement, which will inform interventions to reduce stigma and improve outcomes.
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Neoplasias , Calidad de Vida , Adulto , Humanos , Psicometría , Reproducibilidad de los Resultados , Tanzanía , Encuestas y Cuestionarios , Estigma Social , Neoplasias/terapiaRESUMEN
Appropriate diagnosis and treatment of gynecological cancers in people living with human immunodeficiency virus (HIV) remains a clinical challenge given rapid changes in both HIV and cancer management and a lack of prospective clinical trial data inclusive of the HIV population. A semi-systematic literature review was performed to identify published studies addressing risk factors, screening, treatment efficacy, treatment toxicity, and prognosis for people living with HIV diagnosed with gynecological malignancies, with a focus on radiotherapy and cervical cancer, given the relative paucity of literature on uterine, ovarian, and vulvovaginal cancers in people living with HIV. People living with HIV are more likely to be co-infected with human papilloma virus and more likely to develop human papilloma virus-associated malignancies. People living with HIV are less likely to receive cancer treatment compared with HIV-uninfected cancer patients, even after adjusting for differences in clinical features and sociodemographic variables. The literature on cervical cancer outcomes is mixed, with some studies demonstrating that people living with HIV have inferior treatment tolerability, response rates, and survival following chemoradiotherapy, and others showing no difference in these outcomes, particularly in patients receiving antiretroviral therapy. Importantly, even in the series showing inferior outcomes in people living with HIV, there were long-term survivors after administration of curative therapy. Consistent with published cancer management guidelines, people living with HIV diagnosed with gynecological cancers should be treated with standard cancer therapy. Co-management with the patient's HIV specialist is critical to avoid overlapping toxicities and provide optimal supportive care. The morbidity and mortality caused by gynecologic cancers in this population can be mitigated by early diagnosis, appropriate treatment delivery including inclusion of people with HIV in cancer clinical trials, and diligent HIV management.
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Infecciones por VIH , Neoplasias del Cuello Uterino , Femenino , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Tamizaje Masivo , Factores de Riesgo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
South Africa is facing an established epidemic of methamphetamine, known locally as "tik." Globally, methamphetamine has been linked to high rates of sexual risk behaviors, including sex trading. The goal of this study was to qualitatively examine the experiences of sex trading among methamphetamine users in Cape Town, South Africa. Individual in-depth interviews were conducted with 30 active methamphetamine users (17 men and 13 women) recruited from the community. Interviews were conducted in local languages using a semi-structured guide that included questions on sex trading experiences and perceptions of sex trading among methamphetamine users. Interviews were audio-recorded, transcribed, and analyzed using analytic memos and coding with constant comparison techniques. The data revealed that in a setting of high levels of addiction and poverty, sex was an important commodity for acquiring methamphetamine. Women were more likely to use sex to acquire methamphetamine, but men reported opportunistic cases of trading sex for methamphetamine. Four models of sex trading emerged: negotiated exchange, implicit exchange, relationships based on resources, and facilitating sex exchange for others. The expectation of sex trading created a context in which sexual violence against female methamphetamine users was common. Multiple sexual partners and inconsistent condom use in acts of sex trading put methamphetamine users at high risk of HIV. Interventions in this setting should address addiction, which is the primary driver of sex trading among methamphetamine users. Harm reduction interventions may include education about HIV and other sexually transmitted infections, availability of condoms and HIV testing, and sexual violence prevention.
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Consumidores de Drogas , Metanfetamina/efectos adversos , Asunción de Riesgos , Trabajadores Sexuales , Adulto , Trastornos Relacionados con Anfetaminas/epidemiología , Trastornos Relacionados con Anfetaminas/psicología , Estimulantes del Sistema Nervioso Central/efectos adversos , Condones/estadística & datos numéricos , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Delitos Sexuales , Trabajo Sexual , Conducta Sexual , Medio Social , Sudáfrica/epidemiología , Grabación en Cinta , Adulto JovenRESUMEN
Methamphetamine users in South Africa are at high risk for HIV infection and transmission, but little is known about HIV testing in this population. We examined HIV testing behaviors and attitudes in 362 methamphetamine users recruited using chain referral sampling from one peri-urban community. Many (44 %) had not been HIV tested in the past year. HIV testing was associated with positive testing attitudes, less AIDS stigma, and greater methamphetamine stigma. Among participants who reported HIV infection (8 %), less than half were linked to care. Findings highlight the need to identify barriers to HIV service uptake for methamphetamine users.
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Población Negra , Estimulantes del Sistema Nervioso Central/efectos adversos , Infecciones por VIH/psicología , Metanfetamina/efectos adversos , Aceptación de la Atención de Salud/psicología , Estigma Social , Adulto , Estudios Transversales , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Tamizaje Masivo , Aceptación de la Atención de Salud/estadística & datos numéricos , Vigilancia de la Población , Asunción de Riesgos , Factores Socioeconómicos , Sudáfrica/epidemiología , Encuestas y CuestionariosRESUMEN
PURPOSE: Assessing risk of recurrence for nonmetastatic triple-negative breast cancer (TNBC) is a key determinant of therapeutic strategy. The best predictor of recurrence risk is failure to achieve a pathologic complete response after preoperative chemotherapy, but it imperfectly correlates with the definitive end points of relapse-free and overall survival (OS). The inability to accurately predict recurrence has led to increasingly toxic treatment regimens for patients with early-stage TNBC. Better assays for recurrence risk are needed to tailor aggressive therapy for patients who need it and avoid overtreatment and unnecessary toxicity for those at low risk. The purpose of this study was to determine if patient-derived xenograft (PDX) engraftment of newly diagnosed breast tumors can serve as an accurate predictor of recurrence and death from breast cancer. METHODS: This study was a blinded noninterventional trial comprising 80 patients with newly diagnosed, nonmetastatic, estrogen receptor (ER)-negative or ER-low breast cancer. RESULTS: PDX engraftment was strongly associated with relapse in 1 year: 8 of 18 (44.4%) patients whose tumors engrafted relapsed versus 1 of 62 (1.6%) patients whose tumors did not engraft (P < .0001). Patients whose tumors engrafted had a hazard ratio (HR) for relapse of 17.5. HRs for OS and breast cancer-specific survival in PDX+ patients were 21.1 and 39.5, respectively. CONCLUSION: We report that the ability of a tumor to engraft as a PDX predicts early recurrence by serving as a functional readout of aggressiveness and prospectively identifies the most devastating tumors. This provides new opportunity to develop surrogate assays, such as biomarkers of engraftment, which will extend the clinical feasibility of this finding.
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Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapia , Femenino , Persona de Mediana Edad , Animales , Adulto , Anciano , Ratones , Recurrencia Local de Neoplasia , XenoinjertosRESUMEN
PURPOSE: Stigma is an impediment across the cancer care continuum, leading to delayed presentation to care, elevated morbidity and mortality, and reduced quality of life. The goal of this study was to qualitatively examine the drivers, manifestations, and impacts of cancer-related stigma among individuals who received cancer treatment in Malawi, and to identify opportunities to address stigma. METHODS: Individuals who had completed treatment for lymphoma (n = 20) or breast cancer (n = 9) were recruited from observational cancer cohorts in Lilongwe, Malawi. Interviews explored the individual's cancer journey, from first symptoms through diagnosis, treatment, and recovery. Interviews were audio-recorded and translated from Chichewa to English. Data were coded for content related to stigma, and thematically analyzed to describe the drivers, manifestations, and impacts of stigma along the cancer journey. RESULTS: Drivers of cancer stigma included beliefs of cancer origin (cancer as infectious; cancer as a marker of HIV; cancer due to bewitchment), perceived changes in the individual with cancer (loss of social/economic role; physical changes), and expectations about the individual's future (cancer as death sentence). Cancer stigma manifested through gossip, isolation, and courtesy stigma toward family members. The impacts of cancer stigma included mental health distress, impediments to care engagement, lack of cancer disclosure, and self-isolation. Participants suggested the following programmatic needs: community education about cancer; counseling in health facilities; and peer support from cancer survivors. CONCLUSION: The results highlight multifactorial drivers, manifestations, and impacts of cancer-related stigma in Malawi, which may affect success of cancer screening and treatment programs. There is a clear need for multilevel interventions to improve community attitudes toward people with cancer, and to support individuals along the continuum of cancer care.
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Supervivientes de Cáncer , Infecciones por VIH , Neoplasias , Humanos , Calidad de Vida , Malaui , Infecciones por VIH/psicología , Estigma Social , Neoplasias/diagnóstico , Neoplasias/terapiaRESUMEN
PURPOSE: Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors. METHODS: An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world. RESULTS: Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided. CONCLUSION: Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.
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Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/uso terapéutico , África/epidemiologíaRESUMEN
PURPOSE: There are limited data on treatment and outcomes for acute lymphoblastic leukemia (ALL) among adolescents and young adults in sub-Saharan Africa. We describe a prospective observational cohort in Malawi. METHODS: Patients age 15-39 years with newly diagnosed ALL at Kamuzu Central Hospital, Malawi, were enrolled from 2013 to 2019; follow-up was censored on December 2020. ALL diagnosis was confirmed on-site using immunohistochemistry and telepathology consultation involving pathologists in Malawi and the United States. All but four patients were treated with a modified pediatric-inspired regimen (Cancer and Leukemia Group B 10403 protocol). Key modifications included omission of asparaginase and no dose escalation for methotrexate. RESULTS: Of 19 participants, the median age was 22 (range 15-36) years. Of the 15 patients who initiated treatment, 11 (73%) achieved remission after induction, one (7%) died during induction, two (13%) had refractory disease, and one (7%) absconded. No patients were lost to follow-up. Eventually, 10 of 11 patients (91%) with confirmed remission relapsed. The median duration of first remission was 10 (range 3-22) months. Twelve of 15 treated patients (80%) had died at the time of censoring. Among treated patients, the 12- and 24-month overall survival was 50% (95% CI, 23 to 72) and 17% (95% CI, 3 to 42), respectively. CNS involvement was associated with worse survival. CONCLUSION: It is possible to treat adolescents and young adults with ALL in low-resource settings using a low-cost, pediatric-inspired regimen; however, outcomes are poor. Both cost and limitations in supportive care infrastructure limit intensive cytotoxic approaches such as asparaginase. Patient-reported outcomes are needed to understand the quality of life and cost-effectiveness. Critically, innovative, leap-frog therapies, such as monoclonal or bispecific antibodies, and feasible economic models for resource-limited settings are urgently needed.
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Asparaginasa , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Malaui/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Calidad de Vida , Adulto JovenRESUMEN
Access to antiretroviral therapy (ART) led to epidemiological changes in human immunodeficiency virus (HIV) associated lymphoma in high-income countries such as reductions in diffuse large B-cell lymphoma (DLBCL) and stable or increased Hodgkin lymphoma (HL) and Burkitt lymphoma (BL). In 2016, Malawi implemented a universal ART (UART) policy, expanding ART eligibility to all persons living with HIV (PLWH). We compare the distribution of lymphoma subtypes and baseline HIV and prognostic characteristics for lymphoma patients in Malawi before and after implementation of UART. We enrolled patients with pathologically confirmed incident lymphoproliferative disorders into a observational clinical cohort. At diagnosis, a comprehensive clinicopathological evaluation was performed. Of 412 participants, 156 (38%) were pre-UART (2013-June 2016) and 256 (62%) post-UART (July 2016-2020). HIV prevalence was 50% in both groups. The most common pre-UART diagnoses were DLBCL [75 (48%)], low-grade non-Hodgkin lymphoma (NHL) [19 (12%)], HL [17 (11%)] and, BL [13 (8%)]. For post-UART they were DLBCL [111 (43%)], NHL [28 (11%)], BL [27 11%)] and, HL [20 (8%)]. Among PLWH, 44 (57%) pre-UART initiated ART prior to lymphoma diagnosis compared to 99 (78%) post-UART (p = 0.02). HIV-ribonucleic acid was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p = 0.05). CD4 T-cell counts were similar for both groups. We observed similar findings in the subset of participants with DLBCL. Overall, there were no significant changes in incident lymphoma subtypes (p = 0.61) after implementation of UART, but HIV was better controlled. Emerging trends bear monitoring and may have implications for prognosis and health system priority setting. Trial registration: ClinicalTrials.gov identifier: NCT02835911.
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Linfoma de Burkitt , Infecciones por VIH , Enfermedad de Hodgkin , Linfoma de Células B Grandes Difuso , Antirretrovirales/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/epidemiología , Recuento de Linfocito CD4 , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/patología , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/epidemiología , Malaui/epidemiologíaRESUMEN
PURPOSE: COVID-19 challenged medical practice and graduate medical education. Building on previous initiatives, we describe and reflect on the formative process and goals of the Hematology-Oncology Collaborative Videoconferencing Learning Initiative, a trainee-led multi-institutional virtual COVID-19 learning model. METHODS: Clinical fellows and faculty from 13 US training institutions developed consensus needs, goals, and objectives, recruited presenters, and generated a multidisciplinary COVID-19 curriculum. Weekly Zoom conferences consisted of two trainee-led instructional segments and a trainee-moderated faculty Q&A panel. Hematology-oncology training program faculty and trainees were the targeted audience. Leadership evaluations consisted of anonymized baseline and concluding mixed methods surveys. Presenter evaluations consisted of session debriefs and two structured focus groups. Conference evaluations consisted of attendance, demographics, and pre- or postmultiple-choice questions on topic learning objectives. RESULTS: In 6 weeks, the initiative produced five conferences: antivirals, anticoagulation, pulmonology, provider resilience, and resource scarcity ethics. The average attendance was 100 (range 57-185). Among attendees providing both pre- and postconference data, group-level knowledge appeared to increase: antiviral (n = 46) pre-/postcorrect 82.6%/97.8% and incorrect 10.9%/2.2%, anticoagulation (n = 60) pre-/postcorrect 75%/93.3% and incorrect 15%/6.7%, and pulmonary (n = 21) pre-/postcorrect 66.7%/95.2% and incorrect 33.3%/4.8%. Although pulmonary management comfort appeared to increase, comfort managing of antivirals and anticoagulation was unchanged. At the conclusion of the pilot, leadership trainees reported improved self-confidence organizing multi-institutional collaborations, median (interquartile range) 58.5 (50-64) compared with baseline 34 (26-39), but did not report improved confidence in other educational or leadership skills. CONCLUSION: During crisis, trainees built a multi-institutional virtual education platform for the purposes of sharing pandemic experiences and knowledge. Accomplishment of initiative goals was mixed. Lessons learned from the process and goals may improve future disaster educational initiatives.
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COVID-19 , Educación a Distancia , Hematología , Hematología/educación , Humanos , SARS-CoV-2 , Comunicación por VideoconferenciaRESUMEN
More than 80% of global hepatocellular carcinoma (HCC) patients are estimated to occur in sub-Saharan Africa (SSA) and Eastern Asia. The most common risk factor of HCC in SSA is chronic hepatitis B virus (HBV) infection, with the incidence highest in West Africa. HBV is highly endemic in SSA and is perpetuated by incomplete adherence to birth dose immunization, lack of longitudinal follow-up care, and impaired access to antiviral therapy. HBV may directly cause HCC through somatic genetic alterations or indirectly through altered liver function and liver cirrhosis. Other risk factors of HCC in SSA include aflatoxins and, to a lesser extent, African iron overload. HIV plus HBV co-infection increases the risk of developing HCC and is increasingly becoming more common because of improving the survival of patients with HIV infection. Compared with the rest of the world, patients with HCC in SSA have the lowest survival. This is partly due to the late presentation of HCC with advanced symptomatic disease as a result of underdeveloped surveillance practices. Moreover, access to care and resource limitations further limit outcomes for the patients who receive a diagnosis in SSA. There is a need for multipronged strategies to decrease the incidence of HCC and improve its outcomes in SSA.
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Carcinoma Hepatocelular , Infecciones por VIH , Hepatitis B Crónica , Neoplasias Hepáticas , África del Sur del Sahara/epidemiología , África Occidental , Carcinoma Hepatocelular/epidemiología , Asia Oriental , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , Humanos , Neoplasias Hepáticas/epidemiologíaRESUMEN
BACKGROUND: Cost-effectiveness data for cancer treatment are needed from sub-Saharan Africa, where diffuse large B-cell lymphoma (DLBCL) is a common, curable cancer. In high-income countries, the standard of care for DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemoimmunotherapy. Rituximab is often not available in sub-Saharan Africa due to perceived unaffordability, and treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) is common. We aimed to evaluate the cost-effectiveness of treatment in Malawi, comparing best supportive care, CHOP, or R-CHOP in patients with DLBCL. METHODS: For this cost-effectiveness analysis, we used published Malawi microcosting data, clinical data from a prospective cohort treated with CHOP, and clinical trial data evaluating R-CHOP. We used a decision-tree model to calculate costs per disability-adjusted life-year (DALY) averted from the health system perspective for the treatment of patients with DLBCL with best supportive care, CHOP, or R-CHOP, running the model on a per-patient basis and a Malawi population-level basis. We used the WHO definitions of cost-effective (three times the GDP per capita of the country) and extremely cost-effective (equal to the GDP per capita of the country) as willingness-to-pay thresholds for Malawi. FINDINGS: On a per-patient level, compared with best supportive care, CHOP was estimated to avert a mean 7·4 DALYs at an incremental cost of US$1384, for an incremental cost-effectiveness ratio (ICER) of $189 per DALY averted, which is substantially lower than the willingness-to-pay threshold (extremely cost-effective). Compared with CHOP, R-CHOP was estimated to avert 2·8 DALYs at an incremental cost of $3324, resulting in an ICER of $1204 per DALY averted, which is slightly higher than the cost-effective willingness-to-pay threshold. In probabilistic sensitivity analyses, CHOP remained cost-effective for DLBCL treatment in more than 99% of simulations, whereas R-CHOP was lower than the threshold in 46% of simulations. INTERPRETATION: We estimated CHOP to be cost-effective for DLBCL treatment in Malawi, and that the addition of rituximab might be cost-effective. Despite upfront costs, DLBCL treatment is probably a prudent investment relative to other accepted health interventions in sub-Saharan Africa. FUNDING: National Institutes of Health.
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Linfoma de Células B Grandes Difuso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Análisis Costo-Beneficio , Ciclofosfamida/economía , Ciclofosfamida/uso terapéutico , Doxorrubicina/economía , Doxorrubicina/uso terapéutico , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Malaui , Masculino , Prednisona/economía , Prednisona/uso terapéutico , Rituximab/economía , Rituximab/uso terapéutico , Resultado del Tratamiento , Vincristina/economía , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: Cancer outcomes in sub-Saharan Africa (SSA) remain suboptimal, in part due to poor patient retention. Many patients travel long distances to receive care, and transportation costs are often prohibitively expensive. These are well-known and established causes of delayed treatment and care abandonment in Malawi and across SSA. METHODS: We sent visit reminder texts and offered upfront money to cover transportation costs through a mobile money transfer (MMT) platform to lymphoma patients enrolled in a prospective cohort in Malawi. The primary aim was to test the feasibility of upfront MMTs. RESULTS: We sent 1034 visit reminder texts to 189 participating patients. Of these texts, 614 (59%) were successfully delivered, with 536 (52%) responses. 320/536 (60%) MMTs were sent to interested patients and 312/320 (98%) came to their appointment on time. Of 189 total patients, 120 (63%) were reached via text and 84 (44%) received MMTs a median of three times (IQR 2-5). Median age of reachable patients was 41 (IQR 30-50), 75 (63%) were male, 62 (52%) were HIV+ and 79 (66%) resided outside of Lilongwe. CONCLUSION: MMTs were a feasible way to cover upfront transportation costs for patients reachable via text, however many of our patients were unreachable. Future studies exploring barriers to care, particularly among unreachable patients, may help improve the efficacy of MMT initiatives and guide retention strategies throughout SSA.
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Infecciones por VIH , Linfoma , Estudios de Factibilidad , Femenino , Humanos , Linfoma/terapia , Malaui , Masculino , Estudios Prospectivos , TransportesRESUMEN
BACKGROUND: There are no clinical trials involving patients with diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa since antiretroviral therapy (ART) for HIV became widely available in this region. We aimed to establish the safety and efficacy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL in Malawi. METHODS: This prospective, single-arm, non-randomised phase 1/2 clinical trial was done at Kamuzu Central Hospital Cancer Clinic (Lilongwe, Malawi). Eligible patients were adults (aged 18-60 years) with newly diagnosed DLBCL, an Eastern Cooperative Oncology Group performance status of 0-2, a CD4 count of 100 cells per µL or higher (if HIV-positive), measurable disease by physical examination, an absolute neutrophil count of 1000 × 109 cells per L or higher, a platelet count of 100 × 109 platelets per L or higher, a serum creatinine concentration of 132·60 µmol/L or less, a total bilirubin concentration of 34·21 µmol/L or less, a negative urine pregnancy test in women of childbearing potential, and no previous cytotoxic therapy. Pregnant or breastfeeding women, and individuals with CNS involvement from DLBCL, chronic hepatitis B infection (unless they were receiving tenofovir plus lamivudine), or any other comorbidities that would compromise the protocol objectives were excluded. Eligible patients received intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum 2 mg/m2), and oral prednisone 100 mg or an equivalent drug every 21 days for up to six cycles. HIV-positive patients received concurrent ART. The primary outcome was the proportion of patients with National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4 non-haematological toxic effects or treatment-related deaths after six cycles of treatment. Secondary efficacy outcomes included the proportion of patients with a complete response after six cycles of treatment, and progression-free survival and overall survival at 12 months and 24 months. This trial is registered with ClinicalTrials.gov, NCT02660710. FINDINGS: Between Aug 1, 2016, and July 31, 2019, 76 patients were screened, of whom 37 were eligible for the study and received R-CHOP. The median age of patients was 44 years (IQR 39-49) and 16 (43%) were women. Of all 37 patients, 20 (54%) had stage III or IV DLBCL, and the age-adjusted international prognostic index was 2 or higher in 25 (68%) patients. 27 (73%) patients were HIV-positive, with a median CD4 count of 208 cells per µL (IQR 144-422), and 21 (78%) patients were receiving ART at enrolment. Patients completed a median of six cycles (IQR 4-6). Grade 3 or 4 non-haematological toxic effects were reported in 12 (32% [95% CI 19-49]) patients, the most common of which was infection (nine [24%] patients). Of 16 (43%) deaths, ten were due to progression of DLBCL, four were due to treatment-related complications, and two were due to other causes, yielding a treatment-related mortality of 11% (95% CI 4-26%). Grade 3 or 4 neutropenia was observed in 26 (70%) patients, and grade 3 or 4 anaemia was observed in 11 (29%) patients. A total of 22 (59%) patients had a complete response. Overall survival was 68% (95% CI 50-80) at 12 months and 55% (37-70) at 24 months, and progression-free survival was 59% (42-73) at 12 months and 53% (35-68) at 24 months. INTERPRETATION: R-CHOP could be feasible, safe, and efficacious in patients with DLBCL in Malawi. This is the first completed clinical trial on DLBCL focused on sub-Saharan African populations. Given the paucity of data on treatment of DLBCL from this region, these results could inform emerging cancer treatment programmes in sub-Saharan Africa. FUNDING: The University of North Carolina Lineberger Comprehensive Cancer Center.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Humanos , Malaui , Masculino , Persona de Mediana Edad , Prednisona/efectos adversos , Prednisona/uso terapéutico , Estudios Prospectivos , Rituximab/efectos adversos , Rituximab/uso terapéutico , Resultado del Tratamiento , Vincristina/efectos adversos , Vincristina/uso terapéuticoRESUMEN
People living with HIV or AIDS are at increased risk of Hodgkin and non-Hodgkin lymphoma compared with HIV-negative individuals. Data on the risk of multiple myeloma or leukaemia are inconsistent and of low quality but the risk does not seem to be increased. Specific haematological malignancies occur in different contexts of age, CD4 cell count, HIV control, viral co-infections, or chronic inflammation, and the expansion of combination antiretroviral therapy has led to varied demographic and epidemiological shifts among people with HIV. Increased use of combination antiretroviral therapy has substantially reduced the risks of diffuse large B-cell lymphoma, Burkitt lymphoma, and primary CNS lymphoma, and to a lesser extent, Hodgkin lymphoma. There is no effect of combination antiretroviral therapy use on multiple myeloma or leukaemia. Although many cases of HIV are in low-income and middle-income countries, high-quality epidemiological data for haematological malignancies from these regions are scarce. Closing this gap is an essential first step in decreasing mortality from HIV-associated haematological malignancies worldwide. Finally, although multicentric Castleman disease is not a neoplastic condition, it is an emerging precursor to neoplastic high-grade B-cell lymphoproliferation among people with HIV, especially for individuals on long-term combination antiretroviral therapy with well controlled HIV.
Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Humanos , Incidencia , Vigilancia en Salud PúblicaRESUMEN
Background. Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure, and healthcare providers' confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching are associated with the risk of opportunistic infections (OI) among patients with unrecognized treatment failure is critical to improve patient outcomes. Methods. A retrospective review of 637 adolescents and adults meeting WHO immunological failure criteria was conducted. Timely and delayed switching to second-line ART were defined when switching happened at <3 and ≥3 months, respectively, after failure diagnosis was made. Cox proportional hazard marginal structural models were used to assess the effect of switching to second-line ART on the risk of developing OI. Results. Of 637 patients meeting WHO immunological failure criteria, 396 (62.2%) switched to second-line ART. Of those switched, 230 (58.1%) were delayed. Switching to second-line ART reduced the risk of OI (adjusted hazards ratio [AHR], 0.4; 95% CI, .2-.6). Compared with patients who received timely switch after failure diagnosis was made, those who delayed switching were more likely to develop OI (AHR, 2.2; 95% CI, 1.1-4.3). Conclusion. Delayed switching to second-line ART after failure diagnosis may increase the risk of OI. Serial immunological assessment for switching patients to second-line ART is critical to improve their outcomes.
RESUMEN
BACKGROUND: Since 2000, there has been a dramatic increase in methamphetamine use in South Africa, but little is known about the experiences of out-of-treatment users. This mixed-methods study describes the substance use histories, addiction symptoms, and treatment experiences of a community-recruited sample of methamphetamine users in Cape Town. METHODS: Using respondent driven sampling, 360 methamphetamine users (44% female) completed structured clinical interviews to assess substance abuse and treatment history and computerized surveys to assess drug-related risks. A sub-sample of 30 participants completed in-depth interviews to qualitatively explore experiences with methamphetamine use and drug treatment. RESULTS: Participants had used methamphetamine for an average of 7.06 years (SD=3.64). They reported using methamphetamine on an average of 23.49 of the past 30 days (SD=8.90); 60% used daily. The majority (90%) met ICD-10 criteria for dependence, and many reported severe social, financial, and legal consequences. While only 10% had ever received drug treatment, 90% reported that they wanted treatment. In the qualitative interviews, participants reported multiple barriers to treatment, including beliefs that treatment is ineffective and relapse is inevitable in their social context. They also identified important motivators, including desires to be drug free and improve family functioning. CONCLUSION: This study yields valuable information to more effectively respond to emerging methamphetamine epidemics in South Africa and other low- and middle-income countries. Interventions to increase uptake of evidence-based services must actively seek out drug users and build motivation for treatment, and offer continuing care services to prevent relapse. Community education campaigns are also needed.
Asunto(s)
Trastornos Relacionados con Anfetaminas/psicología , Trastornos Relacionados con Anfetaminas/rehabilitación , Metanfetamina , Adolescente , Adulto , Anciano , Consumidores de Drogas , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Motivación , Aceptación de la Atención de Salud , Fumar , Factores Socioeconómicos , Sudáfrica , Trastornos Relacionados con Sustancias/complicaciones , Adulto JovenAsunto(s)
Trastornos de la Coagulación Sanguínea/epidemiología , COVID-19/epidemiología , Guías de Práctica Clínica como Asunto/normas , Anticoagulantes/uso terapéutico , Biomarcadores/metabolismo , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , COVID-19/diagnóstico , Humanos , SARS-CoV-2 , Estados Unidos/epidemiología , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: South Africa, in the midst of the world's largest HIV epidemic, has a growing methamphetamine problem. Respondent driven sampling (RDS) is a useful tool for recruiting hard-to-reach populations in HIV prevention research, but its use with methamphetamine smokers in South Africa has not been described. This study examined the effectiveness of RDS as a method for engaging methamphetamine users in a Cape Town township into HIV behavioral research. METHODS: Standard RDS procedures were used to recruit active methamphetamine smokers from a racially diverse peri-urban township in Cape Town. Effectiveness of RDS was determined by examining social network characteristics (network size, homophily, and equilibrium) of recruited participants. RESULTS: Beginning with eight seeds, 345 methamphetamine users were enrolled over 6 months, with a coupon return rate of 67%. The sample included 197 men and 148 women who were racially diverse (73% Coloured, 27% Black African) and had a mean age of 28.8 years (SD=7.2). Social networks were adequate (mean network size >5) and mainly comprised of close social ties. Equilibrium on race was reached after 11 waves of recruitment, and after ≤3 waves for all other variables of interest. There was little to moderate preference for either in- or out-group recruiting in all subgroups. CONCLUSIONS: Results suggest that RDS is an effective method for engaging methamphetamine users into HIV prevention research in South Africa. Additionally, RDS may be a useful strategy for seeking high-risk methamphetamine users for HIV testing and linkage to HIV care in this and other low resource settings.