Browsing by Author "Maurer, Toby"

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    A type III effectiveness-implementation hybrid evaluation of a multicomponent patient navigation strategy for advanced-stage Kaposi’s sarcoma: protocol
    (Springer, 2022-05-13) Collier, Sigrid; Semeere, Aggrey; Byakwaga, Helen; Laker-Oketta, Miriam; Chemtai, Linda; Wagner, Anjuli D.; Bassett, Ingrid V.; Wools-Kaloustian, Kara; Maurer, Toby; Martin, Jeffrey; Kiprono, Samson; Freeman, Esther E.; Medicine, School of Medicine
    Background: For people with advanced-stage Kaposi’s sarcoma (KS), a common HIV-associated malignancy in sub-Saharan Africa, mortality is estimated to be 45% within 2 years after KS diagnosis, despite increasingly wide-spread availability of antiretroviral therapy and chemotherapy. For advanced-stage KS, chemotherapy in addition to antiretroviral therapy improves outcomes and saves lives, but currently, only ~50% of people with KS in western Kenya who have an indication for chemotherapy actually receive it. This protocol describes the evaluation of a multicomponent patient navigation strategy that addresses common barriers to service penetration of and fidelity to evidence-based chemotherapy among people with advanced-stage KS in Kenya. Methods: This is a hybrid type III effectiveness-implementation study using a non-randomized, pre- post-design nested within a longitudinal cohort. We will compare the delivery of evidence-based chemotherapy for advanced stage KS during the period before (2016–2020) to the period after (2021–2024), the rollout of a multicomponent patient navigation strategy. The multicomponent patient navigation strategy was developed in a systematic process to address key determinants of service penetration of and fidelity to chemotherapy in western Kenya and includes (1) physical navigation and care coordination, (2) video-based education, (3) travel stipend, (4) health insurance enrollment assistance, (5) health insurance stipend, and (6) peer mentorship. We will compare the pre-navigation period to the post-navigation period to assess the impact of this multicomponent patient navigation strategy on (1) implementation outcomes: service penetration (chemotherapy initiation) and fidelity (chemotherapy completion) and (2) service and client outcomes: timeliness of cancer care, mortality, quality of life, stigma, and social support. We will also describe the implementation process and the determinants of implementation success for the multicomponent patient navigation strategy. Discussion: This study addresses an urgent need for effective implementation strategies to improve the initiation and completion of evidence-based chemotherapy in advanced-stage KS. By using a clearly specified, theory-based implementation strategy and validated frameworks, this study will contribute to a more comprehensive understanding of how to improve cancer treatment in advanced-stage KS.
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    An expanded population of CD8dim T cells with features of mitochondrial dysfunction and senescence is associated with persistent HIV-associated Kaposi’s sarcoma under ART
    (Frontiers Media, 2022-09-29) Clutton, Genevieve T.; Weideman, Ann Marie K.; Goonetilleke, Nilu P.; Maurer, Toby; Dermatology, School of Medicine
    HIV-associated Kaposi’s sarcoma (KS), which is caused by Kaposi’s sarcoma-associated herpesvirus, usually arises in the context of uncontrolled HIV replication and immunosuppression. However, disease occasionally occurs in individuals with durable HIV viral suppression and CD4 T cell recovery under antiretroviral therapy (ART). The underlying mechanisms associated with this phenomenon are unclear. Suppression of viral infections can be mediated by CD8 T cells, which detect infected cells via their T cell receptor and the CD8 coreceptor. However, CD8 T cells exhibit signs of functional exhaustion in untreated HIV infection that may not be fully reversed under ART. To investigate whether KS under ART was associated with phenotypic and functional perturbations of CD8 T cells, we performed a cross-sectional study comparing HIV-infected individuals with persistent KS under effective ART (HIV+ KS+) to HIV-infected individuals receiving effective ART with no documented history of KS (HIV+ KSneg). A subset of T cells with low cell surface expression of CD8 (“CD8dim T cells”) was expanded in HIV+ KS+ compared with HIV+ KSneg participants. Relative to CD8bright T cells, CD8dim T cells exhibited signs of senescence (CD57) and mitochondrial alterations (PGC-1α, MitoTracker) ex vivo. Mitochondrial activity (MitoTracker) was also reduced in proliferating CD8dim T cells. These findings indicate that an expanded CD8dim T cell population displaying features of senescence and mitochondrial dysfunction is associated with KS disease under ART. CD8 coreceptor down-modulation may be symptomatic of ongoing disease.
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    Compression Therapy for HIV-Associated Kaposi Sarcoma Leg Lymphedema: Results of the Kenyan Improvised Compression for Kaposi Sarcoma Randomized Controlled Trial
    (American Society of Clinical Oncology, 2022) Chang, Aileen Y.; Karwa, Rakhi; Odhiambo, Haji; Were, Phelix; Fletcher, Sara L.; Tonui, Edith C.; Kohn, Michael A.; Lee, Jeannette; Chang, Di; Lensing, Shelly; Namaemba, Diana Flora; Busakhala, Naftali; Kiprono, Samson K.; Maurer, Toby; Goodrich, Suzanne; Pastakia, Sonak D.; Dermatology, School of Medicine
    Purpose: Evaluate the effectiveness of compression while receiving chemotherapy compared with chemotherapy alone in the treatment of HIV-associated Kaposi sarcoma (KS) lymphedema. Methods: A randomized controlled trial was conducted in a single oncology clinic in western Kenya (NCT03404297). A computer-generated randomization schedule was used to allocate treatment arms. Randomized block design was used for stratification by lymphedema stage. Participants were HIV positive adults age ≥ 18 years on antiretroviral therapy with biopsy-proven KS associated with leg lymphedema and being initiated on chemotherapy. The intervention was 10 weeks of weekly clinic-based application of two-component paste compression bandages. The primary outcome was change in the Lower Extremity Lymphedema Index (LELI) score from week 0 to week 14. The secondary outcomes were change in the Lymphedema Quality of Life measure (LYMQOL) and change in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 score from week 0 to week 14. Blinded outcome assessments were conducted. Results: Of 30 participants randomly assigned, 25 eligible patients (chemotherapy [control], n = 13; compression plus chemotherapy [intervention], n = 12) returned at week 14. Change in LELI, LYMQOL, and EORTC QLQ-C30 scores between week 14 and week 0 did not significantly differ by arm. The mean (standard deviation) change in LELI score was -25.9 (34.6) for the control arm compared with -13.3 (29.5) for the intervention arm, P = .340. The difference (95% CI) in the change in LELI score was -12.6 (-39.3 to 14.1). Conclusion: Future studies evaluating a 14-week change in LELI for KS lymphedema should assume a standard deviation of approximately 30. Lessons learned from this pilot trial should inform the development of a larger, multicenter trial to evaluate the effectiveness of compression for KS lymphedema.
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    Cost Minimization Analysis of a Teledermatology Triage System in a Managed Care Setting
    (American Medical Association, 2021) Zakaria, Adam; Miclau, Theodore A.; Maurer, Toby; Leslie, Kieron S.; Amerson, Erin; Dermatology, School of Medicine
    Importance: Teledermatology (TD) enables remote triage and management of dermatology patients. Previous analyses of TD systems have demonstrated improved access to care but an inconsistent fiscal impact. Objective: To compare the organizationwide cost of managing newly referred dermatology patients within a TD triage system vs a conventional dermatology care model at the Zuckerberg San Francisco General Hospital and Trauma Center (hereafter referred to as the ZSFG) in California. Design, setting, and participants: A retrospective cost minimization analysis was conducted of 2098 patients referred to the dermatology department at the ZSFG between June 1 and December 31, 2017. Intervention: Implementation of the TD triage system in January 2015. Main outcomes and measures: The main outcome was mean cost to the health care organization to manage newly referred dermatology patients with or without TD triage. To estimate costs, decision-tree models were constructed to characterize possible care paths with TD triage and within a conventional dermatology care model. Costs associated with primary care visits, dermatology visits, and TD visits were then applied to the decision-tree models to estimate the mean cost of managing patients following each care path for 6 months. The mean cost for each visit type incorporated personnel costs, with the mean cost per TD consultation also incorporating software implementation and maintenance costs. Finally, ZSFG patient data were applied within the models to evaluate branch probabilities, enabling calculation of mean cost per patient within each model. Results: The analysis captured 2098 patients (1154 men [55.0%]; mean [SD] age, 53.4 [16.8] years), with 1099 (52.4%) having Medi-Cal insurance and 879 (41.9%) identifying as non-White. In the decision-tree model with TD triage, the mean (SD) cost per patient to the health care organization was $559.84 ($319.29). In the decision-tree model for conventional dermatology care, the mean (SD) cost per patient was $699.96 ($390.24). Therefore, the TD model demonstrated a statistically significant mean (SE) cost savings of $140.12 ($11.01) per patient. Given an annual dermatology referral volume of 3150 patients, the analysis estimates an annual savings of $441 378. Conclusions and relevance: Implementation of a TD triage system within the dermatology department at the ZSFG was associated with cost savings, suggesting that managed health care settings may experience significant cost savings from using TD to triage and manage patients.
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    Evaluation of four chemotherapy regimens for treatment of advanced AIDS-associated Kaposi sarcoma in Kenya: a cost-effectiveness analysis
    (Elsevier, 2022) Freeman, Esther E.; McCann, Nicole C.; Semeere, Aggrey; Reddy, Krishna P.; Laker-Oketta, Miriam; Byakwaga, Helen; Pei, Pamela P.; Hajny Fernandez, Maya E.; Kiprono, Samson; Busakhala, Naftali; Martin, Jeffery N.; Maurer, Toby; Bassett, Ingrid V.; Freedberg, Kenneth A.; Hyle, Emily P.; Dermatology, School of Medicine
    Background: The most effective treatment for advanced AIDS-associated Kaposi sarcoma is paclitaxel or pegylated liposomal doxorubicin (PLD); neither is routinely used in sub-Saharan Africa due to limited availability and high cost. We examined the clinical impact, costs, and cost-effectiveness of paclitaxel or PLD in Kenya, compared with etoposide or bleomycin-vincristine. Methods: In this study, we use the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International Model to project clinical outcomes and costs among people living with HIV and advanced Kaposi sarcoma on antiretroviral therapy. We compared four different treatment strategies: etoposide, bleomycin-vincristine, paclitaxel, or PLD. We derived cohort characteristics and costs from the Kenyan Academic Model for Providing Access to Healthcare network, and adverse events, efficacy, and mortality from clinical trials. We projected model outcomes over a lifetime and included life expectancy, per-person lifetime costs, and incremental cost-effectiveness ratios (ICERs). We conducted budget impact analysis for 5-year total costs and did deterministic and probabilistic sensitivity analyses to evaluate the effect of uncertainty in input parameters. Findings: We found that paclitaxel would be more effective than bleomycin-vincristine and would increase life expectancy by 4·2 years per person. PLD would further increase life expectancy by 0·6 years per person. Paclitaxel would be the most cost-effective strategy (ICER US$380 per year-of-life-saved compared with bleomycin-vincristine) and would remain cost-effective across a range of scenarios. PLD would be cost-effective compared with paclitaxel if its price were reduced to $100 per cycle (base case $180 per cycle). Implementing paclitaxel instead of bleomycin-vincristine would save approximately 6400 life-years and would increase the overall 5-year Kenyan health-care costs by $3·7 million; increased costs would be primarily related to ongoing HIV care given improved survival. Interpretation: Paclitaxel would substantially increase life expectancy and be cost-effective compared with bleomycin-vincristine for advanced AIDS-associated Kaposi sarcoma in Kenya and should be the standard of care. PLD would further improve survival and be cost-effective with a 44% price reduction.
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    Feasibility of Rapid Case Ascertainment for Cancer in East Africa: An Investigation of Community-Representative Kaposi Sarcoma in the Era of Antiretroviral Therapy
    (Elsevier, 2021) Semeere, Aggrey; Byakwaga, Helen; Laker-Oketta, Miriam; Freeman, Esther; Busakhala, Naftali; Wenger, Megan; Kasozi, Charles; Ssemakadde, Matthew; Bwana, Mwebesa; Kanyesigye, Michael; Kadama-Makanga, Philippa; Rotich, Elyne; Kisuya, Job; Sang, Edwin; Maurer, Toby; Wools-Kaloustian, Kara; Kambugu, Andrew; Martin, Jeffrey; Medicine, School of Medicine
    Background: Rapid case ascertainment (RCA) refers to the expeditious and detailed examination of patients with a potentially rapidly fatal disease shortly after diagnosis. RCA is frequently performed in resource-rich settings to facilitate cancer research. Despite its utility, RCA is rarely implemented in resource-limited settings and has not been performed for malignancies. One cancer and context that would benefit from RCA in a resource-limited setting is HIV-related Kaposi sarcoma (KS) in sub-Saharan Africa. Methods: To determine the feasibility of RCA for KS, we searched for all potential newly diagnosed KS among HIV-infected adults attending three community-based facilities in Uganda and Kenya. Searching involved querying of electronic medical records, pathology record review, and notification by clinicians. Upon identification, a team verified eligibility and attempted to locate patients to perform RCA, which included epidemiologic, clinical and laboratory measurements. Results: We identified 593 patients with suspected new KS. Of the 593, 171 were ineligible, mainly because biopsy failed to confirm KS (65%) or KS was not new (30%). Among the 422 remaining, RCA was performed within 1 month for 56% of patients and within 3 months for 65% (95% confidence interval: 59 to 70%). Reasons for not performing RCA included intervening death (47%), inability to contact (44%), refusal/unsuitable to consent (8.3%), and patient re-location (0.7%). Conclusions: We found that RCA - an important tool for cancer research in resource-rich settings - is feasible for the investigation of community-representative KS in East Africa. Feasibility of RCA for KS suggests feasibility for other cancers in Africa.
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    Identifying Gaps in Global Health Dermatology: A Survey of GLODERM Members
    (Oxford University Press, 2021) McMahon, Devon E.; Oyesiku, Linda; Amerson, Erin; Beltraminelli, Helmut; Chang, Aileen Y.; Forrestel, Amy; Hay, Roderick; Knapp, Alexia; Kovarik, Carrie; Maurer, Toby; Norton, Scott A.; Rehmus, Wingfield; Van Hees, Colette; Wanat, Karolyn A.; Williams, Victoria L.; Fuller, L. Claire; Freeman, Esther E.; Dermatology, School of Medicine
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    Implementing a Locally Made Low-Cost Intervention for Wound and Lymphedema Care in Western Kenya
    (Elsevier, 2021) Chang, Aileen Y.; Mungai, Margaret; Coates, Sarah J.; Chao, Tiffany; Odhiambo, Haji Philip; Were, Phelix M.; Fletcher, Sara L.; Maurer, Toby; Karwa, Rakhi; Pastakia, Sonak D.; Dermatology, School of Medicine
    In Western Kenya, the burden of chronic wounds and lymphedema has a significant impact on functionality and quality of life. Major barriers to provision of care include availability, affordability, and accessibility of bandages. At the Academic Model Providing Access to Healthcare, dermatologists and pharmacists collaborated to develop a 2-component compression bandage modeled after the Unna boot, using locally available materials, that is distributed through a revolving fund pharmacy network. In partnership with nursing, use of these bandages at a national referral hospital and a few county facilities has increased, but increasing utilization to an expanded catchment area is needed.
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    LAMP-enabled diagnosis of Kaposi's sarcoma for sub-Saharan Africa
    (American Association for the Advancement of Science, 2023) McCloskey, Duncan; Semeere, Aggrey; Ayanga, Racheal; Laker-Oketta, Miriam; Lukande, Robert; Semakadde, Matthew; Kanyesigye, Micheal; Wenger, Megan; LeBoit, Philip; McCalmont, Timothy; Maurer, Toby; Gardner, Andrea; Boza, Juan; Cesarman, Ethel; Martin, Jeffrey; Erickson, David; Dermatology, School of Medicine
    Kaposi's sarcoma (KS) is an endothelial cancer caused by the Kaposi's sarcoma-associated herpesvirus (KSHV) and is one of the most common cancers in sub-Saharan Africa. In limited-resource settings, traditional pathology infrastructure is often insufficient for timely diagnosis, leading to frequent diagnoses at advanced-stage disease where survival is poor. In this study, we investigate molecular diagnosis of KS performed in a point-of-care device to circumvent the limited infrastructure for traditional diagnosis. Using 506 mucocutaneous biopsies collected from patients at three HIV clinics in Uganda, we achieved 97% sensitivity, 92% specificity, and 96% accuracy compared to gold standard U.S.-based pathology. The results presented in this manuscript show that LAMP-based quantification of KSHV DNA extracted from KS-suspected biopsies has the potential to serve as a successful diagnostic for the disease and that diagnosis may be accurately achieved using a point-of-care device, reducing the barriers to obtaining KS diagnosis while increasing diagnostic accuracy.
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    The role of dermatology in Kaposi sarcoma diagnosis across three regions in sub-Saharan Africa
    (Elsevier, 2020) Seth, Divya; Williams, Victoria L.; McMahon, Devon E.; Regan, Susan; Busakhala, Naftali; Wools-Kaloustian, Kara; Mosoajane, Karen; Ralefala, Tlotlo B.; Kayembe, Mukendi; Iregbu, Kenneth; Kwaghe, Vivian; Jedy-Agba, Elima; Oyesiku, Linda; Maurer, Toby; Jaquet, Antoine; Bassett, Ingrid V.; Martin, Jeff; Grover, Surbhi; Freeman, Esther E.; Medicine, School of Medicine