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1.
Dig Dis ; 42(2): 154-160, 2024.
Article in English | MEDLINE | ID: mdl-38185098

ABSTRACT

INTRODUCTION: Helicobacter pylori (H. pylori) is one of the most important infections globally, affecting more than 50% of the human population. Clarithromycin (CLA)-containing regimens are recommended for empirical eradication of H. pylori in populations with less than 15% resistance. The aim of this study was to estimate the prevalence of CLA resistance in samples collected from Zambian patients to determine if CLA is suitable for first-line H. pylori empirical treatment. METHODOLOGY: We used archival biopsy samples collected from dyspeptic patients undergoing endoscopy. The samples had been snap-frozen immediately after collection and stored at -80°C. We performed multiplex real-time PCR using Bosphore Helicobacter pylori Genotyping Kits v1, Istanbul, Turkey, to determine the presence of wild-type H. pylori and three mutations, A2142G, A2142C, and A2143G, of domain V in 23s rRNA gene. RESULTS: We tested 259 gastric biopsy samples from patients with dyspepsia, of which 136 (53%) were from females. The median age was 48 years (IQR 40-61 years). Endoscopically, most of the patients, 164 (63%), had a normal gastric mucosa. CLA resistance was found in 48 (28%) samples, with A2142G mutation in 23 (13%), A2143G mutation in 32 (18%), and double mutations A2142C and A2143G in 6 (3%). CONCLUSIONS: The presence of significant levels of CLA resistance in Zambia suggests that it should not be used as first-line empirical treatment for H. pylori infection. However, with a limitation of suitable alternatives, there is an urgent need to formulate new treatment approaches.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Female , Humans , Middle Aged , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Helicobacter pylori/genetics , Zambia/epidemiology , Prevalence , Drug Resistance, Bacterial/genetics , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Microbial Sensitivity Tests
2.
J Public Health Afr ; 14(6): 2335, 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37538939

ABSTRACT

In recent years, health partnerships have shared infection prevention and control innovations between United Kingdom hospitals and Low-Middle-Income Countries. However, none had focused on antimicrobial stewardship (AMS), a core component of tackling antimicrobial resistance (AMR). This paper documents an effective approach to developing a program to increase AMS capacity in four African countries: Ghana, Tanzania, Uganda, and Zambia as part of the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) program. A systematic approach was applied to assess gaps in AMS interventions and inform the development of the CwPAMS program through deskbased assessments, including National Action Plans on AMR, online focus group meetings, and expert advisory group reviews. Twelve partnerships were selected for the CwPAMS program. AMS support tools were developed based on recommendations from the scoping, including an AMS checklist tool, a healthcare worker knowledge and attitudes questionnaire, and an antimicrobial prescribing app to support clinical decision-making. Training workshops on AMS were developed and delivered to volunteers in Africa and the UK using a train-the-trainer model. The tools and workshops facilitated capacity building for AMS through the generation and strengthening of knowledge, skills, commitment, structures, systems, and leadership among stakeholders in the UK and Africa. The overall average rating assigned to the program following independent evaluation using the Organisation for Economic Cooperation and Development Assistance Committee Evaluation Criteria was very good. The evaluation also highlighted that the majority of the HPs (75%) focused on AMS and/or improved prescribing practice; all HPs have developed and implemented AMS strategies, guidelines, and tools within their hospitals; and NHS staff were able to translate the knowledge and skills they had received early on in the program into clinical practice in response to COVID-19 challenges.

3.
Bull World Health Organ ; 101(6): 403-411, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37265674

ABSTRACT

Efficient and secure supply chains are vital for effective health services worldwide. In low- and middle-income countries, the accessibility, affordability and availability of essential medicines, including antimicrobials, remain challenging. Ineffective supply chains often cause antimicrobial shortages, leading to inappropriate use of alternative agents and increasing the risk of antimicrobial resistance. Shortages, coupled with insecure supply chains, also encourage the infiltration of substandard and falsified medicines, leading to suboptimal treatment and further promoting antimicrobial resistance. Addressing antimicrobial supply-chain issues should be considered a key component of antimicrobial stewardship programmes. We have explored the link between medicine supply chains and antimicrobial use in seven focus countries: Kenya, Malawi, Nigeria, Sierra Leone, Uganda, United Republic of Tanzania and Zambia. We explored country medicine supply-system structures, national medicine supply-chain policy documents and global study reports. Our aim was to develop evidence-based strategies to enhance the effectiveness and efficiency of the medicine supply chains in supporting antimicrobial stewardship efforts. Better management of medical supply chains involves rational selection, quantification, forecasting, procurement, storage, distribution, use and stock management of antimicrobials. Important supply-chain considerations include pooled procurement networks to ensure consistent pricing of quality-assured antimicrobials, and improved resource utilization and information exchange among relevant stakeholders. We propose adaptable recommendations for integrating medicine supply chains as an essential part of antimicrobial stewardship programmes, with a call for action at the local, regional and national levels in low- and middle-income countries.


Partout dans le monde, les performances des services de santé dépendent de l'efficacité et de la sécurité des chaînes d'approvisionnement. Mais dans les pays à revenu faible et intermédiaire, l'accessibilité et la disponibilité des médicaments à prix abordable, y compris des antimicrobiens, représentent toujours un défi. L'inefficacité des chaînes d'approvisionnement entraîne souvent des pénuries d'antimicrobiens et, par conséquent, un recours à des alternatives inappropriées et une augmentation du risque de résistance aux antimicrobiens. Ces pénuries, alliées à des chaînes d'approvisionnement peu fiables, favorisent également l'introduction de médicaments falsifiés et de qualité inférieure, altérant l'efficacité du traitement et renforçant encore davantage la résistance aux antimicrobiens. Résoudre les problèmes liés aux chaînes d'approvisionnement en antimicrobiens devrait donc figurer parmi les priorités des programmes de gestion des antimicrobiens. Le présent document s'intéresse au lien entre les chaînes d'approvisionnement en médicaments et l'utilisation d'antimicrobiens dans sept pays cibles: le Kenya, le Malawi, le Nigeria, l'Ouganda, la République-Unie de Tanzanie, la Sierra Leone et la Zambie. Pour chacun de ces pays, nous avons examiné les structures du système d'approvisionnement en médicaments, les documents relatifs à la politique d'approvisionnement national et les rapports d'études globaux. Notre objectif consistait à développer des stratégies fondées sur des données factuelles, afin d'améliorer le fonctionnement et l'efficacité des chaînes d'approvisionnement en médicaments et de contribuer ainsi aux efforts de gestion des antimicrobiens. Une meilleure logistique requiert une certaine rationalité dans la sélection, la quantification, la planification, l'approvisionnement, le stockage, la distribution, l'utilisation et la gestion des stocks d'antimicrobiens. Dans ce contexte, plusieurs éléments sont importants tels que les réseaux d'achats groupés, qui assurent la stabilité des prix pour des antimicrobiens de qualité garantie, ou encore l'optimisation des ressources et l'échange d'informations entre les acteurs concernés. Nous formulons des recommandations ajustables en vue de rendre les chaînes d'approvisionnement en médicaments incontournables dans les programmes de gestion des antimicrobiens, avec un appel à agir à l'échelle locale, régionale et nationale dans les pays à revenu faible et intermédiaire.


Unas cadenas de suministro eficientes y seguras son vitales para la eficacia de los servicios sanitarios en todo el mundo. En los países de ingresos bajos y medios, la accesibilidad, asequibilidad y disponibilidad de los medicamentos esenciales, incluidos los antimicrobianos, sigue siendo un reto. Con frecuencia, las cadenas de suministro ineficaces provocan escasez de antimicrobianos, lo que conlleva un uso inadecuado de agentes alternativos y aumenta el riesgo de resistencia a los antimicrobianos. La escasez, sumada a la inseguridad de las cadenas de suministro, también favorece la infiltración de medicamentos de calidad inferior y adulterados, lo que conduce a un tratamiento subóptimo y fomenta aún más la resistencia a los antimicrobianos. Abordar los problemas de la cadena de suministro de antimicrobianos se debería considerar un componente clave de los programas de administración de antimicrobianos. Hemos explorado la relación entre las cadenas de suministro de medicamentos y el uso de antimicrobianos en siete países seleccionados: Kenia, Malawi, Nigeria, Sierra Leona, Uganda, República Unida de Tanzania y Zambia. Exploramos las estructuras de los sistemas de suministro de medicamentos de los países, los documentos de política nacional sobre la cadena de suministro de medicamentos y los informes de estudios globales. Nuestro objetivo era desarrollar estrategias basadas en evidencias para mejorar la eficacia y la eficiencia de las cadenas de suministro de medicamentos en apoyo de los esfuerzos de administración antimicrobiana. Una mejor gestión de las cadenas de suministro de medicamentos implica la selección racional, la cuantificación, la previsión, la adquisición, el almacenamiento, la distribución, el uso y la gestión de las existencias de antimicrobianos. Entre las consideraciones importantes sobre la cadena de suministro se incluyen las redes de adquisición mancomunada para garantizar precios coherentes de antimicrobianos de calidad garantizada y una mejor utilización de los recursos e intercambio de información entre las partes interesadas pertinentes. Proponemos recomendaciones adaptables para integrar las cadenas de suministro de medicamentos como parte esencial de los programas de administración de antimicrobianos, con una llamada a la acción a nivel local, regional y nacional en los países de ingresos bajos y medios.


Subject(s)
Antimicrobial Stewardship , Humans , Kenya , Tanzania , Uganda , Nigeria
4.
Pharmacogenomics ; 24(8): 449-457, 2023 06.
Article in English | MEDLINE | ID: mdl-37248698

ABSTRACT

Background: 6-mercaptopurine usage is associated with myelotoxicity and increased risk in patients carrying metabolism-related genetic variations. This study aimed to determine the frequency of candidate gene polymorphisms and their association with 6-mercaptopurine intolerance. Methods: A total of 41 patients on acute lymphoblastic leukaemia treatment were genotyped for TPMT and NUDT15 (rs116855232) alleles, and their association with dose intensity was analyzed. Results: The defective TPMT*3C allele frequency was 9.8%. The median maintenance dose intensity for TPMT*1/*3C participants was considerably lower (47%) when compared with the TPMT*1/*1 wild-type (77%), although not statistically significant. Conclusion: This is the first pharmacogenetics study carried out in a black Zimbabwean leukemia patient cohort. The high defective TPMT*3C (9.8%) allele frequency points to the potential utility of pharmacogenetics testing for safe usage of 6-mercaptopurine in this population.


Acute lymphoblastic leukemia (ALL) is the most common malignancy affecting children in Zimbabwe and 6-mercaptopurine is frequently used as part of its treatment. However, 6-mercaptopurine is associated with side-effects such as severe neutropenia (a condition where you have a low number of white blood cells called neutrophils in your blood), with increased risk observed in patients carrying variants in genes involved in the metabolism of 6-mercaptopurine. Therefore, this study aimed to determine the frequency of polymorphisms in specific genes as well as their association with drug intolerance. A total of 41 patients on ALL treatment were studied. Review of treatment records was done to determine the cumulative 6-mercaptopurine dose and calculate dose intensity. Genotyping (to determine the versions of a gene a patient carries) for TPMT and NUDT15 (rs116855232) was performed and results correlated with drug dose intensity. The most frequent genotype was TPMT*1/*1, occurring in 80% of the participants. The remaining 20% were carriers with two different copies of TPMT (*1/*3C). The defective TPMT*3C variation occurred at 9.8% and none had TPMT*2, *3A, *3B or NUDT15 rs116855232 variants. Comparison analysis with dose intensity was done for 23 participants (56%) who had maintenance records available. The median dose intensity of 47% for TPMT*1/*3C participants was considerably low when compared to that of a normal TPMT*1/*1 patient, which was 77%. However, no statistically significant difference was observed between TPMT genotype and dose intensity. This is the first study in a group of leukemic Zimbabweans to investigate the frequency of TPMT and NUDT15 variants. With a high variation frequency of 9.8% for the defective TPMT*3C, pharmacogenetics testing for TPMT before treatment with 6-MP is recommended in the Zimbabwean population.


Subject(s)
Mercaptopurine , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Mercaptopurine/adverse effects , Pharmacogenetics , Zimbabwe , Antimetabolites, Antineoplastic/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Methyltransferases/genetics , Pyrophosphatases/genetics
5.
J Pharm Policy Pract ; 16(1): 33, 2023 Mar 02.
Article in English | MEDLINE | ID: mdl-36864477

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) is a global public health concern currently mitigated by antimicrobial stewardship (AMS). Pharmacists are strategically placed to lead AMS actions that contribute to responsible use of antimicrobials; however, this is undermined by an acknowledged health leadership skills deficit. Learning from the UK's Chief Pharmaceutical Officer's Global Health (ChPOGH) Fellowship programme, the Commonwealth Pharmacists Association (CPA) is focused to develop a health leadership training program for pharmacists in eight sub-Saharan African countries. This study thus explores need-based leadership training needs for pharmacists to provide effective AMS and inform the CPA's development of a focused leadership training programme, the 'Commonwealth Partnerships in AMS, Health Leadership Programme' (CwPAMS/LP). METHODS: A mixed methods approach was undertaken. Quantitative data were collected via a survey across 8 sub-Saharan African countries and descriptively analysed. Qualitative data were collected through 5 virtual focus group discussions, held between February and July 2021, involving stakeholder pharmacists from different sectors in the 8 countries and were analysed thematically. Data were triangulated to determine priority areas for the training programme. RESULTS: The quantitative phase produced 484 survey responses. Focus groups had 40 participants from the 8 countries. Data analysis revealed a clear need for a health leadership programme, with 61% of respondents finding previous leadership training programmes highly beneficial or beneficial. A proportion of survey participants (37%) and the focus groups highlighted poor access to leadership training opportunities in their countries. Clinical pharmacy (34%) and health leadership (31%) were ranked as the two highest priority areas for further training of pharmacists. Within these priority areas, strategic thinking (65%), clinical knowledge (57%), coaching and mentoring (51%), and project management (58%) were selected as the most important. CONCLUSIONS: The study highlights the training needs of pharmacists and priority focus areas for health leadership to advance AMS within the African context. Context-specific identification of priority areas supports a needs-based approach to programme development, maximising African pharmacists' contribution to AMS for improved and sustainable patient outcomes. This study recommends incorporating conflict management, behaviour change techniques, and advocacy, amongst others, as areas of focus to train pharmacist leaders to contribute to AMS effectively.

7.
Antibiotics (Basel) ; 11(9)2022 Aug 25.
Article in English | MEDLINE | ID: mdl-36139929

ABSTRACT

Antimicrobial resistance (AMR) is a global health problem threatening safe, effective healthcare delivery in all countries and settings. The ability of microorganisms to become resistant to the effects of antimicrobials is an inevitable evolutionary process. The misuse and overuse of antimicrobial agents have increased the importance of a global focus on antimicrobial stewardship (AMS). This review provides insight into the current AMS landscape and identifies contemporary actors and initiatives related to AMS projects in eight African countries (Ghana, Kenya, Malawi, Nigeria, Sierra Leone, Tanzania, Uganda, and Zambia), which form a network of countries participating in the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme. We focus on common themes across the eight countries, including the current status of AMR, infection prevention and control, AMR implementation strategies, AMS, antimicrobial surveillance, antimicrobial use, antimicrobial consumption surveillance, a one health approach, digital health, pre-service and in-service AMR and AMS training, access to and supply of medicines, and the impact of COVID-19. Recommendations suitable for adaptation are presented, including the development of a national AMS strategy and incorporation of AMS in pharmacists' and other healthcare professionals' curricula for pre-service and in-service training.

8.
Int J Pharm Pract ; 30(4): 360-366, 2022 Aug 09.
Article in English | MEDLINE | ID: mdl-35731635

ABSTRACT

OBJECTIVES: Low job satisfaction levels among pharmacists are associated with poor motivation and performance in the workplace. However, in Zambia, the job satisfaction levels of pharmacists remain unknown. Therefore, the aim of this article was to explore levels of job satisfaction among pharmacists from the public and private health sectors in Zambia. METHODS: We conducted a cross-sectional study among Zambian pharmacists between April and August 2019. We used a previously validated self-administered questionnaire to measure job satisfaction. We sent out 200 questionnaires, of which 156 (78.0%) were returned. Bivariate analysis and an adjusted general linear regression model were fitted to determine factors affecting job satisfaction levels. KEY FINDINGS: Among 156 respondents, 46 (29.5%) were males, 114 (73.1%) and worked in the public sector. Overall, the mean job satisfaction score of the responding pharmacists was 3.05 (SD = 0.64) (on a scale of 1-5). Job satisfaction scores were significantly lower for pharmacists working in the public health sectors (regression coefficient (ß), -0.34; 95% confidence interval (CI), -0.59 to -0.10), adjusting for age, sex and income. Income was independently associated with levels of job satisfaction. CONCLUSIONS: Overall, pharmacists in Zambia were neither satisfied nor dissatisfied with their job. Nevertheless, pharmacists working in the private sector were more likely to report higher job satisfaction levels than those in the public sector. Therefore, the present study findings could contribute to developing and refining rational criteria to increase job satisfaction in pharmacy settings.


Subject(s)
Job Satisfaction , Pharmacists , Cross-Sectional Studies , Female , Humans , Male , Private Sector , Surveys and Questionnaires , Zambia
9.
PLoS One ; 16(7): e0252768, 2021.
Article in English | MEDLINE | ID: mdl-34252117

ABSTRACT

Persons living with HIV (PLWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) risk suffering TDF-associated nephrotoxicity (TDFAN). TDFAN can result in short- and long-term morbidity, including permanent loss of kidney function, chronic kidney disease (CKD), and end-stage kidney disease (ESKD) requiring dialysis. Currently, there is no model to predict this risk or discern which patients to initiate TDF-based therapy. Consequently, some patients suffer TDFAN within the first few months of initiating therapy before switching to another suitable antiretroviral or a lower dose of TDF. In a prospective observational cohort study of adult Zambian PLWH, we modelled the risk for TDFAN before initiating therapy to identify individuals at high risk for experiencing AKI after initiating TDF-based therapy. We enrolled 205 HIV-positive, ART-naïve adults initiating TDF-based therapy followed for a median of 3.4 months for TDFAN at the Adult Infectious Disease Research Centre (AIDC) in Lusaka, Zambia. We defined TDFAN as meeting any of these acute kidney disease (AKD) criteria: 1) An episode of estimated glomerular filtration rate (eGFR)< 60ml/ min/1.73m2 within 3 months, 2) reduced eGFR by> 35% within 3 months or 3) increased serum creatinine by> 50% within 3 months. A total of 45 participants (22%) developed acute kidney disease (AKD) after TDF-based therapy. The development of AKD within the first 3 months of commencing TDF-based therapy was associated with an increase in baseline serum creatinine, age, baseline eGFR and female sex. We concluded that baseline characteristics and baseline renal function biomarkers predicted the risk for AKD within the first 3-months of TDF-based therapy.


Subject(s)
HIV Infections/drug therapy , Kidney/drug effects , Tenofovir/adverse effects , Adult , Cohort Studies , Female , Humans , Kidney/physiopathology , Prognosis , Tenofovir/therapeutic use
10.
Hosp Pract (1995) ; 48(2): 86-91, 2020 Mar 14.
Article in English | MEDLINE | ID: mdl-32078406

ABSTRACT

OBJECTIVE: To explore medical doctors' experiences of, and attitudes to, use of morphine for palliative care at a tertiary hospital in Zambia. METHODS: A qualitative, exploratory case study was undertaken. Semi-structured interviews were used to collect data from 14 medical doctors working in the fields of oncology, pediatrics, and internal medicine at a tertiary hospital in Lusaka, Zambia, regarding their experiences and attitudes to prescribing morphine for palliative care. Thematic analysis of interview transcripts was carried out to establish common themes in the data. The study was approved by BSMS and UNZA research ethics committees. RESULTS: All participants agreed that doctors were becoming more comfortable with the prescribing of morphine, although experiences were notably different for doctors working in oncology, compared to other departments. Themes of difficulty discussing end-of-life, poor recognition of pain, and fear of patient addiction, were more prominent in the responses of non-cancer doctors. Morphine use was generally restricted to cancer and sickle cell disease patients, with most non-cancer doctors stating that they rarely prescribe morphine for outpatient use. Training in pain management and the presence of a palliative care team were perceived to be facilitators to morphine prescribing. CONCLUSIONS: Although there is an increased willingness to prescribe morphine, limited knowledge of pain management, especially for nonmalignant disease, underlies many of the findings in this study. Opportunity exists for professional development in pain management to further improve the acceptance and use of opioids in palliative care, especially for out-patients.


Subject(s)
Attitude of Health Personnel , Morphine/therapeutic use , Pain Management/methods , Pain/drug therapy , Palliative Care/methods , Physicians/psychology , Adult , Female , Humans , Male , Middle Aged , Tertiary Care Centers/statistics & numerical data , Zambia
11.
Front Pharmacol ; 11: 551522, 2020.
Article in English | MEDLINE | ID: mdl-33510634

ABSTRACT

Introduction: Sub-Saharan Africa and other low- and middle-income countries (LMICs) have the highest rates of antimicrobial resistance (AMR) driven by high rates of antimicrobial utilization. This is a concern as AMR appreciably increases morbidity, mortality and costs. Pharmacogenetics (PGx) and precision medicine are emerging approaches to combat AMR. Consequently, as a first step there is a need to assess AMR knowledge and attitudes, and knowledge of PGx, among healthcare professionals and use the findings to guide future interventions. Methodology: We conducted a cross-sectional study involving 304 healthcare professionals at tertiary hospitals in Lusaka, Zambia. Structural Equation Modeling (SEM) was used to analyze relationships among latent variables. Results: Overall correctness of answers concerning AMR among healthcare professionals was 60.4% (7/11). Knowledge of pharmacogenetics was low (38%). SEM showed that high AMR knowledge score correlated with a positive attitude toward combating AMR (p < 0.001). Pharmacists had relatively higher AMR knowledge scores (mean = 7.67, SD = 1.1), whereas nurses had lower scores (mean = 5.57, SD = 1.9). A minority of respondents [31.5% (n = 95)] indicated that poor access to local antibiogram data promoted AMR, with the majority [56.5% (n = 190)] responding that poor adherence to prescribed antimicrobials can lead to AMR. Pharmacists had the highest scores for attitude (mean = 5.60, SD = 1.6) whereas nurses had the lowest scores (mean = 4.02, SD = 1.4). Conclusion: AMR knowledge and attitudes, as well as knowledge on PGx among healthcare professionals in Zambia, is sub-optimal and has the potential to affect the uptake of precision medicine approaches to reduce AMR rates. Educational and positive behavioral change interventions are required to address this and in future, we will be seeking to introduce these to improve the use of antimicrobials.

12.
Am J Clin Nutr ; 110(5): 1240-1252, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31504110

ABSTRACT

BACKGROUND: Environmental enteropathy (EE) refers to villus blunting, reduced absorption, and microbial translocation in children and adults in tropical or deprived residential areas. In previous work we observed an effect of micronutrients on villus height (VH). OBJECTIVE: We aimed to determine, in a randomized controlled trial, if amino acid (AA) or multiple micronutrient (MM) supplementation can improve intestinal structure or barrier dysfunction in Zambian adults with EE. METHODS: AA (tryptophan, leucine, and glutamine) and/or MM supplements were given for 16 wk in a 2 × 2 factorial comparison against placebo. Primary outcomes were changes in VH, in vivo small intestinal barrier dysfunction assessed by confocal laser endomicroscopy (CLE), and mechanistic (or mammalian) target of rapamycin complex 1 (MTORC1) nutrient responsiveness in lamina propria CD4+ lymphocytes. RESULTS: Over 16 wk AA, but not MM, supplementation increased VH by 16% (34.5 µm) compared with placebo (P = 0.04). Fluorescein leak, measured by CLE, improved only in those allocated to both AA and MM supplementation. No effect was seen on MTORC1 activation, but posttreatment MTORC1 and VH were correlated (ρ = 0.51; P = 0.001), and change in MTORC1 was correlated with change in VH in the placebo group (ρ = 0.63; P = 0.03). In secondary analyses no effect was observed on biomarkers of microbial translocation. Metabolomic analyses suggest alterations in a number of microbial- and host-derived metabolites including the leucine metabolite ß-hydroxy-ß-methylbutyrate, which was increased by AA supplementation and correlated with VH. CONCLUSIONS: In this phase 2 trial, AA supplementation protected against a decline in VH over the supplementation period, and improved barrier function when combined with micronutrients. Leucine and MTORC1 metabolism may be involved in the mechanism of effect. This trial was registered at www.pactr.org as PACTR201505001104412.


Subject(s)
Amino Acids/administration & dosage , Intestinal Diseases/prevention & control , Intestinal Mucosa/pathology , Micronutrients/administration & dosage , Adult , Bacterial Translocation , Dietary Supplements , Female , Glutamine/administration & dosage , Humans , Intestine, Small/metabolism , Leucine/administration & dosage , Male , Mechanistic Target of Rapamycin Complex 1/metabolism , Middle Aged , Tryptophan/administration & dosage
13.
J Chemother ; 31(7-8): 378-387, 2019.
Article in English | MEDLINE | ID: mdl-31145043

ABSTRACT

Antimicrobial stewardship (AMS) is a key strategy promoting rational antimicrobial use. In Zambia, information on health professionals' knowledge, attitude, and practice of AMS is limited. This study was undertaken to address this at Zambia's leading specialized teaching hospitals. Descriptive, cross-sectional study involved 137 physicians and 61 pharmacists. AMS knowledge was relatively low among physicians (51%) and pharmacists (39%). Few physicians (9%) and pharmacists (20%) demonstrated sufficient knowledge of the basic principles of AMS. Physicians' and pharmacists' knowledge levels were significantly associated with years of practice, job position or practice rank, and previous AMS training. The majority (95%) perceived AMR as a current problem in their practise. Most physicians (92%) and pharmacists (86%) had not undertaken AMS training before. All indicated the need for context-specific educational interventions to promote AMS in Zambia. Despite positive perceptions, basic knowledge of AMS was relatively low. Context-specific educational interventions and capacity building are needed to address AMS gaps.


Subject(s)
Anti-Bacterial Agents/standards , Antimicrobial Stewardship/standards , Hospitals, Teaching/standards , Pharmacists/standards , Physicians/standards , Tertiary Care Centers/standards , Cross-Sectional Studies , Humans , Knowledge , Zambia
14.
Curr HIV Res ; 16(3): 231-236, 2018.
Article in English | MEDLINE | ID: mdl-29992888

ABSTRACT

The incidence of HIV-associated Kaposi's sarcoma (KS) remains high in Zambia in the antiretroviral therapy era. The most efficacious treatment regimen for KS has yet to be established. In both developed and developing countries, treatment regimens have had limited efficacy. Late presentation in Africa affects therapeutic outcomes. OBJECTIVE: The aim of this study was to determine therapeutic outcomes of epidemic KS patients on combination antiretroviral therapy (cART) after completion of six cycles of Adriamycin, Bleomycin, and Vincristine (ABV) chemotherapy. METHODS: This was a descriptive cross-sectional study. Study participants were drawn from a study database of confirmed incident KS patients seen at the Skin Clinic of the University Teaching Hospitals (UTH) during the period between August, 2015 and September, 2016. RESULTS: Of the 38 successfully recruited study participants, a complete response was documented in 18 (47%) after 6 cycles of ABV whereas 20 (53%) experienced a partial response. KS recurrence was observed in 8 (44%) of the individuals that experienced an initial complete response. At the time of the study, clinical assessment revealed that KS lesions had completely regressed in 21 (55%) of all the patients. CONCLUSION: ABV chemotherapy appears ineffective in long-term resolution of epidemic KS patients on ART. Recurrence rates are high after chemotherapy in patients that experience initially favorable responses to treatment. There is a need to diagnose KS earlier, and to develop more efficacious treatment options in order to reduce recurrence rates for epidemic KS.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Antineoplastic Agents/administration & dosage , Bleomycin/administration & dosage , Doxorubicin/administration & dosage , Sarcoma, Kaposi/drug therapy , Vincristine/administration & dosage , Acquired Immunodeficiency Syndrome/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Retroviral Agents/administration & dosage , Cross-Sectional Studies , Drug Therapy/methods , Female , Humans , Incidence , Male , Middle Aged , Recurrence , Tertiary Care Centers , Treatment Outcome , Young Adult , Zambia
15.
Expert Rev Pharmacoecon Outcomes Res ; 17(5): 459-467, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28770641

ABSTRACT

INTRODUCTION: The 2016 World Health Organization (WHO) consolidated guideline recommends lifelong antiretroviral therapy (ART) for all HIV-infected pregnant and breastfeeding women for preventing mother-to-child HIV transmission (PMTCT). Ambiguity remains about the cost-effectiveness of this strategy in resource-limited developing countries. Areas covered: We reviewed model-based studies on the cost-effectiveness of lifelong ART (formerly Option B+) relative to previous WHO guidelines for PMTCT. Our search using PubMed, Medline and Google Scholar for articles on Option B+ resulted in the final inclusion of seven studies published between 2012 and 2016. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to assess the quality of reporting. Outcomes of interest, which included infant infections averted, maternal quality and length of life, and the Incremental Cost Effectiveness Ratio (ICER), were used in comparing cost-effectiveness. Expert commentary: Despite most model-based studies favouring lifelong ART (Option B+) in terms of its cost-effectiveness in comparison to Options A and B, inclusiveness of the evidence remains weak for generalization. This is largely because setting specificity for providing lifelong ART to all pregnant and breastfeeding women may differ significantly in each setting. Consequently, future cost-effectiveness studies should be robust, setting-specific, and endeavor to assess the willingness and ability to pay of each setting.


Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Africa South of the Sahara , Anti-HIV Agents/economics , Breast Feeding , Cost-Benefit Analysis , Female , HIV Infections/economics , HIV Infections/transmission , Humans , Infectious Disease Transmission, Vertical/economics , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/economics , Pregnancy Complications, Infectious/virology
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