Eligibility for co-trimoxazole prophylaxis among adult HIV-infected patients in South Africa
- Takuva, Simbarashe, Nabyoma, Johnson M, Dawood, Halima, Black, Andrew, Maartens, Gary, Parrish, Andy, Leong, Trudy D
- Authors: Takuva, Simbarashe , Nabyoma, Johnson M , Dawood, Halima , Black, Andrew , Maartens, Gary , Parrish, Andy , Leong, Trudy D
- Date: 2019
- Identifier: http://hdl.handle.net/11260/6352 , vital:45378
- Description: Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) is a broad-spectrum antibiotic used to prevent opportunistic infections in patients with HIV infection. Primary prophylaxis with co-trimoxazole has been shown to decrease hospitalisation, morbidity and mortality among people living with HIV, primarily by decreasing rates of malaria, pneumonia, diarrhoea, Pneumocystis pneumonia, toxoplasmosis and severe bacterial infections.[1-4] Co-trimoxazole is inexpensive and widely available. In standard adult treatment guidelines and essential medicine lists in South Africa (SA), the current recommendation is that co-trimoxazole should be provided for HIV-infected patients with a CD4+ count ˂200 cells/μL, HIV/tuberculosis (TB) co-infection and/or advanced HIV disease (World Health Organization (WHO) stage 3 or 4). Because of expanded access and progression towards initiation of antiretroviral treatment (ART), the WHO issued updated guidelines for co-trimoxazole prophylaxis in 2014.[5] These guidelines recommend co-trimoxazole prophylaxis for adults (including pregnant women) with severe or advanced HIV clinical disease (WHO stage 3 or 4) and/or with a CD4+ count ≤350 cells/μL. In settings with a high prevalence of malaria and/or severe bacterial infections, prophylaxis is recommended for all patients regardless of WHO clinical stage or CD4+ cell count. However, the timing of discontinuation of co-trimoxazole prophylaxis may vary and is dependent on the malarial/ bacterial infection burden in different settings.[5] Therefore, the current WHO guidance should be adapted in the context of a country-specific epidemiological profile and priorities. The impact and benefit of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected patients with a CD4+ count ≤350 cells/μL in regions with high infectious disease burdens (irrespective of CD4+ count) have been shown in a good-quality systematic review and meta-analysis that included both randomised controlled trials (RCTs) and observational cohort studies.[6] This extensive systematic review by Suthar et al.[6] showed that co-trimoxazole prophylaxis reduced the rate of death when initiated at CD4+ counts ≤350 cells/μL with ART in populations in Africa and Asia. Co-trimoxazole prophylaxis in ART-naive patients with CD4+ counts >350 cells/μL reduced the rate of death and malaria, and continuation of prophylaxis after ART-induced recovery with CD4+ counts >350 cells/μL reduced hospital admission, pneumonia, malaria and diarrhoea in African populations (SA, Zimbabwe, Uganda, Malawi, Mozambique and Ethiopia).[6] While this review largely informed the 2014 WHO guideline update, the findings need to be interpreted in the context of studies included and the varied epidemiological profile across middle- and low-income countries. There were only 2 relatively small RCTs with very few events of key endpoints; therefore, the finding of non-significance was likely (e.g. total of ~5 deaths in both arms from both trials).[7,8] One of the 2 studies was unblinded, and the follow-up in the other study was only 4 months. Ongoing co-trimoxazole prophylaxis was better than discontinuation of the drug at CD4+ counts >200 cells/μL for 3 endpoints with an adequate number of events (pneumonia, diarrhoea and malaria). Furthermore, 8 of 9 studies were conducted in countries with a high burden of malaria and bacterial and parasitic diseases, which is generalisable to the SA context.[9] Although seasonal malaria occurs in the north-eastern parts of SA, the incidence of malaria mortality and morbidity has declined remarkably over time (˂10 000 cases annually for the past 10 years).[10] In contrast, in Uganda, >9 million confirmed cases of malaria were reported in the public health sector in 2015.[9] In this review, further stratification of the impact of co-trimoxazole prophylaxis at CD4+ counts ˂200 cells/μL v. 200 - 350 cells/μL was not available. Lower bacterial resistance to co-trimoxazole is possible among populations included in this review, while resistance to co-trimoxazole in SA is common in patients with community-acquired bacterial infections.[11-13] This potential risk of resistance compounded by the lack of long-term toxicity data needs to be weighed against recommending prophylaxis in populations where benefit has not been established. Local observational studies suggest no benefit of co-trimoxazole prophylaxis with a CD4+ count >200 cells/μL or in patients who were not WHO clinical stage 3 or 4.[14,15] In an observational cohort of patients attending the adult HIV clinics at the University of Cape Town, SA, the effect of prophylactic low-dose co-trimoxazole on survival and morbidity was examined over a 5-year follow-up period. Co-trimoxazole reduced the hazards of mortality by ~44% and the incidence of severe HIV-related illnesses by ~48% in patients with evidence of advanced immunosuppression (WHO stage 3 or 4) or laboratory measurement of total lymphocyte count ˂1 250 × 106/L or CD4+ count ˂200 cells/μL. However, no beneficial effect was seen in patients with WHO clinical stage 2 or CD4+ count 200 - 500 cells/μL. A potential limitation of this study was that the sample size of patients with a CD4+ count 200 - 500 cells/μL receiving co-trimoxazole was small and may have been underpowered to observe a significant benefit. In this study, patients on ART were excluded.[14] In another SA cohort study by Hoffmann et al.,[15] examining co-trimoxazole effectiveness in reducing mortality risk during ART among persons with a CD4+ count >200 cells/μL and varying WHO clinical stages, overall co-trimoxazole prophylaxis reduced mortality by 36% across all CD4+ count strata. Analysis stratified by baseline CD4+ count showed a similar reduction in mortality risk among persons with a CD4+ count ˂200 cells/μL, but no statistically significant association was found between co-trimoxazole prophylaxis and survival in the subgroup of persons with a CD4+ count >200 - 350 cells/μL, CD4+ count >350 cells/μL and WHO stage 1 or 2 disease. However, the findings of this study need to be interpreted cautiously for the following reasons: the group with a CD4+ count >350 cells/μL was small (n=917) and might not have had enough events to draw inferences; the study population was a cohort of miners and might not have been potentially representative of the SA population; and, being a non-randomised study, residual confounding might have been a potential limitation. An earlier Cochrane review established the benefit of initiating prophylaxis at a CD4+ count ˂200 cells/μL in those with stage 2, 3 or 4 HIV disease (including TB), and discontinuation once the CD4+ count was >200 cells/μL for >6 months.[16] There was a reduction of ~31% in mortality, 27% in morbid events and 55% in hospitalisation. Significant reductions were also detected for bacterial and parasitic infections and for Pneumocystis jirovecii pneumonia. Considering the above-mentioned evidence gaps and lack of generalisability of studies to SA, the current National Essential Medicines List Committee and Adult Hospital-Level Technical Sub-committee do not support the implementation of the updated guidance by the WHO for co-trimoxazole prophylaxis among adult HIV-infected patients. Efforts should be directed towards exploring several research gaps. The impact of co-trimoxazole prophylaxis on morbidity and mortality at higher CD4+ counts in low-malariaburden areas needs to be investigated further. More data are needed on timing of co-trimoxazole cessation in HIV and TB co-infection in our context.
- Full Text:
- Authors: Takuva, Simbarashe , Nabyoma, Johnson M , Dawood, Halima , Black, Andrew , Maartens, Gary , Parrish, Andy , Leong, Trudy D
- Date: 2019
- Identifier: http://hdl.handle.net/11260/6352 , vital:45378
- Description: Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) is a broad-spectrum antibiotic used to prevent opportunistic infections in patients with HIV infection. Primary prophylaxis with co-trimoxazole has been shown to decrease hospitalisation, morbidity and mortality among people living with HIV, primarily by decreasing rates of malaria, pneumonia, diarrhoea, Pneumocystis pneumonia, toxoplasmosis and severe bacterial infections.[1-4] Co-trimoxazole is inexpensive and widely available. In standard adult treatment guidelines and essential medicine lists in South Africa (SA), the current recommendation is that co-trimoxazole should be provided for HIV-infected patients with a CD4+ count ˂200 cells/μL, HIV/tuberculosis (TB) co-infection and/or advanced HIV disease (World Health Organization (WHO) stage 3 or 4). Because of expanded access and progression towards initiation of antiretroviral treatment (ART), the WHO issued updated guidelines for co-trimoxazole prophylaxis in 2014.[5] These guidelines recommend co-trimoxazole prophylaxis for adults (including pregnant women) with severe or advanced HIV clinical disease (WHO stage 3 or 4) and/or with a CD4+ count ≤350 cells/μL. In settings with a high prevalence of malaria and/or severe bacterial infections, prophylaxis is recommended for all patients regardless of WHO clinical stage or CD4+ cell count. However, the timing of discontinuation of co-trimoxazole prophylaxis may vary and is dependent on the malarial/ bacterial infection burden in different settings.[5] Therefore, the current WHO guidance should be adapted in the context of a country-specific epidemiological profile and priorities. The impact and benefit of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected patients with a CD4+ count ≤350 cells/μL in regions with high infectious disease burdens (irrespective of CD4+ count) have been shown in a good-quality systematic review and meta-analysis that included both randomised controlled trials (RCTs) and observational cohort studies.[6] This extensive systematic review by Suthar et al.[6] showed that co-trimoxazole prophylaxis reduced the rate of death when initiated at CD4+ counts ≤350 cells/μL with ART in populations in Africa and Asia. Co-trimoxazole prophylaxis in ART-naive patients with CD4+ counts >350 cells/μL reduced the rate of death and malaria, and continuation of prophylaxis after ART-induced recovery with CD4+ counts >350 cells/μL reduced hospital admission, pneumonia, malaria and diarrhoea in African populations (SA, Zimbabwe, Uganda, Malawi, Mozambique and Ethiopia).[6] While this review largely informed the 2014 WHO guideline update, the findings need to be interpreted in the context of studies included and the varied epidemiological profile across middle- and low-income countries. There were only 2 relatively small RCTs with very few events of key endpoints; therefore, the finding of non-significance was likely (e.g. total of ~5 deaths in both arms from both trials).[7,8] One of the 2 studies was unblinded, and the follow-up in the other study was only 4 months. Ongoing co-trimoxazole prophylaxis was better than discontinuation of the drug at CD4+ counts >200 cells/μL for 3 endpoints with an adequate number of events (pneumonia, diarrhoea and malaria). Furthermore, 8 of 9 studies were conducted in countries with a high burden of malaria and bacterial and parasitic diseases, which is generalisable to the SA context.[9] Although seasonal malaria occurs in the north-eastern parts of SA, the incidence of malaria mortality and morbidity has declined remarkably over time (˂10 000 cases annually for the past 10 years).[10] In contrast, in Uganda, >9 million confirmed cases of malaria were reported in the public health sector in 2015.[9] In this review, further stratification of the impact of co-trimoxazole prophylaxis at CD4+ counts ˂200 cells/μL v. 200 - 350 cells/μL was not available. Lower bacterial resistance to co-trimoxazole is possible among populations included in this review, while resistance to co-trimoxazole in SA is common in patients with community-acquired bacterial infections.[11-13] This potential risk of resistance compounded by the lack of long-term toxicity data needs to be weighed against recommending prophylaxis in populations where benefit has not been established. Local observational studies suggest no benefit of co-trimoxazole prophylaxis with a CD4+ count >200 cells/μL or in patients who were not WHO clinical stage 3 or 4.[14,15] In an observational cohort of patients attending the adult HIV clinics at the University of Cape Town, SA, the effect of prophylactic low-dose co-trimoxazole on survival and morbidity was examined over a 5-year follow-up period. Co-trimoxazole reduced the hazards of mortality by ~44% and the incidence of severe HIV-related illnesses by ~48% in patients with evidence of advanced immunosuppression (WHO stage 3 or 4) or laboratory measurement of total lymphocyte count ˂1 250 × 106/L or CD4+ count ˂200 cells/μL. However, no beneficial effect was seen in patients with WHO clinical stage 2 or CD4+ count 200 - 500 cells/μL. A potential limitation of this study was that the sample size of patients with a CD4+ count 200 - 500 cells/μL receiving co-trimoxazole was small and may have been underpowered to observe a significant benefit. In this study, patients on ART were excluded.[14] In another SA cohort study by Hoffmann et al.,[15] examining co-trimoxazole effectiveness in reducing mortality risk during ART among persons with a CD4+ count >200 cells/μL and varying WHO clinical stages, overall co-trimoxazole prophylaxis reduced mortality by 36% across all CD4+ count strata. Analysis stratified by baseline CD4+ count showed a similar reduction in mortality risk among persons with a CD4+ count ˂200 cells/μL, but no statistically significant association was found between co-trimoxazole prophylaxis and survival in the subgroup of persons with a CD4+ count >200 - 350 cells/μL, CD4+ count >350 cells/μL and WHO stage 1 or 2 disease. However, the findings of this study need to be interpreted cautiously for the following reasons: the group with a CD4+ count >350 cells/μL was small (n=917) and might not have had enough events to draw inferences; the study population was a cohort of miners and might not have been potentially representative of the SA population; and, being a non-randomised study, residual confounding might have been a potential limitation. An earlier Cochrane review established the benefit of initiating prophylaxis at a CD4+ count ˂200 cells/μL in those with stage 2, 3 or 4 HIV disease (including TB), and discontinuation once the CD4+ count was >200 cells/μL for >6 months.[16] There was a reduction of ~31% in mortality, 27% in morbid events and 55% in hospitalisation. Significant reductions were also detected for bacterial and parasitic infections and for Pneumocystis jirovecii pneumonia. Considering the above-mentioned evidence gaps and lack of generalisability of studies to SA, the current National Essential Medicines List Committee and Adult Hospital-Level Technical Sub-committee do not support the implementation of the updated guidance by the WHO for co-trimoxazole prophylaxis among adult HIV-infected patients. Efforts should be directed towards exploring several research gaps. The impact of co-trimoxazole prophylaxis on morbidity and mortality at higher CD4+ counts in low-malariaburden areas needs to be investigated further. More data are needed on timing of co-trimoxazole cessation in HIV and TB co-infection in our context.
- Full Text:
Improving intravenous fluid prescribing in the Eastern Cape in South Africa
- Luce, Cate, Soffair,Rosie, Parrish, Andy
- Authors: Luce, Cate , Soffair,Rosie , Parrish, Andy
- Date: 2019
- Subjects: South Africa Intravenous fluids Computer File
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/11260/5120 , vital:44351 , https://doi:10.1136/bmjoq-2018-000406
- Description: Intravenous fluids are an essential component of patient care, but a 2013 National Institute for Health and Care Excellence (NICE) guideline noted that inappropriate prescribing or administration may lead to actual or potential patient harm in up to 20% of patients.1 This project aimed to improve prescribing documentation and communication between nurses and doctors regarding intravenous fluid management. This was done through the introduction of a fluid chart, in combination with teaching on appropriate fluid management. It was initiated within the medical department of Cecelia Makiwane Hospital in East London, South Africa. 309 patients were included and data were analysed over a 6-month period. The outcome measures were the standards of intravenous fluid prescribing set by the NICE guidelines. The process measure was the use of the new chart. Baseline data highlighted that there was no standardised location for fluid prescriptions within the bedside notes. Following the intervention, 81% of fluid prescriptions were on a fluid chart. The percentage of fluid scripts with a 24-hour fluid prescription, a recorded indication and recorded input increased after the intervention. Seventy six per cent of patients received more than 50% of the fluids prescribed following the intervention compared with 22% at baseline. These results indicated an increase in the doctor’s awareness of appropriate fluid prescribing and an improvement in the communication between doctors and nurses regarding the patient’s fluid management. The engagement of local stakeholders and staff was fundamental to the success of the project and allowed for this change in practice. Fluid management is a vital part of care in many specialties; therefore, a toolkit has been created to allow similar quality improvement projects to be implemented across other hospitals around the Eastern Cape.
- Full Text:
- Date Issued: 2019
- Authors: Luce, Cate , Soffair,Rosie , Parrish, Andy
- Date: 2019
- Subjects: South Africa Intravenous fluids Computer File
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/11260/5120 , vital:44351 , https://doi:10.1136/bmjoq-2018-000406
- Description: Intravenous fluids are an essential component of patient care, but a 2013 National Institute for Health and Care Excellence (NICE) guideline noted that inappropriate prescribing or administration may lead to actual or potential patient harm in up to 20% of patients.1 This project aimed to improve prescribing documentation and communication between nurses and doctors regarding intravenous fluid management. This was done through the introduction of a fluid chart, in combination with teaching on appropriate fluid management. It was initiated within the medical department of Cecelia Makiwane Hospital in East London, South Africa. 309 patients were included and data were analysed over a 6-month period. The outcome measures were the standards of intravenous fluid prescribing set by the NICE guidelines. The process measure was the use of the new chart. Baseline data highlighted that there was no standardised location for fluid prescriptions within the bedside notes. Following the intervention, 81% of fluid prescriptions were on a fluid chart. The percentage of fluid scripts with a 24-hour fluid prescription, a recorded indication and recorded input increased after the intervention. Seventy six per cent of patients received more than 50% of the fluids prescribed following the intervention compared with 22% at baseline. These results indicated an increase in the doctor’s awareness of appropriate fluid prescribing and an improvement in the communication between doctors and nurses regarding the patient’s fluid management. The engagement of local stakeholders and staff was fundamental to the success of the project and allowed for this change in practice. Fluid management is a vital part of care in many specialties; therefore, a toolkit has been created to allow similar quality improvement projects to be implemented across other hospitals around the Eastern Cape.
- Full Text:
- Date Issued: 2019
Improving TB infection control in a regional hospital in the Eastern Cape, South Africa
- Haeusler, Ilsa Louisa, Knights, Felicity, George, Vishaal, Parrish, Andy
- Authors: Haeusler, Ilsa Louisa , Knights, Felicity , George, Vishaal , Parrish, Andy
- Date: 2019
- Subjects: Quality circles Tuberculosis--Prevention Computer File
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/11260/6399 , vital:45465 , https://doi.org/10.4102/hts.v77i2.6828
- Description: This quality improvement (QI) work was carried out in Cecilia Makiwane Hospital (CMH), a regional public hospital in the Eastern Cape, South Africa (SA). SA has among the highest incidence of tuberculosis (TB) in the world and this is a leading cause of death in SA. Nosocomial infection is an important source of TB transmission. Adherence to TB infection prevention control (IPC) measures in the medical inpatient department was suboptimal at CMH. The overall aim of this QI project was to make sustainable improvements in TB IPC. A multidisciplinary team was formed to undertake a root cause analysis and develop a strategy for change. The main barriers to adherence to IPC measures were limited knowledge of IPC methods and stigma associated with TB. Specifically, the project aimed to increase the number of: ‘airborne precaution’ signs placed above patients’ beds, patients correctly isolated and patients wearing surgical face masks. Four Plan Do-Study-Act cycles were used. The strategy for change involved education and awareness-raising in different formats, including formal in-service training delivered to nurses and doctors, a hospital-wide TB awareness week with engaging activities and competitions, and a World TB Day provincial solidarity march. Data on adherence to the three IPC measures were collected over an 8-month period. Pre-intervention (October 2016), a mean of 2 percent of patients wore face masks, 22 percent were correctly isolated and 12 percent had an airborne precaution sign. Postintervention (May 2017), the compliance improved to 17 percent, 50 percent and 25 percent, respectively. There was a large variation in compliance to each measure. Improvement was greatest in the number of patients correctly isolated. We learnt it is important to work with, not in parallel to, existing teams or structures during QI work. On-the-ground training of nurses and clinicians should be undertaken alongside engagement of senior staff members and managers. This improves the chance of change being adopted into hospital policy.
- Full Text:
- Date Issued: 2019
- Authors: Haeusler, Ilsa Louisa , Knights, Felicity , George, Vishaal , Parrish, Andy
- Date: 2019
- Subjects: Quality circles Tuberculosis--Prevention Computer File
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/11260/6399 , vital:45465 , https://doi.org/10.4102/hts.v77i2.6828
- Description: This quality improvement (QI) work was carried out in Cecilia Makiwane Hospital (CMH), a regional public hospital in the Eastern Cape, South Africa (SA). SA has among the highest incidence of tuberculosis (TB) in the world and this is a leading cause of death in SA. Nosocomial infection is an important source of TB transmission. Adherence to TB infection prevention control (IPC) measures in the medical inpatient department was suboptimal at CMH. The overall aim of this QI project was to make sustainable improvements in TB IPC. A multidisciplinary team was formed to undertake a root cause analysis and develop a strategy for change. The main barriers to adherence to IPC measures were limited knowledge of IPC methods and stigma associated with TB. Specifically, the project aimed to increase the number of: ‘airborne precaution’ signs placed above patients’ beds, patients correctly isolated and patients wearing surgical face masks. Four Plan Do-Study-Act cycles were used. The strategy for change involved education and awareness-raising in different formats, including formal in-service training delivered to nurses and doctors, a hospital-wide TB awareness week with engaging activities and competitions, and a World TB Day provincial solidarity march. Data on adherence to the three IPC measures were collected over an 8-month period. Pre-intervention (October 2016), a mean of 2 percent of patients wore face masks, 22 percent were correctly isolated and 12 percent had an airborne precaution sign. Postintervention (May 2017), the compliance improved to 17 percent, 50 percent and 25 percent, respectively. There was a large variation in compliance to each measure. Improvement was greatest in the number of patients correctly isolated. We learnt it is important to work with, not in parallel to, existing teams or structures during QI work. On-the-ground training of nurses and clinicians should be undertaken alongside engagement of senior staff members and managers. This improves the chance of change being adopted into hospital policy.
- Full Text:
- Date Issued: 2019
How good are our guidelines? Four years of experience with the SAMJ’s AGREE II review of submitted clinical practice guidelines
- Kredo, Tamara, Wiseman, Roger, Gray, Andy, Parrish, Andy, Miot, Jacqui, Jamaloodien, Khadija, Blockman, Marc
- Authors: Kredo, Tamara , Wiseman, Roger , Gray, Andy , Parrish, Andy , Miot, Jacqui , Jamaloodien, Khadija , Blockman, Marc
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/11260/5296 , vital:44431 , http://10.7196/SAMJ.2018.v108i11.13646
- Description: The South African Medical Journal (SAMJ) is an established source of clinical practice guidelines (CPGs) serving the local healthcare community. CPGs link professional societies and clinicians by guiding best practice through the collation and interpretation of the best available evidence. Not only are CPGs important in standardising the quality of patient care, but they also assist with medicine selection and resource allocation decisions, adjudicating medicolegal claims, and promoting equity by influencing medicine access and health system organisation.[1] In 2014, the SAMJ appointed an editorial subcommittee to review CPGs submitted for publication.[2] This was in response to several concerns, including the global shift in CPG quality requirements, the potential effect of poor-quality CPGs on healthcare quality and cost, and the challenges South African (SA) CPG developers face in meeting new standards. This editorial reflects on the SAMJ CPG review subcommittee’s experience over the past 4 years and describes the value of more robust CPG development.
- Full Text:
- Date Issued: 2018
- Authors: Kredo, Tamara , Wiseman, Roger , Gray, Andy , Parrish, Andy , Miot, Jacqui , Jamaloodien, Khadija , Blockman, Marc
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/11260/5296 , vital:44431 , http://10.7196/SAMJ.2018.v108i11.13646
- Description: The South African Medical Journal (SAMJ) is an established source of clinical practice guidelines (CPGs) serving the local healthcare community. CPGs link professional societies and clinicians by guiding best practice through the collation and interpretation of the best available evidence. Not only are CPGs important in standardising the quality of patient care, but they also assist with medicine selection and resource allocation decisions, adjudicating medicolegal claims, and promoting equity by influencing medicine access and health system organisation.[1] In 2014, the SAMJ appointed an editorial subcommittee to review CPGs submitted for publication.[2] This was in response to several concerns, including the global shift in CPG quality requirements, the potential effect of poor-quality CPGs on healthcare quality and cost, and the challenges South African (SA) CPG developers face in meeting new standards. This editorial reflects on the SAMJ CPG review subcommittee’s experience over the past 4 years and describes the value of more robust CPG development.
- Full Text:
- Date Issued: 2018
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