Proactive risk assessment of vincristine use process in a teaching and referral hospital in Kenya and the implications.

INTRODUCTION: The chemotherapy use process is potentially risky for cancer patients. Vincristine, a "High Alert" medicine, has been associated with fatal but preventable medication errors. Consequently, there is a need to improve the use of vincristine especially in lower- and middle-income countries where there are constraints with resources and often a lack of trained personnel to administer cancer medicines. However, where there is a rising prevalence of cancer cases. These concerns can be addressed by performing proactive risk assessments using Healthcare Failure Mode Effect Analysis (HFMEA) and implementing the findings. METHODS: A multidisciplinary health team driven by pharmacists identified and evaluated potential failure modes based on a vincristine use process flow diagram using a hazard scoring matrix in a leading referral hospital in Kenya. RESULTS: The processes evaluated were: prescribing, preparation and dispensing, transportation and storage, administration and monitoring of the use of vincristine. Seventy-seven failure modes were identified over the three-month study period, of which 25 were classified as high risk. Thirteen were adequately covered by existing control measures while 12 including one combined mode required new strategies. Two of the failure modes were single-point weaknesses. Recommendations were subsequently made for improving the administration of vincristine. CONCLUSIONS: HFMEA is a useful tool to identify improvements to medication safety and reduction of patient harm. The HFMEA process brings together the multidisciplinary team involved in patient care in actively identifying potential failure modes and owning the recommendations made, which are now being actively followed up in this hospital. Pharmacists are a key part of this process.

Pharmacological evidence for the folk use of Nefang: antipyretic, anti-inflammatory and antinociceptive activities of its constituent plants.

BACKGROUND: Nefang is a polyherbal anti-malarial composed of Mangifera indica ( MiB and MiL; bark and leaf), Psidium guajava ( Pg ), Carica papaya ( Cp ), Cymbopogon citratus ( Cc ), Citrus sinensis ( Cs ) and Ocimum gratissimum ( Og ) (leaves). Previous studies have demonstrated its in vitro and in vivo antiplasmodial activities, antioxidant properties and safety profile. This study aimed at evaluating the antipyretic, anti-inflammatory and antinociceptive activities of the constituent plants of Nefang which are relevant to the symptomatic treatment of malaria fever. METHODS: Antipyretic activities were determined by the D-Amphetamine induced pyrexia and Brewer's Yeast induced hyperpyrexia methods. Anti-inflammatory activities were investigated using the carrageenan-induced rat paw edema method. Antinociceptive activities were determined by mechanical nociception in the tail pressure and thermal nociception in the radiant heat tail flick and hot plate methods. Data was analysed using the one way ANOVA followed by Neuman-Keuls multiple comparison test. RESULTS: Best percentage inhibition of induced pyrexia (amphetamine/brewer's yeast; p < 0.05) was exhibited by Cc (95/97) followed by Og (85/94), MiL (90/89), MiB (88/84) and Cs (82/89). Cc and Og exhibited comparable activities to paracetamol (100/95). Anti-inflammatory studies revealed paw edema inhibition (%) as follows (p < 0.05): Indomethacin (47), MiL (40), Cp (30), MiB (28) and Og (22), suggesting best activity by MiL. Antinociceptive studies revealed significant (p < 0.01) pain inhibition (%) as follows: Paracetamol (97), Og (113), MiL (108), Pg (84) and MiB (88). Og and MiL exhibited the best activities. CONCLUSION: The results obtained suggest that the constituent plants possess biologically active compounds with antipyretic, anti-inflammatory and antinociceptive activities. These activities are essential in the symptomatic treatment of malaria fever, thereby justifying the folk use of Nefang. This would be useful in its subsequent development for clinical application.

Anti-malarial activity of a polyherbal product (Nefang) during early and established Plasmodium infection in rodent models.

BACKGROUND: The emerging resistance of Plasmodium species to currently available anti-malarials remains a public health concern, hence the need for new effective, safe and affordable drugs. Natural products remain a reliable source of drugs. Nefang is a polyherbal anti-malarial of the Cameroonian folklore medicine with demonstrated in vitro antiplasmodial and antioxidant activities. It is composed of Mangifera indica (bark and leaf), Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, Ocimum gratissimum (leaves). This study aimed at investigating the suppressive, prophylactic and curative activities of Nefang in Plasmodium infected rodent models. METHODS: Systemic acute oral toxicity of Nefang aqueous and ethanol extracts was assessed in mice up to a dose of 5,000 mgkg(-1) body weight. BALB/c mice and Wistar rats were inoculated with Plasmodium chabaudi chabaudi and Plasmodium berghei, respectively, and treated with Nefang, the Mangifera indica bark/Psidium guajava combination and a Psidium guajava leaf aqueous extracts (75, 150, 300 and 600 mgkg(-1) bwt). Their schizonticidal activity was then evaluated using the Peter's 4-day suppressive test). The prophylactic and curative (Rane's Test) activity of Nefang was also evaluated by determining the parasitaemia, survival time, body weight and temperature in pre-treated rodents. RESULTS: Acute oral toxicity of the extract did not cause any observed adverse effects. Percent suppressions of parasitaemia at 600 mgkg(-1) bwt were as follows (P. berghei/P. chabaudi): Nefang - 82.9/86.3, Mangifera indica bark/Psidium guajava leaf combination extract - 79.5/81.2 and Psidium guajava leaf - 58.9/67.4. Nefang exhibited a prophylactic activity of 79.5% and its chemotherapeutic effects ranged from 61.2 - 86.1% with maximum effect observed at the highest experimental dose. CONCLUSION: These results indicate that Nefang has excellent in vivo anti-malarial activities against P. berghei and P. chabaudi, upholding earlier in vitro antiplasmodial activities against multi-drug resistant P. falciparum parasites as well as its traditional use. Hence, Nefang represents a promising source of new anti-malarial agents.

Review of Ongoing Activities and Challenges to Improve the Care of Patients With Type 2 Diabetes Across Africa and the Implications for the Future.

BACKGROUND: There has been an appreciable increase in the number of people in Africa with metabolic syndrome and Type 2 diabetes (T2DM) in recent years as a result of a number of factors. Factors include lifestyle changes, urbanisation, and the growing consumption of processed foods coupled with increasing levels of obesity. Currently there are 19 million adults in Africa with diabetes, mainly T2DM (95%), estimated to grow to 47 million people by 2045 unless controlled. This has a considerable impact on morbidity, mortality and costs in the region. There are a number of issues to address to reduce the impact of T2DM including improving detection rates and current access to services alongside addressing issues of adherence to prescribed medicines. There are also high rates of co-morbidities with infectious diseases such as HIV and tuberculosis in patients in Africa with T2DM that require attention. OBJECTIVE: Document ongoing activities across Africa to improve the care of patients with T2DM especially around issues of identification, access, and adherence to changing lifestyles and prescribed medicines. In addition, discussing potential ways forward to improve the care of patients with T2DM based on ongoing activities and experiences including addressing key issues associated with co-morbidities with infectious diseases. OUR APPROACH: Contextualise the findings from a wide range of publications including internet based publications of national approaches coupled with input from senior level government, academic and other professionals from across Africa to provide future guidance. ONGOING ACTIVITIES: A number of African countries are actively instigating programmes to improve the care of patients with T2DM starting with improved diagnosis. This recognises the growing burden of non-communicable diseases across Africa, which has been neglected in the past. Planned activities include programmes to improve detection rates and address key issues with diet and lifestyle changes, alongside improving monitoring of care and activities to enhance adherence to prescribed medicines. In addition, addressing potential complexities involving diabetes patients with infectious disease co-morbidities. It is too early to fully assess the impact of such activities. CONCLUSION: There are a number of ongoing activities across Africa to improve the management of patients with diabetes including co-morbidities. However, more needs to be done considering the high and growing burden of T2DM in Africa. Ongoing research will help further benefit resource allocation and subsequent care.

Ongoing and planned activities to improve the management of patients with Type 1 diabetes across Africa; implications for the future.

BACKGROUND: Currently about 19 million people in Africa are known to be living with diabetes, mainly Type 2 diabetes (T2DM) (95%), estimated to grow to 47 million people by 2045. However, there are concerns with early diagnosis of patients with Type 1 diabetes (T1DM) as often patients present late with complications. There are also challenges with access and affordability of insulin, monitoring equipment and test strips with typically high patient co-payments, which can be catastrophic for families. These challenges negatively impact on the quality of care of patients with T1DM increasing morbidity and mortality. There are also issues of patient education and psychosocial support adversely affecting patients' quality of life. These challenges need to be debated and potential future activities discussed to improve the future care of patients with T1DM across Africa. METHODOLOGY: Documentation of the current situation across Africa for patients with T1DM including the epidemiology, economics, and available treatments within public healthcare systems as well as ongoing activities to improve their future care. Subsequently, provide guidance to all key stakeholder groups going forward utilizing input from senior-level government, academic and other professionals from across Africa. RESULTS: Whilst prevalence rates for T1DM are considerably lower than T2DM, there are concerns with late diagnosis as well as the routine provision of insulin and monitoring equipment across Africa. High patient co-payments exacerbate the situation. However, there are ongoing developments to address the multiple challenges including the instigation of universal health care and partnerships with non-governmental organizations, patient organizations, and pharmaceutical companies. Their impact though remains to be seen. In the meantime, a range of activities has been documented for all key stakeholder groups to improve future care. CONCLUSION: There are concerns with the management of patients with T1DM across Africa. A number of activities has been suggested to address this and will be monitored.

Response to the Novel Corona Virus (COVID-19) Pandemic Across Africa: Successes, Challenges, and Implications for the Future.

BACKGROUND: The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. OBJECTIVE: Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. OUR APPROACH: Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. ONGOING ACTIVITIES: Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. CONCLUSION: There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other.

In vitro antiplasmodial activities and synergistic combinations of differential solvent extracts of the polyherbal product, Nefang.

Nefang, a polyherbal product composed of Mangifera indica (bark and leaf), Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum gratissimum (leaves), is a potential therapy against P. falciparum malaria. In vitro antiplasmodial activities of its constituent solvent extracts were analyzed on CQ-sensitive (3D7) and multidrug resistant (Dd2) P. falciparum strains. The interactions involving the differential solvent extracts were further analyzed using a variable potency ratio drug combination approach. Effective concentration 50 (EC50) values were determined by nonlinear regression curve-fitting of the dose-response data and used in calculating the fractional inhibitory concentration 50 (FIC50) and combination indices (CI) for each pair. The derived EC50 values (3D7/Dd2, µ g/mL) are Nefang-96.96/55.08, MiB-65.33/34.58, MiL-82.56/40.04, Pg-47.02/25.79, Cp-1188/317.5, Cc-723.3/141, Cs-184.4/105.1, and Og-778.5/118.9. Synergism was obtained with MiB/Pg (CI = 0.351), MiL/Pg (0.358), MiB/Cs (0.366), MiL/Cs (0.482), Pg/Cs (0.483), and Cs/Og (0.414) when analyzed at equipotency ratios. Cytotoxicity testing of Nefang and the solvent extracts on two human cell lines (Hep G2 and U2OS) revealed no significant toxicity relative to their antiplasmodial activities (SI > 20). Taken together, our data confirm the antimalarial activities of Nefang and its constituent plant extracts and identified extract pairs with promising synergistic interactions for exploitation towards a rational phytotherapeutic and evidence-based antimalarial drug discovery.