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

Background: The chemotherapy use process is considered as potentially risky for cancer patients due to its complex process, use of agents with narrow therapeutic indeces, multiple drug use and use of potentially toxic compounds adding to morbidity and mortality for patients with cancer. Vincristine, a "High Alert" medicine, has been associated with fatal but preventable medication errors. Objective: To determine hazards associated with vincristine use process by performing proactive risk assessments using Healthcare Failure Mode Effect Analysis (HFMEA). Methods: A multidisciplinary health team identified and evaluated potential failure modes based on vincristine use process flow diagram using a hazard scoring matrix in a leading referral hospital in Kenya treating patients with cancer. The hazard score matrix was based on the published literature. Failure modes were prioritized using decision tree analysis in which recommendations to counteract the risks were determined. Results: The processes evaluated were; prescribing, preparation and dispensing, transportation and storage, administration and monitoring of use. A total of 77 failure modes were identified over the 3 months period of the study, April to June 2017, of which 25 were classified as high risk. Thirteen were adequately covered by existing control measures while the other 12 required the development of mitigation strategies. Two of the 12 failure modes were single-point weaknesses. Conclusions: Multiple medication errors, some with serious consequences, can occur at each stage of the chemotherapy use process making it a high-risk process. HFMEA is a useful tool to identify improvements to medication safety and reduce patient harm. The HFMEA process brings together the multidisciplinary team involved in patient care in actively identifying potential failure modes and therefore owning the recommendations made. This is now being followed up

Pattern of distribution of AIDS-related Kaposi’s sarcoma lesions in HIV patients in a referral hospital in Kenya

Background: Kaposi’s sarcoma (KS) is an angioproliferative malignancy caused by infection with human herpes virus -8 (HHV-8). The tumour has four subtypes including Classic KS, African- endemic, Iatrogenic and Acquired immunodeficiency syndrome (AIDS)-related KS. AIDS- related KS is the most common malignancy in patients with human immunodeficiency virus (HIV) infection and has variable clinical presentation with diverse distribution of lesions. Objective: To assess the pattern of distribution of KS lesions in patients with AIDS-related KS at Kenyatta National Hospital. Methods: We carried out a descriptive study on patients with HIV infection with histological diagnosis of KS. The study commenced upon approval by KNH-University of Nairobi Ethics and Research Committee. Following consent, clinical and demographic data was obtained from participants through verbal interviews and from medical records using a data capture form. Follow up was until 10 weeks. Management of patients was at the discretion of the attending clinician. Data was analyzed by a statistician using Instat Biostatistics program. Results Seventy-four participants aged between 13 to 55 years were enrolled into the study. Males were 42 (56.7%) and females 32 (43.2%). Mean age was 36.8 years. The distribution of KS lesions was variable. We demonstrate high predilection of lesions for skin and lymph nodes at 62.6%. Other sites were involved were the oral cavity 14.9%. Twenty-eight (38%) of the participants had multifocal lesions with a male predominance in skin and viscera with male to female ratio of skin 1.8:1 and viscera 7:1 respectively. Conclusion: We demonstrate reduced male: female ratio and multifocal distribution of AIDS-related KS lesions with predominance in skin and lymph nodes and male predominance in visceral lesions. Future studies should aim to determine what favours increase in, KS in women and visceral lesions in males among patients with HIV infection. Keywords: Kaposi’s Sarcoma, human immunodeficiency virus (HIV), Acquired Immunodeficiency Syndrome (AIDS

Estrogenic and Anti-Inflammatory Activities of a Steroidal Indoxyl

The estrogenic and anti-inflammatory activities of 3-methoxy-16, 17-seco-16-norestra-1,3,5-trien-15-(2'-indoxyliden)-17-oic acid is reported. After intraperitoneal administration, the dose of this compound required to reduce swelling of the rat paw by 50% (ED50) was 14.1 mg/kg using the carrageenan-induced rat paw oedema anti-inflammatory assay method. Indomethacin had an ED50 of 3.2 mg/kg in this assay while dexamethasone had an ED50 of 1.7 mg/kg. The estrogenic activity of the compound after intramuscular administration in rats was 0.72 relative to diethylstilbestrol, when the two compounds were assayed at three dose levels of 1.0, 0.3 and 0.1 mg/kg. Key Words: Steroidal indoxyl, synthesis, estrogenic, anti-inflammatory East and Central African Journal of Pharmaceutical Sciences Vol.5(3) 2002: 44-4

Abandonment of treatment and loss to follow up: a potential cause of treatment failure in patients with AIDS-related Kaposi’s sarcoma

Background: Management of patients with cancer is complex, multi-disciplinary, longitudinal and costly. Abandonment of treatment by patients and loss to follow up is a common scenario, especially in resource poor countries and severely compromises health outcomes. Objective: To assess the commitment to drug treatment protocol of patients with Acquired Immunodeficiency Syndrome (AIDS)-Related Kaposi’s Sarcoma at Kenyatta National Hospital, Kenya, over a 10 week period . Methods: The study design was prospective, observational, cross-sectional period prevalence study on patients infected with human immunodeficiency virus (HIV) with Kaposi’s sarcoma. Patients with histological diagnosis of Kaposi’s sarcoma were sequentially enrolled into the study as they attended either the Haematology or Radiotherapy clinic or during their admission in the wards. The choice of the treatment protocol was left at the discretion of the attending physician. A pretested data collection form was used to collect demographic and clinical information about the patients, including treatments prescribed and completion of follow up. Results: A total of 74 patients were enrolled into the study, 42 (56.8%) males and 32 (43.2%) females. The age ranged between 13 years to 55 years. Their treatment protocols included: Vincristine only, Vincristine plus Bleomycin, Vincristine plus Bleomycin plus Doxorubicin, Radiotherapy plus Vincristine and Radiotherapy only. Few of the patients were not assigned any antitumor treatment. Antiemetic and other conventional medicines were also prescribed when necessary. Fifty four (73%) of the patients abandoned treatment, five (6.8%) died, 15(20.3%) continued to attend clinic over the 10 week period.  There was no significant association between sex and outcome (p=0.661). Discussion: The results of this study demonstrate that abandonment of treatment is a major problem among patients on treatment for cancer in Kenyatta National Hospital in Kenya. Abandonment of treatment heavily contributes to poor clinical outcome hence complicating the burden of cancer in the country. It is therefore important to develop and establish follow-up systems to improve adherence to treatment for the cancer patients at Kenyatta National Hospital. Key words: Abandonment of treatment, Loss to follow up, AIDS-Related Kaposi’s Sarcom

How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?

Malaria continues to be an enormous global health challenge, with millions of new infections and deaths reported annually. This is partly due to the development of resistance by the malaria parasite to the majority of established anti-malarial drugs, a situation that continues to hamper attempts at controlling the disease. This has spurred intensive drug discovery endeavours geared towards identifying novel, highly active anti-malarial drugs, and the identification of quality leads from natural sources would greatly augment these efforts. The current reality is that other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years. This paper briefly presents both classical as well as some more modern, but underutilized, approaches that have been applied outside the field of malaria, and which could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds

Trends of anticoagulation control among adult outpatients on long-term Warfarin therapy in a Tertiary Teaching and Referral Hospital in Kenya

Background: Anticoagulation control using warfarin therapy has several challenges especially in resource constrained settings.Objective: To describe the trends of anticoagulation control among adult outpatients on warfarin therapy at Kenyatta National Hospital. Design: Cross-sectional study.Setting: Anticoagulation clinics in the hospital. Participants: 180 outpatients aged ≥18 years.Main outcome measures: Level of anticoagulation and adverse drug reactions (ADRs). Methods: Participants’ sociodemographic characteristics and details of ADRs were acquired through face-to-face interviews. The level of anticoagulation was determined through assessment of international normalized ratios (INRs) for the six clinic attendances with INR of 2-3 being considered therapeutic. Data analysis was conducted onto IBM Statistical Package for Social Sciences version 23. Pearson’s Chi square was used to determine the strength of associations between outcome measures and  sociodemographics, with statistical significance set at p≤0.05. Results: Females were majority (76.7%) and the mean age of participants was 43.4 (±13.2) years. Therapeutic anticoagulation was maintained by 35.2-48.4% patients across six follow-ups and was better among the males (p=0.0398) especially those suffering from heart diseases. ADRs were experienced by almost 50% of the patients where bleeding (27.8%) mainly occurred at INR>3(80.0%). ADRs were significantly more common among the participants without spouses, who were primarily suffering from heart diseases (p=0.0081).Conclusions: Anticoagulation control is poor though patients with cardioembolic disorders have better INRs but more ADRs. Clinical and laboratory monitoring of warfarin therapy should be intensified among females. Future studies should correlate warfarin anticoagulation control with patient, clinician or hospital related factors

Predictors of Breast Cancer Treatment Outcomes in Kenyan Women

Background: Breast cancer is the most prevalent cancer among Kenyan women.  Worldwide data show that diverse factors including socio-economic status, co-morbidities, and expression of hormonal receptors, have effect on disease recurrence or metastasis following treatment. Most studies on breast cancer treatment outcomes have been undertaken in developed countries, and there is scarcity of data on predictive indicators of breast cancer treatment outcomes in Africa. Objective: This study was designed to determine the factors that predict the treatment outcomes in breast cancer patients in a Kenyan teaching and referral hospital. Methods: This hospital based retrospective descriptive study was designed to evaluate the effect of the occurrence of estrogen receptor, progesterone receptor, human epidermal growth factor and cancer stage among other factors on the outcome of breast cancer treatment. Patients diagnosed with breast cancer and who had their first visit at the KNH in the period 2007-2008 were identified. Quantitative variables were described with medians or means. Association effects were determined by use of Chi-square test. Categorical variables were summarized using proportions. The time to event analysis was estimated using the Kaplan–Meier product limit method. Results: The mean age of the 219 participants was 46.5 years (range 23 to 92 years), majority (36.1%) of whom were aged between 41 to 50 years. Most study participants had stage 2B (21.9%) cancer type, and the histological grade 3 breast cancer was predominant type (50.2%). Nearly half of the patients (46.1%) developed metastases. In bivariate analyses, cancer stage 2A (OR 0.29, 95% CI 0.12 to 0.77) and stage 2B (OR 0.41, 95% CI 0.21- 0.77), presence of estrogen receptors (OR 0.24, 95% CI 0.12 to 0.77), presence of progesterone receptor (OR 0.26, 95% CI 0.09 to 0.72), human epidermal growth factors (OR 0.05, 95% CI 0.003 to 0.84), and those on hormonal treatment (OR 0.34, 95% CI 0.19 to 0.62) were factors less likely to be associated with development of metastasis after treatment. In multivariate analysis, HIV positive status (OR 0.004, 95% CI 0.002 to 0.75), presence of estrogen (OR 0.23, 95% CI 0.08 to 0.64) and human epidermal growth factors (OR 2.53, 95% CI 1.64 to 3.91) receptors and obesity (OR 2.53, 95% CI 1.64 to 3.91) were independent factors influencing development of metastasis after treatment. Conclusion: This study showed that development of metastasis after breast cancer therapy has associations with the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor -2 (HER-2) as well as the stage of diagnosis.  This study demonstrates the need for enhanced screening for breast cancer to improve early diagnosis and the testing of ER, PR and HER-2 are crucial as they predict outcomes of therapy. Key words: Breast cancer, breast cancer treatment, cancer treatment outcomes, cancer treatment predictors