Risk factors for caesarean delivery and fetal macrosomia among women with gestational diabetes in Nyeri County, Kenya: a cross-section study.

Introduction: gestational diabetes mellitus is an emerging global public health threat due to adverse health outcomes. This study aimed to determine the risk factors for caesarean delivery and macrosomia among women with gestational diabetes in Nyeri County, Kenya. Methods: this study used a cross-section design. Randomly, 152 women with gestational diabetes and attending antenatal clinics and maternity were enrolled in this study. Data was collected using a questionnaire upon consent. Data were subjected to binary logistic regression and binomial multiple logistic regression. Results: the mean age of the women with gestational diabetes was 30.86 (SD 5.81) years. Among women with gestational diabetes, a proportion of 59.9% (n=91) delivered through caesarean delivery. The positive history of diabetes in a family, previous positive history of gestational diabetes and positive previous adverse obstetric history increased chances of caesarean section delivery by more than 3.824 (95% CI = 1.001-14.608, p=0.05), 10.331 (95% CI = 2.464-43.308, p=0.001) and 7.051 (95% CI = 1.577-31.801, 0.01) folds, respectively. Fetal macrosomia incidence was 42.1% (n=64) among women with gestational diabetes. The primary level of education, previous positive history of gestational diabetes and previous positive adverse obstetric history increased the likelihood of fetal macrosomia by more than 6.289 (95% CI = 1.241-31.870, p=0.03), 5.390 (95% CI = 1.498-19.386, p=0.01) and (95% CI = 5.804 1.349-18.423, p=0.02) folds, respectively. Conclusion: antenatal health care programs and delivery facilities should be strengthened in women with gestational diabetes to improve the risk associated with caesarean delivery and fetal macrosomia.

A Systematic Review of the Treatment Outcomes among Prostate Cancer Patients in Africa.

Prostate cancer (PCa) is associated with a significant public health burden in Africa. This systematic review aimed to assess treatment outcomes among PCa patients in Africa. A systematic search of the literature was conducted from 1 December 2021 to 31 March 2022 to identify relevant published studies. PubMed, EMBASE, CINAHL, and Google Scholar databases were used. Twenty-four studies met the inclusion criteria, and the mean age was 68 years. Localized and locally advanced diseases had relatively higher overall survival than metastatic diseases. In metastatic disease, the mean overall five-year survival was 42% which is shorter than the Asian population (61.9%).

Rational use of antibiotics and covariates of clinical outcomes in patients admitted to intensive care units of a tertiary hospital in Kenya.

OBJECTIVES: Rational use of antibiotics implies appropriate choice of an antibiotic administered at correct dose, frequency, and duration using the most suitable route of administration. Irrational antibiotics use is associated with antimicrobial resistance, drug failure, and high mortality in the critical care units (CCUs). This study sought to establish rational use of antibiotics and determinants of clinical outcomes of patients admitted to the CCUs at the Kenyatta National Hospital (KNH). The findings would guide policy formulation of antibiotics use in hospital CCUs in Kenya and the region. METHODS: Retrospective review of 220 admissions to the KNH CCUs over the period February 2018-February 2020 was conducted. Participants' sociodemographics, clinical characteristics, antibiotics therapy, and outcome of admission were extracted from patient files and analyzed using STATA version 23. Determinants of irrational antibiotic use and covariates of clinical outcomes were computed at 95% confidence. RESULTS: The prevalence of rational use of antibiotics was only 18.5%. Inappropriate choice of antibiotics (51.0%) and incorrect duration (32.3%) were the most common irrational practices. Flucloxacillin (100%), cefuroxime (93.3%), cefazolin (85.7%), and ceftriaxone (83.0%) were the most irrationally used antibiotics. Irrational use of ceftriaxone was significantly associated with clinical diagnosis (p = 0.012), while that of amoxiclav was associated with patient risk category (p = 0.039). Mortality in the CCUs was 10%, and the odds of dying were almost six times among intubated patients compared to those who were not (AOR 5.5, 95% CI = 1.1-28.1, p = 0.042). CONCLUSION: Irrational antibiotics prescribing is high in the KNH CCUs, attributable largely to incorrect choice and wrong duration of antibiotic use. Mortality was significantly associated with intubation. Intensification of management in critical care settings should be directed toward intubated patients while ensuring appropriate choice of antibiotics administered for the correct duration. Future studies should explore factors that could promote rational antibiotics use in critical care settings. BACKGROUND: Antibiotics are important in the management of infections. Therefore, they should be used properly as guided by the 5Rs of antimicrobials use, namely, right choice of antibiotic for a particular disease, administered at the right dose, for the right duration, at the right frequency via the right route of administration. AIM: We sought to establish the extent to which the use of antibiotics adheres to the established guidelines in the treatment and prevention of infections among patients admitted to intensive care units (ICUs) of Kenyatta National Hospital (KNH), Kenya. METHODS: We reviewed and analyzed medical records of 220 patients admitted in the KNH ICUs in the period between February 2018 and February 2020. FINDINGS: Antibiotics were used properly in only 18.5% of the cases. Unsuitable choice of antibiotics (51.0%) and incorrect duration (32.3%) were the major contributors to improper use. Flucloxacillin (100%), cefuroxime (93.3%), cefazolin (85.7%), and ceftriaxone (83.0%) were the most inappropriately used antibiotics. Approximately 10% of those admitted to the ICU died. Further, the probability of dying was almost six times among intubated patients compared to those who were not. CONCLUSION: The use of antibiotics in the KNH CCUs is not in tandem with established guidelines, owing to inappropriate selection and wrong duration of use. Though death was associated with intubation, more studies are needed to find out factors promoting appropriate antibiotics use in the ICUs so that clinicians can follow them in the treatment of patients.

Evaluation of the Antimalarial Activity of the Leaf Latex of Aloe weloensis (Aloaceae) against Plasmodium Parasites.

BACKGROUND: The lack of available vaccines and the emerging resistance to antimalarial drugs have provided the necessity to find noble antimalarial plant-based medicines. The leaf latex Aloe weloensis has been used in folk medicine against malarial and other human ailments in Ethiopia. Hence, the present study aimed to investigate the antimalarial activity of the leaf latex of A. weloensis against Plasmodium parasites. MATERIALS AND METHODS: The prophylactic and curative models were employed to determine the in vivo antimalarial activity of the leaf latex A. weloensis against P. berghei infected mice, and the antioxidant activity of the latex was assessed using diphenyl-1-picrylhydrazine (DPPH) assay. Female mice were recruited for toxicity study, and the leaf latex was administered to fasted mice at a dose of 5000 mg/kg. The mice were kept under continuous observation for fourteen days for any signs of overt toxicity. RESULTS: The leaf latex of A. weloensis was safe up to 5000 mg/kg, and the latex endowed free radical inhibition activity (IC50 = 10.25 µg/ml). The latex of A. weloensis leaf demonstrated the inhibitory activity against the 3D7 strain of P. falciparum (IC50 = 9.14 µg/ml). The prophylactic and curative effect of the latex was found to be dose-dependent. The mice's parasitemia level was significantly (p < 0.001) reduced at all tested doses of the leaf latex compared to negative control in the curative test. Parasitemia reduction was significant (200 mg/kg, p < 0.01, and 400 and 600 mg/kg, p < 0.001) in the prophylactic test compared to the control. In addition, the leaf latex significantly (p < 0.01) improved mean survival time, packed cell volume, rectal temperature, and bodyweight of P. berghei infected mice. CONCLUSION: The leaf latex of Aloe weloensis was endowed with the antimalarial activity at various doses, corroborating the plant's claimed traditional use.

Meloxicam emulgels for topical management of rheumatism: Formulation development, in vitro and in vivo characterization.

PURPOSE: The study designed, formulated and evaluated meloxicam emulgels as a potential alternative topical treatment option for rheumatism. METHODS: A 32 factorial design was employed to formulate nine preliminary meloxicam emulgels (Formulations F1 - F9). The influences of carbopol-934 and menthol as gelling agent and drug release enhancer, respectively, were correlated with four pharmaceutical properties of the formulated emulgels namely viscosity, spreadability, and cumulative drug release at one hour and at eight hours. Using the generated data and applying the Design Expert® modelling software, two optimized meloxicam emulgels (Formulations F10 and F11) were designed, formulated and evaluated. In vivo anti-inflammatory efficacy was conducted using carrageenan-induced rat paw oedema method. Drug release kinetics was modelled using DDSolver® dissolution software. RESULTS: All formulations were homogenous with no observable grittiness or phase separation. The optimized Formulations F10 and F11 had pH 6.5 and 6.4, viscosity of 23656 and 24524 mPa.s, spreadability of 9.9 and 9.5 cm, and drug content of 90.4% and 92.9%, respectively, all within optimal values. The cumulative percentage of drug released was 21.0% and 22.9% after one hour and 50.1% and 55.8% after eight hours for Formulations F10 and F11, respectively. Drug release kinetics exhibited Fickian diffusion best described by Korsmeyer-Peppas model. Paw volume inhibition by Formulation F11 at two and three hours after carrageenan injection was statistically significant (p < 0.05). CONCLUSION: The optimized meloxicam emulgels had high pharmaceutical quality and were pharmacologically active. Further optimization could potentially provide a safe and efficacious alternative treatment option for rheumatism.

Rectal microbiota diversity in Kenyan MSM is inversely associated with frequency of receptive anal sex, independent of HIV status.

OBJECTIVE: Both HIV infection and identifying as MSM have been linked to altered rectal microbiota composition, but few studies have studied sexual behavioural associations with rectal microbiota within MSM. In addition, most rectal microbiota studies in MSM have been limited geographically to Europe and North America, and replication of findings in lower and middle-income countries is lacking. DESIGN: A cross-sectional study. METHODS: We enrolled MSM from Nairobi, Kenya, and determined their HIV/sexually transmitted infection status. Rectal specimens were obtained for 16s rRNA sequencing of the rectal microbiota, and sexual behaviour was characterized using a standardized questionnaire. Microbiome differences were modelled using nonparametric statistics, Bray-Curtis ecological distance metrics and analyses of differential taxa abundance. Multivariable linear regression was used to model HIV status and recent sexual activity as predictors of alpha diversity, controlling for a range of covariates. RESULTS: Alpha diversity was consistently lower in Kenyan HIV-infected MSM (n = 80), including those on antiretroviral therapy (ART) compared with HIV-uninfected MSM. A statistical trend was observed for clustering of HIV status by Prevotella or Bacteroides dominance (P = 0.13). Several taxa were enriched in HIV-positive men, including Roseburia, Lachnospira, Streptococcus and Granulicatella. Receptive anal sex with several types of sexual partners (paying, regular, casual) was associated with lower Chao1 and Simpson diversity, independent of HIV status, while HIV infection was associated lower Chao1 (P = 0.030) but not Simpson diversity (P = 0.49). CONCLUSION: Both HIV infection and sexual behaviour were associated with rectal microflora alpha diversity, in particular richness, but not Prevotella spp. dominance, in Kenyan MSM. Associations were more robust for sexual behaviour.

Antihypertensive therapy and adequacy of blood pressure control among adult hypertensive diabetic patients with chronic kidney disease in a tertiary referral hospital.

Background: Tight blood pressure control retards the development of end-stage renal disease in hypertensive diabetic patients with chronic kidney disease. There is limited literature on blood pressure control among this patient population in a resource-limited setting. Research design and methods: A tertiary hospital-based cross-sectional study with 237 hypertensive diabetic patients with chronic kidney disease was conducted. A pre-tested questionnaire was used to assess patients' awareness of their ideal blood pressure. Data on blood pressure readings and antihypertensive therapies were abstracted into predesigned data collection forms and analyzed using STATA software version 13.0. Results: The participants' mean age was 61.8 ± 12.7 years and 106 (44.7%) patients were aware of the blood pressure targets. Adequate blood pressure control was found in 30.8%. Most (58.7%) were using ≥ 3 antihypertensive drug classes. Calcium channel blockers (51.1%), with principally amlodipine (26.2%) and nifedipine (24.1%), were the most preferred agents. Bivariate analysis showed enalapril (p = 0.009) and nifedipine (p = 0.022) being associated with adequate blood pressure control. However, nifedipine (AOR 2.79; 95% CI: 1.12-6.9, p = 0.028) and awareness of ideal blood pressure targets (AOR 4.57; 95% CI: 1.25-16.7, p = 0.022) were independent predictors of good control. Conclusion: Adequacy of blood pressure among hypertensive diabetic patients with chronic kidney disease is low and may be attributable to unawareness of its target level and using inappropriate therapy. Future studies should correlate level of blood pressure control with patient-, clinician-, and hospital-related factors.

Treatment Outcomes and Associated Factors among Hospitalized Stroke Patients at Shashemene Referral Hospital, Ethiopia.

BACKGROUND: The 2013 Global Burden of Disease report indicated that 80% of stroke deaths occur in low- and middle-income regions. Although stroke has been consistently reported as one of the three leading causes of morbidity and mortality in the past years in Ethiopia, there is a paucity of data regarding treatment outcomes of stroke if sufficient. Hence, the present study aimed to assess patterns of treatment outcomes and associated factors among hospitalized stroke patients at Shashemene Referral Hospital. METHODS: A retrospective cross-sectional study was conducted at the medical ward of Shashemene Referral Hospital. A total of 73 hospitalized stroke patients during the period 2012-2017 were included in the study. Demographic characteristics, risk factors, and stroke types and their hospital outcomes were reviewed from the medical records of the patients. The data were entered and analyzed using SPSS version 16.0. Descriptive statistics such as percent and frequency were used to summarize patients' characteristics. Binary logistic regression was used to investigate the potential predictors of treatment outcome. A p-value ≤0.05 was considered statistically significant. RESULT: Ischemic stroke was the most common type of stroke (65.8%) diagnosed in our setting. Hypertension (52.05%) was the common comorbid condition. More than half (54.79%) of the stroke patients improved on treatment. Dyslipidemics were prescribed to 68.49% of patients and the most popular antiplatelet was aspirin, which was prescribed to 61.64% of the study participants. Age, sex, type of stroke, and type of comorbidity were not significant factors of stroke treatment outcome. CONCLUSION: Ischemic stroke was the most common type of stroke diagnosed among the study participants while aspirin and statins were the most frequently used drugs in the management of stroke. Approximately 50% of hospitalized stroke patients had good treatment outcome and none of the investigated variables were significantly associated with the treatment outcomes.

Assessment of drug therapy problems among patients with cervical cancer at Kenyatta National Hospital, Kenya.

BACKGROUND: Although cervical cancer is preventable, it is still the second leading cause of cancer deaths among women in the world. Further, it is estimated that around 5-10% of hospital admissions are due to drug related problems (DRPs), of which 50% are avoidable. In cancer therapy, there is an immense potential for DRPs due to the high toxicity of most chemotherapeutic regimens. Hence, this study sought to assess DRPs among patients with cervical cancer at Kenyatta National Hospital (KNH). METHODS: A cross-sectional study was conducted at the oncology units of KNH. A total of 81 study participants were recruited through simple random sampling. Data were collected from medical records and interviewing patients. The appropriateness of medical therapy was evaluated by comparing with National Compressive Cancer Network and European Society for Medical Oncology practice guideline of cervical cancer treatment protocol. The degree of adherence was determined using eight-item Morisky medication adherence scale. The likelihood of drug interaction was assessed using Medscape, Micromedex and Epocrates drug interaction checkers. The data were entered in Microsoft Excel and analysed using statistical software STATA version 13.0. Descriptive statistics such as mean, percent and frequency were used to summarise patients' characteristics. Univariable and multivariable binary logistic regression were used to investigate the potential predictors of DRPs. RESULT: A total of 215 DRPs were identified from 76 patients, translating to a prevalence of 93.8% and a mean of 2.65 ± 1.22 DRPs. The predominant proportion of DRPs (48.2%) was identified in patients who had been treated with chemoradiation regimens. Adverse drug reactions 56(69.1%) and drug interactions 38(46.9%) were the most prevalent DRPs. Majority (67.9%) of the study population were adherent to their treatment regimens. Forgetfulness 18(69.2%), expensive medications 4(15.4%) and side effects of medications 4(15.4%) were the main reasons for medication non-adherence. Patients with advanced stage cervical cancer were 15.4 times (AOR = 15.4, 95% CI = 1.3-185.87, p = 0.031) more likely to have DRPs as compared to patients with early stage disease. CONCLUSION: Adverse drug reactions, drug interactions, and need of additional drug therapy were the most common DRPs identified among cervical cancer patients. Advanced stage cervical cancer was the only predictor of DRPs.

Antischistosomal Activity of Pyrido[1,2-a]benzimidazole Derivatives and Correlation with Inhibition of ß-Hematin Formation.

The extensive use of praziquantel against schistosomiasis raises concerns about drug resistance. New therapeutic alternatives targeting critical pathways within the parasite are therefore urgently needed. Hemozoin formation in Schistosoma presents one such target. We assessed the in vitro antischistosomal activity of pyrido[1,2-a]benzimidazoles (PBIs) and investigated correlations with their ability to inhibit ß-hematin formation. We further evaluated the in vivo efficacy of representative compounds in experimental mice and conducted pharmacokinetic analysis on the most potent. At 10 µM, 48/57 compounds resulted in >70% mortality of newly transformed schistosomula, whereas 37 of these maintained >60% mortality of adult S. mansoni. No correlations were observed between ß-hematin inhibitory and antischistosomal activities against both larval and adult parasites, suggesting possible presence of other target(s) or a mode of inhibition of crystal formation that is not adequately modeled by the assay. The most active compound in vivo showed 58.7 and 61.3% total and female worm burden reduction, respectively. Pharmacokinetic analysis suggested solubility-limited absorption and high hepatic clearance as possible contributors to the modest efficacy despite good in vitro activity. The PBIs evaluated in this report thus merit further optimization to improve their efficacy and to elucidate their possible mode of action.

Antimalarial Pyrido[1,2-a]benzimidazoles: Lead Optimization, Parasite Life Cycle Stage Profile, Mechanistic Evaluation, Killing Kinetics, and in Vivo Oral Efficacy in a Mouse Model.

Further structure-activity relationship (SAR) studies on the recently identified pyrido[1,2-a]benzimidazole (PBI) antimalarials have led to the identification of potent, metabolically stable compounds with improved in vivo oral efficacy in the P. berghei mouse model and additional activity against parasite liver and gametocyte stages, making them potential candidates for preclinical development. Inhibition of hemozoin formation possibly contributes to the mechanism of action.

Computer-Aided Drug Discovery Approaches against the Tropical Infectious Diseases Malaria, Tuberculosis, Trypanosomiasis, and Leishmaniasis.

Despite the tremendous improvement in overall global health heralded by the adoption of the Millennium Declaration in the year 2000, tropical infections remain a major health problem in the developing world. Recent estimates indicate that the major tropical infectious diseases, namely, malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for more than 2.2 million deaths and a loss of approximately 85 million disability-adjusted life years annually. The crucial role of chemotherapy in curtailing the deleterious health and economic impacts of these infections has invigorated the search for new drugs against tropical infectious diseases. The research efforts have involved increased application of computational technologies in mainstream drug discovery programs at the hit identification, hit-to-lead, and lead optimization stages. This review highlights various computer-aided drug discovery approaches that have been utilized in efforts to identify novel antimalarial, antitubercular, antitrypanosomal, and antileishmanial agents. The focus is largely on developments over the past 5 years (2010-2014).

Ethnobotanical survey of food and medicinal plants of the Ilkisonko Maasai community in Kenya.

AIM OF THE STUDY: Pastoralist communities such as the Maasai are heavily reliant on traditional foods and medicines. This survey sought to identify traditional foods and/or medicinal plants of the Ilkisonko Maasai community living in Kenya. MATERIALS AND METHODS: Ethnobotanical knowledge of traditional plants used as food and human/veterinary medicine was obtained using structured and semi-structured questionnaires administered through face to face interviews of key informants. RESULTS: A total of 30 species from 21 families and 25 genera were reportedly used as food and/or medicine by 48 respondents. The most commonly encountered genus was the Fabaceae. The growth forms encountered were tree (47%), shrub (33%) and herb (20%). Plants that were commonly mentioned by respondents were Salvadora persica (85%), Grewia villosa (52%), Ximenia americana (52%), Albizia anthelmintica (50%), Acacia robusta (46%) and Acacia nilotica (42%). The root/root bark was the most commonly used plant part (35%), followed by the stem/stem bark (30%), fruit (15%), leaves (11%) and whole plant (9%). Common ailments treated were stomach aches, constipation, back aches, joint aches, body pains and sexually transmitted infections. The plants were also used as tonics, digestives, and restoratives. CONCLUSION: It was evident that traditional medicine was the preferred health care system for the Ilkisonko Maasai community. It is important to document and use this knowledge in producing novel products that could improve nutrition and healthcare in rural communities.

Design, Synthesis, and Antiplasmodial Activity of Hybrid Compounds Based on (2R,3S)-N-Benzoyl-3-phenylisoserine.

A series of hybrid compounds based on (2R,3S)-N-benzoyl-3-phenylisoserine, artemisinin, and quinoline moieties was synthesized and tested for in vitro antiplasmodial activity against erythrocytic stages of K1 and W2 strains of Plasmodium falciparum. Two hybrid compounds incorporating (2R,3S)-N-benzoyl-3-phenylisoserine and artemisinin scaffolds were 3- to 4-fold more active than dihydroartemisinin, with nanomolar IC50 values against Plasmodium falciparum K1 strain.