Association between psychosis and substance use in Kenya. Findings from the NeuroGAP-Psychosis study.

Background: Substance use is prevalent among people with mental health issues, and patients with psychosis are more likely to use and misuse substances than the general population. Despite extensive research on substance abuse among the general public in Kenya, there is a scarcity of data comparing substance use among people with and without psychosis. This study investigates the association between psychosis and various substances in Kenya. Methods: This study utilized data from the Neuro-GAP Psychosis Case-Control Study between April 2018 and December 2022. The KEMRI-Wellcome Trust Research Programme recruited participants from various sites in Kenya, including Kilifi County, Malindi Sub-County, Port Reitz and Coast General Provincial Hospitals, and Moi Teaching and Referral Hospital, as well as affiliated sites in Webuye, Kapenguria, Kitale, Kapsabet, and Iten Kakamega. The collected data included sociodemographic information, substance use, and clinical diagnosis. We used the summary measures of frequency (percentages) and median (interquartile range) to describe the categorical and continuous data, respectively. We examined the association between categorical variables related to psychosis using the chi-square test. Logistic regression models were used to assess the factors associated with the odds of substance use, considering all relevant sociodemographic variables. Results: We assessed a total of 4,415 cases and 3,940 controls. Except for alcohol consumption (p-value=0.41), all forms of substance use showed statistically significant differences between the case and control groups. Cases had 16% higher odds of using any substance than controls (aOR: 1.16, 95%CI: 1.05-1.28, p=0.005). Moreover, males were 3.95 times more likely to use any substance than females (aOR:3.95; 95%CI: 3.43-4.56). All the categories of living arrangements were protective against substance use. Conclusion: The findings of this study suggest that psychotic illnesses are associated with an increased likelihood of using various substances. These findings are consistent with those of previous studies; however, it is crucial to investigate further the potential for reverse causality between psychosis and substance abuse using genetically informed methods.

Risk of Bleeding Associated With Outpatient Use of Rivaroxaban in VTE Management at a National Referral Hospital in Western Kenya.

There is limited data on the bleeding safety profile of direct oral anticoagulants, such as rivaroxaban, in low- and middle-income country settings like Kenya. In this prospective observational study, patients newly started on rivaroxaban or switching to rivaroxaban from warfarin for the management of venous thromboembolism (VTE) within the national referral hospital in western Kenya were assessed to determine the frequency of bleeding during treatment. Bleeding events were assessed at the 1- and 3-month visits, as well as at the end of follow-up. The International Society of Thrombosis and Hemostasis (ISTH) and the Bleeding Academic Research Consortium (BARC) criteria were used to categorize the bleeding events, and descriptive statistics were used to summarize categorical variables. Univariate and multivariate logistic regression model was used to calculate unadjusted and adjusted associations between patient characteristics and bleeding. The frequency of any type of bleeding was 14.4% (95% CI: 9.3%-20.8%) for an incidence rate of 30.9 bleeding events (95% CI: 20.1-45.6) per 100 patient-years of follow-up. The frequency of major bleeding was 1.9% while that of clinically relevant non-major bleeding was 13.8%. In the multivariate logistic regression model, being a beneficiary of the national insurance plan was associated with a lower risk of bleeding, while being unemployed was associated with a higher bleeding risk. The use of rivaroxaban in the management of VTE was associated with a higher frequency of bleeding. These findings warrant confirmation in larger and more targeted investigations in a similar population.

Severe abacavir hypersensitivity reaction in a patient with human immunodeficiency virus infection: a case report.

BACKGROUND: Abacavir is a nucleoside reverse transcriptase inhibitor that is used as a component of the antiretroviral treatment regimen in the management of the human immunodeficiency virus for both adults and children. It is efficacious, but its use may be limited by a hypersensitivity reaction linked with the HLA-B*57:01 genotype. HLA-B*57:01 has been reported to be rare in African populations. Because of the nature of its presentation, abacavir hypersensitivity is prone to late diagnosis and treatment, especially in settings where HLA-B*57:01 genotyping is not routinely done. CASE REPORT: We report a case of a severe hypersensitivity reaction in a 44-year-old Kenyan female living with the human immunodeficiency virus and on abacavir-containing antiretroviral therapy. The patient presented to the hospital after recurrent treatment for a throat infection with complaints of fever, headache, throat ache, vomiting, and a generalized rash. Laboratory results evidenced raised aminotransferases, for which she was advised to stop the antiretrovirals that she had recently been started on. The regimen consisted of abacavir, lamivudine, and dolutegravir. She responded well to treatment but was readmitted a day after discharge with vomiting, severe abdominal pains, diarrhea, and hypotension. Her symptoms disappeared upon admission, but she was readmitted again a few hours after discharge in a hysterical state with burning chest pain and chills. Suspecting abacavir hypersensitivity, upon interrogation she reported that she had taken the abacavir-containing antiretrovirals shortly before she was taken ill. A sample for HLA-B*57:01 was taken and tested positive. Her antiretroviral regimen was substituted to tenofovir, lamivudine, and dolutegravir, and on subsequent follow-up she has been well. CONCLUSIONS: Clinicians should always be cognizant of this adverse reaction whenever they initiate an abacavir-containing therapy. We would recommend that studies be done in our setting to verify the prevalence of HLA-B*57:01.

Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa.

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.

Treatment of tungiasis using a tea tree oil-based gel formulation: protocol for a randomised controlled proof-of-principle trial.

INTRODUCTION: Tungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment. METHODS AND ANALYSIS: This trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6-15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction. ETHICS AND DISSEMINATION: The trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.

Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations.

Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.

Three year survival among patients with aids-related Kaposi sarcoma treated with chemotherapy and combination antiretroviral therapy at Moi teaching and referral hospital, Kenya.

BACKGROUND: AIDS-related Kaposi sarcoma (AIDS-KS), a common malignancy in Kenya is associated with high morbidity and mortality. AIDS-KS is treated using bleomycin and vincristine (BV) plus or minus doxorubicin in most low resource settings, with response rates ranging from 24.8 to 87%. Survival in low resource settings has not been well documented. We report the three-year survival in a cohort of seventy patients referred to Moi Teaching and Referral Hospital (MTRH). METHODS: Study participants are part of a randomized phase IIA trial on the use of gemcitabine compared to bleomycin plus vincristine for the treatment of Kaposi sarcoma after combination antiretroviral therapy (cART) in Western Kenya. All patients were followed for three years in MTRH. Survival was determined by three monthly physical examination and analysed using Kaplan-Meier method, while possible determinants of survival such as baseline characteristics, type of chemotherapy, initial CD4 counts, age at enrolment, gender and early response to chemotherapy were analysed using univariate and multivariate Cox regression. RESULTS: Participants were aged between 19 and 70 years with 56% being male. The median CD4 count was 224 cells/µl, median duration of HIV diagnosis was 12.0 months and median duration of KS lesions after histology diagnosis before initiating chemotherapy was 4.8 weeks. At three years, 60 (85.7%) patients were alive. Six of those who died were under treatment with BV while four with gemcitabine. There was no difference in the probability of survival between the patients on either treatment arm (HR = 0.573 [95% C. I 0.143, 2.292; p = 0.4311]). Additionally, the hazard ratio (HR) for response after six weeks, age at enrolment and gender indicated that they were not significant determinants of survival. Patients with normal CD4 cell counts (> = 500/µl), had a HR of 0.401(0.05,3.23; p = 0.391), suggesting better survival. CONCLUSIONS: Patients with AIDS-KS treated with combined antiretroviral drugs had excellent three-year survival regardless of whether they were treated with BV or gemcitabine as first line therapy. An initial CD4 cell count of > = 500/µl appeared to improve survival while gender, age and early response to chemotherapy were not predictors of survival after three years. TRIAL REGISTRATION: Number PACTR201510001.

Ethnomedical Survey of the Plants Used by Traditional Healers in Narok County, Kenya.

Most of the plants used by herbalists amongst the various Kenyan communities have not been documented despite their widespread use. The purpose of this research was to document the medicinal plants used by the herbalists from the Maasai, a community that still relies on herbal medicine to a large extent for the provision of medical services. Semistructured interviews, direct observations, group discussions, and in-depth interviews were used to collect information from the traditional healers. A total of 47 plant species belonging to 31 families were identified. They were used in the treatment of 33 medical and 4 veterinary conditions.

Enhancement of saquinavir absorption and accumulation through the formation of solid drug nanoparticles.

BACKGROUND: Nanotechnology is now considered a promising drug delivery method for orally administered hydrophobic drugs to their sites of action. The effect of nanodispersion on cellular transport and accumulation of saquinavir (SQV) was investigated. METHODS: The transport of five solid drug nanoparticle (SDN) SQV formulations along Caco-2 cell monolayers (CCM) was compared to that of standard SQV. The SDNs were prepared using SQV mesylate (20%), Pluronic F127 (10%) plus five other excipients (HPMC, PVP, PVA, Lecithin S75 and Span 80) in different proportions. Cellular accumulation in CEM parental and CEMVBL (P-gp overexpressing) cells was conducted to ascertain the effect of nanodispersion on P-gp mediated efflux of SQV. All SDN formulations were dissolved in water, whereas SQV in DMSO to improve solubility. Quantification was via HPLC. RESULTS: From transport results, an SDN sample composed of SQV mesylate/Pluronic F127 plus HPMC (70%) and had a 24% increase in apparent absorption compared to standard SQV, largely driven by a 38% reduction in basolateral to apical permeation. Additionally, the formulation and two others (SQV mesylate/Pluronic F127 alone; and + HPMC (65%)/Lecithin [5%]) accumulated more significantly in CEM cells, suggesting enhanced delivery to these cells. Moreover, accumulation and transport of the three SDNs compared well to that of SQV despite being dissolved in water, suggestive of improved dissolution. The inclusion of PVA resulted in increased efflux. CONCLUSION: The use of HPMC and Pluronic F127 produced SQV SDNs with improved permeation in Caco-2 cells and improved accumulation in CEM cells, but negative effects with PVA.

Randomized Phase IIA Trial of Gemcitabine Compared With Bleomycin Plus Vincristine for Treatment of Kaposi's Sarcoma in Patients on Combination Antiretroviral Therapy in Western Kenya.

PURPOSE: Kaposi's sarcoma (KS) is a spindle cell tumor resulting from growth dysregulation in the setting of infection with human herpes virus-8 (also called KS herpes virus). Advanced KS is characterized by poor responses to antiretroviral therapy and some of the chemotherapy readily accessible to patients in low-resource areas. Gemcitabine induced partial and complete regression of AIDS-associated KS (AIDS-KS) in 11 of 24 patients in a pilot study. The current study compares the antimetabolite gemcitabine with the standard care bleomycin and vincristine (BV) in the treatment of chemotherapy-naïve patients with AIDS-KS in a resource-limited setting. PATIENTS AND METHODS: Patients with persistent or progressive KS despite treatment with combined antiretroviral therapy were randomly assigned to receive gemcitabine 1,000 mg/m2 or bleomycin 15 IU/ m2 and vincristine 1.4 mg/m2 given twice weekly. The main end point was objective response by bidirectional measurement, adverse events, and quality of life after three cycles of chemotherapy. RESULTS: Of 70 participants enrolled, 36 received gemcitabine and 34 received BV. Complete response was achieved in 12 patients (33.3%) in the gemcitabine arm and six (17.6%) in the BV arm ( P = .175). The partial response rate was 52.8% (n = 19) in the gemcitabine arm and 58.8% (n = 20) in the BV arm. Both study arms reported similar neurologic and hematologic adverse events; there was statistically significant baseline to post-treatment improvement in health-related quality-of-life scores. CONCLUSION: The results of this randomized, phase IIA trial demonstrate gemcitabine activity in chemotherapy-naïve patients with AIDS-KS, on the basis of response rates, adverse events, and health-related quality-of-life scores.

Characteristics of patients with thromboembolic disorders on warfarin therapy in resource limited settings.

BACKGROUND: Warfarin is a drug with narrow therapeutic index used in the management of thromboembolic disorders. Several factors affect its plasma concentrations with a resultant risk of toxicity. We examined the database of patients on warfarin therapy in order to establish the factors that affect the stability of INR and correlated them to clinical outcomes in resource limited settings. METHODS: We analysed retrospective data of patients admitted to adult medical wards at Moi Teaching and Referral Hospital (MTRH) in 2015. Inclusion criteria were patients with thromboembolic and related disorders and on warfarin treatment. Derived data included demographics, indications for warfarin use, co-prescribed drugs, co-morbidities, INR measurements, duration of hospital stay and clinical outcomes. Descriptive statistics were used to summarize the data. Pearson's correlation coefficient was used to assess relationships between duration of hospitalization and number of INR tests. Regression splines were used to capture INR trends during the follow up period. Data was analysed using R v. 3.3.1. RESULTS: A total of 310 patients had thromboembolic disorders, out of which 63 met the study criteria. The median age was 48 years, while the mean number of INR measurements was once every four days. Majority of patients did not achieve stable INR values, with only two having consecutive INR values within therapeutic goal. Patients who died had high INR levels. The median duration of hospital stay was 9 days (IQR: 7.0, 16.5). There was a significant correlation between length of stay in hospital and the number of times that INR were measured (Corr = 0.667, p < 0.001). The two most common indications for warfarin were DVT (64.4%) and atrial fibrillation (24.7%). All the patients had one or more comorbid conditions except for 11 with DVT alone, with cardiovascular diseases and infections being the most frequent, and on concomitant medications, majority of which are known to interact with warfarin. CONCLUSIONS: It was difficult to achieve stable INR under the prevailing conditions despite the frequent tests. The potential factors that may have contributed to the fluctuations include drug-drug interactions, frequency of INR tests, comorbidities and the short duration of hospital stay.

Medicinal Plants Used by Traditional Healers in Sangurur, Elgeyo Marakwet County, Kenya.

BACKGROUND: Although herbal medical products are still widely used in Kenya, many of the medicinal plants used by traditional medical practitioners (TMPs) have not been documented, despite several challenges that are now threatening the sustainability of the practice. OBJECTIVE: To document the medicinal plants and healing methods used by TMPs in a region of Kenya with several recognized herbalists for potential research. MATERIALS AND METHODS: Semi-structured interviews, group discussions, and direct observations were used to collect ethnopharmacological information. The participant's bio-data, clinical conditions treated, methods of treatment, medicinal plants used, methods of preparation and administration, and dosage forms were recorded. RESULTS: A total of 99 medicinal plants and 12 complementary preparations employed in the treatment of 64 medical conditions were identified. The most widely used plant was Rotala tenella which was used to treat nine medicinal conditions; seven each for Aloe tweediae and Dovyalis abyssinica; and six each for Basella alba and Euclea divinorum. The plants belonged to 55 families with Fabaceae family being the most frequently used (10), followed by Apocynaceae and Solanaceae, each with six species, respectively. We identified plants used to determine the sex of an unborn baby and those used to treat several conditions including anthrax and cerebral malaria and herbs used to detoxify meat from an animal that has died from anthrax. Of special interest was R. tenella which is used to prevent muscle injury. CONCLUSIONS: We have documented several plants with potential therapeutic effects. Further research may be conducted to determine their efficacy. SUMMARY: The medicinal plants used by traditional healers in a community which still practices herbal medicine in Kenya were documented. A total of 99 medicinal plants and 12 complementary preparations employed in the treatment of 64 medical conditions were identified. Further research may be carried out in order to determine their therapeutic efficacies. Abbreviations Used: Fic: Informant consensus factor, Nur: Number of use reports in each category, Ns: Number of reported species, TMPs: Traditional medical practitioners.

Factors associated with the high prevalence of oesophageal cancer in Western Kenya: a review.

Oesophageal carcinoma (OC) is highly prevalent in Western Kenya especially among the members of the Kalenjin community who reside in the Northern and Southern areas of the Rift Valley. Previous authors have suggested potential association of environmental and genetic risk factors with this high prevalence. The environmental factors that have been suggested include contamination of food by mycotoxins and/or pesticides, consumption of traditional alcohol (locally referred to "Busaa" and "Chan'gaa"), use of fermented milk ("Mursik"), poor diet, tobacco use and genetic predisposition. The aim of this paper is to critically examine the potential contribution of each of the factors that have been postulated to be associated with the high prevalence of the disease in order to establish the most likely cause. We have done this by analyzing the trends, characteristics and behaviours that are specifically unique in the region, and corroborated this with the available literature. From our findings, the most plausible cause of the high incidence of OC among the Kalenjin community is mycotoxins, particularly fumonisins from the food chain resulting from poor handling of cereals; particularly maize combined with traditional alcohol laced with the toxins interacting synergistically with other high-risk factors such as dietary deficiencies associated alcoholism and viral infections, especially HPV. Urgent mitigating strategies should be developed in order to minimize the levels of mycotoxins in the food chain.

Reversal of tenofovir induced nephrotoxicity: case reports of two patients.

The use of the antiretroviral drug tenofovir has been associated with nephrotoxicity. However, the overall impact of this adverse effect has not comprehensively evaluated. Some researchers have reported that it is quite severe to warrant monitoring for renal toxicity, while others have concluded that the magnitude may not be that significant. We report two clinical cases seen in our renal clinic with high creatinine levels suggestive of nephrotoxicity who reverted back to normality upon withdrawal of tenofovir.

Early neurosyphilis presenting with facial palsy and an oral ulcer in a patient who is human immunodeficiency virus positive: a case report.

BACKGROUND: Neurosyphilis is the tertiary stage of Treponema pallidum infection that involves the central nervous system, which occurs within days or weeks after an initial syphilis infection, especially in immunocompromised patients. The diagnosis of neurosyphilis is quite challenging as it is uncommon and often presents with obscure symptoms since any organ system may be involved. CASE PRESENTATION: We describe a case of a 40-year-old African man who is human immunodeficiency virus positive with early neurosyphilis who presented with a stiff neck, headache, confusion, restlessness, and a left-sided chest pain; he did not respond to an empiric treatment of ceftriaxone and fluconazole for meningitis, and tramadol for headache. Ten days after admission, he developed generalized tonic-clonic convulsions; on examination he had ipsilateral facial nerve palsy and an oral ulcer, and responded well to benzathine penicillin treatment. CONCLUSIONS: Laboratory diagnosis of neurosyphilis is challenging because to date there is no single laboratory test which is considered sensitive enough for diagnosis of the disease, especially in resource-limited settings. Clinical judgment is still an important part of diagnosis; and neurosyphilis should be considered a diagnostic differential in patients with Human Immunodeficiency Virus presenting with central nervous system involvement and in other high-risk patients.

Drug-transporter mediated interactions between anthelminthic and antiretroviral drugs across the Caco-2 cell monolayers.

BACKGROUND: Drug interactions between antiretroviral drugs (ARVs) and anthelminthic drugs, ivermectin (IVM) and praziquantel (PZQ) were assessed by investigating their permeation through the Caco-2 cell monolayers in a transwell. The impact of anthelminthics on the transport of ARVs was determined by assessing the apical to basolateral (AP → BL) [passive] and basolateral to apical (BL → AP) [efflux] directions alone, and in presence of an anthelminthic. The reverse was conducted for the assessment of the influence of ARVs on anthelminthics. METHODS: Samples from the AP and BL compartments were taken at 60, 120, 180 and 240 min and quantified either by HPLC or radiolabeled assay using a liquid scintillating counter for the respective drugs. Transepithelial resistance (TEER) was used to assess the integrity of the monolayers. The amount of compound transported per second (apparent permeability, Papp) was calculated for both AP to BL (PappAtoB), and BL to AP (PappBtoA) movements. Samples collected after 60 min were used to determine the efflux ratio (ER), quotient of secretory permeability and absorptive permeability (PappBL-AP/PappAP-BL). The reverse, (PappAP-BL/PappBL-AP) constituted the uptake ratio. The impact of SQV, EFV and NVP on the transport of both IVM and PZQ were investigated. The effect of LPV on the transport of IVM was also determined. The influence of IVM on the transport of SQV, NVP, LPV and EFV; as well as the effect PZQ on the transport of SQV of was also investigated, and a two-tailed p value of <0.05 was considered significant. RESULTS: IVM significantly inhibited the efflux transport (BL → AP movement) of LPV (ER; 6.7 vs. 0.8, p = 0.0038) and SQV (ER; 3.1 vs. 1.2 p = 0.00328); and increased the efflux transport of EFV (ER; 0.7 vs. 0.9, p = 0.031) suggesting the possibility of drug transporter mediated interactions between the two drugs. NVP increased the efflux transport of IVM (ER; 0.8 vs. 1.8, p = 0.0094). CONCLUSIONS: The study provides in vitro evidence of potential interactions between IVM, an anthelminthic drug with antiretroviral drugs; LPV, SQV, NVP and EFV. Further investigations should be conducted to investigate the possibility of in vivo interactions.

Intracellular accumulation of Praziquantel in T lymphoblastoid cell lines, CEM (parental) and CEMVBL(P-gp-overexpressing).

BACKGROUND: Praziquantel (PZQ) is an antihelminthic drug whose P-glycoprotein (P-gp) substrate specificity has not been conclusively characterized. We investigated its specificity by comparing its in vitro intracellular accumulation in CEM (parental), and CEMVBL cells which over express P-gp, a drug efflux transporter. Saquinavir (SQV), a known substrate of efflux transporters was used as control. METHODS: A reversed phase liquid chromatography method was developed to simultaneously quantify PZQ and SQV in cell culture media involving involved a liquid - liquid extraction followed by ultra-high performance liquid chromatography using a Hypurity C18 column and ultraviolet detection set at a wavelength of 215 nm. The mobile phase consisted of ammonium formate, acetonitrile and methanol (57:38:5 v/v). Separation was facilitated via isocratic elution at a flow rate of 1.5 ml/min, with clozapine (CLZ) as internal standard. This was validated over the concentration range of 1.6 to 25.6 µM for all analytes. Intracellular accumulation of SQV in CEMVBL was significantly lower compared to that in CEM cells (0.1 ± 0.031 versus 0.52 ± 0.046, p = 0.03 [p <0.05]). RESULTS: Accumulation of PZQ in both cell lines cells were similar (0.05 ± 0.005 versus 0.04 ± 0.009, p = 0.4) suggesting that it is not a substrate of P-gp in CEM cells. In presence tariquidar, a known inhibitor of P-gp, the intracellular accumulation of SQV in CEMVBL cells increased (0.52 ± 0.068 versus 0.61 ± 0.102, p = 0.34 in CEM cells and 0.09 ± 0.015 versus 0.56 ± 0.089, p = 0.029 [p < 0.05] in CEMVBL cells). PZQ did not significantly affect the accumulation of SQV in either CEM (0.52 ± 0.068 versus 0.54 ± 0.061, p = 0.77), or in CEMVBL cells (0.09 ± 0.015 versus 0.1 ± 0.031, p = 0.89) cells compared to tariquidar, implying that PZQ is not an inhibitor of P-gp in CEMVBL cells. CONCLUSIONS: PZQ is neither a substrate nor an inhibitor of the efflux drug transporter P-gp in T-lymphoblastoid cells, CEM and CEMVBL. We also report a simple, accurate and precise method for simultaneous quantification of PZQ and SQV.

Screening by Clinical Breast Examination in Western Kenya: Who Comes?

PURPOSE: More than 80% of women with breast cancer in Kenya present to medical care with established late-stage disease. We sought to understand why women might not participate in breast cancer screening when it is offered by comparing the views of a cohort of those who attended a screening special event with those of community controls who did not attend. METHODS: All residents living close to three health centers in western Kenya were invited to participate in screening. Participants (attendees) underwent clinical breast examination by trained physician oncologists. In addition, women who consented were interviewed by using a modified Breast Cancer Awareness Module questionnaire. Nonattendees were interviewed in their homes the following day. RESULTS: A total of 1,511 attendees (1,238 women and 273 men) and 467 nonattendee women participated in the study. Compared with nonattendees, the women attendees were older, more often employed, knew that breast cancer presented as a lump, and were more likely to have previously felt a lump in a breast. In addition, they were more likely to report previously participating in screening activities, were more likely to have performed breast self-examination, and were less concerned about wasting a doctor's time. Almost all those surveyed (attendees and nonattendees) expressed interest in future breast cancer screening opportunities. CONCLUSION: The women who volunteer for breast cancer screening in western Kenya are more aware of breast cancer than those who do not volunteer. Screening recruitment should seek to close these knowledge gaps to increase participation.

Palmar-plantar erythrodysesthesia associated with capecitabine chemotherapy: a case report.

We report a case of a 62 year-old patient who developed Palmar-plantar erythrodysesthesia upon receiving four cycles of capacitabine-based chemotherapy. She was on post surgical adjuvant treatment for invasive well differentiated adenocarcinoma of the colon. The clinical and therapeutic aspects of this chemotherapeutic adverse effect are discussed.

A Review of the Ingredients Contained in Over the Counter (OTC) Cough Syrup Formulations in Kenya. Are They Harmful to Infants?

BACKGROUND: Cough syrups are widely used in the developing world, but safety of their use in infants and children less than two years has not been well documented. Some syrups contain multiple combinations of such drugs as promethazine, diphenhydramine and ephedrine; which are individually now contraindicated in children less than two years. Despite this, the syrups are available as over the counter drugs and may be dispensed to mothers who are unaware of the potentially hazardous effects to their infants. A descriptive cross-sectional study was used to investigate suitability of cough syrups sold within Eldoret municipality for use in children less than two years of age based on their formulations and available literature. METHODS: Two semi-structured questionnaires were administered to pharmacy attendants and mothers attending sick child clinic at a referral hospital to establish whether cough syrups containing more than one active ingredient of compounds, now contraindicated in children are administered to infants, and awareness of potential serious adverse effects. Data from labeled contents of cough syrups from retail pharmacies was recorded and corroborated with information from literature to determine those deemed to contain the ingredients. The second questionnaire was administered to mothers with children less than two years to ascertain whether they had used the identified syrups. A total of 260 mothers and 55 pharmacy attendants were interviewed. RESULTS: There was widespread use of the syrups in children, including infants, with 192 (74%) of the respondents having used identified syrups and over 90% of these on children less than 2 years including those less than three months.146 (76%) mothers had administered the syrup at double the recommended dose. CONCLUSION: The regulatory authorities should make concerted efforts to discourage use of cough syrups containing ingredients that pose adverse events to infants, including campaigns to educate pharmacy workers and mothers.