Publications

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.

We deployed the Blended Genome Exome (BGE), a DNA library blending approach that generates low pass whole genome (1-4x mean depth) and deep whole exome (30-40x mean depth) data in a single sequencing run. This technology is cost-effective, empowers most genomic discoveries possible with deep whole genome sequencing, and provides an unbiased method to capture the diversity of common SNP variation across the globe. To evaluate this new technology at scale, we applied BGE to sequence >53,000 samples from the Populations Underrepresented in Mental Illness Associations Studies (PUMAS) Project, which included participants across African, African American, and Latin American populations. We evaluated the accuracy of BGE imputed genotypes against raw genotype calls from the Illumina Global Screening Array. All PUMAS cohorts had R2 concordance >=95% among SNPs with MAF>=1%, and never fell below >=90% R2 for SNPs with MAF<1%. Furthermore, concordance rates among local ancestries within two recently admixed cohorts were consistent among SNPs with MAF>=1%, with only minor deviations in SNPs with MAF<1%. We also benchmarked the discovery capacity of BGE to access protein-coding copy number variants (CNVs) against deep whole genome data, finding that deletions and duplications spanning at least 3 exons had a positive predicted value of \~{}90%. Our results demonstrate BGE scalability and efficacy in capturing SNPs, indels, and CNVs in the human genome at 28% of the cost of deep whole-genome sequencing. BGE is poised to enhance access to genomic testing and empower genomic discoveries, particularly in underrepresented populations.Competing Interest StatementThe authors have declared no competing interest.

Key Clinical Message Chronic myelomonocytic leukemia, a rare case of hematological malignancy mainly affects the elderly and may present with life threatening pericardial effusion as an initial manifestation. High index of suspicion is hence key for early management. Abstract We present a case of an 81-year-old African male who presented with progressive cough, respiratory distress and bilateral lower limb swelling, and was diagnosed with life-threatening pericardial effusion resulting from chronic myelomonocytic leukemia following complete blood count, peripheral blood film, bone marrow aspirate with trephine biopsy, and flow cytometry studies.

Polymyxin B is a reserve antibiotic, but there has been an upsurge in its use due to a rise in multidrug-resistant gram-negative bacteria. However, nephrotoxicity and resistance concerns persist, with global resistance rates reaching 29%. Effectiveness of Polymyxin B (clinical and microbiological response) and the frequency of nephrotoxicity is not well documented in resource limited settings. Research is essential to guide optimization of Polymyxin B therapy and inform the adoption of measures for early detection of kidney injury to prevent damage. This study aimed to assess the effectiveness of Polymyxin B by evaluating clinical and microbiological responses and determining nephrotoxicity incidence using KDIGO criteria in ICU patients at Moi Teaching and Referral Hospital (MTRH). A prospective observational cohort study was conducted at MTRH ICUs between December 2021 and November 2022, on patients treated with Polymyxin B. Data on demographics, comorbidities, Polymyxin B dosage regimens, clinical responses, and microbiological results were collected. Descriptive statistics summarized patient characteristics, while associations between dosage regimens and outcomes were evaluated using Fisher's exact test and multivariate regression, with a p<0.05 considered statistically significant. Forty-four patients with a mean age of 48 years were included; 66% were male, and cerebrovascular disease was the most common comorbidity. All patients had multidrug-resistant gram-negative infections qualifying for Polymyxin B therapy. Most (89%) received monotherapy, with 86% achieving a good clinical response, 7% experiencing treatment failure, and 7% dying. Doses of 20,000–25,000 IU/Kg/day were associated with microbiological eradication and good clinical response (p<0.001), while 15,000 IU/Kg/day was associated with treatment failure. Acute kidney injury occurred in 48% of patients, with 68% developing hypomagnesemia. Polymyxin B at doses of between 20,000-25,000IU/Kg/day should be considered as a starting dose due to the association with good clinical response, with alternate-day monitoring of serum creatinine levels for early detection of nephrotoxicity.

Background: Dexmedetomidine is the preferred drug for light sedation in intensive care units (ICU) where sedation plays an important role in patient comfort. Its advantages include shorter weaning time and earlier extubating from mechanical ventilation without respiratory depression. However, dexmedetomidine has been associated with over 50% incidence of hemodynamic adverse effects (hypotension and bradycardia) that has led to poor clinical outcomes. This limits its widespread use. Factors such as age, comorbidities, concomitant medications, dosage, baseline mean arterial pressure (MAP) and heart rate (HR) have been associated with adverse effects. Despite the high number of reported adverse effects, there is limited data on incidence and associated factors in resource limited settings. Therefore, its burden at Moi Teaching and Referral Hospital (MTRH) remains unknown. Knowledge on incidence and associated factors may inform future practice on safe use of dexmedetomidine at MTRH. Objective: To determine incidence and clinical factors associated with dexmedetomidine induced adverse effects among patients sedated with dexmedetomidine at MTRH ICU. Methods: This was a prospective observational study done at MTRH ICU. Hemodynamically stable eligible participants on dexmedetomidine were enrolled through census method between mid-April and mid-October 2022.The dependent variable was incidence of dexmedetomidine induced hemodynamic adverse effects. Data on MAP, HR were collected at selected time points within 24 hours. Independent variables which included factors such as age, gender, comorbidities, concomitant medication, renal, liver functions and drug dosages were obtained from patient records. Cutoff for hypotension was a MAP less than 60mmHg or a drop in MAP of 30% within the first hour, while bradycardia was a HR less than 60bpm or a drop in HR of 30% within first hour of drug administration. Continuous, data was summarized using means, medians and categorical data as frequencies and proportions. Fisher’s exact test and Kruskal Wallis test was used to assess for associations between categorical variables and continuous independent variables. The association between the clinical factors and development of dexmedetomidine induced hemodynamic adverse effects was analyzed using logistic regression model. Results: A total of 61 participants were recruited and 41% had traumatic brain injury. The mean age was 37 years and males were 63.9%. All participants had baseline HR>60bpm and MAP>60mmHg during drug initiation. Five patients (8.2%) developed hypotension and one (1.6%) developed bradycardia at the first hour. Mean baseline MAP was 90.49mmHg and mean decline was 5.16mmHg at 1hour. Mean baseline HR was 98.75bpm and mean decline was 0.91bpm within the first hour. Majority of patients received drug doses ranging from 0.2 to 0.7mcg/kg/hr for less than 24 hours. Lower baseline MAP <70mmHg was significantly associated with dexmedetomidine hemodynamic adverse effects (OR 2.17[95%CI 1.08-2.97, p<0.01]). However, there was no significant association between gender (0.21), baseline HR (0.88), comorbidities (0.19), concomitant medications (0.15), dose and duration (1), renal (0.28), liver functions (0.17) and occurrence of hemodynamic adverse effects. Conclusion: This study reported a low incidence of dexmedetomidine induced adverse effects compared to previous studies. Lower baseline MAP<70mmHg was an independent predictor of dexmedetomidine induced hypotension and bradycardia. Recommendations: Patients with lower baseline MAP<70mmHg and on dexmedetomidine should be monitored more frequently within the first hour.

Background: Dyslipidemia is the presence of abnormal blood lipid parameters, characterized by increased LDL-C, triglycerides, and total cholesterol but reduced HDL-C. It is a common finding in patients with T2DM, occurring at a prevalence rate of between 70% and 85%, and promotes the development of long-term cardiovascular complications, which are the leading cause of mortality in this population. Statins are the first-line drugs, but lipid control varies from patient to patient despite being widely used.Objective: To assess lipid control and the factors associated with LDL-C control in patients with type 2 DM who are on statins at a national referral hospital in Western Kenya.Methods: A retrospective study on 211 patients with type 2 DM who had been on a statin for at least three months. Data was obtained from patient records and lipid measures categorized as controlled or uncontrolled based on the Kenya National Guidelines for the Management of Diabetes Mellitus, 2018. Chi-square and Fischer’s exact test determined the association between variables. A multivariate logistic regression model was fit for variables significant at the bivariate level, and a P value of <0.05 was considered significant.Results: Most (99%) were on a single lipid-lowering drug, mainly atorvastatin, and 92% were on moderate-intensity dosing. Regarding lipid control, 50.3% had uncontrolled LDL-C, 30% had uncontrolled HDL-C, and 47% had uncontrolled triglyceride levels. Being on a high-intensity statin increased the likelihood of LDL-C control compared to moderate-intensity dosing (OR 8.57 [95% CI 4.3-16.9, P<0.001]).Conclusion: LDL-C was the most poorly controlled parameter. Patients on high-intensity statins had better LDL-C control; therefore, high-intensity statin therapy should be initiated in diabetic patients who do not achieve their LDL-C targets.