Attitudes of Older Adult Patients and Caregivers Towards Deprescribing of Medications in Ethiopia.

Background: Deprescribing is essential for reducing inappropriate medication use and polypharmacy. For a holistic approach, it is essential to know how older adult patients and their caregivers perceive deprescribing. Objective: To assess the attitude of older adult patients and caregivers towards deprescribing medication at Ambo University Referral Hospital. Methodology: Institutional-based cross-sectional study was conducted using the revised Patients' Attitude Towards Deprescribing tool (rPATD). The data was analyzed using the SPSS-25 software. Backward linear regression and logistic regression were used to measure association between outcome and determinant variables. The two-sided P-value ≤0.05 with 95% confidence interval was utilized for reporting significant factors. Results: One hundred fifty-six (81.3%) of the respondents (ie, 85.0% of older adult and 77.2% of caregivers) agreed to stop one or more of their regular medications if the physician said it was possible despite 98 (51.0%) of them (ie, 49.0% of older adult and 53.3% of caregivers) being satisfied with their/their care recipient's medications. On the overall aggregate mean score, the respondents had a neutral position (2.6-3.59) regarding the burden and concerns of stopping medications whereas the majority of them disagree (1.0-2.59) with the inappropriateness of the medication they were taking and agreed (3.6-5.0) with the need for their involvement in treatment decision making. Concerns about stopping medicine scores (AOR = 0.440, 95% CI = 0.262-0.741, P = 0.035) and perceived levels of medication inappropriateness (AOR = 0.653, 95% CI = 0.456-0.936, P = 0.020) was significantly associated with the willingness to discontinue and overall satisfaction with their medicine regimen respectively. Conclusion: The majority of older adult patients and caregivers would like to deprescribe if the physicians recommended it. The perceived concerns of stopping and inappropriateness of the medicines were associated with the willingness to deprescribe and overall satisfaction with their medicine respectively. Healthcare providers should prompt the deprescribing process with older adult patients and caregivers by addressing their concerns about stopping medications.

Traditional medicines for COVID-19: Perspectives from clinical pharmacologists.

There has been high interest in the use of traditional medicines for COVID-19 from early in the course of the pandemic. Significant advances in the science of ethnopharmacology have helped to introduce chemical entities identified from natural sources into modern medicine. However, the wider integration of natural products into the modern drug discovery process will require enhanced collaboration amongst the pharmaceutical industry, academic research units, regulatory bodies, ethics review committees and local, regional, continental and international organizations. Revisiting this topic holds promise of benefit for both the current and future pandemics.

Antimalarial activity of hydromethanolic extract and its solvent fractions of Vernonia amygdalina leaves in mice infected with Plasmodium berghei.

BACKGROUND: Vernonia amygdalina Del. (Asteraceae) is reported to be traditionally used for the treatment of malaria. Based on folkloric repute of this plant in Ethiopian traditional medicine and crude extract-based ethnopharmacological studies conducted in few countries, this study was undertaken to evaluate the in vivo antimalarial activity of 80% methanol extract and its solvent fractions of the leaves of V. amygdalina in mice infected with Plasmodium berghei. METHODS: A 4-day suppressive test was conducted on mice infected with P. berghei to find out antimalarial effect of chloroform, butanol and aqueous fractions obtained from the 80% methanol crude extract. In all the activity tests, mice were randomly assigned in five groups (three tests and two controls) of six animals in each and received respective treatments. Data were analyzed using one way analysis of variance followed by Tukey's post hoc test for multiple comparisons. RESULTS: Acute oral toxicity test showed that all solvent fractions of the leaves of V. amygdalina revealed neither mortality nor overt signs of toxicity up to 2000 mg/kg. This study indicated that the percentage parasitemia suppression of 80% methanol extract was 32.47% (±2.65), 35.40% (±3.14) and 37.67% (±2.50) at 200, 400 and 600 mg/kg, respectively. All doses of the 80% methanol extract of V. amygdalina prolonged survival time and prevented weight loss and packed cell volume reduction in infected mice. All doses of chloroform and butanol fractions significantly suppressed parasitemia (p < 0.05), increased survival time (p < 0.05) compared to negative control and exhibited a significant reduction in rectal temperature (p < 0.05). All solvent fractions significantly prevented weight loss (p < 0.05) at all tested doses. The 80% methanol extract and chloroform and butanol fractions significantly (p < 0.05) prevented further reduction in rectal temperature of P. berghei-infected mice at all doses. CONCLUSION: The results of this study indicated that 80% methanol extract and solvent fractions of the leaves of V. amygdalina demonstrated promising antimalarial activity. The study corroborated the folklore use of this plant for the treatment of malaria in ethnomedicine in Ethiopia.

Vitamin D Status and Association of VDR Genetic Polymorphism to Risk of Breast Cancer in Ethiopia.

Emerging evidence associates vitamin D deficiency and vitamin D receptor (VDR) genetic variations with risk for breast cancer. This study investigated the prevalence of vitamin D deficiency and its association with tumor characteristics and the implications of VDR genetic variations for risk of breast cancer in Ethiopia. This unmatched case⁻control study involved 392 female breast cancer patients and 193 controls. The plasma 25-hydroxyvitamin D (25(OH)D3) level was quantified in chemotherapy-naïve (N = 112) and tamoxifen-treated patients (N = 89). Genotyping for the VDR common variant alleles rs7975232 (ApaI), rs2228570 (FokI), and rs731236 (TaqI) was done. Eighty-six percent of the patients were vitamin D deficient (<50 nmol/L). Chemotherapy-naïve breast cancer patients had a higher prevalence of vitamin D deficiency (91.9% vs. 78.3%) compared to the tamoxifen-treated group (p < 0.001). The prevalence of severe vitamin D deficiency (<25 nmol/L) was significantly higher in chemotherapy-naïve (41.1%) than tamoxifen-treated (11.2%) patients. Vitamin D deficiency was not significantly associated with tumor characteristics or VDR genotype. The rs2228570 GG genotype was associated with increased risk of breast cancer (OR = 1.44, 95% confidence interval = 1.01-2.06). Our result indicates that rs2228570 might be a moderate risk factor for breast cancer development in the Ethiopian population. The high prevalence of severe vitamin D deficiency in treatment-naïve breast cancer patients indicates the need for nutritional supplementation of vitamin D at the time of chemotherapy initiation.

Prevalence and risk factors for efavirenz-based antiretroviral treatment-associated severe vitamin D deficiency: A prospective cohort study.

Initiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors including efavirenz pharmacokinetics for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) cotreatment are not explored. We investigated the prevalence of SVDD in HIV and TB-HIV coinfected patients and associated risk factors for treatment-induced SVDD.Treatment-naïve Ethiopian HIV patients with (n = 102) or without (n = 89) TB co-infection were enrolled prospectively and received efavirenz-based cART. In TB-HIV coinfected patients, rifampicin-based anti-TB treatment was initiated 4 or 8 weeks before starting cART. Plasma 25-hydroxyvitamin D (25 [OH]D), cholesterol and 4-beta hydroxycholesterol concentrations were measured at baseline, 4, 16, and 48 week of cART. Plasma efavirenz concentrations were determined at 4 and 16 weeks of cART.TB-HIV patients had significantly lower plasma 25 (OH)D3 levels than HIV-only patients at baseline. TB co-infection, low Karnofsky score, high viral load, and high CYP3A activity as measured by plasma 4ß-hydroxycholesterol/cholesterol ratios were significant predictors of low 25 (OH)D3 levels at baseline. In HIV-only patients, initiation of efavirenz-based cART increased the prevalence of SVVD from 27% at baseline to 76%, 79%, and 43% at 4, 16, and 48 weeks of cART, respectively. The median 25 (OH)D3 levels declined from baseline by -40%, -50%, and -14% at 4, 16, and 48 weeks of cART, respectively.In TB-HIV patients, previous anti-TB therapy had no influence on 25 (OH)D3 levels, but the initiation of efavirenz-based cART increased the prevalence of SVDD from 57% at baseline to 70% and 72% at the 4 and 16 weeks of cART, respectively. Median plasma 25 (OH)D3 declined from baseline by -17% and -21% at week 4 and 16 of cART, respectively.Our results indicate low plasma cholesterol, high CYP3A activity, and high plasma efavirenz concentrations as significant predictors of early efavirenz-based cART-induced vitamin D deficiency. Low plasma 25 (OH)D3 level at baseline is associated with TB co-infection and HIV diseases progression. Initiation of efavirenz-based cART is associated with high incidence of SVDD, whereas rifampicin based anti-TB therapy co-treatment has no significant effect. Supplementary vitamin D during cART initiation may be beneficial for HIV patients regardless of TB coinfection.

Effect of Rumex Abyssinicus on preneoplastic lesions in dimethylhydrazine induced colon carcinogenesis in rats.

BACKGROUND: Cancer as a multistage process can be reversed or blocked by using chemopreventive agents. Colon cancer chemoprevention has been widely investigated using cyclooxygenase inhibitors and many other chemicals of synthetic or natural origin. This particular study was carried out to assess the colon cancer chemopreventive effect of hydro-methanol extract of Rumex abyssinicus rhizome on rats. METHOD: Colon cancer chemopreventive potential of hydro-methanol extract of Rumex abyssinicus rhizome was determined based on the number and multiplicity of aberrant crypt foci (ACF). Fifteen DMH (1, 2-dimethylhydrazine) treated and five untreated Wistar female rats were used. DMH was administered subcutaneously 30 mg/kg, after its pH was adjusted to 6.5-7. Treatment groups started receiving extract after six weeks of weekly DMH injections. The rats were divided in to four groups: Group 1 received only oral normal saline, Group 2 received DMH and normal saline, Group 3 and 4 received DMH plus 250 mg/kg and 500 mg/kg extract, respectively. Specific phytoconstituents of the plant, which were reviewed from original articles, were virtually evaluated for cyclooxygenase-2 (COX-2) inhibition. The binding energies and interactions of the phytochemicals from Rumex abyssinicus against COX-2 were determined by Autodock4.2. RESULTS: There was a statistically significant reduction (p-value < 0.05) in the number of aberrant crypt (AC) and aberrant crypt foci (ACF) at both administered doses. However, significant association (p-value > 0.05) was not observed in reducing crypt multiplicity. The docking process resulted in estimated binding energies [-6.83 kcal/mol to -7.9 kcal/mol] which are closer to the positive controls or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) [-4.55 kcal/mol to -10.84 kcal/mol]. The phytochemical-COX-2 interaction indicated the involvement of key amino acid residues in inhibition of cyclooxygenase like ARG120, TYR355, TYR385, SER530 and GLY526. CONCLUSIONS: Rumex abyssinicus had demonstrated a chemopreventive potential at post-initiation stage. As the virtual screening data suggested, COX-2 inhibition by the anthraquinones in the extract could be one mechanism for the observed chemopreventive effect.