Department of Centre for Tropical Clinical Pharmacology and Therapeutics

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    Diabetes self-management education interventions and self-management in low resource settings; a mixed methods study
    (PLOS ONE, 2023) Lamptey, R.; Amoakoh-Coleman, M.; Djobala, B.; Grobbee, D.E.; Adjei, G.O.; Klipstein-Grobusch, K.
    Introduction Diabetes is largely a self-managed disease; thus, care outcomes are closely linked to self management behaviours. Structured self-management education (DSME) interventions are, however, largely unavailable in Africa. Aim We sought to characterise DSME interventions in two urban low-resource primary settings; and to explore diabetes self-management knowledge and behaviours, of persons living with diabetes (PLD). Research design and methods A convergent parallel mixed-methods study was conducted between January and February 2021 in Accra, Ghana. The sampling methods used for selecting participants were total enu meration, consecutive sampling, purposive and judgemental sampling. Multivariable regres sion models were used to study the association between diabetes self-management knowledge and behaviours. We employed inductive content analysis of informants’ experi ences and context, to complement the quantitative findings. Results In total, 425 PLD (70.1% (n = 298) females, mean age 58 years (SD 12), with a mean blood glucose of 9.4 mmol/l (SD 6.4)) participated in the quantitative study. Two managers, five professionals, two diabetes experts and 16 PLD participated in in-depth interviews. Finally, 24 PLD were involved in four focus group discussions. The median diabetes self-manage ment knowledge score was 40% ((IQR 20–60). For every one unit increase in diabetes self management knowledge, there were corresponding increases in the diet (5%;[95% CI: 2%- 9%, p<0.05]), exercise (5%; [95% CI:2%-8%, p<0.05]) and glucose monitoring (4%;[95% CI:2%-5%, p<0.05]) domains of the diabetes self-care activities scale respectively. The DSME interventions studied, were unstructured and limited by resources. Financial con straints, conflicting messages, beliefs, and stigma were the themes underpinning self-man agement behaviour. Conclusions The DSME interventions studied were under-resourced, and unstructured. Diabetes self management knowledge though limited, was associated with self-management behaviour. DSME interventions in low resource settings should be culturally tailored and should incor porate sessions on mitigating financial constraints. Future studies should focus on creating structured DSME interventions suited to resource-constrained settings.
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    Long‑term safety of COVID vaccination in individuals with idiopathic infammatory myopathies: results from the COVAD study
    (Springer Science and Business Media Deutschland GmbH, 2023) Dey, D.; Day, J.; Doskaliuk, B.; et al.
    Abstract Limited evidence on long-term COVID-19 vaccine safety in patients with idiopathic infammatory myopathies (IIMs) continues to contribute to vaccine hesitancy. We studied delayed-onset vaccine adverse events (AEs) in patients with IIMs, other systemic autoimmune and infammatory disorders (SAIDs), and healthy controls (HCs), using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. A validated self-reporting e-survey was circulated by the COVAD study group (157 collaborators, 106 countries) from Feb–June 2022. We collected data on demographics, comorbidities, IIM/SAID details, COVID-19 history, and vaccination details. Delayed-onset (>7 day) AEs were analyzed using regression models. A total of 15165 respondents undertook the survey, of whom 8759 responses from vaccinated individuals [median age 46 (35–58) years, 74.4% females, 45.4% Caucasians] were analyzed. Of these, 1390 (15.9%) had IIMs, 50.6% other SAIDs, and 33.5% HCs. Among IIMs, 16.3% and 10.2% patients reported minor and major AEs, respectively, and 0.72% (n=10) required hospitalization. Notably patients with IIMs experienced fewer minor AEs than other SAIDs, though rashes were expectedly more than HCs [OR 4.0; 95% CI 2.2–7.0, p<0.001]. IIM patients with active disease, overlap myositis, autoimmune comorbidities, and ChadOx1 nCOV-19 (Oxford/AstraZeneca) recipients reported AEs more often, while those with inclusion body myositis, and BNT162b2 (Pfzer) recipients reported fewer AEs. Vaccination is reassuringly safe in individuals with IIMs, with AEs, hospitalizations comparable to SAIDs, and largely limited to those with autoimmune multimorbidity and active disease. These observations may inform guidelines to identify high-risk patients warranting close monitoring in the post-vaccination period.
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    A Strategy for Promoting Improved Pharmaceutical Use: The International Network for Rational Use of Drugs
    (Social Science & Medicine, 1992) Ross-Degnan, D.; Laing, R.; Quick, J.; Ali, H.M.; Ofori-Adjei, D.; Salako, L.; Santo, B.
    Over the last decade, pharmaceutical selection, procurement, distribution, and financing have improved as a result of essential drugs programs. However, despite improved availability, pharmaceuticals are frequently used irrationally. The International Network for the Rational Use of Drugs (INRUD) has been established to help address this problem. The Network joins core groups of researchers from four African and three Asian countries with support groups in Boston, Sweden, WHO, and Australia. The activities of the Network are supported by multilateral, bilateral, foundation donors and by Management Sciences for Health. INRUD functions as a participatory organization in which members are involved in decision-making. The primary objective of the Network is to identify through a coordinated set of country-based research projects a set of effective interventions to recommend as policy options for the promotion of rational drug use. In developing these research projects, INRUD stresses the importance of a multi-disciplinary perspective for adequately understanding the reasons underlying inappropriate use of drugs. To better enable country groups to utilize strong research methodologies and to blend the strengths of multiple disciplines effectively, a major activity of the Network thus far has been the building of local research capacity.
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    Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1
    (Proceedings of the National Academy of Sciences (PNAS), 1995) Mcglynn, K.A.; Rosvold, E.A.; Ofori-Adjei, D.; et al.
    Aflatoxin B1 (AFB1) has been postulated to be a hepatocarcinogen in humans, possibly by causing p53 mutations at codon 249. AFB1 is metabolized via the phase I and II detoxification pathways; hence, genetic variation at those loci may predict susceptibility to the effects of AFB1. To test this hypothesis, genetic variation in two AFB1 detoxification genes, epoxide hydrolase (EPHX) and glutathione S-transferase Ml (GSTM1), was contrasted with the presence of serum AFB,-albumin adducts, the presence of hepatocellular carcinoma (HCC), and with p53 codon 249 mutations. Mutant alleles at both loci were significantly overrepresented in individuals with serum AFB1-albumin adducts in a cross sectional study. Mutant alleles of EPHX were significantly overrepresented in persons with HCC, also in a case-control study. The relationship of EPHX to HCC varied by hepatitis B surface antigen status and indicated that a synergistic effect may exist. p53 codon 249 mutations were observed only among HCC patients with one or both high-risk genotypes. These results indicate that individuals with mutant genotypes at EPHX and GSTM1 may be at greater risk of developing AFB1 adducts, p53 mutations, and HCC when exposed to AFB1. Hepatitis B carriers with the high-risk genotypes may be an even greater risk than carriers with low-risk genotypes. These findings support the existence of genetic susceptibility in humans to the environmental carcinogen AFB1 and indicate that there is a synergistic increase in risk of HCC with the combination of hepatitis B virus infection and susceptible genotype.
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    Pattern of drug utilization for treatment of uncomplicated malaria in urban Ghana following national treatment policy change to artemisinin-combination therapy
    (Malaria Journal, 2009) Dodoo, A.N.O.; Fogg, C.; Asiimwe, A.; et al.
    Change of first-line treatment of uncomplicated malaria to artemisinin-combination therapy (ACT) is widespread in Africa. To expand knowledge of safety profiles of ACT, pharmacovigilance activities are included in the implementation process of therapy changes. Ghana implemented first-line therapy of artesunate-amodiaquine in 2005. Drug utilization data is an important component of determining drug safety, and this paper describes how anti-malarials were prescribed within a prospective pharmacovigilance study in Ghana following anti-malarial treatment policy change. Methods: Patients with diagnosis of uncomplicated malaria were recruited from pharmacies of health facilities throughout Accra in a cohort-event monitoring study. The main drug utilization outcomes were the relation of patient age, gender, type of facility attended, mode of diagnosis and concomitant treatments to the anti-malarial regimen prescribed. Logistic regression was used to predict prescription of nationally recommended first-line therapy and concomitant prescription of antibiotics. Results: The cohort comprised 2,831 patients. Curative regimens containing an artemisinin derivative were given to 90.8% (n = 2,574) of patients, although 33% (n = 936) of patients received an artemisinin-based monotherapy. Predictors of first-line therapy were laboratory-confirmed diagnosis, age >5 years, and attending a government facility. Analgesics and antibiotics were the most commonly prescribed concomitant medications, with a median of two co-prescriptions per patient (range 1–9). Patients above 12 years were significantly less likely to have antibiotics co-prescribed than patients under five years; those prescribed non-artemisinin monotherapies were more likely to receive antibiotics. A dihydroartemisinin-amodiaquine combination was the most used therapy for children under five years of age (29.0%, n = 177). Conclusion: This study shows that though first-line therapy recommendations may change, clinical practice may still be affected by factors other than the decision or ability to diagnose malaria. Age, diagnostic confirmation and suspected concurrent conditions lead to benefit:risk assessments for individual patients by clinicians as to which anti-malarial treatment to prescribe. This has implications for adherence to policy changes aiming to implement effective use of ACT. These results should inform education of health professionals and rational drug use policies to reduce poly-pharmacy, and also suggest a potential positive impact of increased access to testing for malaria both within health facilities and in homes.
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    Special Journal Issue on Neglected Diseases
    (Ghana Medical Journal, 2005-03) Ofori-Adjei, D.
    Neglected Diseases have become topical in international health and there are various initiatives addressing aspects of the subject. What constitutes a neglected disease, however, differs according to the perspective of the individual or organization. More often than not malaria, tuberculosis and HIV/AIDS have received attention and massive international support under the banner of neglected diseases. The Global Fund to Fight AIDS, Tuberculosis and Malaria is an example of such activity. However, there are other diseases whose burden on human life and development, particularly in low income countries, are equally important but receive little support and attention. International organizations like the UNICEF-UNDP-World Bank-WHO Special Programme for Research and Training in Tropical Diseases, Mèdicin sans Frontières (MSF) and the Drugs for Neglected Diseases Initiative have been in the fore articulating the need to find solutions to the increased mortality and morbidity caused by such diseases despite adequate understanding of their pathophysiology.
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    Findings from a Buruli Ulcer Mouse Model Study
    (Ghana Medical Journal, 2005-09) Addo, P.; Owusu, E.; Adu-Addai, B.; Quartey, M.; Abbas, M.; Dodoo, A.; Ofori-Adjei, D.
    Introduction: Buruli ulcer disease is endemic in many developing countries in Africa. It is caused by Mycobacterium ulcerans, a toxin-producing bacterium with predilection for the skin and its deeper tissues. The exact mode of transmission is unclear and the pathogenesis is also not well un-derstood, necessitating further elucidation through animal studies. Objective: The study assessed the infectivity of a Ghanaian Mycobacterium ulcerans isolate and the dose-response pattern in BALB/c mice. Method: Ten standardized bacterial suspensions of different concentrations were prepared from the M. ulcerans isolate and inoculated into the foot-pads of the mice. Thereafter they were observed for clinical signs of Buruli ulcer, upon which they were serially euthanised and evaluated for patho-logical and microbiological changes. Results: Irrespective of the inoculum dose, all the experimentally infected mice developed similar clinical lesions, from erythema to foot ulceration (3.1 to 6.7 weeks after inoculation). However, the higher the inoculum dose the earlier the onset of the lesions. After the development of foot ulcera-tion, mice that had received between 1 to 4 doses developed gangrene (5.7 to 7.2 weeks after inocu-lation) and died within a week, while those that had received 5 to 10 doses lost their limbs sponta-neously (5.6 to 6.1 weeks after inoculation), fol-lowed by sudden clinical recovery. Eight weeks after the spontaneous amputation the amputees relapsed with concomitant metastasis, anasarca and death. Acid-fast bacilli (AFBs) were detected in inoculated and non-inoculated limbs, tails, vis-ceral organs, faecal pellets and caecal contents of the mice. The AFBs detected in the caecal samples were innumerable and unusually long. Though AFBs were consistently detected in lymph nodes they were never detected in blood samples. Conclusion: The findings suggest that the pro-gression and final outcome of an M. ulcerans in-fection maybe dose related. The unequivocal ab-sence of AFBs in the blood, but their consistent presence in lymph nodes located in the lower limbs right up to the neck, suggests that the mi-crobes are disseminated through the lymphatic system rather than through the blood.
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    Safety of “Sachet Water” and Raw Milk
    (Ghana Medical Journal, 2007-06) Ofori-Adjei, D.
    In recent times non-biodegradeable materials, especially containers of commercially baged drinking water has been a source of environmental concern to public health institutions and metropolitan, municipal and district administrations. These containers are not properly disposed of after use and choke drains and fill refuse dumping sites. Apart from the environmental problems these containers are sources of stagnant water conducive to the breeding of mosquitoes. The regulatory environment in which manufacturers of sachet water operate has seen marked challenges and there is proliferation of manufacturers with little or no control of the industry.
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    Buruli ulcer disease
    (Ghana medical journal, 2011-03) Ofori-Adjei, D.
    Buruli ulcer is a disease that affects the skin and subcutaneous tissues. It is caused by an environmental pathogen, Mycobacterium ulcerans, that produces a toxin, mycolactone, now known to be responsible for the extensive debilitating late lesions. Early lesions include nodules, papules or raised plagues distributed mainly on the limbs and trunk. These lesions subsequently develop into ulcers which if left untreated may result in amputation, contracture deformities, significant disability and sepsis. About a quarter of patients develop permanent disability. The cost of clinical management is quite high
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    Reversible Binocular Visual Loss in Temporal Association with Artesunate-Amodiaquine Treatment in a Child on Mefloquine Chemoprophylaxis
    (Ghana medical journal, 2012-09) Adjei, G.O.; Adabayeri, V.M.; Annobil, S.H.
    A case of an acute reversible visual loss in a 10-yearold child who was on mefloquine prophylaxis, and was treated with artesunate-amodiaquine for an acute febrile illness diagnosed clinically as uncomplicated malaria, is reported. On admission the patient could not perceive light and had bilateral papilloedema. She was treated with dexamethasone and recovered her sight gradually over a 21-day period. There has been no previous report to our knowledge, of an association between acute visual loss and mefloquine, amodiaquine, or artesunate in the published literature, even though mefloquine is associated with blurring of vision, and antimalarials of the quinoline class have been associated with retinopathy (during long term use). While causality is difficult to ascribe in this case, it may be prudent to avoid the use of quinoline-based antimalarials for treating acute malaria in travelers taking mefloquine prophylaxis, because information on the safety of concurrent use of artemisinin combination therapies and mefloquine, or other recommended prophylactic regimens, is limited.