Senior Lecturer, university of Uyo
Progressive observational study to monitor functions of liver and kidney after use of ACTs
Sub-saharan Africa is endemic with malaria infection. The region contributed about 90% of global malaria cases in 2015. It also accounted for 90% of global deaths caused by malaria. Among under-fives, malaria is a major killer of children in the region, it took a life every 2 minutes. Domestic funding for National malaria control programs in Africa was estimated at US$550 million in 2014. The ability to bridge the gaps of intervention coverages in the region is hindered by weaknesses in health systems of African countries which pose greatest malaria burden. In 2014, 337 million packs of ACT were produced by manufacturers and 98% of the ACT were procured in Africa. As more efforts were made to educate the populace on effective treatment of malaria, more ACTs are being used. ACTs are recommended for pregnant women, infants, adolescents, men and other women. The evidence of impacts of ACTs are yet to be ascertained on liver and kidney functions of consumers. Many questions are yet to be answered: how safe are the ACTs in pregnancy? How safe are the ACTs in neonates and infants? In this regards, we intend to evaluate the effects of ACTs on the consumers. A local study in Nigeria was conducted as follows:
74 patients were recruited for the study after ethical approval was received from the health institution and they all gave consent to participate in the study. Questionnaires were distributed to them to fill and were returned. 3ml blood samples were collected from participants and were analysed for creatinine and ALT and AST.Participants were requested to return the clinic 7days later to collect another blood samples for analysis of creatinine, ALT and AST. The results showed that creatinine clearance was slightly increased while ALT was slightly elevated. The study indicated that continuous or repeated use of ACTs may lead to hepatotoxicity most especially in endemic areas.
Abstract: Management of chronic kidney disease (CKD) patients often requires the use of multiple drugs due to a high number of cardiovascular risk factors and complications associated with the disease. Multiple drugs predispose to potential drug-drug interactions (DDIs) which may be associated with increased morbidity, mortality, length of hospital stay and health-care cost.This study determined the prevalence and pattern of potential DDIs among CKD patients attending Kidney Care Centre, in Ondo City, Nigeria.It was an 18-month retrospective study that involved the reviewed CKD patients' records. The Lexi-Interact database was used to evaluate patients' medications for potential DDIs.One hundred and twenty-three (123) CKD patients, made up of 82 (66.67%) males and 41 (33.33%) females were studied. The mean age of the CKD patients was 53.81 ± 16.03 years. The most common comorbid conditions were hypertension in 103 (83.74%) and diabetes mellitus in 39 (31.71%). A total of 1237 prescriptions were made and the mean number of prescribed medications per patient was 10.06 ± 3.97. A total number of 1851 potential DDIs were observed among 118 patients. The prevalence of potential DDIs was 95.9% while the mean DDIs per prescription was 1.27. Among the potential DDIs observed, the severity was mild in 639 (34.5%), moderate in 1160 (62.7%), major in 51 (2.8%) and only 1 (0.1%) was of avoid drug combination. The most frequent DDI was between calcium carbonate and oral ferrous sulphate.The prevalence of potential DDIs is high among CKD patients. About 63% of these interactions have moderate severity. Clinicians and pharmacists should utilise available DDI software to avoid harmful DDIs in CKD patients.
Pub.: 02 Aug '17, Pinned: 08 Sep '17
Abstract: To explore the opinions of patient reporters to the UK Yellow Card Scheme (YCS) on the importance of the scheme.Postal questionnaires were distributed on our behalf to all patient reporters submitting a Yellow Card to the Medicines and Healthcare Regulatory Agency (MHRA) between March and December 2008, with one follow-up reminder to non-responders. Qualitative analysis was undertaken of responses to an open question asking why respondents felt patient reporting was important. This was followed up by telephone interviews with a purposive sample of selected respondents.There were 1362 evaluable questionnaires returned from 2008 distributed (68%) and 1238 (91%) respondents provided a total of 1802 comments. Twenty-seven interviews were conducted, which supported and expanded the views expressed in the questionnaire. Four main themes emerged, indicating views that the YCS was of importance to pharmacovigilance in general, manufacturers and licensing authorities, patients and the public and health professionals. Reporters viewed the YCS as an important opportunity to describe their experiences for the benefit of others and to contribute to pharmacovigilance. The scheme's independence from health professionals was regarded as important, in part to provide the patient perspective to manufacturers and regulators, but also because of dismissive attitudes and under-reporting by health professionals.Direct patient reporting through the YCS is viewed as important by those who have used the scheme, in order to provide the patient experience for the benefit of pharmacovigilance, as an independent perspective from those of health professionals.
Pub.: 19 Apr '11, Pinned: 23 Aug '17
Abstract: The monitoring of adverse drug reactions (ADRs) through pharmacovigilance is vital to patient safety. Spontaneous reporting of ADRs is one method of pharmacovigilance, and in the UK this is undertaken through the Yellow Card Scheme (YCS). Yellow Card reports are submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) by post, telephone or via the internet. The MHRA electronically records and reviews information submitted so that important safety issues can be detected. While previous studies have shown differences between patient and health-care professional (HCP) reports for the types of drugs and reactions reported, relatively little is known about the pharmacovigilance impact of patient reports. There have also been few studies on the views and experiences of patients/consumers on the reporting of suspected ADRs.To evaluate the pharmacovigilance impact of patient reporting of ADRs by analysing reports of suspected ADRs from the UK YCS and comparing reports from patients and HCPs. To elicit the views and experiences of patients and the public about patient reporting of ADRs.(1) Literature review and survey of international experiences of consumer reporting of ADRs; (2) descriptive analysis of Yellow Card reports; (3) signal generation analysis of Yellow Card reports; (4) qualitative analysis of Yellow Card reports; (5) questionnaire survey of patients reporting on Yellow Cards; (6) qualitative analysis of telephone interviews with patient reporters to the scheme; (7) qualitative analysis of focus groups and usability testing of the patient YCS; and (8) national omnibus telephone survey of public awareness of the YCS.Patients (n = 5180) and HCPs (n = 20,949) submitting Yellow Card reports from October 2005 to September 2007. Respondents to questionnaire survey (n = 1362). Participants at focus groups and usability testing sessions (n = 40). National omnibus telephone survey (n = 2028).The literature review included studies in English from across the world. All other components included populations from the UK; the omnibus survey was restricted to Great Britain.None.Characteristics of patient reports: types of drug and suspected ADR reported; seriousness of reports; and content of reports. The relative contributions of patient reports and of HCP reports to signal generation. Views and experiences of patient reporters. Views of members of the public about the YCS, including user-friendliness and usability of different ways of patient reporting. Public awareness of the YCS. Suggestions for improving patient reporting to the YCS.Compared with HCPs, patient reports to the YCS contained a higher median number of suspected ADRs per report, and described reactions in more detail. The proportions of reports categorised as 'serious' were similar; the patterns of drugs and reactions reported differed. Patient reports were richer in their descriptions of reactions than those from HCPs, and more often noted the effects of ADRs on patients' lives. Combining patient and HCP reports generated more potential signals than HCP reports alone; some potential signals in the 'HCP-only' data set were lost when combined with patient reports, but fewer than those gained; the addition of patient reports to HCP reports identified 47 new 'serious' reactions not previously included in 'Summaries of Product Characteristics'. Most patient reporters found it fairly easy to make reports, although improvements to the scheme were suggested, including greater publicity and the redesign of web- and paper-based reporting systems. Among members of the public, 8.5% were aware of the YCS in 2009.Patient reporting of suspected ADRs has the potential to add value to pharmacovigilance by reporting types of drugs and reactions different from those reported by HCPs; generating new potential signals; and describing suspected ADRs in enough detail to provide useful information on likely causality and impact on patients' lives. These findings suggest that further promotion of patient reporting to the YCS is justified, along with improvements to existing reporting systems. In order of priority, future work should include further investigation of (1) the pharmacovigilance impact of patient reporting in a longer-term study; (2) the optimum approach to signal generation analysis of patient and HCP reports; (3) the burden of ADRs in terms of impact on patients' lives; (4) the knowledge and attitudes of HCPs towards patient reporting of ADRs; (5) the value of using patient reports of ADRs to help other patients and HCPs who are seeking information on patient experiences of ADRs; and (6) the impact of increasing publicity and/or enhancements to reporting systems on the numbers and types of Yellow Card reports from patients.The National Institute for Health Research Health Technology Assessment programme.
Pub.: 07 May '11, Pinned: 23 Aug '17
Abstract: Monitoring adverse drug reactions (ADRs) through pharmacovigilance are vital to patient safety. Spontaneous ADR reporting is one method of pharmacovigilance, and in Canada all reporter types admitted to report an ADR to the Canadian Vigilance Program at Health Canada. Reports are submitted to Health Canada by post, telephone, or via the internet. The Canada Vigilance Program electronically records submitted information to detect medication safety alerts. Although previous studies have shown differences between patients and healthcare professionals (HCPs) on the types of drugs and reactions reported, relatively little is known about the importance of patient reports to pharmacovigilance activities. This article proposed a multi-method approach to evaluate the importance of patient ADR reporting on pharmacovigilance activities, by systematically review the available literature, comparing patient-versus HCPs-generated ADR reports that were submitted to the Canada Vigilance Program, and exploring patient views and experiences regarding the Canadian ADR reporting system.Guided by a risk-perception theoretical lens, the proposed multi-methods research study will involve three phases. Phase I is a systematic review of all studies that analyse the factors influence ADR reporting by patients to the pharmacovigilance schemes. Phase II is a descriptive statistical analysis of all ADR reports received by the Canada Vigilance Program database between 1 January 2000 and 31 December 2014 from patients and HCPs to compare ADRs reported by patients with those reported by HCP reports in terms of ADR seriousness, ADR classification by system organ class, and the medication involved based on the anatomical therapeutic class system. In phase III, an interpretative descriptive approach will be used to explore patient's views and experiences on ADR reporting and usability of the Canadian Vigilance ADR report. Participants will be purposefully selected to ensure diverse backgrounds and experiences. Interviews will be digitally-recorded, transcribed verbatim, and inductively analysed to identify themes. Patients will be interviewed until theoretical saturation is achieved.Findings from this research will highlight the role of the patients in directly reporting ADRs, and provide information that may guide streamline and optimizing patient ADR reporting. Policy makers, public health officials, and regulatory agencies will require this critical information in order to improve medication safety in Canada and worldwide.
Pub.: 31 Mar '16, Pinned: 23 Aug '17
Abstract: In this study, a somatic cell genetic approach was used to study the regulation of liver/bone/kidney alkaline phosphatase (ALPL) gene expression in osteoblasts. ALPL plays an important role in skeletal mineralization and serves as a good index of bone formation. A series of intertypic hybrids constructed by fusion of the human osteosarcoma TE-85 with the mouse fibrosarcoma La-t- demonstrated a 10-fold reduction of ALPL steady-state mRNA and enzyme activity, a phenomenon termed extinction. Hybrid subclones which reexpressed ALPL contained reduced numbers of fibroblast chromosomes compared to earlier passages. This suggests that a trans-acting negative regulatory factor expressed from the fibroblast genome regulates ALPL expression. Two factors known to influence ALPL expression are 1,25-dihydroxyvitamin D3 (1,25D3) and transforming growth factor-beta1 (TGFbeta1). 1,25D3 is involved in mobilizing bone calcium stores and TGFbeta1 plays a critical role in bone remodeling. The extinguished hybrids were exposed to 1,25D3, TGFbeta1, and a combination of these factors. For two hybrids, the combination induced reexpression of ALPL activity to levels comparable to the TE-85 parent, indicating a competition between the factors and the extinguisher(s). Neither factor alone could induce ALPL reexpression to the levels observed with the combination. In only one hybrid, the combination of factors synergistically increased ALPL expression. These data help define the cis sequence element(s) in the ALPL promoter which are involved in the negative regulation of this gene.
Pub.: 10 Jul '96, Pinned: 23 Aug '17
Abstract: Responses to drugs and pharmacological treatments differ considerably between individuals. Importantly, only 50%-75% of patients have been shown to react adequately to pharmacological interventions, whereas the others experience either a lack of efficacy or suffer from adverse events. The liver is of central importance in the metabolism of most drugs. Because of this exposed status, hepatotoxicity is amongst the most common adverse drug reactions and hepatic liabilities are the most prevalent reason for the termination of development programs of novel drug candidates. In recent years, more and more factors were unveiled that shape hepatic drug responses and thus underlie the observed inter-individual variability. In this review, we provide a comprehensive overview of different principle mechanisms of drug hepatotoxicity and illustrate how patient-specific factors, such as genetic, physiological and environmental factors, can shape drug responses. Furthermore, we highlight other parameters, such as concomitantly prescribed medications or liver diseases and how they modulate drug toxicity, pharmacokinetics and dynamics. Finally, we discuss recent progress in the field of in vitro toxicity models and evaluate their utility in reflecting patient-specific factors to study inter-individual differences in drug response and toxicity, as this understanding is necessary to pave the way for a patient-adjusted medicine.
Pub.: 19 Oct '16, Pinned: 20 Aug '17
Abstract: Drug-induced liver injury (DILI) is a major challenge for the pharmaceutical industry, regulatory authorities, and clinicians. It is usually categorized into 'intrinsic' and 'idiosyncratic', but DILI caused by most drugs is of an idiosyncratic nature and usually cannot be predicted from the regulatory required animal toxicity studies. Unfortunately, some individuals exposed to therapeutic dose will develop idiosyncratic DILI that might involve severe clinical outcome, and no biomarker is available to identify the susceptible patients prior to drug treatment. In this editorial, we summarized the recent advances in predicting idiosyncratic DILI and provided the perspectives to improve the prediction.
Pub.: 27 May '14, Pinned: 20 Aug '17
Abstract: Drug-induced liver injury (DILI) is among the most challenging acute or chronic liver conditions to be handled by physicians. Despite its low incidence in the general population, DILI is a frequent cause of acute liver failure. As such, the possibility of DILI should be considered in all patients who present with acute liver damage, independent of any known pre-existing liver disease. DILI can be classified as intrinsic/dose-dependent (e.g., acetaminophen toxicity) or idiosyncratic/dose-independent, with the latter form being relatively uncommon. Amoxicillin-clavulanate is the antimicrobial that is most frequently associated with idiosyncratic DILI. Large, ongoing, prospective studies in western countries have reported other drugs associated with DILI, including nonsteroidal anti-inflammatory drugs, statins, and herbal and dietary supplements. An important safety issue, DILI is one of the most frequently cited reasons for cessation of drug development during or after preclinical studies and for withdrawal of a drug from the market. This review summarizes the epidemiology, risk factors, commonly implicated drugs, clinical features, and diagnosis of DILI, with the aim of aiding physicians in the management of this debated problem. Old and new biomarkers for DILI and pharmacogenetic studies are also described.
Pub.: 02 Feb '16, Pinned: 20 Aug '17