Navigating duplication in pharmacovigilance databases: a scoping review.

OBJECTIVES: Pharmacovigilance databases play a critical role in monitoring drug safety. The duplication of reports in pharmacovigilance databases, however, undermines their data integrity. This scoping review sought to provide a comprehensive understanding of duplication in pharmacovigilance databases worldwide. DESIGN: A scoping review. DATA SOURCES: Reviewers comprehensively searched the literature in PubMed, Web of Science, Wiley Online Library, EBSCOhost, Google Scholar and other relevant websites. ELIGIBILITY CRITERIA: Peer-reviewed publications and grey literature, without language restriction, describing duplication and/or methods relevant to duplication in pharmacovigilance databases from inception to 1 September 2023. DATA EXTRACTION AND SYNTHESIS: We used the Joanna Briggs Institute guidelines for scoping reviews and conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Two reviewers independently screened titles, abstracts and full texts. One reviewer extracted the data and performed descriptive analysis, which the second reviewer assessed. Disagreements were resolved by discussion and consensus or in consultation with a third reviewer. RESULTS: We screened 22 745 unique titles and 156 were eligible for full-text review. Of the 156 titles, 58 (47 peer-reviewed; 11 grey literature) fulfilled the inclusion criteria for the scoping review. Included titles addressed the extent (5 papers), prevention strategies (15 papers), causes (32 papers), detection methods (25 papers), management strategies (24 papers) and implications (14 papers) of duplication in pharmacovigilance databases. The papers overlapped, discussing more than one field. Advances in artificial intelligence, particularly natural language processing, hold promise in enhancing the efficiency and precision of deduplication of large and complex pharmacovigilance databases. CONCLUSION: Duplication in pharmacovigilance databases compromises risk assessment and decision-making, potentially threatening patient safety. Therefore, efficient duplicate prevention, detection and management are essential for more reliable pharmacovigilance data. To minimise duplication, consistent use of worldwide unique identifiers as the key case identifiers is recommended alongside recent advances in artificial intelligence.

Novel Oral Poliovirus Vaccine 2 Safety Evaluation during Nationwide Supplemental Immunization Activity, Uganda, 2022.

Given its enhanced genetic stability, novel oral poliovirus vaccine type 2 was deployed for type 2 poliovirus outbreak responses under World Health Organization Emergency Use Listing. We evaluated the safety profile of this vaccine. No safety signals were identified using a multipronged approach of passive and active surveillance.

Cost and availability of selected medicines after implementation of increased import verification fees.

BACKGROUND: Uganda imports approximately 90% of its medicines, with about 60% being distributed by the private sector. To discourage importation and promote local production of 37 selected locally manufactured medicines, the Ugandan government through the Ministry of Health in 2017 increased the import verification fees from 2 to 12%. The increase in verification fees ultimately affects cost and availability of these medicines. This study aimed to assess the cost and availability of the selected essential medicines after the 12% increase in verification fees in Uganda. METHODS: A cross sectional study among 328 wholesale and retail pharmacies and seven key informant interviews was conducted using a pretested data collection checklist and in-depth interview guide from February to September 2021 in Uganda. Data on the availability and prices of the medicines before (2017) and after (2020) the increase in verification fees was collected. Paired sample T-Test was used to test if there is a significant difference in prices before and after the 12% increase in verification fees. RESULTS: Mean availability of imported medicines was higher (54.8%, CI: 49.3-60.4) than the locally produced medicines (37.1%, CI: 31.9-42.7) except for locally manufactured parenteral preparations (54.6.%, CI: 49.1-60.1). Availability of locally produced medicines was mainly low (45%) while the imported medicines were fairly high (74%). Most commonly available locally manufactured medicines were Surgical spirit (89.9%), ORS (86%), Dextrose 5% solution (74.4%), Paracetamol 500 mg Tablets (73.8%) and Sodium Chloride 0.9% solution (72.9%). Most commonly available imported medicines were; Omeprazole 20 mg (94.2%), Amoxicillin Trihydrate 125 mg/5 ml (92.4%), Ciprofloxacin 500 mg (91.4%), Paracetamol Suspension 120 mg/5 ml (91.5%) and Metronidazole 200 mg Tablets (88.1%). Increase in lowest-priced local and imported medicines was significant for 10 (23.8%) and 7 (15.9%) of the medicines respectively. The median prices of imported medicines were generally higher than locally produced medicines. The median unit prices of 12 (28.6%) locally produced medicines and 20 (47.6%) imported medicines were higher than the international median unit prices. CONCLUSIONS: The overall availability of imported medicines was still higher than the local medicines. The median prices of local and imported medicines generally increased or remained the same after the introduction of import verification fees. There is a need for price controls and transparency in the private sector.

Expanding regulatory science: Regulatory complementarity and reliance.

Drug regulatory institutions, infrastructures, and systems are becoming increasingly interconnected across national boundaries and increasingly global in outlook. This process is reflected in the broadening and deepening application of the principles and practice of Regulatory Reliance, and parallel initiatives to strengthen the capacities of regulatory institutions in low- and middle-income countries (LMICs). Although these developments are important and constructive, they have tended to be framed in terms of the transfer of systems, knowledge, and skills from relatively "mature" regulatory agencies in high-income countries (HICs) to less-well-resourced regulatory agencies in LMICs. This framing recognizes and foregrounds the considerable practical challenges that many LMIC regulatory agencies face, but in doing so, also backgrounds and underestimates the significance of the different contextual insights that LMIC health researchers and regulators can bring to the regulatory deliberations of their HIC counterparts. This position paper argues that the systematic pursuit, identification, and sharing of these different contextual insights-a dimension of regulatory science that we term "Regulatory Complementarity"-can augment the current practice and goals of Regulatory Reliance, and further invigorate the emerging global regulatory ecosystem.

Antimicrobial consumption surveillance in Uganda: Results from an analysis of national import data for the human health sector, 2018-2021.

BACKGROUND: The surveillance of antimicrobial consumption (AMC) is critical to developing appropriate antimicrobial stewardship interventions. It is a key component of World Health Organization's (WHO) Global Action Plan on Antimicrobial Resistance and the Uganda Antimicrobial Resistance National Action Plan 2018-2023. Our study's objective was to determine the national consumption of all antimicrobials. METHODS: Data on all imported antimicrobials were retrieved from paper-based records and entered in the web-based National Drug Authority (NDA) management information system from 2021. The import data for the year is a proxy for nationwide consumption because they account for 95% of all medical products. The NDA authorizes all imports to the country regardless of final distribution in the supply chain. The data were analyzed in accordance with WHO Anatomical Therapeutic Chemical codes and defined daily dose (DDD) methodology. We also retrieved consumption data for 2018, 2019, and 2020 that were previously submitted by Uganda to WHO's Global Antimicrobial Resistance and Use Surveillance System. RESULTS: In 2021, the average DDD per 1000 inhabitants was 29.02 for all antimicrobials; 80.7% of antimicrobials consumed were oral. Penicillins (27.6%) were the most consumed antimicrobial class, followed by sulfonamides and trimethoprim (15.5%). Based on WHO's Access, Watch, and Reserve (AWaRe) antibiotic classification, 62.91% of AMC was from the access class, with watch class averaging 14.51% in the period 2018-2021. Watch class AMC spiked in 2021 (34.2%) during COVID-19 pandemic compared to 2020 (24.29%). Azithromycin and ciprofloxacin were the most consumed watch class antimicrobials in 2021. CONCLUSIONS: The relatively high consumption of injectable antimicrobials and year over year increase in watch class AMC requires urgent stewardship interventions. Further work is needed to establish a system for longitudinal AMC surveillance that is well resourced and funded to overcome the challenges of estimation and provide more accurate data on consumption and use patterns.

Drug safety in Africa: a review of systems and resources for pharmacovigilance.

INTRODUCTION: Pharmacovigilance on the African continent has developed over time, with 50 of the 54 countries currently being members of the WHO Programme for international drug monitoring. However, there are still challenges, such as weak regulation, insufficient resources, and differing policies. This expert opinion provides unique insights from long-term experience overcoming some of these challenges and proposes some solutions for implementing pharmacovigilance in resource-limited settings. AREAS COVERED: This was an expert opinion on the pharmacovigilance landscape in Africa with a focus on reporting, good pharmacovigilance practice inspections, resources available, and the adoption of artificial intelligence. The literature search for the review was carried out in June 2023 on selected electronic databases that included PubMed, Embase, and Web of Science to identify relevant literature published from 2017 up to date while the expert opinion is an informed position from decades of practice in the area. EXPERT OPINION/COMMENTARY: African countries are at different maturity levels and pharmacovigilance competence. A few countries have outstanding pharmacovigilance systems, while the majority do not have fully functional systems. African countries may pool resources through regional blocs to implement joint pharmacovigilance activities. With advancements in technology, countries are expected to embrace artificial intelligence to ensure sustainable pharmacovigilance practices.

Facilitators and Barriers to Uptake of the Med Safety Mobile App for Adverse Drug Reaction Reporting by Health Workers in Uganda: A Qualitative Study.

INTRODUCTION: Adverse drug reactions (ADRs) are an important public health challenge worldwide; however, pharmacovigilance systems are plagued by under-reporting. Mobile technologies, including mobile applications such as Med Safety, could strengthen ADR reporting. We explored the acceptability, and factors that could influence uptake of, Med Safety for ADR reporting by health workers in Uganda. METHODS: The study took place between July and September 2020 in 12 HIV clinics in Uganda and employed a qualitative exploratory research design. We conducted 22 in-depth interviews and 3 mixed-gender focus group discussions (49 participants) with a diverse range of health workers. We analysed the data using a thematic approach. RESULTS: There was goodwill among the health workers to adopt Med Safety for ADR reporting and the majority would recommend the app to other health workers. Training with practice increased acceptability of the app. Uptake of the app was favoured by the younger, technology proficient, health worker demographic; the app's offline and two-way risk communication functionalities; availability of free internet hotspots at some health facilities; goodwill and willingness of health workers to report ADRs; and the cumbersome nature of conventional ADR reporting tools. Potential barriers to the uptake of Med Safety were the perceived lengthy processes of initial app registration and completion of multiple screens during ADR reporting; challenges with health workers' smartphones (incompatibility with application, no space for more applications, low battery charge); high cost of internet data; poor internet connectivity; difficulty in recognising ADRs, language barrier and poor feedback to ADR reporters. CONCLUSION: There was goodwill among the health workers to adopt Med Safety for ADR reporting and the majority would recommend the app to other health workers. Training with practice increased acceptability of the app and should be integral in all future app roll-out campaigns. The identified facilitators and barriers could be used to appropriately guide future research and implementation to promote the uptake of Med Safety for pharmacovigilance in low- and middle-income countries.

The impact of the increase in import verification fees on local production capacity of selected medicines in Uganda.

BACKGROUND: The local manufacture of pharmaceuticals is an opportunity to develop a broader manufacturing and knowledge-based economy and reduce over dependence on imports. To promote local production, the Ugandan government introduced Buy Uganda Build Uganda policy geared towards promoting use of locally manufactured goods. It also increased import verification fees in 2017 for 37 selected locally manufactured essential medicines from 2 to 12% to discourage importation of these medicines. This study assessed the impact of the increase in verification fees on local production capacity of the medicines. METHODS: This was a mixed methods study looking at production capacity before and after introduction of the 12% import verification fees. It was conducted among six (6) local pharmaceutical industries in Uganda and seven (7) key informant interviews with experts in the pharmaceutical sector between February and September 2021. RESULTS: The overall increase in local production capacity of the selected medicines was 8.2% from 2017 to 2020. The most significant increases were in the production of capsules (100.6%, P = 0.03) and oral liquids (170.8%, P = 0.0001). All the industries registered an increase in number of employees between 2017 and 2020 with an average percentage increase of 42%. There was a 14.7% (95% CI 2.76-17.6%) change in installed capacity of the compression machine (P = 0.033) and 27.7% (95% CI 24.6-33.9%) change in installed capacity of the Blow-Fill-Seal (BFS) filling machines (P = 0.011). There was also an increase in the number and capacity of installed utilities such as the heating ventilation and air conditioning (968%) and standby generators (131%). Only two (2) industries registered an increase in critical quality control equipment and one had all the critical equipment available by 2020. Most of the key informants reported positive impact of the increment of import verification on local manufacturing capacity. CONCLUSIONS: Local pharmaceutical production capacity increased with the increase in import verification fees with significant increases in production of oral liquids and capsules. Successful implementation of policies supporting local production will promote the development of local pharmaceutical industries. Governments should consider increasing the list of medicines to benefit from the import verification fees increase by adding all essential generic medicines for which there is adequate domestic production capacity and technical skills.

Patient experiences of sexual dysfunction after transition to dolutegravir-based HIV treatment in mid-Western Uganda: a qualitative study.

BACKGROUND: The literature on dolutegravir (DTG)-based HIV treatment has focused on assessing therapeutic efficacy particularly with regard to viral load suppression. However, little empirical attention has been devoted to understanding the effects of DTG on quality of life, in particular sexual health and functioning in PLHIV. This study focused on understanding patient experiences of sexual dysfunction, after transition to DTG-based regimens in Rwenzori region in Mid-Western Uganda. METHODS: We adopted a qualitative exploratory research design. Between August and September 2021, we conducted sixteen in-depth interviews and six focus group discussions (48 participants) with patients reporting 'new' sexual dysfunction after transition to DTG-based regimens at seven health facilities in mid-Western Uganda. Data were analyzed by thematic approach. RESULTS: Decreased libido was reported in both sexes of patients within weeks of transition to DTG-based regimens. Diminished interest in sex was more frequently reported among women while men complained of a marked reduction in the frequency of sex. Women reported loss of psycho-social attraction to their long-term male partners. Erectile dysfunction was common among men in this sample of patients. Patients described their experiences of sexual dysfunction as an affront to their socially-constructed gender identities. Patients described tolerating sexual adverse drug reactions (ADRs) as a necessary tradeoff for the extension in life granted through antiretroviral therapy. A number of women reported that they had separated from their spouses as a result of perceived drug-induced sexual dysfunction. Marital strife and conflict arising from frustration with sexual-partner dysfunction was frequently reported by participants in both sexes. Several participants indicated experiencing insecurity in their heterosexual relationships due to difficulties in sexual functioning. CONCLUSION: Sexual dysfunction following transition to DTG-based regimens is common in both sexes of PLHIV, who indicated that they had no prior experience of difficulties in sexual health. Our findings demonstrate that sexual ADRs negatively impact self-esteem, overall quality of life and impair gender relations. DTG-related sexual health problems merit increased attention from HIV clinicians. Further research is warranted to assess the prevalence of DTG-associated sexual dysfunction in patients in Uganda.

Effectiveness of the Med Safety mobile application in improving adverse drug reaction reporting by healthcare professionals in Uganda: a protocol for a pragmatic cluster-randomised controlled trial.

INTRODUCTION: Combination antiretroviral therapy (cART) has massively reduced HIV mortality. However, long-term cART increases the risk of adverse drug reactions (ADRs), which can lead to higher morbidity, mortality and healthcare costs for people living with HIV (PLHIV).Pharmacovigilance-monitoring the effects of medicines-is essential for understanding real-world drug safety. In Uganda, pharmacovigilance systems have only recently been developed, and rates of ADR reporting for cART are very low. Thus, the safety profile of medicines currently used to treat HIV and tuberculosis in our population is poorly understood.The Med Safety mobile application has been developed through the European Union's Innovative Medicines Initiative WEB-Recognising Adverse Drug Reactions project to promote digital pharmacovigilance. This mobile application has been approved for ADR-reporting by Uganda's National Drug Authority. However, the barriers and facilitators to Med Safety uptake, and its effectiveness in improving pharmacovigilance, are as yet unknown. METHODS AND ANALYSIS: A pragmatic cluster-randomised controlled trial will be implemented over 30 months at 191 intervention and 191 comparison cART sites to evaluate Med Safety. Using a randomisation sequence generated by the sealed envelope software, we shall randomly assign the 382 prescreened cART sites to the intervention and comparison arms. Each cART site is a cluster that consists of healthcare professionals and PLHIV receiving dolutegravir-based cART and/or isoniazid preventive therapy. Healthcare professionals enrolled in the intervention arm will be trained in the use of mobile-based, paper-based and web-based reporting, while those in the comparison arm will be trained in paper-based and web-based reporting only. ETHICS AND DISSEMINATION: Ethical approval was given by the School of Biomedical Sciences Research and Ethics Committee at Makerere University (SBS-REC-720), and administrative clearance was obtained from Uganda National Council for Science and Technology (HS1366ES). Study results will be shared with healthcare professionals, policymakers, the public and academia. TRIAL REGISTRATION NUMBER: PACTR202009822379650.

Implementation of a peer support intervention to promote the detection, reporting and management of adverse drug reactions in people living with HIV in Uganda: a protocol for a quasi-experimental study.

INTRODUCTION: Patients have contributed <1% of spontaneous adverse drug reaction (ADR) reports in Uganda's pharmacovigilance database. Peer support combined with mobile technologies could empower people living with HIV (PLHIV) to report ADRs and improve ADR management through linkage to care. We seek to test the feasibility and effect of a peer support intervention on ADR reporting by PLHIV receiving combination antiretroviral therapy (cART) in Uganda; identify barriers and facilitators to the intervention; and characterise ADR reporting and management. METHODS AND ANALYSIS: This is a quasi-experimental study to be implemented over 4 months at 12 intervention and 12 comparison cART sites from four geographical regions of Uganda. Per region, two blocks each with a tertiary, secondary and primary care cART site will be selected by simple random sampling. Blocks per region will be randomly assigned to intervention and comparison arms.Study units will include cART sites and PLHIV receiving cART. PLHIV at intervention sites will be assigned to peer supporters to empower them to report ADRs directly to the National Pharmacovigilance Centre (NPC). Peer supporters will be expert clients from among PLHIV and/or recognised community health workers.Direct patient reporting of ADRs to NPC will leverage the Med Safety App and toll-free unstructured supplementary service data interface to augment traditional pharmacovigilance methods.The primary outcomes are attrition rate measured by number of study participants who remain in the study until the end of follow-up at 4 months; and number of ADR reports submitted to NPC by PLHIV as measured by questionnaire and data abstraction from the national pharmacovigilance database at baseline and 4 months. ETHICS AND DISSEMINATION: The study received ethical approval from: School of Health Sciences Research and Ethics Committee at Makerere University (MAKSHSREC-2020-64) and Uganda National Council for Science and Technology (HS1206ES). Results will be shared with PLHIV, policy-makers, the public and academia. TRIAL REGISTRATION NUMBER: ISRCTN75989485.

Provider perspectives on the acceptability and tolerability of dolutegravir-based anti-retroviral therapy after national roll-out in Uganda: a qualitative study.

BACKGROUND: The World Health Organization recommends dolutegravir (DTG) as the for first-line and second-line antiretroviral therapy (ART) worldwide. However, little is known about the acceptability and tolerability of DTG-based ART at routine points-of-care in Uganda. We set out to explore the perceptions of clinicians in ART clinics regarding the acceptability and tolerability of DTG-based ART since national roll-out in March 2018 in Uganda. METHODS: We adopted a qualitative exploratory design involving 49 participants. Between September 2020 and February 2021, we conducted 22 in-depth interviews with clinicians in the ART clinics of 12 purposively selected health facilities across Uganda. The selection of study sites ensured diversity in facility ownership-type (public/private), level of service delivery (tertiary/secondary/primary) and the four major geographic sub-regions of Uganda. We conducted three focus group discussions with 27 clinicians in the participating facilities. Data were analyzed by thematic approach. RESULTS: Clinicians in ART clinics acknowledged that DTG-based ART is well tolerated by the majority of their patients who appreciate the reduced pill burden, perceived less side effects and superior viral load suppression. However, they reported that a number of their patients experience adverse drug reactions (ADRs) after being transitioned to DTG. Hyperglycemia is, by far, the most commonly reported suspected ADR associated with DTG-based regimens and was cited in all but two participating facilities. Insomnia, weight gain and reduced libido are among the other frequently cited suspected ADRs. In addition, clinicians in ART clinics perceived some of the suspected ADRs as resulting from drug interactions between dolutegravir and isoniazid. Weak diagnostic capacities and shortage of associated commodities (e.g. glucometers and test kits) were reported as impediments to understanding the full extent of ADRs associated DTG-based ART. CONCLUSION: While DTG-based regimens were perceived by clinicians in ART clinics to be well tolerated by the majority of their patients, they also reported that a number of patients experience suspected ADRs key among which were hyperglycemia, insomnia and reduced libido. Based on the perspectives of clinicians, we recommend that future studies examine the prevalence of dolutegravir-induced hyperglycemia in patients in Uganda.

Evaluation of the Clinical Use of Ceftriaxone among In-Patients in Selected Health Facilities in Uganda.

Ceftriaxone has a high propensity for misuse because of its high rate of utilization. In this study, we aimed at assessing the appropriateness of the clinical utilization of ceftriaxone in nine health facilities in Uganda. Using the World Health Organization (WHO) Drug Use Evaluation indicators, we reviewed a systematic sample of 885 patients' treatment records selected over a three (3)-month period. Our results showed that prescriptions were written mostly by medical officers at 53.3% (470/882). Ceftriaxone was prescribed mainly for surgical prophylaxis at 25.3% (154/609), respiratory tract infections at 17% (104/609), and sepsis at 11% (67/609), as well as for non-recommended indications such as malaria at 7% (43/609) and anemia at 8% (49/609). Ceftriaxone was mostly prescribed once daily (92.3%; 817/885), as a 2 g dose (50.1%; 443/885), and for 5 days (41%; 363/885). The average score of inappropriate use of ceftriaxone in the eight indicators was 32.1%. Only 58.3% (516/885) of the ceftriaxone doses prescribed were administered to completion. Complete blood count and culture and sensitivity testing rates were 38.8% (343/885) and 1.13% (10/885), respectively. Over 85.4% (756/885) of the patients improved and were discharged. Factors associated with appropriate ceftriaxone use were gender, pregnancy status, days of hospitalization, health facility level of care, health facility type, and type of prescriber.

Pharmacovigilance of suspected or confirmed therapeutic ineffectiveness of artemisinin-based combination therapy: extent, associated factors, challenges and solutions to reporting.

BACKGROUND: Therapeutic ineffectiveness of artemisinin-based combination therapy (ACT) increases the risk of malaria-related morbidity and mortality, and raises healthcare costs. Yet, little has been done to promote the pharmacovigilance (PV) of ACT ineffectiveness in sub-Saharan Africa, particularly in Uganda. This study aimed to determine the extent and associated factors of the past 6 months reporting of suspected or confirmed ACT therapeutic ineffectiveness by healthcare professionals (HCPs), and difficulties and potential solutions to the PV of ACT therapeutic ineffectiveness. METHODS: Survey of 685 HCPs conducted using a self-administered questionnaire from June to July 2018 in a nationally representative sample of public and private health facilities in Uganda. HCPs disclosed if they had spontaneously reported ACT therapeutic ineffectiveness to appropriate authorities in the previous 6 months. Multivariable logistic regression models were used to identify determinants of past 6-months, HCP-reported ACT therapeutic ineffectiveness. RESULTS: One in five (20%, 137/685; 95% CI 17-23%) HCPs reported ACT therapeutic ineffectiveness to an appropriate authority in the previous 6 months. HCPs commonly reported ACT therapeutic ineffectiveness to immediate supervisors (72%, 106/147), mostly verbally only (80%, 109/137); none had ever submitted a written report of ACT therapeutic ineffectiveness to Uganda's National Pharmacovigilance Centre. Common difficulties of reporting ACT therapeutic ineffectiveness were: unavailability of reporting procedures (31%, 129/421), poor follow-up of treated patients (22%, 93/421) and absence of reporting tools (16%, 68/421). Factors associated with reporting ACT therapeutic ineffectiveness in the past 6 months were: hospital-status (vs other; OR = 2.4, 95% CI 1.41-4.21), HCPs aged under 25 years (OR = 2.2, 95% CI 1.29-3.76), suspicion of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.3, 95% CI 1.29-3.92), receipt of patient-complaint(s) of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.9, 95% CI 1.62-5.12) and HCPs from northern (vs central; OR = 0.5, 95% CI 0.28-0.93) and western (vs central; OR = 0.4, 95% CI 0.17-0.77) parts of Uganda. CONCLUSION: One in five HCPs reported ACT therapeutic ineffectiveness, mostly verbally to supervisors. The existing adverse drug reaction (ADR)-reporting infrastructure could be leveraged to promote the PV of ACT therapeutic ineffectiveness.

Prescription of Levofloxacin and Moxifloxacin in Select Hospitals in Uganda: A Pilot Study to Assess Guideline Concordance.

Background: In Uganda, national tuberculosis (TB) treatment guidelines were revised to include the newer generation fluoroquinolones among the second-line treatment options for multidrug-resistant TB. This study was designed to analyze if the prescription of these quinolones is compliant with country recommendations. Methods: This was an observational retrospective study of consumption data for 2017 and 2018 across four selected regional referral hospitals. The sources of consumption data were hospital pharmacy stock cards and the dispensing register. The medical files of patients who had been prescribed fluoroquinolones were also assessed to study compliance with the Uganda Clinical Guidelines and the British National Formulary (BNF). Results: None of the 371 levofloxacin prescriptions analyzed complied with the Uganda Clinical Guidelines, although 250 (67.3%) were prescribed for indications included in the BNF. According to WHO prescription indicators, only 220 (59.3%) prescriptions were appropriate. Conclusion: The prescription of levofloxacin and moxifloxacin increased in the hospitals studied, but in a high proportion of cases, they were not compliant with country recommendations. The findings call for the strengthening of national antimicrobial stewardship programs.

Healthcare professionals' perspective can guide post-marketing surveillance of artemisinin-based combination therapy in Uganda.

BACKGROUND: Efficient testing to identify poor quality artemisinin-based combination therapy (ACT) is important to optimize efforts to control and eliminate malaria. Healthcare professionals interact with both ACT and malaria patients they treat and hence could observe, first-hand, suspect poor quality artemisinin-based combinations linked to poor malaria treatment outcomes and the factors associated with inappropriate use or treatment failure. METHODS: A cross-sectional study of 685 HCP perspectives about the efficacy of ACT between June and July 2018 at selected health facilities in Uganda. Medicine samples were obtained from the seven regions of Uganda and tested for quality using the Germany Pharma Health Fund™ minilabs. RESULTS: The average age of the 685 respondents was 30 (SD = 7.4) years. There was an almost equal distribution between male and female respondents (51:49), respectively. Seventy percent (n = 480) were diploma holders and the nurses contributed to half (49%, n = 334) of the study population. Sixty-one percent of the HCPs reported having ever encountered ACT failures while treating uncomplicated malaria. Nineteen percent of HCPs thought that dihydroartemisinin/piperaquine gave the most satisfactory patient treatment outcomes, while 80% HCPs thought that artemether/lumefantrine gave the least satisfactory patient treatment outcomes, possibly due to dosing schedule and pill burden. Healthcare professionals from the Central region (OR = 3.0, CI 0.3-1.0; P = 0.0001), Eastern region (OR = 5.4, CI 2.9-9.8; P = 0.0001) and Northern region (OR = 5.3, CI 2.9-9.9; P = 0.0001) had a higher chance of encountering ACT failure in 4 weeks prior to the survey as compared to those from the western region. Healthcare professionals from private health facilities also had higher chances of encountering ACT failures in past 4 weeks as compared to those from public health facilities (OR = 2.7, CI 1.7-3.9; P = 0.0001). All 192 samples passed the quality screening tests. The random sample of 10% of all samples randomly obtained by the laboratory staff also passed the chemical content analysis and dissolution tests. CONCLUSION: ACT medicines are widely available over-the-counter to the public and it is very difficult to report and monitor a decrease in efficacy or treatment failure. The perspectives of HCPs on treatment failure or lack of efficacy may potentially guide optimization efforts of sampling methodologies for the quality survey of ACT medicines.

The effect of community dialogues and sensitization on patient reporting of adverse events in rural Uganda: Uncontrolled before-after study.

BACKGROUND: Patients experiencing adverse drug events (ADE) in many developing countries are in the best position to report these events to the authorities but need to be empowered to do so. Systematic evaluation of community engagement and patient support especially in rural areas would provide evidence for a program to monitor potential harm from medicines. The aim of this study was to assess the effects of a community dialogue and sensitization (CDS) program on the knowledge, attitude and practises of community members for reporting ADE. METHODS: This an uncontrolled before-after study was conducted in two eastern Ugandan districts between September 2016 and August 2017. RESULTS: After implementation of the community dialogue and sensitization (CDS) program, there was an overall 20% (95% CI:16% to 25%) increase in knowledge about ADE in the community compared to before the program began. Awareness levels increased by 50% (95% CI: 37% to 63%) among those with little or no education and by41% (95% CI: 31% to 52%) among young people (15-24 years). Furthermore, 5% (95% CI: 3% to 7%) more respondents recognized the need for reporting ADEs compared to before the program. Finally, there was a significant increase of 115% (95% CI:137% to 217%) in respondent recognition and reporting of ADEs compared to the beginning of the CDS program. Overall, this community found the CDS program acceptable and proposed aspects that could be improved for future use. CONCLUSION: Our evaluation showed that the CDS program increased knowledge and improved attitudes by catalyzing discussions among community members and healthcare professionals on health issues and monitoring safety of medicines compared to before the program. Successful implementation of the program depends on holistic health systems strengthening and adaptation to the community's way of life.

Adverse Drug Reaction Onsets in Uganda's VigiBase®: Delayed International Visibility, Data Quality and Illustrative Signal Detection Analyses.

INTRODUCTION: Developing countries can improve their pharmacovigilance systems by analysing their own medication safety data. OBJECTIVE: The aims of this study were to characterize Uganda's reported adverse drug reaction (ADR) onsets in 2012-2015 that were registered on VigiBase® by 31 December 2017, to document delays in international visibility and the influence of covariates on this delay from ADR onsets in 2013 + 2014, to examine data quality, and to illustrate analytical approaches for safety data, particularly for patients receiving antiretroviral therapy (ART). METHODS: International delay was defined as elapsed time from complete ADR onset date to entry date on VigiBase®, with covariates examined using Cox proportional hazards regression. Simple random sampling was used to locate the paper-based ADR forms for data quality assurance. Disproportionality for signal detection focused on serious singleton ADR onsets in patients receiving ART. RESULTS: Uganda's VigiBase® had 1018 patient entries with complete ADR onset dates: 260 in 2012, 293 in 2013, 305 in 2014 and 160 in 2015. Only 16% (154/953) of ADR onsets in 2012-2015 were in patients aged < 20 years for whom randomly sampled ADR forms were less fully completed; 87% (889/1018) comprised a singleton sign/symptom; half were serious. Median delay from ADR onset to international visibility was 11 months for ADR onsets in 2013 + 2014, and longest for healthcare professionals other than pharmacists and physicians. Disproportionality for serious ADR onsets in patients receiving ART included anaemia with zidovudine, renal impairment with tenofovir, Stevens-Johnson syndrome with nevirapine and skin rash with efavirenz. CONCLUSIONS: Barely one ADR onset per day was registered on VigiBase® from those submitted to Uganda's National Pharmacovigilance Centre during 2012-2014; only one in six was from patients aged < 20 years. Paediatric pharmacovigilance requires more emphasis in Uganda. Delays from reported ADR onset to international visibility on VigiBase® need to reduce dramatically. Quality assurance revealed rectifiable data entry deficits. Signal detection performed well for patients receiving ART.