Awareness, knowledge, and attitude toward adverse drug reaction (ADR) reporting among healthcare professionals in Ghana.

Background: Spontaneous reporting systems are the commonest means of reporting adverse drug reactions (ADRs) worldwide. Under-reporting remains a challenge particularly in developing countries among healthcare professionals (HCPs) who are considered the primary stakeholders in the reporting of ADRs. The challenge with studies in countries such as Ghana is that the focus has been on a single professional group or health facility. This study examines the rate of reporting as well as awareness, knowledge, and attitudes toward ADR reporting across professional groups (doctors, nurses, and pharmacist) and selected health facilities (ownership types: government, quasi-government, and private; hierarchy: district, regional, and teaching) in Ghana. Method: A cross-sectional survey was conducted to select and interview 424 healthcare professionals (HCPs) from 8 hospitals in the Greater Accra and Eastern regions of Ghana on issues of ADR reporting, awareness, knowledge, and attitudes toward ADR reporting. Valid responses from 378 HCPs were obtained and analyzed using frequencies and percentages. Findings: The results suggest that about 82.8% of the HCPs interviewed have come across an ADR incidence, but only 52.6% of them have reported such incidence, with pharmacist (66.7%) being the most likely to report. The results further suggest that about 85.8% of HCPs are aware of ADR reporting procedures and display positive attitudes toward same. In addition, the knowledge of HCPs on ADR reporting is low with training being a major area of need. Conclusion: There is the need for healthcare managers and the regulator to pay attention to existing gaps in awareness, attitudes, and most importantly knowledge of HCPs on structures and modalities for ADR reporting. Plain Language Summary: Awareness, knowledge, and attitude toward adverse drug reaction (ADR) reporting among healthcare professionals in Ghana Reporting of unpleasant reactions related to the use of medicinal products has been very low in less developed countries. Studies conducted in Ghana to examine the reporting of unpleasant reactions associated with the use of medicinal products have focused mainly on one health facility or health care provider group. This article examines the level of awareness, knowledge, and attitudes toward the reporting of unpleasant reactions to the use of medicinal products.The authors used a quantitative method to examine the level of awareness, knowledge, and attitude toward reporting of unpleasant reactions to medicinal products. The study was conducted in eight hospitals in Greater Accra and Eastern regions of Ghana using a structured questionnaire. Only 378 out of 424 healthcare providers returned the completed questionnaire.The findings of the study show that 213 of the healthcare providers have encountered at least one patient with an unpleasant reaction to the use of medicinal products, although only 112 reported the unpleasant reactions. Pharmacists were found to be more likely to report unpleasant reactions as 12 out of 18 pharmacists who responded to the questionnaire indicated that they report the unpleasant reactions seen.In addition, 321 of the healthcare providers knew of the reporting procedures for unpleasant reactions to a medicinal product in Ghana. Only 219 healthcare providers knew of the reporting procedures in the facilities in which they worked, however. Furthermore, the knowledge of healthcare providers on the method of reporting is low.

Corrigendum to "Prenatal household air pollutant exposure is associated with reduced size and gestational age at birth among a cohort of Ghanaian infants" [Environ. Int. 155 (2021) 106659].

[This corrects the article PMC8628363.].

Prenatal Household Air Pollution Exposure, Cord Blood Mononuclear Cell Telomere Length and Age Four Blood Pressure: Evidence from a Ghanaian Pregnancy Cohort.

Associations between prenatal household air pollution exposure (HAP), newborn telomere length and early childhood blood pressure are unknown. Methods: Pregnant women were randomized to liquefied petroleum gas (LPG) stove, improved biomass stove or control (traditional, open fire cook stove). HAP was measured by personal carbon monoxide (CO) (n = 97) and fine particulate matter (PM2.5) (n = 60). At birth, cord blood mononuclear cells (CBMCs) were collected for telomere length (TL) analyses. At child age four years, we measured resting blood pressure (BP) (n = 97). We employed multivariable linear regression to determine associations between prenatal HAP and cookstove arm and assessed CBMC relative to TL separately. We then examined associations between CBMC TL and resting BP. Results: Higher prenatal PM2.5 exposure was associated with reduced TL (ß = -4.9% (95% CI -8.6, -0.4), p = 0.03, per 10 ug/m3 increase in PM2.5). Infants born to mothers randomized to the LPG cookstove had longer TL (ß = 55.3% (95% CI 16.2, 109.6), p < 0.01)) compared with control. In all children, shorter TL was associated with higher systolic BP (SBP) (ß = 0.35 mmHg (95% CI 0.001, 0.71), p = 0.05, per 10% decrease in TL). Increased prenatal HAP exposure is associated with shorter TL at birth. Shorter TL at birth is associated with higher age four BP, suggesting that TL at birth may be a biomarker of HAP-associated disease risk.

Prenatal and Postnatal Household Air Pollution Exposures and Pneumonia Risk: Evidence From the Ghana Randomized Air Pollution and Health Study.

BACKGROUND: Nearly 40% of the world's population is exposed daily to household air pollution. The relative impact of prenatal and postnatal household air pollution exposure on early childhood pneumonia, a leading cause of mortality, is unknown. RESEARCH QUESTION: Are prenatal or postnatal household air pollution, or both, associated with pneumonia risk in the first year of life? STUDY DESIGN AND METHODS: The Ghana Randomized Air Pollution and Health Study enrolled 1,414 nonsmoking, pregnant women before 24 weeks' gestation with prospective follow-up to the child's age of 1 year. We measured 72-h personal household air pollution exposures, indexed by carbon monoxide (CO), four times prenatally and three times postnatally. Weekly fieldworker surveillance identified ill-appearing children for physician pneumonia assessment. We used quasi-Poisson models to examine associations between prenatal and postnatal CO and physician-diagnosed pneumonia and severe pneumonia. Sex-specific effects were examined. RESULTS: Of the 1,306 live births, 1,141 infants were followed up with 55,605 child-weeks of fieldworker surveillance. The estimated risk for pneumonia and severe pneumonia in the first year of life increased by 10% (relative risk [RR], 1.10; 95% CI, 1.04-1.16) and 15% (RR, 1.15; 95% CI, 1.03-1.28), respectively, per 1-part per million (ppm) increase in average prenatal CO exposure and by 6% (RR, 1.06; 95% CI, 0.99-1.13) per 1-ppm increase in average postnatal CO exposure. Sex-stratified analyses suggest that in girls, higher prenatal CO exposure was associated with pneumonia risk, while no association was seen in boys. INTERPRETATION: Prenatal household air pollution exposure increased risk of pneumonia and severe pneumonia in the first year of life. Clean-burning interventions may be most effective when begun prenatally. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01335490; URL: www.clinicaltrials.gov.

Prenatal household air pollutant exposure is associated with reduced size and gestational age at birth among a cohort of Ghanaian infants.

BACKGROUND: Low birth weight and prematurity are important risk factors for death and disability, and may be affected by prenatal exposure to household air pollution (HAP). METHODS: We investigate associations between maternal exposure to carbon monoxide (CO) during pregnancy and birth outcomes (birth weight, birth length, head circumference, gestational age, low birth weight, small for gestational age, and preterm birth) among 1288 live-born infants in the Ghana Randomized Air Pollution and Health Study (GRAPHS). We evaluate whether evidence of malaria during pregnancy, as determined by placental histopathology, modifies these associations. RESULTS: We observed effects of CO on birth weight, birth length, and gestational age that were modified by placental malarial status. Among infants from pregnancies without evidence of placental malaria, each 1 ppm increase in CO was associated with reduced birth weight (-53.4 g [95% CI: -84.8, -21.9 g]), birth length (-0.3 cm [-0.6, -0.1 cm]), gestational age (-1.0 days [-1.8, -0.2 days]), and weight-for-age Z score (-0.08 standard deviations [-0.16, -0.01 standard deviations]). These associations were not observed in pregnancies with evidence of placental malaria. Each 1 ppm increase in maternal exposure to CO was associated with elevated odds of low birth weight (LBW, OR 1.14 [0.97, 1.33]) and small for gestational age (SGA, OR 1.14 [0.98, 1.32]) among all infants. CONCLUSIONS: Even modest reductions in exposure to HAP among pregnant women could yield substantial public health benefits, underscoring a need for interventions to effectively reduce exposure. Adverse associations with HAP were discernible only among those without evidence of placental malaria, a key driver of impaired fetal growth in this malaria-endemic area.

Examining the relationship between household air pollution and infant microbial nasal carriage in a Ghanaian cohort.

BACKGROUND: Pneumonia, a leading cause of childhood mortality, is associated with household air pollution (HAP) exposure. Mechanisms between HAP and pneumonia are poorly understood, but studies suggest that HAP may increase the likelihood of bacterial, instead of viral, pneumonia. We assessed the relationship between HAP and infant microbial nasal carriage among 260 infants participating in the Ghana Randomized Air Pollution and Health Study (GRAPHS). METHODS: Data are from GRAPHS, a cluster-randomized controlled trial of cookstove interventions (improved biomass or LPG) versus the 3-stone (baseline) cookstove. Infants were surveyed for pneumonia during the first year of life and had routine personal exposure assessments. Nasopharyngeal swabs collected from pneumonia cases (n = 130) and healthy controls (n = 130) were analyzed for presence of 22 common respiratory microbes by MassTag polymerase chain reaction. Data analyses included intention-to-treat (ITT) comparisons of microbial species presence by study arm, and exposure-response relationships. RESULTS: In ITT analyses, 3-stone arm participants had a higher mean number of microbial species than the LPG (LPG: 2.71, 3-stone: 3.34, p < 0.0001, n = 260). This difference was driven by increased bacterial (p < 0.0001) rather than viral species presence (non-significant). Results were pronounced in pneumonia cases and attenuated in healthy controls. Higher prevalence bacterial species were Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Exposure-response relationships did not yield significant associations between measured CO and nasal microbial carriage. CONCLUSIONS: Our intention-to-treat findings are consistent with a link between HAP and bacterial nasal carriage. No relationships were found for viral carriage. Given the null results in exposure-response analysis, it is likely that a pollutant besides CO is driving these differences.

Prenatal Household Air Pollution Is Associated with Impaired Infant Lung Function with Sex-Specific Effects. Evidence from GRAPHS, a Cluster Randomized Cookstove Intervention Trial.

RATIONALE: Approximately 2.8 billion people are exposed daily to household air pollution from polluting cookstoves. The effects of prenatal household air pollution on lung development are unknown. OBJECTIVES: To prospectively examine associations between prenatal household air pollution and infant lung function and pneumonia in rural Ghana. METHODS: Prenatal household air pollution exposure was indexed by serial maternal carbon monoxide personal exposure measurements. Using linear regression, we examined associations between average prenatal carbon monoxide and infant lung function at age 30 days, first in the entire cohort (n = 384) and then stratified by sex. Quasi-Poisson generalized additive models explored associations between infant lung function and pneumonia. MEASUREMENTS AND MAIN RESULTS: Multivariable linear regression models showed that average prenatal carbon monoxide exposure was associated with reduced time to peak tidal expiratory flow to expiratory time (ß = -0.004; P = 0.01), increased respiratory rate (ß = 0.28; P = 0.01), and increased minute ventilation (ß = 7.21; P = 0.05), considered separately, per 1 ppm increase in average prenatal carbon monoxide. Sex-stratified analyses suggested that girls were particularly vulnerable (time to peak tidal expiratory flow to expiratory time: ß = -0.003, P = 0.05; respiratory rate: ß = 0.36, P = 0.01; minute ventilation: ß = 11.25, P = 0.01; passive respiratory compliance normalized for body weight: ß = 0.005, P = 0.01). Increased respiratory rate at age 30 days was associated with increased risk for physician-assessed pneumonia (relative risk, 1.02; 95% confidence interval, 1.00-1.04) and severe pneumonia (relative risk, 1.04; 95% confidence interval, 1.00-1.08) in the first year of life. CONCLUSIONS: Increased prenatal household air pollution exposure is associated with impaired infant lung function. Altered infant lung function may increase risk for pneumonia in the first year of life. These findings have implications for future respiratory health. Clinical trial registered with www.clinicaltrials.gov (NCT 01335490).

Post-licensure safety evaluation of dihydroartemisinin piperaquine in the three major ecological zones across Ghana.

BACKGROUND: Uncommon and rare adverse events (AEs), with delayed onset may not be detected before new drugs are licensed and deployed. The present study examined the post licensure safety of dihydroartemisinin-piperaquine (DHP) as an additional treatment for malaria in Ghana. The relationship between the incidence of AEs, treatment completion rate, participant characteristics and concomitant medications are reported. METHODS: A study conducted from September 2013 to June 2014 in Navrongo, Kintampo and Dodowa health research centres in Ghana is presented. Participants had confirmed malaria and no known allergy to study drug. Patients provided informed consent and had their symptoms and results of their clinical examinations documented. Treatment with Eurartesim® (20/160mg dihydroartemisinin and 40/320mg piperaquine by Sigma-Tau Incorporated) was given, according to the body weight of patients. First treatment doses were under observation but the second and third doses were taken at home except in a sub-study involving a nested cohort. Patients were contacted at Day 5 (± 2 days) either on telephone or by a home visit to document any AEs experienced. Patients were asked to report to the study team any other AEs that occurred within 28 days post-treatment. All patients in the nested cohort had electrocardiogram (ECG). FINDINGS: A total of 4563 patients, 52.1% females and 48.2% <6 years completed the study. A total of 444 patients were enrolled into the nested cohort. About 33% had temperature ≥ 37.5°C at enrolment. Approximately 3.4% reported taking prior antimalarials, 19.4% other medications and 86% took at least one concomitant medication. Incidence of AEs was 7.6% including infections (4.6%), gastrointestinal disorders (1.0%) and local reactions at the site of venesection (0.5%). Others were respiratory disorders (0.4%) and nervous system disorders (0.3%). There were nine adverse events of special interest (AESI); itching/pruritus (7), dizziness (1), and skin lesions (1). Patients who took medications prior to enrolment had higher incidence of AEs compared with those without (9.3% vs. 6.1%; P<0.001). Statistically significant associations were found between the reported AEs and age of patients (P<0.001), their body mass index (BMI) (P< 0.001) and parasite densities (P< 0.001). CONCLUSION: Dihydroartemisinin-Piperaquine was well tolerated with no serious safety concerns identified. Obesity and prior enrolment medication were among significant factors associated with increased AEs reporting.

Multi-Country Evaluation of Safety of Dihydroartemisinin/Piperaquine Post-Licensure in African Public Hospitals with Electrocardiograms.

The antimalarial drug piperaquine is associated with delayed ventricular depolarization, causing prolonged QT interval (time taken for ventricular de-polarisation and re-polarisation). There is a lack of safety data regarding dihydroartemisinin/piperaquine (DHA/PPQ) for the treatment of uncomplicated malaria, which has limited its use. We created a platform where electrocardiograms (ECG) were performed in public hospitals for the safety assessment of DHA/PPQ, at baseline before the use of dihydroartemisinin/piperaquine (Eurartesim®), and on day 3 (before and after administration of the final dose) and day 7 post-administration. Laboratory analyses included haematology and clinical chemistry. The main objective of the ECG assessment in this study was to evaluate the effect of administration of DHA/PPQ on QTc intervals and the association of QTc intervals with changes in blood biochemistry, full and differential blood count over time after the DHA/PPQ administration. A total of 1315 patients gave consent and were enrolled of which 1147 (87%) had complete information for analyses. Of the enrolled patients 488 (42%), 323 (28%), 213 (19%) and 123 (11%) were from Ghana, Burkina Faso, Tanzania and Mozambique, respectively. Median (lower-upper quartile) age was 8 (5-14) years and a quarter of the patients were children under five years of age (n = 287). Changes in blood biochemistry, full and differential blood count were temporal which remained within clinical thresholds and did not require any intervention. The mean QTcF values were significantly higher than on day 1 when measured on day 3 before and after administration of the treatment as well as on day 7, four days after completion of treatment (12, 22 and 4 higher, p < 0.001). In all age groups the values of QT, QTcF and QTcB were highest on day 3 after drug intake. The mean extreme QTcF prolongation from baseline was lowest on day 3 before drug intake (33 ms, SD = 19) and highest on day 3 after the last dose (60 ms, SD = 31). There were 79 (7%) events of extreme mean QTcF prolongation which were not clinically significant. Nearly a half of them (n = 37) were grade 3 and mainly among males (33/37). Patients in Burkina Faso, Mozambique and Tanzania had significantly lower mean QTcF than patients in Ghana by an average of 3, 4 and 11 ms, respectively. We found no evidence that Eurartesim® administered in therapeutic doses in patients with uncomplicated malaria and no predisposing cardiac conditions in Africa was associated with adverse clinically significant QTc prolongation.

Ghana randomized air pollution and health study (GRAPHS): study protocol for a randomized controlled trial.

BACKGROUND: Household air pollution exposure is a major health risk, but validated interventions remain elusive. METHODS/DESIGN: The Ghana Randomized Air Pollution and Health Study (GRAPHS) is a cluster-randomized trial that evaluates the efficacy of clean fuels (liquefied petroleum gas, or LPG) and efficient biomass cookstoves in the Brong-Ahafo region of central Ghana. We recruit pregnant women into LPG, efficient cookstove, and control arms and track birth weight and physician-assessed severe pneumonia incidence in the first year of life. A woman is eligible to participate if she is in the first or second trimester of pregnancy and carrying a live singleton fetus, if she is the primary cook, and if she does not smoke. We hypothesize that babies born to intervention mothers will weigh more and will have fewer cases of physician-assessed severe pneumonia in the first year of life. Additionally, an extensive personal air pollution exposure monitoring effort opens the way for exposure-response analyses, which we will present alongside intention-to-treat analyses. Major funding was provided by the National Institute of Environmental Health Sciences, The Thrasher Research Fund, and the Global Alliance for Clean Cookstoves. DISCUSSION: Household air pollution exposure is a major health risk that requires well-tested interventions. GRAPHS will provide important new evidence on the efficacy of both efficient biomass cookstoves and LPG, and will thus help inform health and energy policies in developing countries. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov on 13 April 2011 with the identifier NCT01335490 .

Prospective observational study to evaluate the clinical safety of the fixed-dose artemisinin-based combination Eurartesim® (dihydroartemisinin/piperaquine), in public health facilities in Burkina Faso, Mozambique, Ghana, and Tanzania.

BACKGROUND: The World Health Organization recommends artemisinin-based combination (ACT) for the treatment of uncomplicated malaria. Post-licensure safety data on newly registered ACT is critical for evaluating their risk/benefit profile in malaria endemic countries. The clinical safety of the newly registered combination, Eurartesim®, following its introduction into the public health system in four African countries was assessed. METHODS: This was a prospective, observational, open-label, non-comparative, longitudinal, multi-centre study using cohort event monitoring. Patients with confirmed malaria had their first dose observed and instructed on how to take the second and the third doses at home. Patients were contacted on day 5 ± 2 to assess adherence and adverse events (AEs). Spontaneous reporting of AEs was continued till day 28. A nested cohort who completed full treatment course had repeated electrocardiogram (ECG) measurements to assess effect on QTc interval. RESULTS: A total of 10,925 uncomplicated malaria patients were treated with Eurartesim®. Most patients,95% (10,359/10,925), did not report any adverse event following at least one dose of Eurartesim®. A total of 797 adverse events were reported. The most frequently reported, by system organ classification, were infections and infestations (3. 24%) and gastrointestinal disorders (1. 37%). In the nested cohort, no patient had QTcF > 500 ms prior to day 3 pre-dose 3. Three patients had QTcF > 500 ms (509 ms, 501 ms, 538 ms) three to four hours after intake of the last dose. All the QTcF values in the three patients had returned to <500 ms at the next scheduled ECG on day 7 (470 ms, 442 ms, 411 ms). On day 3 pre- and post-dose 3, 70 and 89 patients, respectively, had a QTcF increase of ≥ 60 ms compared to their baseline, but returned to nearly baseline values on day 7. CONCLUSION: Eurartesim® single course treatment for uncomplicated falciparum malaria is well-tolerated. QT interval prolongation above 500 ms may occur at a rate of three per 1,002 patients after the third dose with no association of any clinical symptoms. QT interval prolongation above 60 ms was detected in less than 10% of the patients without any clinical abnormalities.

Prospective observational study to evaluate the clinical safety of the fixed-dose artemisinin-based combination Eurartesim® (dihydroartemisinin/piperaquine), in public health facilities in Burkina Faso, Mozambique, Ghana, and Tanzania

Background: The World Health Organization recommends artemisinin-based combination (ACT) for the treatment of uncomplicated malaria. Post-licensure safety data on newly registered ACT is critical for evaluating their risk/benefit profile in malaria endemic countries. The clinical safety of the newly registered combination, Eartesim®, following its introduction into the public health system in four African countries was assessed. Methods: This was a prospective, observational, open-label, non-comparative, longitudinal, multi-centre study using cohort event monitoring. Patients with confirmed malaria had their first dose observed and instructed on how to take the second and the third doses at home. Patients were contacted on day 5 ± 2 to assess adherence and adverse events (AEs). Spontaneous reporting of AEs was continued till day 28. A nested cohort who completed full treatment course had repeated electrocardiogram (ECG) measurements to assess effect on QTc interval. Results: A total of 10,925 uncomplicated malaria patients were treated with Eurartesim®. Most patients,95% (10,359/10,925), did not report any adverse event following at least one dose of Eurartesim®. A total of 797 adverse events were reported. The most frequently reported, by system organ classification, were infections and infestations (3. 24%) and gastrointestinal disorders (1. 37%). In the nested cohort, no patient had QTcF > 500 ms prior to day 3 pre-dose 3. Three patients had QTcF > 500 ms (509 ms, 501 ms, 538 ms) three to four hours after intake of the last dose. All the QTcF values in the three patients had returned to <500 ms at the next scheduled ECG on day 7 (470 ms, 442 ms, 411 ms). On day 3 pre- and post-dose 3, 70 and 89 patients, respectively, had a QTcF increase of ≥ 60 ms compared to their baseline, but returned to nearly baseline values on day 7. Conclusion: Eurartesim® single course treatment for uncomplicated falciparum malaria is well-tolerated. QT interval prolongation above 500 ms may occur at a rate of three per 1,002 patients after the third dose with no association of any clinical symptoms. QT interval prolongation above 60 ms was detected in less than 10% of the patients without any clinical abnormalities.