Adverse drug reactions to chloroquine/hydroxychloroquine in combination with azithromycin in COVID-19 in-patients: data from intensive pharmacovigilance in Morocco, 2020.

In Morocco, chloroquine/hydroxychloroquine + azithromycin have been used off-label for COVID-19 treatment. This study aimed to describe the distribution, nature and seriousness of the adverse drug reactions (ADRs) associated with the two drug combinations in COVID-19 in-patients. We conducted a prospective observational study based on intensive pharmacovigilance in national COVID-19 patients' management facilities from April 1 to June 12, 2020. Hospitalized patients treated with chloroquine/hydroxychloroquine + azithromycin and who experienced ADRs during their hospital stay were included in the study. The causality and seriousness of the ADRs were assessed using the World Health Organization-Uppsala Monitoring Centre method and the agreed criteria in the ICH guideline (E2A) respectively. A total of 237 (51.7%) and 221 (48.3%) COVID-19 in-patients treated respectively with chloroquine + azithromycin and hydroxychloroquine + azithromycin experienced 946 ADRs. Serious ADRs occurred in 54 patients (11.8%). Gastrointestinal system was most affected both in patients taking chloroquine + azithromycin (49.8%) or hydroxychloroquine + azithromycin (54.2%), followed by nervous system and psychiatric. Eye disorders were more frequent in patients receiving chloroquine + azithromycin (10.3%) than those receiving hydroxychloroquine + azithromycin (1.2%). Cardiac ADRs accounted for 6.4% and 5.1% respectively. Chloroquine + azithromycin caused more ADRs by patients than hydroxychloroquine + azithromycin (2.6 versus 1.5 ADRs/patient). Causality assessment was possible for 75.7% of the ADRs. Diabetes was identified as a risk factor for serious ADRs (ORa 3.56; IC: 95% 1.5-8.6). The off-label use of the two drug combinations in COVID-19 in-patients according to the national therapeutic protocol seems to be safe and tolerable. ADRs were mainly expected. However, precaution should be taken in using the drugs in diabetic patients to prevent the risk of serious ADRs.

Construction and analysis of a database for medication errors in a pharmacovigilance centre-the Moroccan experience.

PURPOSE: The study aimed to describe the epidemiological profile of medication errors (MEs) reported to the Moroccan Pharmacovigilance Center (MPVC), to determine factors associated with serious MEs, and to describe signals related to them. METHODS: We carried out a retrospective descriptive analysis of MEs reported to the MPVC from 2006 to 2016 and a secondary analysis of the seriousness of MEs with adverse drug reactions (ADRs). The reports were sorted by demographic profile and by ME and ADR characteristics. For signal detection, a quantitative approach was adopted, and the root cause analysis was completed. Epi info 7 software was used to perform descriptive and analytical statistics. The statistical significance level was set at p < 0.05. RESULTS: A total of 1618 ME reports were retrieved. The proportion of MEs associated with serious ADRs was 23.9%. The factors statistically associated with serious MEs were as follows: (i) the age group 16 years old and less (p < 0.001), (ii) the gender (p = 0.01), (iii) the administration and the prescription stages (p < 0.001), and (iv) the ME types related to inappropriate schedule of drug administration, drug prescribing error (p < 0.001), and incorrect drug administration dosage form (p = 0.04). Fourteen signals related to MEs were detected, for which risk minimization actions were implemented. CONCLUSION: The establishment of a ME unit within the MPVC was an opportunity to further improve the pharmacovigilance centre performance and consequently its contribution to medication safety. The lessons learned from MEs should be shared through pharmacovigilance networks and with institutions involved in medication safety for synergistic results to achieve patient safety worldwide.

Outbreak Investigation of a Multipathogen Foodborne Disease in a Training Institute in Rabat, Morocco: Case-Control Study.

BACKGROUND: On June 18, 2017, the public health service was alerted about 43 students in the training institute in Rabat who were admitted to the emergency room for acute gastroenteritis following the uptake of a meal a day before. OBJECTIVE: This study aimed to investigate the foodborne disease outbreak by confirming the outbreak, identifying the source of contamination, and recommending control measures. METHODS: We conducted a case-control study. Cases and controls were selected in a ratio of 1:1. We defined a case as any member of the training institute who attended the Ramadan buffet in the institute's restaurant and who had presented, in the weekend of June 16 to 20, 2017, symptoms of diarrhea or vomiting with at least one of the following signs: abdominal pain, fever, headache, nausea, and dizziness. A control was defined as anyone who attended the Ramadan buffet in the institute's restaurant but had not presented any symptoms from June 16 to 20, 2017. We conducted a bivariate and multivariable analysis. Stools of ill students were collected, and a food specimen was collected for bacterial testing. RESULTS: A total of 50 cases and 50 controls were selected. Among the cases, males were predominant (43/50, 86%); the median age was 21 years. A total of 47 cases sought medical care. There were no hospitalizations and no deaths. The episode was short with an estimated average incubation period of 9 hours. The epidemic curve oriented toward a common source of contamination. Among food items, briwates were strongly associated with the illness with an odd ratio of 14.23 (95% CI 5.04-40.04; P<.001). Laboratory testing of briwates showed presence of Escherichia coli O157 and Staphylococcus aureus. CONCLUSIONS: This foodborne disease outbreak was likely caused by briwates that was contaminated with S aureus and E coli. We recommended strengthening hygiene measures. Food handling techniques should be taught as part of continuous professional development for food handlers.

Evaluation of the Yield of Histopathology in the Diagnosis of Lymph Node Tuberculosis in Morocco, 2017: Cross-Sectional Study.

BACKGROUND: The frequency of occurrence of extrapulmonary tuberculosis (EPTB) has been increasing globally over the last two decades. In Morocco, EPTB cases account for 46% of the patients reported with a new episode of tuberculosis (TB). Lymph node TB (LNTB) is the most common form of EPTB. In line with the guidelines of the National TB Program, the diagnosis is mainly based on clinical evidence, including histopathology. OBJECTIVE: This study aimed to evaluate the yield of histopathology testing in the diagnosis of LNTB. METHODS: This cross-sectional, prospective study was conducted among patients with cervical lymph node who were enrolled in the study from November 2016 to May 2017 in three regions of Morocco. We compared the outcomes of histopathological testing with those of bacteriology. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of histopathology testing were calculated. Culture and Xpert tests were used as the gold standard Laboratoty Testing. RESULTS: A total of 262 patients were enrolled in this study. The Se, Sp, PPV, and NPV of histopathology testing were 95.6% (129/135), 64.6% (82/127), 74.1% (129/174), and 93.2% (82/88), respectively, in the presence of granuloma with or without caseous necrosis and were 84.4% (114/135), 74.8% (95/127), 78.1% (114/146), and 81.9% (95/116), respectively, in the presence of granuloma with caseous necrosis. The granuloma with caseous necrosis was associated with increased PPV and Sp of histopathology testing (P<.05). CONCLUSIONS: The presence of the granuloma with caseous necrosis in the histopathological examination had significantly improved the yield of histopathology testing for the diagnosis of LNTB. The findings recommend to maintain histopathology testing in establishing the LNTB diagnosis and to explore other techniques to improve it.

Prevalence of uncontrolled blood pressure in Meknes, Morocco, and its associated risk factors in 2017.

BACKGROUND: Uncontrolled high blood pressure (UBP) can lead to various cardiovascular complications causing an estimated nine million deaths per year worldwide. In Meknes, epidemiologic data on UBP are scarce, depriving programs from evidence-based information that would allow a better management of hypertension. Hence, we aimed to assess UBP prevalence in hypertensive patients treated in Meknes and identify UBP-associated risk factors. METHODS: Between November and December 2017, we conducted a cross-sectional study enrolling 922 hypertensive patients managed at Meknes's primary health care facilities using the multistage sampling method. We interviewed patients face to face to collect their socio-demographic-characteristics, lifestyle behaviours, clinical parameters and the triad care system-patient-physician. Another questionnaire was self-administered by physicians to characterize therapeutic inertia. A multivariate logistic regression analysis highlighted the risk factors associated with UBP. RESULTS: UBP prevalence was 73% with a mean age of 61±11 years (mean±standard deviation) and a male/female ratio of 1/3. Risk factors associated with UBP were: therapeutic inertia (adjusted odds ratio to other variables (AOR) = 18.2, 95% CI [8.35-39.84]), drug non-adherence (AOR = 1.8, 95% CI [1.07-3.04]), obesity/overweight (AOR = 1.6, 95% CI [1.03-2.58]), unemployment (AOR = 1.9, 95% CI [1.09-3.01]), low income (AOR = 2.6, 95% CI [1.01-6.86]), family history of hypertension (AOR = 1.5, 95% CI [1.07-2.08]) and male sex (AOR = 1.6, 95% CI [1.04-2.58]). CONCLUSION: UBP prevalence is high in Meknes. Prevention should firstly focus on raised awareness of hypertensive patients' self-care management. Secondly, health professionals should better comply to the guidelines of anti-hypertensive treatments. Lastly, health professionals should frequently be reminded to reach therapeutic goals to overcome therapeutic inertia.

Innovative Approaches to Improve Public Health Practice in the Eastern Mediterranean Region: Findings From the Sixth Eastern Mediterranean Public Health Network Regional Conference.

Public health professionals in the Eastern Mediterranean region (EMR) have limited access to continuing education, including workshops and conferences in public health. Held under the theme Innovative Approaches: Adapting to the Current EMR Context, the Eastern Mediterranean Public Health Network (EMPHNET) organized and conducted the Sixth EMPHNET Regional Conference from March 26 to 29, 2018. This paper summarizes the key activities including workshops, roundtable discussions, oral and poster presentations, keynote speeches, and side meetings. Before the opening, 5 preconference workshops were held: "Field Epidemiology Training Program (FETP) Accreditation," "Innovative Public Health Surveillance," "Human and Animal Brucellosis," "Rapid Response Teams," and "Polio Transition and Routine Immunization." The conference hosted 6 roundtable discussions: "Consolidation of the FETP Network," "One Health to Achieve Global Health Security," "Polio Eradication Efforts and Transition Planning for Measles Elimination," "Mobile Data Collection and Other Innovative Tools to Enhance Decision Making," "Confronting Candida auris: An Emerging Multidrug-resistant Global Pathogen," and "Functioning and Sustainable Country Public Health Emergency Response Operation Framework." One of the conference's key objectives was to provide a space for FETP residents, graduates, and public health professionals to showcase achievements. A total of 421 abstracts were submitted and after professional review, 34.9% (147/421) were accepted (111 for oral presentations and 36 for poster presentations) and published by Iproceeding. The conference met the primary objectives of showcasing the public health accomplishments and contributions of the EMR, encouraging the exchange of ideas and coordination among stakeholders, and engaging cross-sectoral workforce in producing recommendations for approaching regional and global health concerns. Moreover, the conference presented a unique opportunity for FETPs and other public health professionals from the Mediterranean region to present their significant scientific work and also facilitated networking among professionals. EMPHNET strives to continue to present similar exchange opportunities for public health professionals in the region.

Assessment of a new instrument for detecting preventable adverse drug reactions.

BACKGROUND: Pharmacovigilance centres (PVCs) in the World Health Organization (WHO) Programme for International Drug Monitoring have demonstrated their ability to detect preventable adverse drug reactions (ADRs) in their databases. In this field, there is no gold-standard method for detecting medication errors and evaluating ADR preventability. Therefore, we developed, from existing tools, a preventability assessment method: the 'P Method' (PM). OBJECTIVE: To present the PM and to evaluate its inter-rater reliability. METHODS: The PM includes 20 explicit criteria for assessing ADR preventability. This approach is based on identification of any potentially preventable risk factor that increases the likelihood of ADR occurrence. The outcome of the preventability assessment results in one of three possible scores: 'preventable', 'non-preventable' or 'not assessable'. The PM was tested in a multicentre study involving nine national PVCs. Two experienced reviewers at each participating PVC independently analysed the preventability of 183 ADRs, applying the PM. RESULTS: The overall agreement between all reviewers for assessment of ADR preventability was 'fair', with a kappa value of 0.27 [95 % confidence interval (CI) 0.21-0.40]. The level of agreement between reviewer pairs ranged from 'slight', with a kappa value of 0.12 (95 % CI -0.03 to 0.27), to 'substantial', with a kappa value of 0.69 (95 % CI 0.48-0.89). CONCLUSION: The analysis of the agreements and disagreements between reviewers highlighted where improvements might be made. Given that no standard assessment tool exists in the WHO Programme, the transparency of the assessment process in this method provides a substantial basis for further development and for support in signalling possible preventability.

[Peganum harmala L. poisoning in Morocco: about 200 cases]. / L'intoxication au Peganum harmala L. au Maroc : à propos de 200 cas.

AIM OF THE STUDY: Peganum harmala L. is commonly used in traditional medicine in Morocco for its sedative and emmenagogue properties but expose to the risk of overdose and poisoning. The aim of our study was to analyze a series of 200 cases of poisoning collected in poison control and pharmacovigilance center of Morocco in order to describe the epidemiological, clinical, therapeutic features and outcome of patients and indicate the toxicity of this plant used primarily for therapeutic purposes. METHODS: This retrospective study performed over a period of twenty four years from January 1984 to December 2008. RESULTS: The mean age of patients was 24.4±16.8 years with a female predominance (167 women against 33 men). Therapeutic circumstance was found in 32.5%, followed by suicide (28.5%) and abortion (13.5%). The symptomatology was dominated by neurological, gastrointestinal and cardiovascular signs respectively 34.4%, 31.9 % and 15.8%. The evolution has been specified in 114 cases, 7 deaths have been deplored with a fatality rate of 6.2%.

[Pesticide poisoning in Moroccan children: epidemiological and prognostic aspects (1990-2008)]. / L'intoxication par les pesticides chez l'enfant au Maroc : profil épidémiologique et aspects pronostiques (1990-2008).

OBJECTIVE: The purpose of this paper is to describe the epidemiological profile of acute pesticide poisoning in children (APP) treated by the Moroccan Poison Control Center (CAPM) and to analyze death cases in order to determine factors predictive of severity. METHOD: the study is based on a retrospective study of all cases of APP collected by the CAPM over a period of eighteen years (January 1990 to December 2008). Univariate analysis was performed to identify risk factors. RESULTS: 2,672 cases of childhood poisoning by pesticide were collected. The mean age was 5.6 ± 4.57 years. The sex ratio was 1.12. The cause of poisoning was accidental in 87.1% of cases, followed by attempted suicide (12.1%). Organophosphates were the most frequent poison (50.7%), followed by alpha-chloralose (26.5%). The case fatality rate was 3.3%. Mortality was attributed to organophosphates in 30 cases, followed by inorganic derivatives (7 cases) and carbamates (6 cases). A univariate analysis comparing survivors and groups who died showed that rural origin (p = 0.04), voluntary circumstances (p = 0.001), and the type of chemical class of pesticide (p < 0.001) significantly influence fatal poisoning. CONCLUSION: Acute pesticide poisoning among children is a reality in Morocco. Preventive measures may be needed.

Classification of clinical consequences of scorpion stings: consensus development.

The objective of our consensus process was to develop a unique classification of the natural history of scorpion stings and their clinical signs and symptoms. The technique used was an adapted Delphi approach completed by a nominal group meeting. Researchers included in a study received a questionnaire in which we listed all terms used in published studies to characterize clinical consequences of scorpion stings and all signs and symptoms belonging to each class. For each term, experts had to judge the relevance for classifying clinical consequences of scorpion stings and state whether they agreed with the terminology; they could also propose new terms or classes. For each sign or symptom, they had to choose in which class it belonged and also propose if any other sign or symptom should be added. Sixteen researchers participated. Consensus was reached to include four classes: local manifestations; minor systemic manifestations; major systemic manifestations; lethal envenomation. Signs and symptoms associated with each class were defined. A second Delphi round is planned to define indicators to follow the epidemiological situation within and across countries and to develop recommendations for an optimal management of scorpion envenomations. These consensus-based tools should facilitate development of international clinical studies.

The involvement of Pharmacovigilance Centres in medication errors detection: a questionnaire-based analysis.

OBJECTIVES: This study assesses the ability of Pharmacovigilance Centres (PVCs) to detect medication errors (ME) and to proceed to building Patient Safety (PS) via their information networks and to underline the limits for this challenge. METHODS: This was an exploratory study conducted in PVCs members of the World Health Organization International Drug Monitoring network. A questionnaire specifically designed for the needs of the study was sent to a network via a confidential email system. The questionnaire asked for information, progress and improvement made by PVCs in PS and ME. RESULTS: Among the 88 countries, 21 answered. Reporting of Adverse Drug Reactions (ADRs) by health care professionals (HCP) is mandatory for 42% of PVCs. 100% of countries receive reports from HCP, 66% from patients and 24% from PCCs. ADRs reports are received by all communications means. There is an heterogeneity between countries regarding PVCs and PS activities. Among them, 4 PVCs have the prime activity of PS organization. CONCLUSION: PVCs are able to detect and analyze ME. There is a need to coordinate efforts between countries to optimize ME detection, and its analysis. Bridges need to be built linking PVCs, PCCs and PS organizations in order to avoid duplication of workload.

[Reactive airways dysfunction syndrome (Brooks syndrome)]. / Syndrome de dysfonctionnement réactif des voies aériennes (syndrome de Brooks).

INTRODUCTION: Although the existence of classical occupational asthma is well known and described after fairly prolonged exposure to moderate levels of air-contaminators, authentic asthma can be provoked by rapid single inhalation of a high dosed corrosive gas: this is Brooks' syndrome. OBSERVATION: A 30 year-old woman, without respiratory past history and no atopy presented with post-toxic asthma following a single accidental inhalation of hydrochloric acid. The diagnosis was established on the 8 criteria of Brooks and the clinical outcome remained stable with, however, excellent response to the inhalation of broncho-dilatators during asthma attacks. COMMENTS: The relationship with the accidental inhalation may have been ignored by the victim. The outcome of this syndrome is good in 50% of cases; in 25% the symptomatology worsens and in the remaining 25% it remains stable.