Neuromuscular Junction Defects in a Mouse Model of Charcot-Marie-Tooth Disease Type 2O

Charcot Marie Tooth disease (CMT) represents the most common inheritable peripheral group of motor and sensory disorders; affecting 1 in 2500 people worldwide. Individuals with CMT experience slow progressing weakness of the muscle, atrophy, mild loss of motor coordination and in some cases loss of sensory function in the hands and feet which could ultimately affect mobility. Dynein is an essential molecular motor that functions to transport cargos in all cells. A point mutation in the dynein heavy chain was discovered to cause CMT disease in humans, specifically CMT type 2O. We generated a knock-in mouse model bearing the same mutation(H304R) in the dynein heavy chain to study the disease. We utilized behavioral assays to determine whether our mutant mice had a phenotype linked to CMT disease. The mutant mice had motor coordination defects and reduced muscle strength compared to normal mice. To better understand the disease pathway, we obtained homozygous mutants from a heterozygous cross, and the homozygotes show even more severe deficits compared to heterozygotes. They also developed an abnormal gait which separates them from heterozygous mice. In view of the locomotor deficits observed in mutants, we examined the neuromuscular junction (NMJ) for possible impairments. We identified defects in innervation at the later stages of the study and abnormal NMJ architecture in the muscle as well. The dysmorphology of the NMJ was again worse in the homozygous mutants with reduced complexity and denervation at all the timepoints assessed. Our homozygous dynein mutants can live up to two years and therefore make the design of longitudinal studies possible. Altogether, this mouse model provides dynein researchers an opportunity to work towards establishing the link between dynein mutations, dynein dysfunction and the onset and progression of disease

Sex differences on the acute effects of caffeine on maximal strength and muscular endurance

This document is the Accepted Manuscript version. The original publication is available at https://doi.org/10.3920/CEP150010.The aim of this study was to look at the effects of caffeine on strength performance and to examine any differences between sexes. Sixteen moderately active, resistance-trained individuals (10 males and 8 females) performed 2 trials (excluding a familiarisation trial). The effect of 5 mg/kg body mass (BM) caffeine or a placebo on bench press (BP) one repetition maximum (1RM), squat 1RM, the number of BP reps to failure at 40% 1RM (total weight lifted; TWL), pain rating (0-10) were recorded after each final successful lift. BP 1RM was significantly greater (P=0.016), with an increase of 5.91% for males and an increase of 10.69% for females. However, there was no sex difference in squat 1RM with males producing 130.3±27.8 and 134.0±28.9 kg and females producing 66.9±6.2 and 65.3±7.0 kg for placebo and caffeine, respectively. TWL tended to increase with caffeine for males from 1,246.8±704.9 to 1,545.5±920.3 kg; with females having no effect of caffeine (397.8±245.1 to 398.8±182.7kg; P=0.06). Caffeine had no effect on pain perception. This study found that 5 mg/kg BM caffeine improved BP 1RM in resistance-trained males and females. However, for TWL there was a tendency towards improvement in males only, suggesting a sex difference to caffeine ingestion for TWL.Peer reviewedFinal Accepted Versio

Exploring animation as a medium for running political commentary; An analysis of “Rule of thumb”

Ghana as a country is run by a democratic system of governance. This system has seen the election of 5 presidents. Despite the adoption of this system of governance since 1992, the rate of Ghana’s growth does not entirely mirror developmental traits of a democratic state. As an artist and storyteller within such a society, the creator of the project – “Rule of Thumb” seeks to run political commentary with animation through a story that will cater to both Ghanaians and universal audiences. The phrase “Rule of Thumb” in this project does not function as the known expression that refers to important guidelines but as a phrase coined to describe the power that a thumb may wield in some societies. As a form of strategy, research is conducted into African modes of storytelling. This research identifies folklore as a medium through which stories were told in ancient Africa by griots. Folktales in this instance serve as a useful communication tool for the animated short film's intended viewership. ‘Rule of Thumb’ seeks to mimic a folktale in terms of its structure, and its ambiguous qualities when used in critiquing a society. Drawing inspiration from George Orwell’s fable (The Animal farm), “Rule of Thumb” intends to use a folktale to critique political leaders without a direct allusion to them. The project breaks down a folktale's essential elements and conveys them via an animated movie. The film, having been produced based on additional research into specific aspects of animation like visual aesthetics, story structure, and, technique is also projected to serve as a good resource material for other filmmakers to produce films with similar themes and related ideas.Media files notes: "Rule of Thumb" animation video file Description: "Rule of Thumb" is an animated short thesis film produced in the Re:Anima European Joint Masters program

Adverse drug reaction reporting by doctors in a developing country: A case study from Ghana

Background: Spontaneous adverse drug reaction reporting is the most widely used and cost effective method of monitoring the safety of drugs. This method is heavily afflicted by underreporting by healthcare professionals. The study aims at assessing adverse drug reaction (ADR) reporting rate by doctors, knowledge of the reporting system and attitudes to SADR in the Greater Accra region.Methods: This was a cross sectional survey of 259 doctors randomly  selected from 23 hospitals classified as government 199 (76.8%), quasi-governmental 43(16.6%) and private 17 (6.6%) hospitals in the Greater Accra Region of Ghana. Data collection was by self-administered  questionnaire from May 5, 2012- July 6, 2012. Descriptive statistics was used to describe the background characteristics of the doctors and the outcome measures like training and reasons for ADR reporting were summarized as frequencies and percentages.Results: One-third (27.4%) of doctors surveyed had received previous training on drug safety monitoring and ADR reporting; training and  knowledge of the reporting system was found to improve reporting. Morethan half 154 (59.5%) of the doctors had seen a patient with suspected ADR in the past one year although only 31 (20%) had reported it by completing the SADR reporting form. Doctors working in government hospitals were about 5 times more likely to report than those in private hospitals [OR=4.94, 95%CI (1.55-15.69)].Conclusion: Training and knowledge of the ADR reporting system were found to be associated with the likelihood of reporting an ADR. Most of the doctors had not previously received training on ADR reporting.Keywords: Spontaneous reporting, adverse drug reaction, underreporting, doctors, Ghan

Patient preferences and expectation for feedback on adverse drug reaction reports submitted in Ghana

Background: Personalized feedback received for spontaneous adverse drug reaction (ADR) reports serves as motivation for future reporting and the effectiveness of the feedback is dependent on the medium used in delivering the information. Objective: Explore expectation for feedback from patients on ADR reports submitted to the National Pharmacovigilance Centre (NPvC) in Ghana and the preferred medium for receiving the feedback information. Methods: Cross-sectional study using structured questionnaire administered through face-to-face interview from August to September 2016 to patients selected by convenience sampling. Pearson chi-square (§2) or Fisher's exact test was used to determine associations between background variables such as age, gender and level of education. Results: The response rate was 86.7% (n=442). Of the participants interviewed, 96.5% expected to receive feedback for ADR reports submitted. Age and level of education were the two variables significantly associated with patients' expectation for feedback.The preferred medium for receiving feedback in decreasing order of preference were, telephone call (60.4%), mobile phone short messaging services (23.0%), email (8.3%), face-to-face meeting (3.4%), personalized letter (3.4%) and publication in a newsletter (1.4%). Conclusion: Patients' expectation for receiving feedback for ADR reports submitted to the NPvC is in line with modern trends in communication. NPvC should explore these alternatives for providing feedback to patients. This study is limited to what patients' expectations and preferences were for receiving feedback on ADR reports submitted, additional study to further explore the type of information patients expect to be contained in the feedback will be useful to National Pharmacovigilance Centres. Funding: None declared

Evaluation of pharmacovigilance systems for reporting medication errors in Africa and the role of patients using a mixed-methods approach

BACKGROUND: Reviewing the epidemiological profile of medication errors (MEs) reported by African countries and the systems put in place to report such errors is crucial because reporting plays an important role in improving patient safety. The objectives of this study were to characterize the profile of spontaneously reported MEs submitted by African countries to VigiBase; the World Health Organization (WHO) global database of individual case safety reports, describe systems in place for reporting these errors, and explore the challenges and facilitators for spontaneous reporting and understand the potential role of patients. METHODS: In the present study, we used, a mixed-methods sequential explanatory design involving a quantitative review of ME reports over a 21-year period (1997–2018) and qualitative interviews with employees from African countries that are members of the WHO Program for International Drug Monitoring (WHO PIDM). Descriptive statistics were used to summarize key variables of interest. RESULTS: A total of 4,205 ME reports were submitted by African countries to VigiBase representing 0.4% of all reports in the database. Only 15 countries out of the 37 WHO PIDM members from Africa contributed ME to reports, with 99% (3,874) of them reports originating from Egypt, Morocco, and South Africa. The reasons given for low reporting of MEs were weak healthcare and pharmacovigilance systems, lack of staff capacity at the national centers, illiteracy, language difficulties, and socio-cultural and religious beliefs. Some facilitators suggested by the participants to promote reporting included proactive engagement of patients regarding issues relating to MEs, leveraging on increased technology, benchmarking and mentoring by more experienced national centers. Sixteen of the twenty countries interviewed had systems for reporting MEs integrated into adverse drug reaction reporting with minimal patient involvement in seven of these countries. Patients were not involved in directly reporting MEs in the remaining 13 countries. CONCLUSIONS: MEs are rarely reported through pharmacovigilance systems in African countries with limited patient involvement. The systems are influenced by multifactorial issues some of which are not directly related to healthcare

Reporting of adverse events following immunizations in Ghana–Using disproportionality analysis reporting ratios

Background: Timely reporting of safety information post vaccination is pivotal for the success of any vaccination program. Reports of adverse events following immunization (AEFI) of 6 different vaccinations from Ghana were analysed for signals. Methods: De-identified data from active surveillance for AEFIs after 2009 AH1N1 influenza, yellow fever, meningitis, measles-rubella, pneumococcal-rotavirus and human papilloma virus vaccinations were used. All vaccinations occurred between January 2010 and December 2013. The ten most occurring events for each vaccination were captured and arranged using Medical Dictionary for Regulatory Authorities (MedDRA) Preferred Term (PT) and System Organ Classification (SOC) codes. Adverse event incidence rates were calculated for each vaccine type, and signals were generated using proportional reporting ratios (PRR). Results: A total number of 5,141 reports were analysed ranging from 33 (human papilloma virus) to 1958 (measles-rubella). Between 22% and 55% of all AEFIs per vaccine type were collected on the day of vaccination. For each vaccine type, at least 87% of all reported AEFIs occurred in the first 7 days post-vaccination. Multiple reports were received per vaccine type. For the MR vaccine, urticarial recorded the highest attack rate of 6.6 (95% CI 6.2, 7.1) per 100,000 vaccines. The AEFI with the highest PRR for both human papilloma and measles-rubella vaccines was abdominal pain, recording a PRR of 8.15 (95% CI 3.46, 19.23) and 43.75 (95% CI 17.81, 107.45) respectively. Conclusion: These results underscore the competency of public health systems in sub-Saharan African countries (like Ghana) to identify most frequently occurring and important vaccine related safety issues

Preliminary findings from stimulated spontaneous reporting of adverse drug reactions during COVID-19 pandemic: an experience from Ghana

Background: The novel coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is limited information on the safety of drugs used for the treatment of COVID-19.Objective: Objective of this study is to describe the pattern of stimulated spontaneous adverse drug reaction (ADR) reports received from healthcare professionals for SARS-CoV-2 positive patients in Ghana and lessons learnt particularly for low- and middle-income countries.Methods: This is a study of individual case safety reports (ICSRs) received from healthcare professionals between 1st April 2020 to 31st July 2020 in SARS-CoV-2 positive patients in Ghana. The ICSRs were retrieved from the SafetyWatch System and descriptive statistics used to describe the ADRs by System Organ Classification and Preferred Term.Results: Information was received from 40 COVID-19 Treatment Centres across the country with 9 centres submitting a total of 53 ICSRs containing 101 ADRs; approximately two ADRs per ICSR. Females accounted for 29(54.7%) of the ICSRs and males 24(45.3%). Newly reported ADRs of interest were one report each of tremor for doxycycline; scrotal pain, dyspnoea, gait disturbances and dysgeusia for chloroquine; and dry throat, hyperhidrosis, restlessness and micturition frequency increased for hydroxychloroquine. A strong spontaneous system with the availability of focal persons at the Treatment Centres played a key role in reporting ADRs during the pandemic.Conclusion: This is the first experience with spontaneous reporting during COVID-19 pandemic in Ghana. The profile of most of the ADRs reported appears consistent with what is expected from the summary of product characteristics. A study with a larger sample size with well-defined denominator in future studies is paramount in determining the relative risk of these medications in SARS-CoV-2 positive patients

Assessment of occupational stress among certified registered anesthetists in the Greater Accra region

BackgroundWork-related stress is a prevailing concern within the community of Certified Registered Anesthetists (CRAs), significantly impacting both the health and professional performance of these individuals. This study aimed to assess work-related stress and its influencing factors among CRAs practicing in the Greater Accra region was examined.MethodsUsing convenience sampling techniques, data were gathered from 140 participants via a Google form questionnaire distributed through WhatsApp. Descriptive statistics were employed to analyze the collected data, focusing on frequencies and proportions for categorical variables. For continuous variables, bivariate analysis (Chi-square) and ordinal logistic regression were conducted using STATA 16. A p-value <0.05 was considered significant.ResultsAmong the 140 CRAs, 20 individuals (14.3%) reported experiencing mild stress levels according to the Weiman Occupational Stress Scale. Approximately 3 out of 4 CRAs (73.6%) reported having moderate stress levels, and 12.1% reported severe stress levels. This indicated that the majority of CRAs experienced moderate levels of stress, which was notably affected by the type of health facility and the use of inadequate or sub-standard equipment in the hospitals.ConclusionBased on these findings, the study recommends educational programs and counseling for CRAs to heighten awareness of the demanding nature of their job. Additionally, it suggests the provision of proper resources and standard equipment for CRAs. Facility-level motivation for CRAs is also advised to alleviate their stress. Finally, the study proposes further investigations into the factors contributing to work-related stress among CRAs