Regulatory approval of clinical trials: is it time to reinvent the wheel?

Less than 1% of all clinical trials are conducted in Africa. In 2019, only six of 26 oncology clinical trials conducted in Africa were conducted in countries with subjects of African ancestry. There are multiple barriers that hinder the conduct of cancer clinical trials in Africa. Time to trial activation (TTA) is the administrative and regulatory process required before a study can be activated-an important metric and often a major barrier for site selection. In Kenya, TTA involves review by Institutional Review Board (IRB), Pharmacy and Poisons Board, National Commission for Science, Technology and Innovation and Ministry of Health, all in a sequential fashion. We performed a prospective review of TTA for all clinical trials initiated and began enrolment at the Aga Khan University-Clinical Research Unit between June 2020 and November 2022. TTA was defined as total time from submission of study documents (to regulatory bodies) to site activation by the sponsor. A total of 12 studies were submitted for regulatory review. Eleven (nine industry sponsored and two investigator initiated) were approved for activation. Three were COVID-19-related studies and eight were non-COVID-19-related studies. Mean TTA for COVID-related studies was 80 days (range 40-120). Mean TTA for non-COVID-related studies was 259 days (range 190-399). This TTA difference was statistically significant (p=0.02). TTA remains a significant barrier to the efficient regulatory approval of and subsequent conduct of clinical trials in Africa. COVID-19 pandemic revealed that parallel processing and expedited review of clinical trials allows efficient TTA without compromising human subject safety or data integrity. These lessons need to be applied to all clinical trials in order for African sites to become competitive and contribute data from African patients to global knowledge.

Short Stature for Age in Children of 5 to 16 Years: The First Research from the Northern Himalayan Region of India.

Introduction: Anthropometric parameters play vital role in monitoring growth in pediatrics. Many etiological factors lead to short stature. So, before assessing the etiological factors short stature needs to be addressed. This study aimed to screen short stature for age in school-going children aged 5 to 16 years in Uttarakhand. Material and Methods: In this cross-sectional observational study, the height (through stadiometer) and weight (through weight machine) of 4189 students of government and private school in Rishikesh (Uttarakhand) aged 5-16 years were measured after the verbal assent of the students and individual's height is in the 3rd percentile for the mean height of a given age, sex, and population group and was considered short stature. The data collection was performed from October 2019 to July 2021. The data were categorized according to different age groups to 5-8 years, 9-12 years, and 13-16 years. The data were recorded in Microsoft (MS) Excel spreadsheet program. Statistical Package for the Social Sciences (SPSS) v23 (IBM Corp.) was used for data analysis. Descriptive statistics were elaborated in the form of means or standard deviations and medians or Interquartile range IQRs for continuous variables and frequencies and percentages for categorical variables. The Chi-square test was used for group comparisons for categorical data. Results: 7.1% of children were short stature (height 143.16 ± 15.09 cm) in the Himalayan belt, and males were more prone to short stature at age of 9-12 years. Conclusion: In the growing phase of children, the etiology of short stature has to be rectified, so the children can achieve such proper growth. Parents and physicians have to assess and monitor the growth of children timely. This study can be a stepping stone for further epidemiological studies.

Discrimination and Abuse Among Healthcare Workers from Patients and their Relatives at a Tertiary Hospital in Kenya.

Discrimination and abuse of healthcare workers (HCWs) by patients and their relatives remains a pressing and prevalent problem in various healthcare settings, negatively affecting professional outcomes. Despite this, little has been reported about discrimination and abuse in many low- and middle-income countries such as Kenya. We conducted a cross-sectional survey study between May - August 2021 among healthcare workers at a hospital in Kenya. Email invitations were sent, and the survey was in English, and the data was collected through and online survey. Discrimination based on gender was reported by 24.9% of all HCWs; 39.9% of doctors, 17.2% of nurses, and 10.9% of allied staff whereas racial discrimination was reported by 28.8% of all HCWs; 49.0% of doctors, 18.9% of nurses, and 8.9% of allied staff. Verbal or emotional abuse was the most common form of abuse and was reported by 56.8% of all HCWs while physical abuse was reported by 4.9% of all HCWs. For those that reported discrimination based on gender, 77.4% reported patient and their family members as the main source, whereas 81.2% of those that reported discrimination based on race reported the main source was from patient and their family members. Despite strict laws against discrimination and abuse, a significant portion of healthcare providers suffer from discrimination and abuse primarily from patients and their family members. In addition to education programs and policies to curb such behavior in the work environment, coping mechanisms should be actively sought to help healthcare providers deal with such actions.

A pilot phase Ib/II study of whole-lung low dose radiation therapy (LDRT) for the treatment of severe COVID-19 pneumonia: First experience from Africa.

BACKGROUND: Low dose radiation therapy (LDRT) has been used for non-malignant conditions since early 1900s based on the ability of single fractions between 50-150 cGy to inhibit cellular proliferation. Given scarcity of resources, poor access to vaccines and medical therapies within low and middle income countries, there is an urgent need to identify other cost-effective alternatives in management of COVID-19 pneumonia. We conducted a pilot phase Ib/II investigator-initiated clinical trial to assess the safety, feasibility, and toxicity of LDRT in patients with severe COVID-19 pneumonia at the Aga Khan University Hospital in Nairobi, Kenya. Additionally, we also assessed clinical benefit in terms of improvement in oxygenation at day 3 following LDRT and the ability to avoid mechanical ventilation at day 7 post LDRT. METHODS: Patients with both polymerase chain reaction (PCR) and high-resolution computer tomogram (HRCT) confirmed severe COVID-19 pneumonia, not improving on conventional therapy including Dexamethasone and with increasing oxygen requirement were enrolled in the study. Patients on mechanical ventilation were excluded. Eligible patients received a single 100cGy fraction to the whole lung. In the absence of any dose limiting toxicity the study proposed to treat a total of 10 patients. The primary endpoints were to assess the safety/feasibility, and toxicity within the first 24 hours post LDRT. The secondary endpoints were to assess efficacy of LDRT at Day 3, 7, 14 and 28 post LDRT. RESULTS: Ten patients were treated with LDRT. All (100%) of patients were able to complete LDRT without treatment related SAE within the first 24 hours post treatment. None of the patients treated with LDRT experienced any acute toxicity as defined by change in clinical and respiratory status at 24hr following LDRT. Majority (90%) of patients avoided mechanical ventilation within 7 days of LDRT. Four patients (40%) demonstrated at least 25% improvement in oxygen requirements within 3 days. Six patients (60%) were discharged and remained off oxygen, whereas four progressed and died (1 due to sepsis and 3 in cytokine storm). Median time to discharge (n = 6) was 16.5 days and median time to death (n = 4) was 11.0 days. Patients who ultimately died showed elevated inflammatory markers including Ferritin, CRP and D-dimers as compared to those who were discharged alive. CONCLUSION: LDRT was feasible, safe and shows promise in the management of severe COVID-19 pneumonia including in patients progressing on conventional systemic treatment. Additional phase II trials are warranted to identify patients most likely to benefit from LDRT.

Promoting Best Practice in Cancer Care in Sub Saharan Africa.

Promoting best practice in the management of a cancer patient is rooted in the application of new knowledge derived through various sources including population science, laboratory advances, and translational research. Ultimately, the impact of these advances depends on their application at the patient's bedside. A close collaboration between the oncologist and the pathologist is critical in underwriting progress in the management of the cancer patient. Recent advancements have shown that more granular characteristics of the tumor and the microenvironment are defining determinants when it comes to disease course and overall outcome. Whereas, histologic features and basic immunohistochemical characterization were previously adequate to define the tumor and establish treatment recommendation, the growing capability of the pathologist to provide molecular characterization of the tumor and its microenvironment, as well as, the availability of novel therapeutic agents have revolutionized cancer treatment paradigms and improved patient-outcomes and survival. While such capacity and capability appear readily available in most developed high-income countries (HIC), it will take a concerted and collaborative effort of all stakeholders to pave the way in the same stride in the low and middle-income countries (LMIC), which bear a disproportionate burden of human illness and cancers. Patients in the LMIC present with disease at advanced stage and often display characteristics unlike those encountered in the developed world. To keep stride and avoid the disenfranchisement of patients in the LMIC will require greater participation of LMIC patients on the global clinical trial platform, and a more equitable and affordable sharing of diagnostic and therapeutic capabilities between the developed and developing world. Key to the success of this progress and improvement of patient outcomes in the developing world is the close collaboration between the oncologist and the pathologist in this new era of precision and personalized medicine.

Perceptions and Knowledge towards COVID-19 Vaccine Hesitancy among a Subpopulation of Adults in Kenya: An English Survey at Six Healthcare Facilities.

Background: Vaccine hesitancy, as defined by the WHO, is the reluctance or refusal to vaccinate despite the availability of vaccines and is one of the ten threats to global health in 2019. Vaccine hesitancy remains a complex matter influenced by multiple factors, especially in sub-Saharan Africa. Methods: We conducted a cross-sectional study between November 2021 and January 2022 among the general adult public seeking care at six different healthcare facilities in Kenya. The survey, in English, consisted of questions based on demographics, knowledge, and attitudes, including hesitancy towards the COVID-19 vaccine. Results: Of the 3996 surveys collected, 55.1% were from private, 19.5% from faith-based and 25.3% from government facilities., Approximately 81.0% of all the participants reported it was important to get a vaccine to protect other people from COVID-19, 79.9% reported they would take a vaccine to protect against COVID-19, yet 40.5% reported being hesitant to take the vaccine primarily due to side effects. Most of the variables were associated with receiving a vaccine. Only 52.1% of those seeking care from the government facility and 54.5% of those seeking care from the faith-based facility were vaccinated, compared to 81.5% seeking care from the private facilities (p < 0.001). More participants from private facilities felt that vaccines are safe as compared to those at the faith-based and government facilities (p < 0.001). Conclusion: Vaccine hesitancy in Kenya, even though much lower than reported in other countries, remains a dynamic problem. Mitigating strategies specific to Africa need to be developed to help address vaccine hesitancy in this part of the continent.

Be Wary of Hiccups: An Unusual Case of COVID-19.

Hiccups, involuntary contraction of the diaphragm and intercostal muscle followed by an abrupt closure of the glottis, are a bothersome symptom that can be caused by a variety of illnesses or medications. Hiccups that persist for more than 48 hours should raise the suspicion of an underlying cause. Pneumonias, especially caused by the novel coronavirus, have rarely been reported to trigger hiccups. To the best of our knowledge, we present the first case in sub-Saharan Africa of a patient presenting to our institution with persistent hiccups and no other objective signs suggestive of underlying pneumonia. His high-resolution CT was suggestive of coronavirus disease 2019 (COVID-19) and a polymerase chain reaction (PCR) test confirmed the diagnosis. Our case highlights the need for a thorough history and physical examination in patients presenting with hiccups and the need to include COVID-19 in the differential diagnosis in such patients.

Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease: First Reported Case from East Africa.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare prion disease that causes rapidly progressive fatal neurodegeneration. The rarer Heidenhain variant of sCJD presents with visual symptoms and is rarely reported in the literature from sub-Saharan Africa. We report the case of a 57-year-old male with a three-week history of losing direction when driving home and visual hallucinations described as seeing rainbows. Magnetic resonance imaging (MRI) of the brain revealed unilateral parieto-occipital sulcal hyperintensities with restriction on diffusion-weighted imaging (DWI), and electroencephalography (EEG) showed right para-central slowing leading to an initial diagnosis of non-convulsive status epilepticus. He was treated with anti-epileptic medication but was re-admitted less than a month later with worsening spatial memory, aggression, ataxia, dysarthria, myoclonic jerks and a positive startle response, later developing generalised tonic-clonic seizures. Repeat MRI brain scan showed widespread posterior-predominant sulcal DWI restriction in a cortical ribboning pattern pathognomonic for sCJD. EEG showed diffuse slowing, and cerebrospinal fluid was analyzed for abnormal prion protein using real-time quaking-induced conversion but was inconclusive due to suboptimal sample collection. The patient fulfilled the diagnostic criteria for probable sCJD, Heidenhain variant; the family declined brain biopsy for definitive diagnosis. He was subsequently palliated at a local hospice where he died approximately three months after the onset of symptoms. Our case highlights the presence of a rare form of sCJD, and the diagnostic challenges faced in our resource-limited setting.

Delivery of Difficult News Among Residents at a Tertiary Hospital In Kenya Using a Short Training Video (UNMASKES).

This article was migrated. The article was marked as recommended. Background Delivery of difficult news (DDN) remains a challenging task for even the most experienced of providers. Little has been studied about delivery of difficult news among resident physicians in sub-Saharan Africa (SSA). We developed a 4-minute, graphic video using the acronym UNMASKES to help improve delivery of difficult news between resident physicians and their patients. Objective To determine the impact of the UNMASKES training video in improving resident communication when delivering difficult news. Methods We conducted a prospective study amongst all residents at the Aga Khan University hospital in Nairobi, Kenya and Dar es Salaam, Tanzania from February to September, 2019. After completing a pretest survey, residents received a one-hour comprehensive training on delivery of difficult news using UNMASKES. A link to the UNMASKES video was provided to the residents for real-time reference. Post-test surveys were completed at 4 and 12 weeks respectively. Results A total of 102 (68%) residents completed the surveys. At 12 weeks, we found that residents improved in 6 key areas; notified their patients before delivering difficult news, ensured a private and quiet room, provided information in small amounts to patients and family members, provided a summary after delivery of difficult news, followed up with patients at 24-48 hours after delivering difficult news, and felt better prepared to deal with patient and family emotions when delivering difficult news. Conclusions UNMASKES, a 4-minutes, easily accessible, graphic video showed promising results in training our residents to foster effective communication while delivering difficult news to their patients.

Case Report of Kikuchi-Fujimoto Disease from Sub-Saharan Africa: An Important Mimic of Tuberculous Lymphadenitis.

Kikuchi-Fujimoto disease (KFD) is a rare form of painful lymphadenopathy, usually cervical, which is more common in Southeast Asia and rarely reported from Africa. Symptoms are usually nonspecific (fever, night sweats, etc.), and can mimic more common diseases such as tuberculosis (TB) in endemic areas. We report a case of a 29-year-old black African woman who was admitted with headache, neck pain, fever, and lymphadenopathy. She was found to have aseptic meningitis, eventually attributed to TB based on cervical node biopsy, although further histology suggested KFD. Blood tests for systemic lupus erythematosus (SLE) were negative; she had already been commenced on anti-TB treatment and had responded well and so was continued with this therapy. She was also later diagnosed with Hashimoto's thyroiditis 3 months after her diagnosis of KFD. Five months after stopping TB treatment, she was readmitted with the same symptoms and associated painless lymphadenopathy. Repeat biopsy was morphologically similar to that of 2017, and repeat evaluation confirmed SLE. She has since been managed by a rheumatologist and continues to do well.

Adult secondary hemophagocytic lymphohistiocytosis.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation and tissue destruction due to abnormal immune activation. HLH carries a very high mortality, and while delays in patients' presentation to hospital, time to suspicion of HLH, investigation, and initiation of therapy all play a part, mortality remains high even with timely diagnosis and treatment. Classical manifestations of HLH include persistent fever, cytopenias, and liver dysfunction. Case presentation: We present four cases of secondary HLH, highlighting the demographic and clinical characteristics of these patients, underlying triggers (including systemic lupus erythematosus, lymphoproliferative disorders, and leishmaniasis), together with challenges associated with the diagnosis and treatment of this rare disorder and a brief review of literature. Conclusion: HLH has protean manifestations and requires a high index of suspicion as it can be a great clinical masquerader. Mortality due to multiorgan failure is often high even with early recognition and treatment.

Phenytoin Toxicity Treatment with Haemodialysis in Epilepsy due to Glioblastoma Multiforme: Case Report and Review of the Literature.

Phenytoin is one of the most commonly used anticonvulsants in the developing world, but lack of monitoring and concurrent medications can easily lead to toxicity. We report the case of a 35-year-old female on phenytoin for symptomatic epilepsy due to previously treated glioblastoma multiforme, who presented with status epilepticus 1 week after being treated for a urinary tract infection. She was loaded with phenytoin and levetiracetam as per emergency protocol but had a persistently low level of consciousness, and her preloading phenytoin level result came back in the toxic range. She was managed conservatively, but after 4 days with no change she was dialyzed and her level of consciousness improved within 24 h, allowing for safe discharge home shortly after. Our case illustrates the option of haemodialysis in phenytoin-toxic patients who do not improve with conservative measures or who may need urgent reduction due to potentially fatal complications of phenytoin toxicity.