Using FIB-4 score as a screening tool in the assessment of significant liver fibrosis (F2) in patients with transfusion dependent beta thalassaemia: a cross sectional study

Objective To evaluated the performance of FIB-4 score as a screening tool to detect significant liver fibrosis (F2) compared to transient elastography (TE) among chronic transfusion-dependent beta-thalassemia (TDT) patients, in a resource-poor setting. Design A cross-sectional study Setting Adolescent and Adult Thalassaemia Care Center (University Medical Unit) Kiribathgoda Sri Lanka. Participants 45 TDT patients who have undergone more than 100 blood transfusions with elevated serum ferritin more than 2000ng/mL were selected for the study. Patients who were serologically positive for hepatitis C antibody were excluded. Outcome measures TE and FIB-4 score were estimated at the time of recruitment in all participants. Pre-defined cut-off values for F2 extracted from previous studies for TE and FIB-4 score were compared. A new cut-off value for FIB-4 score was estimated using ROC curve analysis to improve the sensitivity for F2 prediction. Results Of the selected 45 TDT patients 22(49%) were males. FIB-4 score showed a significant linear correlation with TE (r= 0.52 p< 0.0003). The FIB-4 score was improbable to lead to a false classification of TDT patients to have F2 when the FIB-4 cut-off value was 1.3. On the other hand it had a very low diagnostic yield in missing almost all (except one) of those who had F2. Using a much-lowered cut-off point of 0.32 for FIB-4 we improved the pick-up rate of F2 to 72%. Conclusions Regardless of the cut-off point FIB-4 score cannot be used as a good screening tool to pick-up F2 in patients with TDT irrespective of their splenectomy status. On the contrary at 1.3 cut off value though FIB-4 is a very poor detector for F2 fibrosis it will not erroneously diagnose F2 fibrosis in those who do not have it.

Ethical Considerations in Conducting Paediatric Research

Health research is a moral duty because it is the foundation for evidence-based care by all health care practitioners. Hence, paediatric research is essential for improving health outcomes of children. Waiting for adult studies before conducting paediatric studies may prolong the denial of effective treatment for children. The CIOMS and other guidelines clearly allow research procedures that involve a low degree of risk. However, the critical need for pediatric research on drugs and biological products underscores the responsibility to ensure that children are enrolled in clinical research that is both scientifically necessary and ethically sound. Even in a resource poor setting of a developing country like Bangladesh, the things that should be taken under considerations are the status of children as a vulnerable population; the appropriate balance of risk and potential benefit in research; ethical considerations underlying study design, including clinical equipoise, placebo controls, and non-inferiority designs; the use of data; compensation; and parental permission and child assent where applicable to participate in research. Such ethical dilemmas are more evident in paediatric research especially when a collaborative research is done by a developed country in a developing country setting. It is the role of the health policy makers, and community of paediatric physicians, nurses, and caregivers to advocate not only for more research for children but also to ensure that the research conducted is of the highest quality from ethical viewpoint. CBMJ 2020 July: Vol. 09 No. 02 P: 54-58

Acquired Aplastic Anemia Patients Using Single Agent Cyclosporine a, in Resource Poor Setting

Abstract: Aplastic Anemia (AA) is a syndrome characterized by peripheral blood pancytopenia and bone marrow hypo-cellularity. Acquired AA is considered to have an underlying autoimmune etiology. Hematopoietic stem cell transplantation (HSCT) still remains the treatment of choice for AA patients. However, due to cost restrictions, cyclosporine A has been tried in resource poor setting as a single agent. Aim: The aim of this study is to observe the single agent Cyclosporine treatment response in AA patients. Materials and Methods: The following study is a retrospective study. Patients diagnosed for the first time between January 2010 and December 2020, aged 14 years old and up, treated with cyclosporine A and supportive therapy, were included in this study. Statistical analysis for this study was performed using SPSS. All subjects were started on 5mg/kg per day of cyclosporine. The patients were divided into three groups according to the IAASG classification criteria (Non severe AA, Severe AA and Very severe AA). Another subgroup analysis related to sex (females to males) and age was performed, classifying the patients into three subgroups (14-29; 30-59; 60+ years old). Overall Survival (OS) was evaluated using Kaplan-Meier method with Log-Rank test. Overall survival (OS) was defined as the duration from the first day of treatment to all-cause death. T-test and Chi-square test were used for categorical and continuous parameters analysis. P value lower than 0.05 was considered statistically significant. Results: A total of 35 patients were diagnosed as Acquired Aplastic Anemia between 2010-2020. The median age at diagnosis was 51 years old. The incidence of Aplastic Anemia in Albania is 1.35 per million inhabitants. 5 patients (19.2%) developed complete response. NSAA showed the best treatment response (38.5%). The relation between the treatment response at the end of the first year of cyclosporine treatment and the 5-year survival was statistically significant, Pearsons' correlation coefficient 0.441 (P=0.035). The estimated mean survival time of AA patients in our study is 68.6 months. When compared the survival to the severity, the SAA group showed a better OS (53 months) (P=0.081). The 5-year cumulative survival of the patients resulted 71.9%. VSAA group had the worst estimated survival (45.5%). The youngest age group showed the worst 5-year survival on cyclosporine alone (33.3%) (P=0.016). The subgroup analysis between males and females resulted in women having a slightly better survival than men, 59 and 58 months respectively (P=0.276). Those patients who failed the treatment with cyclosporine alone at the end of the first year, showed the worse 5-year survival (50%). Conclusions: This study emphasizes once again the importance of the IAASG classification on AA patients' prognosis and treatment outcome. The youngest patients should be considered for HSCT rather than be treated on cyclosporine alone. Treatment on cyclosporine alone and supportive therapy is a reasonable option for older patients in poor resource countries as Albania. Abbreviations: AA- Aplastic Anemia, NSAA- Non severe aplastic anemia, SAA- Severe aplastic anemia, VSAA- Very severe aplastic anemia, HSCT- Hematopoietic stem cell transplantation, IAASG-International Aplastic Anemia Study Group, SPSS-Statistical Package for the Social Sciences. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

ALK-Positive Anaplastic Large Cell Lymphoma: A Diagnostic Dilemma for the Otolaryngologist in a Resource Poor Setting

Anaplastic large cell lymphoma is a rare subtype of non-Hodgkin’s lymphoma. The morphological diversity with which its anaplastic cells confer make the diagnosis of this hematological entity extremely challenging to the pathologist in a resource poor setting. We present a case of a 35-year-old male with a nasopharyngeal mass and cervical lymphadenopathy and the adversities faced by out otolaryngology department with obtaining the diagnosis of ALK-positive anaplastic large cell lymphoma.

Childlessness and health seeking behavior in resource poor setting of dang and Udayapur district of Nepal

Background: Childlessness is not problem in resource-poor area where fertility rates are high. The consequence of childlessness is very severe in low-income countries like Nepal, particularly for women. Childless women are frequently stigmatized, isolated, ostracized, disinherited and neglected by the family and local community. This may result in physical and psychological abuse, polygamy and even suicide. The aim of the study is to explore the perception of childlessness, its cause and consequences and health seeking behavior among couples in order to develop strategies for action and policy-setting.Methods: This was a qualitative study conducted in Dang and Udayapur district of Nepal. Childlessness couple were recruited through snowball sampling. Information was also gathered from key informant and Focus group discussion. All interview were audiotaped using a digital recorder.Results: Women expressed that they are being discriminated, humiliated and intimated by their family members and society for being childlessness. Despite childlessness problem with husband, women experience emotional and physical abuse. Financial constraints and unaffordable service as one of the major problems among couple that led to withdrawal or stop attending their follow up for modern treatment.Conclusions: The study concludes that childlessness women suffer from all spare of their personal and social life although childlessness is a biomedical cause. Financial hardship and family pressure made them to seek traditional healer for first treatment approach for childlessness rather than modern method of treatment. Therefore, childlessness needs to be seen as a public health issue rather than a pure medical condition. Hence, multi-sectoral (i.e., Preventive, promotive and social dimension) response to address childlessness could be valuable.

CUTANEOUS LEISHMANIASIS: A CASE REPORT OF A DIAGNOSTIC DILEMMA

Cutaneous Leishmaniasis (CL) is the most prevalent clinical form of leishmaniasis. CL is difficult for the clinicians to diagnose because of the rarity of the disease and non-specific presentation. As CL is rare and given the limitation of available diagnostic modalities in a resource poor setting, diagnosis can be confusing.

Hepatitis D Review: Challenges for the Resource-Poor Setting

Hepatitis D is the smallest virus known to infect humans, the most aggressive, causing the most severe disease. It is considered a satellite or defective virus requiring the hepatitis B surface antigen (HBsAg) for its replication with approximately 10–70 million persons infected. Elimination of hepatitis D is, therefore, closely tied to hepatitis B elimination. There is a paucity of quality data in many resource-poor areas. Despite its aggressive natural history, treatment options for hepatitis D to date have been limited and, in many places, inaccessible. For decades, Pegylated interferon alpha (Peg IFN α) offered limited response rates (20%) where available. Developments in understanding viral replication pathways has meant that, for the first time in over three decades, specific therapy has been licensed for use in Europe. Bulevirtide (Hepcludex®) is an entry inhibitor approved for use in patients with confirmed viraemia and compensated disease. It can be combined with Peg IFN α and/or nucleos(t)ide analogue for hepatitis B. Early reports suggest response rates of over 50% with good tolerability profile. Additional agents showing promise include the prenylation inhibitor lonafarnib, inhibitors of viral release (nucleic acid polymers) and better tolerated Peg IFN lambda (λ). These agents remain out of reach for most resource limited areas where access to new therapies are delayed by decades. strategies to facilitate access to care for the most vulnerable should be actively sought by all stakeholders.

Advanced-stage Wilms tumor arising in a horseshoe kidney of a 9-year-old child: a case report

Background Horseshoe kidney (HK) is one of the most common renal fusion abnormalities, with an incidence of 1:400 in the normal population. However, Wilms tumor (WT) arising in an HK is a rare occurrence. We report the case of a 9-year-old boy who presented with an advanced WT in an HK and also highlight the management challenges in a resource-poor setting such as ours. Case presentation The patient was a 9-year-old Nigerian boy presented to the Pediatrics Outpatient Clinic of the University of Maiduguri Teaching Hospital (UMTH) with a history of progressive abdominal swelling, weight loss, abdominal pain, and cough. Abdominal examination revealed an irregular, firm, and non-tender mass in the right lumbar region. A computed tomography (CT) scan of the abdomen showed a heterogeneously dense mass that was predominantly to the right side of the abdomen and crossed the midline to the left side, where it continued with the relatively normal renal tissue. Chest CT revealed pulmonary metastases. A diagnosis of WT in an HK was made. The patient had a 6-week course of neoadjuvant chemotherapy, and a right nephrectomy and left partial nephrectomy was performed. The final histologic diagnosis of WT was made. Radiotherapy was intended but was not available in our facility, and the parents could not afford referral to another center. Conclusions Children with a clinically suspected HK with WT should undergo a careful imaging evaluation such as CT before any surgical intervention. Neoadjuvant chemotherapy to reduce tumor bulk might be a good treatment method to reduce surgical morbidity and aid in complete excision and potential for preserving renal function.