Low Middle-income Country Settings Research Articles

Exploring rehabilitation providers’ perspectives of assistive technology access after the implementation of a paediatric AT provision program in rural South India

A paediatric Assistive Technology (AT) Provision Program was implemented by a non-governmental rehabilitation facility in rural South India to support rehabilitation providers in providing needed AT access for children with disabilities. Capacity-building measures for providers and other supports based on the AT needs, barriers, and facilitators to AT access were implemented that aligned with the AT global report for low-middle income countries (LMIC). This study explores how the initiatives from the AT Provision Program have influenced the perspectives of rehabilitation providers on AT access. Using a qualitative design eight paediatric rehabilitation providers were purposively sampled for virtual semi-structured interviews. Findings were analysed using thematic analysis. Six overarching themes were identified: (1) Stigma associated with AT use, (2) Organisational response to changing needs, (3) Financial factors related to family socioeconomic status and the organisation providing AT services, (4) Inequity of AT service access in rural areas, (5) Provider AT awareness and confidence and, (6) Quality assurance. Rehabilitation providers’ experiences informed future AT capacity-building strategies within a low-resource context. Our findings provide valuable insights for the development of comprehensive AT Provision Program initiatives to provide AT access for children with disabilities in LMIC settings.

Real-life study on dexamethasone intravitreal implant (Ozurdex) for macular edema at a Colombian reference center

ABSTRACT Purpose To evaluate the real-life safety, morphological, and visual outcomes of the dexamethasone intravitreal implant (Ozurdex) in patients with macular edema (ME) within a low-middle-income country (LMIC) setting. Methods Patients with ME who received Ozurdex injections between 2012 and 2018 were included. Central retinal thickness (CRT), best-corrected visual acuity (BCVA), lens status, and intraocular pressure (IOP) at baseline and last follow-up were compared. Univariate and multivariate analyses identified factors associated with visual improvement. Results 154 patients were enrolled. Diabetic ME was the most common etiology (32.4%), followed by central retinal vein occlusion (18.8%), branch retinal vein occlusion (14.2%), and uveitis (9.99%). CRT was significantly reduced in all patients except those with uveitis but did not correlate with BCVA improvement. Lower baseline visual acuity (OR=1.67), younger age (OR=1.87), and ME secondary to branch retinal vein occlusion (OR=1.34) were associated with BCVA improvement (p < 0.05). During follow-up, 11 patients (7.14%) developed cataracts, and 22 (14.2%) showed increased IOP; these complications resolved without affecting final BCVA improvement. Conclusion In an LMIC setting, Ozurdex effectively reduces CRT in diabetic and retinal vein occlusion-related ME but not in uveitis. BCVA improvement depends on factors beyond CRT reduction. Cataracts and elevated IOP are manageable complications.

Global perspective of barriers in research among oncologists from low-middle income countries.

e13781 Background: Cancer research in low-middle income countries (LMICs) face unique challenges, hindering advancements in patient care. Understanding the practices, barriers and strategic needs encountered by oncologists in LMICs is essential for enhancing research capacities and patient outcomes. This study aimed to assess the barriers and facilitators of research among oncologists in LMICs. Methods: This online cross-sectional survey engaged a diverse group of practicing oncologists from LMICs between December 8, 2023 and February 6, 2024. Respondents include both oncology trainees and consultants primarily from Asia (63%), Africa (18%) and Europe (10%). Using a validated questionnaire (test-retest reliability: 0.98), data analysis was performed using frequency and percentages to detail the survey responses, with 95% confidence intervals calculated to ensure the findings reliability. Results: A total of 276 participants from 29 countries, with a mean age of 38 years, responded to the survey. Fifty three percent (n=146) were male and 46% (n = 126) were female, four participants chose not to disclose. Majority of the respondents were trained in medical oncology and related specialties, 71% (n = 196). Forty one percent (n = 113) of them had less than 5 years’ experience as a cancer physician, while a significant proportion were mid-career oncologists with 5 to 15 years of experience. Regarding individual level barriers; 3% (n = 7) had 60 - 100% protected research time, 3% (n = 8) had local and international mentors, 36% (n = 100) had no biostatistical training, 50% (n = 138) had no clinical trial design training, 11% (n = 29) had utilized qualitative design, 60% (n = 165) had not participated in a population-based study, and 83% (n = 228) had not participated in translational research. In relation to system-level barriers; 30% (n = 84) had inadequate research infrastructure and 43% (n = 120) had no clinical trials unit. Respondents rated the degree of implementation of new research findings into local clinical practice as 3 on a five-point Likert scale. Conclusions: This study highlights the critical gaps in research capacity, resource availability, and infrastructure among oncologists from LMICs. Addressing these barriers through targeted interventions is imperative for advancing cancer research and improving patient outcomes in LMIC settings.

A Comprehensive Perspective on Intracranial Pressure Monitoring and Individualized Management in Neurocritical Care: Results of a Survey with Global Experts.

Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management.

Short-term Outcomes of Elective Abdominal Aortic Aneurysm Repair.

To evaluate the presentations, aetiologies, and outcomes (survival and morbidity) of patients who underwent abdominal aortic aneurysm (AAA) repair at a tertiary care centre in a low middle-income country (LMIC). Case-series study. Place and Duration of the Study:Section of Vascular Surgery, Department of Surgery, The Aga Khan University Hospital, Karachi, Pakistan, from January 2000 till April 2022. All patients who underwent elective open repair for AAA were identified using ICD coding 10. Patients' demographics, presentations, treatment options, and outcomes were recorded on a specially designed proforma. Outcomes were measured in terms of 30-day survival and perioperative complications. Forty-two patients were included in the study. Thirty-nine (92.9%) of them were males. The mean age was 63.8 + 12.6 years. Thirty-four (81%) patients had an infrarenal aortic aneurysm. The average aneurysm diameter was 8.0 + 2.73 cm. The in-hospital survival rate was 95.2% whereas 2 (4.8%) patients had in-hospital mortality. Acute kidney injury (AKI) was the most common complication, seen in 5 (11.9%) patients. Adverse outcomes were seen more in diabetic patients whereas increased incidence of AKI was noted in operations with supra-renal clamping (p<0.05). Most patients presented with symptoms and large aneurysm size. Open AAA repair was performed safely with 4.8% in-hospital mortality and acceptable morbidity in the LMIC setting. Abdominal aortic aneurysm repair, Low middle-income country.

Improving health outcomes among older adults in India: effectiveness and implementability of a novel comprehensive geriatric assessment based intervention

Background There is significant evidence on the benefits of comprehensive assessment in older adults. But this evidence is primarily from western countries and in secondary care settings. National policies in India recognize this need and envision community-based screening and facility-based assessment programs integrated into the care pathways for the elderly. However, this is yet to translate into specific interventions, primarily due to lack of complex interventions necessary and evidence of their effectiveness. This study aims to design and pilot an integrated (Community + Facility) Elderly Health Status Assessment and Screening (EHSAS) intervention to improve health outcomes of older adults and assess its feasibility for implementation in Indian rural settings. Methods We propose a hybrid design where we will build the complex intervention, develop and validate the tools needed, pilot it using an exploratory cluster randomized trial and evaluate its implementatbility using the Exploration-Preparation-Implementation-Sustainment (EPIS) framework. Conclusions This study will fill critical gaps in evidence regarding the effectiveness of geriatric screening and assessment in community and primary care settings in low-middle income countries and provide validated tools and implementation models for adoption into national programs. Registration CTRI/2023/07/055661

In Hospital Outcome of Pharmaco-invasive Therapy versus Primary PCI In ST-segment elevation Myocardial Infarction in Dhaka, Bangladesh

Background &amp; Objectives: In many low middle income countries (LMIC), it is difficult to treat patients with ST-segment elevation Myocardial Infarction (STEMI) with timely PPCI. Thus, many undergo fibrinolysis. Whether early fibrinolysis followed by timely coronary angiography provides a clinical outcome similar to that of primary percutaneous coronary intervention (PPCI) after acute STEMI in LMIC settings remains a question. In this observational study we primarily aimed to compare in-hospital outcomes of primary PCI versus pharmaco-invasive strategy (immediate fibrinolysis followed by coronary angiography with possible PCI within 3-24 hours) for reperfusion in eligible patients with STEMI at a tertiary cardiac care center. Methods: This prospective observational study was done in Ibrahim Cardiac Hospital &amp; Research Institute, Dhaka from April 2022 to July 2022 where consecutive patients presenting with STEMI were enrolled and divided into two groups: those who underwent primary PCI (Group-I) and those who underwent immediate fibrinolysis with subsequent coronary angiography with PCI within 3 to 24 hours (Group-II). The main outcomes analyzed were all-cause death, cardiogenic shock, acute left ventricular failure, life threating arrhythmia, acute stent thrombosis, CVD, Contrast induced nephropathy (CIN), re-infarction, target-vessel revascularization, and major bleeding up to 7 days. Results: A total 122 patients presented with acute STEMI, 61 in each group. One group underwent primary PCI and another group treated with fibrinolysis by tenecteplase. The mean age of the studied patients was 53.86±9.72 years (range 18-75 years). Eighteen percent of patients presented with Extensive Anterior MI,19.7% showed Anterior MI, 21.3% showed Antero-septal MI, 21.3% showed Inferior MI, 9.8% showed Inferior with posterior and 3.3% showed Lateral MI. 35.5% had Single vessel disease, 31.1% had double vessel disease,28.7% had triple vessel disease, LM with LAD was 0.8% and 0.8% had recanalized infarct related artery in both groups overall. In group-I 45.9% of PPCI were undertaken in LAD and 32.8% patient. of group-II was done PCI in LAD. There were no significant differences between two groups in primary outcome and mortality. Conclusion: Immediate fibrinolysis followed by coronary angiography within 3-24 hours resulted in similar short-term outcomes in patients with STEMI compared to PPCI. Our study suggests that, compared with PPCI, fibrinolysis performed in the hospital setting is associated with similar mortality rates, acute CVD, CIN and acute left ventricular failure in with PPCI than STEMI. University Heart Journal 2023; 19(1): 10-14

Global perspectives on risk factors for major joint burn contractures: A literature review

Contractures are a frequent consequence of burn injuries, yet our knowledge of associated risk factors is limited. This paper provides an extensive review of relevant literature from both High-Income Countries (HICs) and Low-Middle Income Countries (LMICs). Ninety-four papers (up to June 2019) and eight subsequent publications (up to March 2022) were included, 76% of which were from HICs. The majority of publications were either descriptive studies (4 from HICs, 9 from LMICs) or papers citing putative risk factors (37 from HICs, 10 from LMICs). Seventeen publications (all from HICs) reported on the effects of individual non-surgical therapeutic interventions, often with conflicting results. Two published systematic reviews emphasised the poor quality of evidence available. Only fifteen studies (3 from LMICs) examined potential contracture risk factors with statistical comparisons of outcomes; significant findings from these included demographic, burn, comorbidities, and treatment risk factors. LMIC papers included socioeconomic and healthcare system factors as potential risks for contracture; these were rarely considered in HIC publications. Methodological issues identified from this review of literature included differences in contracture definitions, populations studied, standards of care, joints included and the timing and nature of contracture assessments.This review is the first to collate existing knowledge on risk factors for burn contractures from both HIC and LMIC settings, revealing a surprising lack of robust evidence for many accepted risk factors. In LMICs, where burns are particularly common, universal health provision is lacking and specialist burn care is both scarce and difficult to access; consequently, socioeconomic factors may have more immediate impact on contracture outcomes than specific burn treatments or therapies. Much more work is indicated to fully understand the relative impacts of risk factors in different settings so that context-appropriate contracture prevention strategies can be developed.

Improving health outcomes among older adults in India: effectiveness and implementability of a novel comprehensive geriatric assessment based intervention

Background: There is significant evidence on the benefits of comprehensive assessment in older adults. But this evidence is primarily from western countries and in secondary care settings. National policies in India recognize this need and envision community-based screening and facility-based assessment programs integrated into the care pathways for the elderly. However, this is yet to translate into specific interventions, primarily due to lack of complex interventions necessary and evidence of their effectiveness. This study aims to design and pilot an integrated (Community + Facility) Elderly Health Status Assessment and Screening (EHSAS) intervention to improve health outcomes of older adults and assess its feasibility for implementation in Indian rural settings. Methods: We propose a hybrid design where we will build the complex intervention, develop and validate the tools needed, pilot it using an exploratory cluster randomized trial and evaluate its implementatbility using the Exploration-Preparation-Implementation-Sustainment (EPIS) framework. Conclusions: This study will fill critical gaps in evidence regarding the effectiveness of geriatric screening and assessment in community and primary care settings in low-middle income countries and provide validated tools and implementation models for adoption into national programs. Registration: CTRI/2023/07/055661

Synthesizing Electronic Health Records for Predictive Models in Low-Middle-Income Countries (LMICs).

The spread of machine learning models, coupled with by the growing adoption of electronic health records (EHRs), has opened the door for developing clinical decision support systems. However, despite the great promise of machine learning for healthcare in low-middle-income countries (LMICs), many data-specific limitations, such as the small size and irregular sampling, hinder the progress in such applications. Recently, deep generative models have been proposed to generate realistic-looking synthetic data, including EHRs, by learning the underlying data distribution without compromising patient privacy. In this study, we first use a deep generative model to generate synthetic data based on a small dataset (364 patients) from a LMIC setting. Next, we use synthetic data to build models that predict the onset of hospital-acquired infections based on minimal information collected at patient ICU admission. The performance of the diagnostic model trained on the synthetic data outperformed models trained on the original and oversampled data using techniques such as SMOTE. We also experiment with varying the size of the synthetic data and observe the impact on the performance and interpretability of the models. Our results show the promise of using deep generative models in enabling healthcare data owners to develop and validate models that serve their needs and applications, despite limitations in dataset size.

Pulmonary hemorrhage and associated risk factors among newborns admitted to a tertiary level neonatal unit in Botswana.

Pulmonary hemorrhage (PH) is a life-threatening complication seen in very sick newborns with high morbidity and mortality. There is little data on the incidence, risk factors, and ultimate survival of newborns with pulmonary hemorrhage in sub-Saharan countries, where the healthcare provision and facility differ in many ways compared to high-income countries. Hence, this study aimed to determine the incidence, identify the risk factors, and describe the outcome of pulmonary hemorrhage in newborns in a low middle income country setting. A cohort study with prospective data collection was conducted in a public, tertiary-level hospital in Botswana, the Princess Marina Hospital (PMH). All newborns admitted to the neonatal unit from 1 January 2020 to 31 December 2021 were included in the study. Data were collected using a checklist developed on the RedCap database (https//:ehealth.ub.ac.bw/redcap). The incidence rate of pulmonary hemorrhage was calculated as the number of newborns who had pulmonary hemorrhage per 1,000 newborns in the 2-year period. Group comparisons were made using X2 and Student's t-tests. Multivariate logistic regression was used to identify risk factors independently associated with pulmonary hemorrhage. There were 1,350 newborns enrolled during the study period, of which 729 were male newborns (54%). The mean (SD) birth weight was 2,154(±997.5) g, and the gestational age was 34.3 (±4.7) weeks. In addition, 80% of the newborns were delivered in the same facility. The incidence of pulmonary hemorrhage was 54/1,350 {4% [95% CI (3%-5.2%)]} among the newborns admitted to the unit. The mortality rate in those diagnosed with pulmonary hemorrhage was 29/54 (53.7%). Multivariate logistic regression identified birth weight, anemia, sepsis, shock, disseminated intravascular coagulopathy (DIC), apnea of prematurity, neonatal encephalopathy, intraventricular hemorrhage, mechanical ventilation, and blood transfusion as risk factors independently associated with pulmonary hemorrhage. This cohort study identified a high incidence and mortality rate of pulmonary hemorrhage in newborns in PMH. Multiple risk factors, such as low birth weight, anemia, blood transfusion, apnea of prematurity, neonatal encephalopathy, intraventricular hemorrhage, sepsis, shock, DIC, and mechanical ventilation, were identified as independently associated risk factors for PH.

Late surgical ventricular septal defect closure in a low middle-income country setting: a case series

BackgroundVentricular septal defect (VSD) is the commonest type of congenital heart lesion accounting for up to 40% of congenital heart defects. Well timed VSD closures are reported to yield excellent long-term outcomes. Late surgical VSD closures, particularly from the developing countries, are infrequently reported.Case presentationWe report three cases of African children aged between 13 and 14 years who had late VSD presentations. They reported complaints of growth failure and recurrent respiratory infections since early infancy which necessitated frequent visits to primary health care facilities. They were found to have large ventricular septal defects by thoracic echocardiography. Diagnostic cardiac catheterization was done to all three patients to rule out irreversible pulmonary hypertension. After promising cardiac catheterization findings, they all underwent successful surgical VSD repair with good early outcomes.ConclusionVSD surgical closure is ideal in children below 2 years, however, it can be done in children who present at advanced age despite being considered high risk patients. All three of our patients who presented late had successful surgical VSD repairs with promising immediate outcome. The role of genetics in the protection against developing irreversible pulmonary vascular disease in these patients is a possible area for future studies.

Formulation and validation of a baseline prognostic score for osteosarcoma treated uniformly with a non-high dose methotrexate-based protocol from a low middle income healthcare setting: a single centre analysis of 594 patients.

The outcomes of osteosarcoma in low middle income countries (LMICs) are different due to patients presenting in advanced stages, resource constraints and the use of non-high-dose-methotrexate (HDMTX)-based regimens. This study derived and validated a prognostic score for osteosarcoma that integrates biologic and social factors and is tailored for patients from an LMIC setting using a non-HDMTX-based protocol. A retrospective study including osteosarcoma patients enrolled for treatment at a single tertiary care centre in India between 2003-19 was conducted. Baseline biologic and social characteristics were extracted from medical records and survival outcomes were noted. The cohort was randomised into a derivation and validation cohort. Multivariable Cox regression was used to identify baseline characteristics that were independently prognostic for survival outcomes in the derivation cohort. A score was derived from the prognostic factors identified in the derivation cohort and further validated in the validation cohort with estimation of its predictive ability. 594 patients with osteosarcoma were eligible for inclusion in the study. Around one-third of the cohort had metastatic disease with 59% of the patients residing in rural areas. The presence of metastases at baseline (HR 3.39; p<0.001; score=3), elevated serum alkaline phosphatase (SAP) >450 IU/L (HR 1.57; p=0.001; score=1) and baseline tumour size > 10 cm (HR 1.68; p<0.001; score=1) were identified to be independent factors predicting inferior event free survival (EFS) and were included in development of the prognostic score. Patients were categorized as low risk (score 0), intermediate risk (score 1-3) and high risk (4-5). Harrell's c-indices for the score were 0.682, 0.608 and 0.657 respectively for EFS in the derivation, validation and whole cohort respectively. The timed AUC of ROC was 0.67 for predicting 18-month EFS in the derivation, validation and whole cohorts while that for 36-month EFS were 0.68, 0.66 and 0.68 respectively. The study describes the outcomes among osteosarcoma patients from an LMIC treated uniformly with a non-HDMTX-based protocol. Tumor size, baseline metastases and SAP were prognostic factors used to derive a score with good predictive value for survival outcomes. Social factors did not emerge as determinants of survival.

Psychiatric comorbidities among people with epilepsy: A population-based assessment in disadvantaged communities

Psychiatric disorders are frequent among people with epilepsy but often under-recognized. The diagnosis and treatment of these disorders in low- and low-middle-income countries (LMICs) are challenging. MethodsThis cross-sectional survey included people recruited during a community epilepsy screening program involving 59,509 individuals from poor communities in Ludhiana in Northwest India. Adults (age ≥18 years) with confirmed epilepsy on antiseizure medications were screened for depression and anxiety using the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Generalized Anxiety Disorder-7 (GAD-7) twice over two years of follow-up. They were later interviewed for symptoms using the Brief Psychiatric Rating Scale, which was then confirmed by assessments by an experienced psychiatrist. ResultsOf the 240 people with confirmed epilepsy, 167 (70%) were adults, of whom, 116 (70%) eventually participated in the study. The NDDI-E with a cut-off of 15 identified depression in 14 (12%) of 116 people after one year of follow-up and 17 (15%) at two years. The GAD-7 using a cut-off of 6 identified 22 (19%) at one year and 32 (28%) with anxiety at two years. The area under the curves for NDDI-E was estimated as 0.62 (95%CI, 0.51–0.73; SE: 0.06; p = 0.04) and for GAD-7 as 0.62 (95%CI, 0.46–0.78; SE: 0.08; p = 0.12). Brief Psychiatric Rating Scale identified 63 (54%) people with psychiatric symptoms, for whom, a psychiatric diagnosis was confirmed in 60 (52%). A psychiatric diagnosis was associated with education below high school [Odds Ratio (OR): 2.59, 95%CI, 1.12–5.1; p = 0.03], later age of seizure onset (OR, 1.05, 95%CI: 1.0–1.10; p = 0.04), seizure frequency of at least one/year at enrolment (OR, 2.36, 95%CI: 1.0–5.58; p = 0.05) and the use of clobazam (OR, 5.09, 95%CI, 1.40–18.42; p = 0.01). ConclusionDepression and anxiety are common in people with epilepsy. Our findings underscore the low yields of screening instruments, NDDI-E and GAD-7, and comparatively better professionally-administered diagnostic assessments in resource-limited settings in LMICs. Moreover, previously established cut-offs do not apply to the community studied.

Evaluating the effects of supplementing ward nurses on quality of newborn care in Kenyan neonatal units: protocol for a prospective workforce intervention study

BackgroundData from High Income Countries have now linked low nurse staff to patient ratios to poor quality patient care. Adequately staffing hospitals is however still a challenge in resource-constrained Low-middle income countries (LMICs) and poor staff-to-patient ratios are largely taken as a norm. This in part relates to limited evidence on the relationship between staffing and quality of patient care in these settings and also an absence of research on benefits that might occur from improving hospital staff numbers in LMICs. This study will determine the effect on the quality of patient care of prospectively adding extra nursing staff to newborn units in a resource constrained LMIC setting and describe the relationship between staffing and quality of care.MethodsThis prospective workforce intervention study will involve a multi-method approach. We will conduct a before and after study in newborn units of 4 intervention hospitals and a single time-point comparison in 4 non-intervention hospitals to determine if there is a change in the level of missed nursing care, a process measure of the quality of patient care. We will also determine the effect of our intervention on routinely collected quality indicators using interrupted time series analysis. Using three nurse staffing metrics (Total nursing hours, nursing hours per patient day and nursing hours per patient per shift), we will describe the relationship between staffing and the quality of patient care.DiscussionThere is an urgent need for the implementation of staffing policies in resource constrained LMICs that are guided by relevant contextual data. To the best of our knowledge, this is the first study to evaluate the prospective addition of nursing staff in resource-constrained care settings. Our findings are likely to provide the much-needed evidence for better staffing in these settings.Trial registrationThis study was retrospectively registered in the Pan African Clinical Trial Registry (https://pactr.samrc.ac.za/Default.aspx?Logout=True) database on the 10th of June 2022 with a unique identification number-PACTR202206477083141.

Chronic kidney disease causes and outcomes in children: Perspective from a LMIC setting.

Chronic kidney disease (CKD) constitutes a major public health challenge, with a global prevalence of 15-74.7 cases /million children. Preventing CKD in children, slowing its progression and management of complications are essential, especially in challenged health systems in low middle income countries (LMIC). We conducted a retrospective review to assess the underlying cause and stage of CKD at presentation and clinical outcomes in children and adolescents at the Indus Hospital and Health Network (IHHN) in Karachi, Pakistan. Children 0-16 years with CKD stage 1 and/or higher at presentation were included. Data including demographics, clinical status and lab results at presentation and during follow-up, surgical intervention if any, kidney function at last visit and outcome at last follow-up was recorded. A total of 229 children diagnosed with CKD are included in our study. The median age at diagnosis was 10 years with male: female ratio of 1.8:1. Only 5% children presented in stage 1 CKD. The rate of adverse outcomes is 4.5 times higher in children with CKD stage 3-5 compared to early CKD. Congenital anomaly of kidney and urinary tract (CAKUT) was the underlying cause in 49% children. Children with glomerular disease had comparatively worse outcome. Proteinuria, hypertension, anemia and bone disease were associated with high morbidity and mortality. The true epidemiology of childhood CKD is unknown in Pakistan. Our cohort showed better CKD outcomes in children diagnosed early with appropriate surgical and medical follow-up. Prompt diagnosis, treatment and prevention of progression can be life-saving in our setting. CKD registry data can inform policy changes that can prevent poor outcomes.

DIPG-32. Paediatric histone-mutant diffuse midline glioma: real world outcomes from a low-middle income country (LMIC) setting

Abstract BACKGROUND: Histone-mutant diffuse midline glioma (H3K27M) is a distinct high-grade central nervous system (CNS) tumor arising in the midline structures of the brain and/or spinal cord in children and young adults with dismal clinical outcomes. Real world data on this entity, particularly from the low-middle income countries (LMICs) is lacking. We report outcomes of pediatric histone-mutant diffuse midline gliomas treated between 2014-2021 at our comprehensive cancer centre in India. METHODS: Children (&amp;lt;16 years) with biopsy-proven diffuse midline glioma demonstrating histone mutation (H3K27M) on gene expression profiling were identified through electronic search of neuro-pathology database. Clinico-demographic characteristics, histo-molecular features, treatment details, and survival outcomes were retrieved retrospectively from institutional records. All children had undergone biopsy and occasionally debulking surgery prior to definitive radiotherapy (RT). Upfront temozolomide (TMZ) either concurrent and/or adjuvant was at the discretion of treating oncologist. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods and expressed as point estimates with 95% confidence interval (CI). RESULTS: Median age of the study cohort (N=51) was 11 years (inter-quartile range 6-14 years) with no gender predilection. Metastatic disease (leptomeningeal dissemination, sub-ependymal spread, or distant brain involvement) was seen at presentation in 7 (13.7%) patients and at first progression after definitive RT in 10 (19.6%) patients. At a median follow up of 10.3 months, 1-year Kaplan-Meier estimates of PFS and OS were 21.5% (95%CI: 12.2-37.9%) and 45.6% (33.1-62%) yielding median PFS and OS of 7.8 months (95%CI: 5.6-11 months) and 11.3 months (95%CI: 9.4-14.9 months) respectively. CONCLUSIONS: We report aggressive biological course and dismal outcomes in pediatric histone-mutant diffuse midline gliomas (H3K27M) treated in a LMIC setting. High incidence of metastatic CNS failure in our cohort suggests a potential role for testing neuraxial irradiation and aggressive systemic therapy to improve survival.

Assessment of vaccination service delivery and quality: a cross-sectional survey of over 1300 health facilities from 29 districts in Sindh, Pakistan conducted between 2017–18

BackgroundRoutine childhood immunization coverage in Pakistan remains sub-par, in part, due to suboptimal utilization of existing vaccination services. Quality of vaccine delivery can affect both supply and demand for immunization, but data for immunization center quality in Pakistan is sparse and in Sindh province in Southern Pakistan, no comprehensive health facility assessment has ever been conducted at a provincial level. We assessed health facilities, specifically immunization centers, and their associated health workers throughout the province to summarize quality of immunization centers. MethodsAn exhaustive list of health facilities obtained from Sindh’s provincial government was included in our analysis, comprising a total of 1396 public, private, and public-private health facilities. We adapted a health facility and health worker assessment survey developed by BASICS and EPI-Sindh to record indicators pertaining to health facility infrastructure, processes and human resources. Using expert panel ranking, we developed critical criteria (the presence of a cold box/refrigerator, vaccinator and vaccination equipment at the immunization center) to indicate the bare minimum items required by immunization centers to vaccinate children. We also categorized other infrastructure, process, and human resource items to determine high, low and moderate function requirements to ascertain quality. We evaluated presence of critical criteria, calculated scores for high, moderate and low function requirements, and displayed frequencies of infrastructure, process and human resource indicators for all immunization centers across Sindh. We analyzed results at the division level and utilized a two-sample independent clustered t-test to test differences in average function requirement scores between facilities that met critical criteria and those that did not.ResultsOut of the 1396 health facilities assessed across Sindh province from October 2017 to January 2018, 1236 (88.5%) were operational while 1209 (86.6%) offered vaccination services (immunization centers). Only 793 (65.6%; 793/1209) immunization centers met the critical criteria of having all the following items: vaccinator, a cold box or refrigerator and vaccine supplies. Of the 416 (34.4%; 416/1209) immunization centers that did not meet the critical criteria, most of the centers did not have a cold box or refrigerator (28.3%; 342/1209), followed by lack of vaccines (19.9%; 240/1209), and a vaccinator (13.0%; 157/1209). Of the 2153 healthcare workers interviewed, 1875 (87.1%) were vaccinators, of which 1745 (81.0%; 1745/2153) were male, and had an average of 12.4 years of schooling. A total of 1805 (96.3%; 1805/1875), 1655 (88.3%; 1655/1875) and 1387 (74.0%; 1387/1875) of the vaccinators were trained in vaccination, cold chain and inventory management respectively.ConclusionOne out of three immunization centers in Sindh lack the critical components essential for quality vaccination services. While the majority of health workers (>80%) were trained on vaccination and cold chain management, the proportion trained on inventory management was comparatively low. Our findings therefore suggest that suboptimal immunization center quality is partly due to inadequate infrastructure and inefficient processes contributed to an extent, by low levels of inventory management training among vaccinators. Our study presents critical research findings with high-impact policy implications for identifying and addressing gaps to improve vaccination uptake within a low-middle income country setting.

Alternatives of Risk Prediction Models for Preeclampsia in a Low Middle-Income Setting

Abstract&#x0D; Objectives: To develop prediction models for the first-trimester prediction of PE (PE) using the established biomarkers including maternal characteristics and history, mean arterial pressure (MAP), uterine artery Doppler pulsatility index (UtA-PI ), and Placental Growth Factor (PlGF)) in combination with Ophthalmic artery Doppler peak ratio (PR).&#x0D; Methods: This was a prospective observational study in women attending a first-trimester screening at 11-14 weeks’ gestation. Maternal characteristics and history, measurement of MAP, ultrasound examination for UtA-PI measurement, maternal ophthalmic PR Doppler measurement, and serum PlGF collection were performed during the visit. Logistic regression analysis was used to determine if the maternal factor had a significant contribution in predicting PE. The Receiving Operator Curve (ROC) analysis was used to determine the area under the curve (AUC), positive predictive value (PPV), negative prefictive value (NPV) and positive screening cut-off in predicting the occurrence of PE at any gestational age.&#x0D; &#x0D; Results: Of the 946 eligible participants, 71 (7,49%) subjects were affected by PE. Based on the ROC curves, optimal high-risk cutoff value for prediction of preeclampsia at any gestational age for model 2 (primary care model) in this Indonesia study population were 63% with the sensitivity and specificity of 71.8% and 71.2%, respectively. Both sensitivity and specificity for model 3 (complete model) were 70.4% and 74.9%, respectively for the cutoff value 58%. The area under the curve of model 2, model 3 was 0.7651 (95% CI: 0.7023-0.8279)) and 0.7911 (95% CI: 0.7312-0.8511), respectively, for predicting PE. In addition, PPV and NPV for model 2 were 16.8% and 96.9%, respectively. PPV and NPV for model 3 were 18.55 and 96.9%, respectively.&#x0D; &#x0D; Conclusion: The prediction models of preeclampsia vary depending upon healthcare resource. Complete model is clinically superior to primary care model but it is not statistically significant. Prognostic models should be easy to use, informative and low cost with great potential to improve maternal and neonatal health in Low Middle Income Country settings.

Clinical Benefit of Comprehensive Genomic Profiling for Advanced Cancers in India.

PURPOSEComprehensive genomic profiling (CGP) assay is increasingly used in low-middle–income countries to detect clinically relevant genomic alterations despite its clinical benefits not being well known. Here, we describe the proportion of patients with advanced cancer in India who received targeted therapy for an actionable genetic alteration identified on CGP assays.METHODSThis was a multicenter, retrospective cohort study in adult patients with advanced nonhematologic malignancies who underwent a CGP test. If patients received a targeted therapy for ≥ 6 months, they were considered to have obtained a clinical benefit from the medication, whereas those continuing for ≥ 12 months were considered to have attained an exceptional response. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy.RESULTSDuring 2019-2020, 12 medical oncologists provided CGP reports for 297 patients; 221 met the inclusion criteria. Patients received a median of two lines (range: 0-5) of prior systemic therapy. On the basis of the CGP assay, 21 patients (10%) received targeted therapy. Among them, 33% was for human epidermal growth factor receptor 2 (HER2) amplification (nonbreast cancer) and 19% for HER2 or epidermal growth factor receptor exon 20 insertion mutation (lung cancer). After excluding patients with HER2 or epidermal growth factor receptor exon 20 insertions, 8% of 217 patients received targeted therapy. In the overall cohort of 221 patients, clinical benefit was seen in nine patients (4%), of whom two were exceptional responders (1%).CONCLUSIONWe observed that in a low-middle–income country setting, 10% of patients received targeted therapy on the basis of CGP assay. Only 4% of patients who underwent CGP testing obtained a clinical benefit.