Association of Modifiable Health Conditions and Social Determinants of Health With Late Mortality in Survivors of Childhood Cancer.

Importance: Associations between modifiable chronic health conditions (CHCs), social determinants of health, and late mortality (defined as death occurring ≥5 years after diagnosis) in childhood cancer survivors are unknown. Objective: To explore associations between modifiable CHCs and late mortality within the context of social determinants of health. Design, Setting, and Participants: This longitudinal cohort study used data from 9440 individuals who were eligible to participate in the St Jude Lifetime Cohort (SJLIFE), a retrospective cohort study with prospective clinical follow-up that was initiated in 2007 to characterize outcomes among childhood cancer survivors. Eligible individuals had survived 5 or more years after childhood cancer diagnosis, were diagnosed between 1962 and 2012, and received treatment at St Jude Children's Research Hospital were included in mortality estimates. A total of 3407 adult SJLIFE participants (aged ≥18 years) who completed an on-campus assessment were included in risk factor analyses. Vital status, date of death, and cause of death were obtained by linkage with the National Death Index (coverage from inception to December 31, 2016). Deaths occurring before inception of the National Death Index were obtained from the St Jude Children's Research Hospital Cancer Registry. Data were analyzed from June to December 2022. Exposures: Data on treatment exposures and causes of death were abstracted for individuals who were eligible to participate in the SJLIFE study. Information on modifiable CHCs (dyslipidemia, hypertension, diabetes, underweight or obesity, bone mineral deficiency, hypogonadism, hypothyroidism, and adrenal insufficiency, all graded by the modified Common Terminology Criteria for Adverse Events), healthy lifestyle index (smoking status, alcohol consumption, body mass index [calculated as weight in kilograms divided by height in meters squared], and physical activity), area deprivation index (ADI; which measures neighborhood-level socioeconomic disadvantage), and frailty (low lean muscle mass, exhaustion, low energy expenditure, slowness, and weakness) was obtained for participants. Main Outcomes and Measures: National Death Index causes of death were used to estimate late mortality using standardized mortality ratios (SMRs) and 95% CIs, which were calculated based on US mortality rates. For the risk factor analyses (among participants who completed on-campus assessment), multivariable piecewise exponential regression analysis was used to estimate rate ratios (RRs) and 95% CIs for all-cause and cause-specific late mortality. Results: Among 9440 childhood cancer survivors who were eligible to participate in the SJLIFE study, the median (range) age at assessment was 27.5 (5.3-71.9) years, and the median (range) duration of follow-up was 18.8 (5.0-58.0) years; 55.2% were male and 75.3% were non-Hispanic White. Survivors experienced increases in all-cause mortality (SMR, 7.6; 95% CI, 7.2-8.1) and health-related late mortality (SMR, 7.6; 95% CI, 7.0-8.2). Among 3407 adult SJLIFE participants who completed an on-campus assessment, the median (range) age at assessment was 35.4 (17.9-69.8) years, and the median (range) duration of follow-up was 27.3 (7.3-54.7) years; 52.5% were male and 81.7% were non-Hispanic White. Models adjusted for attained age, sex, race and ethnicity, age at diagnosis, treatment exposures, household income, employment status, and insurance status revealed that having 1 modifiable CHC of grade 2 or higher (RR, 2.2; 95% CI, 1.2-4.0; P = .01), 2 modifiable CHCs of grade 2 or higher (RR, 2.6; 95% CI, 1.4-4.9; P = .003), or 3 modifiable CHCs of grade 2 or higher (RR, 3.6; 95% CI, 1.8-7.1, P < .001); living in a US Census block with an ADI in the 51st to 80th percentile (RR, 5.5; 95% CI, 1.3-23.5; P = .02), an ADI in the 81st to 100th percentile (RR, 8.7; 95% CI, 2.0-37.6; P = .004), or an unassigned ADI (RR, 15.7; 95% CI, 3.5-70.3; P < .001); and having frailty (RR, 2.3; 95% CI, 1.3-3.9; P = .004) were associated with significant increases in the risk of late all-cause death. Similar associations were observed for the risk of late health-related death (1 modifiable CHC of grade ≥2: RR, 2.2 [95% CI, 1.1-4.4; P = .02]; 2 modifiable CHCs of grade ≥2: RR, 2.5 [95% CI, 1.2-5.2; P = .01]; 3 modifiable CHCs of grade ≥2: RR, 4.0 [95% CI, 1.9-8.4; P < .001]; ADI in 51st-80th percentile: RR, 9.2 [95% CI, 1.2-69.7; P = .03]; ADI in 81st-100th percentile: RR, 16.2 [95% CI, 2.1-123.7; P = .007], unassigned ADI: RR, 27.3 [95% CI, 3.5-213.6; P = .002]; and frailty: RR, 2.3 [95% CI, 1.2-4.1; P = .009]). Conclusions and Relevance: In this cohort study of childhood cancer survivors, living in a Census block with a high ADI and having modifiable CHCs were independently associated with an increased risk of late death among survivors of childhood cancer. Future investigations seeking to mitigate these factors will be important to improving health outcomes and developing risk-stratification strategies to optimize care delivery to childhood cancer survivors.

Infection Prevention and Control Measures at the Children Hospital Lahore: A My Child Matters Collaborative Project.

PURPOSE: Infection prevention among children with cancer is a major challenge at Children Hospital Lahore (CHL), a public health care facility in Pakistan with 1,000 new pediatric cancer admissions annually. The objective has been to reduce infections through collaboration between CHL and the St Jude Children's Hospital Global Infectious Disease program via a grant by the Sanofi Espoir foundation through the My Child Matters program. The aim of the current study was to describe the effect of the collaborative improvement strategy on existing infection prevention and control (IPC) standards at CHL. MATERIALS AND METHODS: Our work was a prospective before-and-after study to improve IPC standards. We compared the WHO Hand Hygiene Self-Assessment Framework and four modules of the St Jude modified Infection Control Assessment Tool (ICAT) scores over a 3-year period. Our strategy included creating a multidisciplinary team of pediatric oncologists, infectious disease physicians, nurses, a microbiologist, and a data manager; engaging in monthly online IPC mentoring sessions with St Jude Children's Hospital Global Infectious Disease program and My Child Matters mentors; performing daily inpatient health care-associated infection surveillance rounds; and performing regular hand hygiene training and compliance audits. RESULTS: Baseline needs assessment showed health care-associated infections identified by positive blood cultures as 8.7 infections per 1,000 patient-days. Deficient hand hygiene supplies, health education measures, and bed sharing of neutropenic patients were identified as major challenges. Our hand hygiene facility level, per WHO scores, increased from Inadequate to Intermediate/Consolidation by the end of the 3-year implementation (122 v 352 WHO Hand Hygiene Self-Assessment Framework scores). The sink:bed and hand sanitizer:bed ratios improved to 1:6 and 1:1, respectively. The ICAT general infection control module increased by 40% (45 v 78 ICAT scores) and hygiene compliance improved by 20%. CONCLUSION: Implementing a collaborative improvement strategy improved IPC standards in our center, which can be easily replicated in other pediatric oncology centers in lower- and middle-income countries.

A case of Guillain-Barre syndrome with pregnancy who delivered in ICU: a rare outcome of rare co-occurrence.

Guillain-Barre syndrome (GBS) in pregnancy is a rare co-occurrence and it is generally accepted that it carries a high maternal risk. We report a 40-year-old housewife who developed GBS with respiratory failure during the third trimester (31 weeks of gestation). She had preterm vaginal delivery on ventilator support at 34 weeks of gestation in neurology intensive care unit. She managed successfully with ventilatory support, intravenous immunoglobulin and other supportive measures.

Implementing a Childhood Cancer Outcomes Surveillance System Within a Population-Based Cancer Registry.

PURPOSE: Approximately 80% of cases of childhood cancer occur in low- and middle-income countries and are associated with high mortality rates. Assessing outcomes is essential for designing effective strategies to improve outcomes equally worldwide. We implemented a real-time surveillance system, VIGICANCER, embedded in a population-based cancer registry (PBCR) to assess childhood cancer outcomes. METHODS: VIGICANCER was established in 2009 as an integral part of Cali's PBCR to collect real-time data on outcomes of patients (age < 19 years) with a new diagnosis of cancer treated in pediatric oncology units in Cali, Colombia. Baseline and follow-up data (death, relapse, treatment abandonment, second neoplasms) were collected from medical records, hospital discharge logs, pathology reports, death certificates, and the National Public Health Insurance database. A quality assurance process was implemented for the system. RESULTS: From 2009 to 2013, data from 1,242 patients were included in VIGICANCER: 32% of patients were younger than 5 years, 55% were male, and 15% were Afro-descendants. International Classification of Childhood Cancer group I diagnoses predominated in all age groups except children younger than 1 year old, in whom CNS tumors predominated. Five-year overall survival for all cancers was 51.7% (95% CI, 47.9% to 55.4%) for children (< 15 years), and 39.4% (95% CI, 29.8% to 50.5%) for adolescents (15 to 18.9 years). Five-year overall survival for acute lymphoblastic leukemia was 55.6% (95% CI, 48.5% to 62.2%). CONCLUSION: Our study demonstrates the feasibility of implementing a real-time childhood cancer outcomes surveillance system embedded in a PBCR that can guide interventions to improve clinical outcomes in low- and middle-income countries.

The My Child Matters programme: effect of public-private partnerships on paediatric cancer care in low-income and middle-income countries.

In low-income and middle-income countries, an excess in treatment failure for children with cancer usually results from misdiagnosis, inadequate access to treatment, death from toxicity, treatment abandonment, and relapse. The My Child Matters programme of the Sanofi Espoir Foundation has funded 55 paediatric cancer projects in low-income and middle-income countries over 10 years. We assessed the impact of the projects in these regions by using baseline assessments that were done in 2006. Based on these data, estimated 5-year survival in 2016 increased by a median of 5·1%, ranging from -1·5% in Venezuela to 17·5% in Ukraine. Of the 26 861 children per year who develop cancer in the ten index countries with My Child Matters projects that were evaluated in 2006, an estimated additional 1343 children can now expect an increase in survival outcome. For example, in Paraguay, a network of paediatric oncology satellite clinics was established and scaled up to a national level and has managed 884 patients since initiation in 2006. Additionally, the African Retinoblastoma Network was scaled up from a demonstration project in Mali to a network of retinoblastoma referral centres in five sub-Saharan African countries, and the African School of Paediatric Oncology has trained 42 physicians and 100 nurses from 16 countries. The My Child Matters programme has catalysed improvements in cancer care and has complemented the efforts of government, civil society, and the private sector to sustain and scale improvements in health care to a national level. Key elements of successful interventions include strong and sustained local leadership, community engagement, international engagement, and capacity building and support from government.

Management of Concurrent Pregnancy and Acute Lymphoblastic Malignancy in Teenaged Patients: Two Illustrative Cases and Review of the Literature.

The usual age range of acute lymphoblastic malignancies (acute lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma) includes teenagers and young adults (<22 years of age) and coincides with the age of fertility. Concurrence of acute lymphoblastic malignancy with pregnancy is therefore most likely to happen during the younger childbearing ages. However, the therapeutic challenges posed by the dual diagnosis of lymphoblastic malignancy and pregnancy have not specifically been studied in the context of age, and management guidelines for pregnant young patients are lacking. Inconsistency in defining the legal decision-making rights of pregnant teenaged patients adds a further level of complexity in this age group. Management of this challenging combination in the young patient therefore entails unique ethical considerations. Here we present two illustrative cases of teenage pregnancy complicated by acute lymphoblastic malignancy, review the available literature, and offer suggestions for the therapeutic management of such cases in adolescent and young adult patients. Importantly, practical management recommendations are provided in the context of clinical ethics principles that are universally applicable, including in developing countries, where the highest incidence of adolescent pregnancies has been documented.

Death analysis of childhood acute lymphoblastic leukaemia; experience at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan.

OBJECTIVES: To analyze the common causes of death in childhood Acute Lymphoblastic Leukaemia (ALL) patients during therapy at Paediatric Oncology Department of Shaukat Khanum Memorial Cancer Hospital. METHODS: Retrospective descriptive study conducted at Paediatric Oncology department at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore Pakistan. All registered cases of ALL from 12 months to 18 years of age who expired between May 2001 to December 2005 were included. Mortality data was collected and analyzed regarding age, sex, WBC count, immunophenotype, treatment protocol, remission, and timing of death with respect to treatment protocol and the cause of death. RESULTS: Out of 304 new cases of ALL registered in the study period, 74 (24%) died during treatment. During induction 39 of 74 (52.7%) died, 33 (44.5%) in first remission and 2 (2.8%) before initiation of therapy. Infection alone or in combination with other factors was responsible for deaths in 63 of 74 (85%) cases. Septicemia, pulmonary and gastrointestinal infections were documented in 37/63 (58.7%), 44/63 (69%) and 8/63 (12.6%) cases respectively. Eight (10.8%) died due to haemorrhage. Three (4%) deaths were secondary to chemotherapy induced toxicity. CONCLUSION: Infection is the major cause of mortality in ALL patients in our study population. To improve survival it is imperative to improve supportive care especially prevention and management of infection.

Clinical characteristics and outcome analysis of pediatric B-cell non-Hodgkin's lymphoma. Experience with FAB-LMB 96 and UKCCSG B-cell NHL guidelines in a developing country.

AIM: To analyze the clinical characteristics of B-cell non-Hodgkin's lymphoma (NHL) patients and the therapeutic efficacy of French-American-British Lymphoma Malins de Burkitt 96 and the recent United Kingdom Children's Cancer Study Group B-cell NHL guidelines in the tertiary care hospital of a developing country. METHODS: Patients aged < or =18 years registered at our hospital between January 1995 and December 2006 with histologically proved B-Cell NHL were selected for retrospective analysis. RESULTS: Of the total of 131 patients registered, 122 patients were eligible for evaluation. Of these 95 had Burkitt's lymphoma, 22 diffuse large B-cell lymphoma and five had B-cell NHL not otherwise specified. The mean age was 8.4 years. Overall 42 children had a baseline weight less than the 10th centile. A total of 37 had uric acid >10 mg/dl and 55 had a lactate dehydrogenase level >500; 73 had stage III and 31 had stage IV while only four presented at stage I and 14 at stage II. The abdomen was the commonest site of disease. A total of 45 patients died; 28 due to infection, nine due to tumor lysis syndrome and six of uncontrolled disease. All deaths occurred within an average of 35 days from starting treatment. Our 5-year overall survival rate was 68 percent and our event-free survival was 55 percent. CONCLUSION: Late presentation with advanced disease, poor nutritional status and high risk of exposure to infective agents all contribute to the high mortality in patients treated with intensive protocols in resource-poor countries.

Granulocytic sarcoma of the small intestine: an unusual presentation of acute myelogenous leukaemia.

Granulocytic sarcoma is an extramedullary tumour of primitive granulocytic cells. It can develop at any anatomic site and is often a forerunner to the development of acute myelogenous leukaemia. Granulocytic sarcoma of the small intestine presents with abdominal pain and obstruction. We report a case of a 17-years-old boy who presented with epigastric pain. His endoscopy revealed multiple polypoid lesions throughout the duodenum and small bowel. Histopathology and flow cytometery confirmed the diagnosis of granulocytic sarcoma associated with acute myelogenous leukaemia. To our knowledge there have been only two previous case reports of multiple granulocytic sarcomas in the small intestine, both of these were adult patients. This is the first patient in the paediatric age group with multiple granulocytic sarcomas of the small intestine.

Age-standardized incidence rates for childhood cancers at a cancer hospital in a developing country.

BACKGROUND: Cancer registration is a neglected area in several developing countries of the world including Pakistan due to funding problems and apathy of most health professionals towards reporting of cancer data. METHODS: The epidemiologic review is the first of its type reporting cancers recorded at a cancer hospital in Lahore, Pakistan, in children less than 15 years of age, belonging to Lahore District, in a one year time period from January 1, 2008 to December 31, 2008. The results have been stratified by gender, 5-year age-groups (0-4, 5-9 and 10-14), and the International Classification of Childhood Cancers diagnostic groups. Crude- and age-specific-rates by age-groups were estimated and standardized by applying the direct method of age-standardization using the world standard of Segi (1960) to determine the incidence of childhood cancers per 100,000 population in one year. RESULTS: In order of ranking, the age-standardized incidence rates (ASR) per 100,000 were as follows: amongst boys, leukemias 1.3, lymphomas and reticuloendothelial neoplasms 1.3, CNS and miscellaneous intracranial/intraspinal tumors 0.7, malignant bone tumors 0.4, and soft tissue sarcomas 0.4; amongst girls, leukemias 0.7, lymphomas and reticuloendothelial neoplasms 0.5, malignant bone tumors 0.3, CNS and miscellaneous intracranial/intraspinal tumors 0.3, and renal tumors 0.3. CONCLUSION: The results represent one institution. However, as pediatric cancer care units are rare and specialized, hospital cancer registries in developing countries are likely to record a significant proportion of pediatric cases diagnosed in the area. Hence, it may be worthwhile to generate yearly incidence reports in an attempt to evaluate the trends in childhood cancers in Lahore.

Pediatric nasopharyngeal carcinoma: A review of 27 cases over 10 years at Shaukat Khanum Memorial Cancer Hospital and Research Center, Pakistan.

PURPOSE: This study aims to review the clinical features, treatment and outcome of pediatric nasopharyngeal Carcinoma at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH and RC) over ten years. METHODS: Retrospective review of pediatric patients who were diagnosed with nasopharyngeal carcinoma and treated at SKMCH and RC from July 1996 to June 2006. RESULTS: A total of 27 children with NPC were included. The male to female ratio was 4.4:1. The mean age at diagnosis was 14 years (8-18 years). The most common presenting symptom was neck swelling (81.5%, 22/27). The mean duration of symptoms before diagnosis was 10.3 months (3-36 months). The majority of patients (70%, 19/27) presented at stage IV. All received a combination of chemotherapy and radiotherapy. Survival analysis was performed for 22 patients; of these 8 patients died and 4 were lost to follow-up. The median follow-up time of the surviving patients was 53 months (5-116 months). At 5 years, the cumulative overall survival (OS) was 55% while the cumulative EFS was 54% with a flattening of the curve at 2 years. There was a significant difference in OS (p= 0.001) and EFS (p= 0.057) in patients diagnosed with NPC under 14 years of age (n= 11) and those between 14 and 18 years (n= 11). CONCLUSION: In our institutional study, NPC presents late and in advanced stage. The outcome is better in younger children. Our survival rates, while comparable to developing countries, are less than those seen in the developed world. We feel a strong need for collaborative studies in view of small numbers in individual centres.

Pre-operative renal function and selective renal vein renin levels as markers of favourable outcome in renovascular hypertension.

OBJECTIVE: To evaluate factors that affect outcome following revascularization in patients with renovascular hypertension. METHODS: This study was conducted at the Aga Khan University Hospital. It included all the patients diagnosed to have Renovascular hypertension confirmed by renal angiography between July 1996 to September 2000. Using ANOVA (Analysis of variance) and paired-sample t-test, several preoperative factors were evaluated for their ability to predict postoperative improvement of blood pressure and renal function. For descriptive purpose patients were divided into cured, improved and failure groups. RESULTS: Of the total 15 patients, 9 were males and 6 were females. Before the surgical procedure, 13 patients were on 3 or more antihypertensive drugs. Eleven patients received vein grafts, three patients had PTFE (polytetraflouroethyline) grafts while one patient underwent angioplasty and stenting. The patients had a median follow-up period of nine months with a range of 2 to 84 months. Five were completely cured, as they became normotensive without antihypertensive therapy after operation, whereas four showed marked improvement in BP control postoperatively, requiring two antihypertensive drugs. Six patients showed no improvement requiring 3 or more drugs. Extended cure or improvement of renovascular hypertension was achieved in nine patients. Normal preoperative serum creatinine level, high preoperative unstimulated peripheral renin levels and renal vein renin ratio of at least 1.75:1 were the most significant predictive factors for favorable outcome. CONCLUSION: This study confirms the long term effectiveness and safety of renovascular reconstruction in the relief of severe hypertension. The results further suggest that normal preoperative renal function, high renal vein renin ratio and high preoperative unstimulated peripheral renin levels are associated with the most favourable postoperative outcome (p <0.01). Preoperative severity and duration of hypertension and degree of disparity in kidney sizes do not affect the overall results in terms of postoperative improvement in renal function and blood pressure control (p=0.734).

Hodgkin's lymphoma in Pakistan: a clinico-epidemiological study of 658 cases at a cancer center in Lahore.

OBJECTIVES: To study the clinico-epidemiological profile of Hodgkin's lymphoma (HL) in Pakistan. PATIENTS AND METHODS: We retrospectively studied all histopathologically proven cases of HL, who presented between Dec 1995 to June 2003 at Shaukat Khanum Memorial Cancer Hospital and Research Hospital (SKMCH & RC). All the relevant information was obtained through the hospital based cancer registry and medical records of the selected patients. RESULTS: Six hundred and fifty eight histopathologically confirmed cases of HL were identified. There were 505 males and 153 females, with a male to female ratio of 3.3: 1. Patients ranged in age from 1 year - 84 years. The mean age at presentation was 23.8 years. Three hundred and twenty cases (48.6%) belonged to age group 18 years of age. Histopathologically, mixed cellularity (MC) constituted 63.8% of cases, followed by nodular sclerosis (NS) 19.9%, lymphocyte predominant (LP) 7.3% and lymphocyte depleted (LD) 1.2%. Early stage (stage I and II) disease was present in 43.9% of patients at presentation, while 56.1% patients presented with advanced stage (stage III and IV). The majority of patients (81.2%) presented with cervical lymphadenopathy. CONCLUSION: The clinico-epidemiological pattern of Hodgkin's lymphoma in Pakistan manifested is similar to that observed in other developing countries, with male predominance, mixed cellularity as the commonest histological type, advanced stage at presentation and absence of bimodal age distribution.

Renovascular hypertension: factors affecting the outcome following surgical revascularisation.

This study was conducted at the Aga Khan University Hospital, Karachi, Pakistan to evaluate factors that affect outcome following revascularisation in patients with renovascular hypertension. We included all the patients diagnosed to have renovascular hypertension, confirmed by renal angiography, between July 1997 and September 2000. Of the total 15 patients, nine were males and six were females. Eleven patients received venous grafts, three received polytetraflouroethyline (PTFE) grafts while one patient underwent angioplasty and stenting. All were followed-up for a period of nine months (median) with the range from 2 to 84 months. A total of 33.3% of the study patients were completely cured, as they became normotensive without anti-hypertensive therapy after operation, while 27% showed marked improvement in blood pressure control post-operatively. Thus, extended cure or improvement of renovascular hypertension was achieved in 60% of patients. Normal pre-operative serum creatinine level, high pre-operative unstimulated peripheral renin levels and renal vein renin ratio of at least 1.75:1 were the most significant predictive factors for favorable outcome (p < 0.012). The pre-operative severity and duration of hypertension as well as degree of disparity in kidney sizes did not predict the post-operative improvement in renal function and blood pressure control.