Singh, Manraj

Abstract Nonmyeloablative-related haploidentical allogeneic stem cell transplantation (NMAC-HID allo-HSCT) has emerged as an additional treatment to achieve durable remission in sickle cell disease (SCD), a prevalent blood disorder characterized by painful vaso-occlusive crises and chronic anemia. The standard of care (SOC) for SCD includes hydroxyurea, pain management, and blood transfusion, but patients with SCD still lose several decades of life expectancy. Gene therapy (GT) for SCD is the other treatment for lifelong disease amelioration in SCD, with accessibility limited by cost and manufacturing capacity in the United States and globally. Two recent prospective studies that evaluated NMAC-HID allo-HSCT validated haploidentical allotransplantation as an efficacious and accessible treatment option in the era of GT. Given the ongoing price negotiation across jurisdictions for GT implementation and the absence of cost-effectiveness data comparing NMAC-HID allo-HSCT and GT, we conducted a cost-effectiveness analysis of NMAC-HID allo-HSCT vs GT vs SOC for adults and children living with SCD. The primary outcomes were the incremental cost-effectiveness ratio and the net monetary benefits across these 3 strategies. The secondary outcome was the maximum cost-effective threshold price for GT compared with NMAC-HID allo-HSCT. Treatment with SOC, NMAC-HID allo-HSCT, and GT accrued 14.3, 20.1, and 22.1 quality-adjusted life-years at costs of $1.22 million, $1.15 million, and $2.75 million, respectively. NMAC-HID allo-HSCT was the cost-effective strategy compared with GT in 100% of 10 000 Monte Carlo iterations across the base case and all scenario analyses. The maximum cost-effective thresholds for GT vs SOC were $1.4 million in the United States and $4200 to $22 000 across India, Nigeria, and Tanzania, depending on willingness-to-pay thresholds.

Abstract Maternal iron deficiency (ID) affects nearly 85% of all pregnancies worldwide by the third trimester and is strongly linked with maternal morbidity, poor birth outcomes, and cognitive and behavioral developmental deficits in children. Despite its burden on maternofetal health, no guidelines exist for routine screening of ID in pregnant individuals in the United States. The World Health Organization uses a diagnostic (ie, nonscreening) ferritin threshold of 15 μg/L for ID in the first trimester of pregnancy, with no guidance for the second and third trimesters. Routine screening for ID in pregnancy could identify a large proportion of mothers who remain undiagnosed and untreated under the current clinical status quo. Accordingly, we conducted, to our knowledge, the first cost-effectiveness analysis of ferritin-based ID screening in pregnant women in the United States, comparing thresholds of (1) 30 μg/L vs (2) 15 μg/L vs (3) no screening from a modified US societal perspective accounting for wages lost to infusion time, infusion administration costs, and the cost of annual hematology follow-up. We found that screening at 30 μg/L was the preferred strategy across extensive base-case, threshold, and sensitivity analyses and across all examined willingness-to-pay thresholds, with an incremental cost-effectiveness ratio of $34 000/quality-adjusted life year (QALY; 95% credible interval, $32 000-$36 200/QALY) compared with no screening. No parameter variation changed this outcome, and screening at 30 μg/L was favored in 100% of 10 000 Monte Carlo iterations. Population-level regular second- and third-trimester screening for ID using physiologically informed ferritin ranges should be considered for all pregnant women in the United States.

ABSTRACT Background Fosaprepitant is non‐inferior to aprepitant in adults receiving highly emetogenic chemotherapy (HEC). We evaluated whether fosaprepitant is non‐inferior to aprepitant in children receiving HEC. Methods In this open‐label, non‐inferiority trial, children aged 5–18 years, receiving their first cycle of HEC, were randomized 1:1 to the fosaprepitant or aprepitant group. The fosaprepitant group received a single intravenous dose of 4 mg/kg (max 150 mg). The aprepitant group received oral aprepitant capsules (weight 15 to <30 kg: 80 mg Days 1–3; weight ≥30 kg, or age ≥12 years: 125 mg Day 1, 80 mg Days 2 and 3). Both groups received ondansetron and dexamethasone. The primary outcome was the complete response (CR) rate of vomiting during the acute phase (AP) with a non‐inferiority margin of 15%. Secondary outcomes included CR rates in the delayed (DP) and overall phases (OP), grade of vomiting, incidence and severity of nausea, and adverse effects. Results A total of 279 children were included in the modified intention‐to‐treat analysis (fosaprepitant group: 140; aprepitant group: 139). In AP, the difference of CR rate between fosaprepitant [76 (54.3%)] and aprepitant groups [84 (60.4%)] was −6.1% [90% CI: −15.7% to +3.6%], with the lower limit exceeding −15%, failing to establish non‐inferiority. The CR rate with fosaprepitant versus aprepitant was 62.1% ( n = 87) versus 65.5% ( n = 91) in DP (difference: –3.4%; 90% CI: –12.7% to 6.1%) and 42.9% ( n = 60) versus 49.6% ( n = 69) in the OP (difference: –6.7%; 90% CI: –16.5% to 3.1%). Grade of vomiting, incidence and severity of nausea, and adverse effects were similar between the two groups. Conclusions Non‐inferiority of fosaprepitant compared to aprepitant was not demonstrated in children undergoing their first cycle of HEC. Trial Registration Clinical Trials Registry, India (CTRI/2019/05/019082).

Abstract Iron-deficiency anemia (IDA) affects nearly one-third of women globally, with heavy menstrual bleeding (HMB) being a significant risk factor among those of reproductive age. Despite the substantial burden of HMB-related IDA, patients often face delays in receiving effective treatment. Oral iron is typically used as first-line therapy, despite frequent gastrointestinal side effects and challenges in treatment adherence. This study evaluated the reproductive life span cost-effectiveness of first-line intravenous (IV) vs oral iron therapy for women with HMB and IDA. We developed a Markov model simulating a cohort of women aged 18 to 51 years, comparing first-line treatment with IV iron dextran, IV ferumoxytol, IV iron sucrose, or oral ferrous sulfate. Costs and quality-adjusted life years (QALYs) were estimated from the societal perspective. IV iron dextran was the cost-effective treatment, yielding 19.26 QALYs at a cost of $157 500, compared with 19.10 QALYs at $152 900 for oral ferrous sulfate. The incremental cost-effectiveness ratio for IV iron dextran was $28 600 per QALY. Treatment with IV ferumoxytol and iron sucrose cost $158 300 and $163 500, respectively, and did not provide additional QALY benefit compared with IV iron dextran, which remained the cost-effective treatment across a range of scenarios and sensitivity analyses. Our findings indicate that first-line treatment with IV iron dextran is the cost-effective strategy for managing IDA in women with HMB at commonly accepted willingness-to-pay thresholds. These results support expanding access to IV iron as a first-line option, and highlight the need to reduce treatment delays and insurance-related barriers.

PURPOSE Gender bias against girls may affect health-seeking behavior and outcomes of childhood cancer. This study aimed to study the nature and extent of gender bias in health care among caregivers of childhood patients with cancer and also in community. METHODS This cross-sectional mixed-methods study was conducted in a tertiary cancer hospital and an urban community between July 2021 and July 2023. Qualitative component included 26 in-depth interviews (IDI) and four focus group discussions (FGDs) with caregivers of children with cancer. IDIs and FGDs were conducted by a psychologist and continued until thematic saturation was reached. For quantitative part, a gender-bias questionnaire was finalized which was administered to 230 caregivers in hospital and 311 participants from the community, with children in family. RESULTS Most participants did not perceive personal gender bias; however, many acknowledged noticing gender bias in others. This bias was linked to girls being considered financial burdens and having reduced marital prospects due to illness. Reducing treatment costs, improving access, and education targeting societal mindsets were suggested measures to mitigate bias. In community, no significant difference was observed among the respondents based on sex of youngest child in family. However, in hospital, caregivers of male children were less likely to offer similar care to a child of opposite sex than that reported by caregivers of female children ( P = .01) for ailments like fever/diarrhea. Similar difference was not observed for other health care scenarios. CONCLUSION Gender bias against girls, including that in health care access, is influenced by societal norms. Even with little personal perception of bias, there was a significant perceived bias observed in others by the participants. This study identified the existence of gender bias affecting health care choices, including cancer care.

ABSTRACTBackgroundComplementary and alternative medicine (CAM) usage among childhood cancer patients remains understudied. Factors associated with CAM use and motivations of caregivers for using CAM remain poorly understood.MethodsThis cross‐sectional mixed‐methods study was conducted among caregivers of patients aged ≤18 years with confirmed cancer diagnoses. Caregivers were interviewed regarding CAM use, reasons for using/non‐using CAM, and views on CAM. Logistic regression identified factors associated with CAM use, whereas qualitative interviews explored motivations and barriers. The impact of CAM usage on 2‐year overall survival was explored.ResultsOut of 450 respondents, CAM usage was reported by 35.78% (n = 161), with home remedies (28.44%, n = 128) and AYUSH (Ayurveda, Unani, Siddha, Yoga, Homeopathy) therapies (13.56%, n = 61) being most common. CAM use was associated with symptom duration ≥30 days (adjusted odds ratio [aOR]: 1.71; 95% CI: 1.09–2.67; p = 0·019) and hematological malignancies (aOR: 2.05; 95% CI: 1.33–3.17; p = 0·001). Major motivations for CAM use included belief in effectiveness (44.72%, n = 72) and family recommendations (34.16%, n = 55). Qualitative interviews highlighted cost, accessibility issues, and diagnostic delays as key drivers of CAM adoption. The 2‐year survival probabilities of CAM users and nonusers were comparable (0.88 [95% CI: 0.83–0.94] vs. 0.87 [95% CI: 0.83–0.92], log‐rank p = 0.75).ConclusionCAM is frequently used by pediatric cancer patients, driven by caregiver beliefs, family influence, and access barriers. Addressing caregiver practices and integrating CAM discussions into care may enhance supportive strategies without impacting survival outcomes.

ABSTRACTBackgroundWhile teleconsultation has proven feasible for adult cancer patients, its utility in childhood cancer care in India is unknown. This study assesses caregiver satisfaction, feasibility, and the economic impact of teleconsultation for children with cancer.ProcedureThis mixed methods study was conducted in the pediatric cancer outpatient service at a tertiary care cancer center in India. Routine care teleconsultations were performed via telephone or email. Caregivers who received teleconsultations during the study period or 6 months prior were interviewed by phone. Data collected included demographic details, teleconsultation usage patterns, caregiver satisfaction, reasons for satisfaction or dissatisfaction, and cost savings. Logistic regression identified baseline characteristics associated with satisfaction. In‐depth interviews were conducted in a separate cohort till thematic saturation.ResultsCaregivers of 465 children were included for telephonic and eight for in‐depth interviews Among the respondents, 72.8% (n = 339) were satisfied with teleconsultation, and 85.4% (n = 397) of those planned to continue using it. Significant reasons for satisfaction were cost and time savings, while difficulty explaining issues caused dissatisfaction. Multivariable analysis showed parental education above high school [OR: 1.59, p = 0.035] increased satisfaction likelihood, while a residential distance of greater than 100 km from the hospital [OR: 0.62, p = 0.033] decreased it. Median cost savings per visit was $24.2 (range: $1–$846). Cost savings did not determine satisfaction magnitude. Frequently cited themes included cost and time savings and the need for literacy to benefit from teleconsultation.ConclusionsTeleconsultation is feasible and effective for routine childhood cancer care, even in resource‐constrained settings.