Risk Predictors of Glycaemic Control in Children and Adolescents With Type 1 Diabetes
For children and adolescents with type 1 diabetes mellitus, the use of insulin pump, high-frequency sensor monitoring, prospective follow-up, good family support and reasonable diet are conducive to blood glucose control, while selective admission and DKA are not. Disease characteristics and demographic characteristics of children are closely related to subsequent blood glucose control
KEY FINDINGS: For children and adolescents with type 1 diabetes mellitus, the use of insulin pump, high-frequency sensor monitoring, prospective follow-up, good family support and reasonable diet are conducive to blood glucose control, while selective admission and DKA are not. Disease characteristics and demographic characteristics of children are closely related to subsequent blood glucose control, and the relationship between diagnosis age and blood glucose control needs to be further explored.
BACKGROUND: Aim of the study is to conduct systematic evaluation of the risk predictors of glycaemic control in children and adolescents with type 1 diabetes mellitus.
DETAILS: Cohort studies on risk predictors of glycaemic control in children and adolescents with type 1 diabetes were retrieved from CNKI, PubMed, Web of Science, Embase databases, etc. from the construction of the repository to 3 February 2023. Literature screening was conducted according to inclusion and exclusion criteria, then data extraction of region, sample size, age, follow-up time, risk predictors, outcome indicators, etc., and quality evaluation of The Newcastle-Ottawa Scale were conducted by two researchers while the third researcher makes decisions if there are disagreements. Finally, Revman5.4 and StataMP17 were used for meta-analysis. A total of 29 studies were included, and the results showed that insulin pump [Weighed mean difference (WMD) = -.48, 95% CI (-.73, -.24), p < .01], high-frequency sensor monitoring, early use of insulin pumps, prospective follow-up male, white race, large body mass index-standardised scoring, conscientiousness, agreeableness of mothers, eicosapentaenoic acid, leucine and protein (p < .05) were beneficial for reducing HbA1c levels in children and adolescents with diabetes. Ketoacidosis [WMD = .39, 95% CI (.28, .50), p < .01], selective admission, higher HbA1c level at one time (p < .01), higher glutamate decarboxylase antibody at 1 month after diagnosis, lower socio-economic status, non-living with biological parents, non-two-parent family, family disorder, family history of diabetes and high carbohydrate intake (p < .05) increased HbA1c levels in children and adolescents with diabetes.
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Source: Gangqiang, G., Hua, C., and Hongyu, S., (2024). Risk Predictors of Glycaemic Control in Children and Adolescents With Type 1 Diabetes: A Systematic Review and Meta-Analysis. J Clin Nurs. 2024; 33(7): 2412-2426. Published: July, 2024. DOI: 10.1111/jocn.17110.
Broad-Spectrum Antibiotic Use Is Lower Among Hospice Patients With Cancer at the End of Life
In this nationwide Korean cohort, hospice utilization was associated with lower broad-spectrum antibiotic use as death approached, particularly during the final week and final 3 days of life. The findings suggest that hospice involvement may be associated with a transition toward more selective antimicrobial use and less intensive treatment near the end of life. However, the study was observational, and causality cannot be established. Important clinical variables, including infection severity, microbiological findings, functional status, symptom burden, cancer stage, and treatment intent, were unavailable in the claims data.
KEY FINDINGS: Among adults with cancer approaching death, hospice utilization was associated with less frequent and lower-intensity broad-spectrum antibiotic exposure, particularly during the final days of life. The findings are consistent with a transition toward comfort-focused care, although they do not establish that hospice care itself caused the reduction. Hospice initiation occurred relatively close to death, with a mean interval of 39.9 days and a median of 22.0 days, and some antibiotic treatment may have preceded hospice enrollment. In addition, cancer stage, treatment status, infection severity, microbiological findings, functional status, symptom burden, and treatment intent were unavailable in the claims data.
BACKGROUND: Antibiotic treatment remains common during end-of-life care for patients with cancer, despite uncertain benefits for survival and potential burdens including drug toxicity, intravenous administration, adverse effects, and antimicrobial resistance. This retrospective cohort study evaluated whether hospice involvement was associated with differences in broad-spectrum antibiotic use among adults with cancer during the final 3 months of life.
DETAILS: Investigators analyzed Korean National Health Insurance Service claims data for adults aged ≥18 years who died between January 1, 2018, and December 31, 2021, with one of the 10 leading cancer-related causes of death. Hospice users had received inpatient, home-based, or consultation-based hospice care before death. Broad-spectrum antibiotic exposure included anti-pseudomonal penicillins, anti-pseudomonal cephalosporins, carbapenems, and glycopeptides. The final 90 days of life were divided into four intervals: 1–3 months before death, 1 week to 1 month before death, the final week, and the final 3 days. Antibiotic exposure was assessed by the proportion of patients receiving antibiotics and by days of therapy (DOT) per 1,000 patient-days. Propensity score matching was performed at a 1:2 ratio.
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After matching, 38,102 hospice users and 75,736 non-hospice users were analyzed. During the final 3 months of life, 74.6% of hospice users and 79.0% of non-hospice users received at least one broad-spectrum antibiotic (P0.001). Antibiotic use was initially slightly higher among hospice users during the period 1–3 months before death, at 34.0% versus 32.2% (P0.001), but became consistently lower among hospice users thereafter. From 1 week to 1 month before death, use was 31.1% versus 32.8%; during the final week, 11.3% versus 18.5%; and during the final 3 days, 4.8% versus 10.3% among hospice and non-hospice users, respectively (all P0.001).
Days of therapy per 1,000 patient-days were also consistently lower among hospice users, with the greatest differences occurring during the final week and final 3 days of life. Carbapenems and glycopeptides demonstrated particularly pronounced differences between the groups. In cancer-specific analyses, patients with hematologic malignancies had the highest overall antibiotic exposure, followed by those with pancreatobiliary and gastric cancers, while exposure was comparatively lower among patients with breast and liver cancers.
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Source: Jeung, Y. S., Kim, H. J., Yu, J., et al. Comparison of Broad-Spectrum Antibiotic Use According to Hospice Utilization Among Patients with Cancer at the End of Life in South Korea: A Nationwide Analysis. Journal of Hospice and Palliative Care. 2026; 29(2): 41-50. Published: June 1, 2026. DOI: 10.14475/jhpc.2026.29.2.41.
Paternal Valproate Use During Spermatogenesis Not Linked to Neurodevelopmental Disorders in Offspring
A large Swedish-Norwegian cohort found no significant association between paternal valproate use during spermatogenesis and neurodevelopmental disorders in offspring compared with paternal lamotrigine or levetiracetam use. Findings were consistent across dose-response analyses and among fathers with epilepsy, supporting reassessment of paternal valproate restrictions.
Summary
A population-based cohort study in Sweden and Norway.
[Posted 17/Aug/2026]
AUDIENCE: Neurology, Psychiatry
KEY FINDINGS: In this large Nordic population-based cohort, paternal valproate monotherapy during spermatogenesis was not significantly associated with neurodevelopmental disorders in offspring compared with paternal lamotrigine or levetiracetam monotherapy. Findings were consistent across dose-response analyses and among fathers with epilepsy. The results do not support an increased neurodevelopmental risk from paternal valproate exposure, although limitations inherent to registry-based observational research remain.
BACKGROUND: Valproate is an effective antiseizure medication, but its established teratogenic effects with maternal exposure have led to regulatory restrictions for women of reproductive potential. Concerns about possible paternal effects on offspring neurodevelopment have also prompted precautionary recommendations for men. This study evaluated whether paternal valproate use during spermatogenesis was associated with neurodevelopmental disorders (NDDs) in offspring.
DETAILS: This population-based cohort study used nationwide Swedish and Norwegian health registries. It included singleton live births at >=22 completed gestational weeks between 1 January 2007 and 31 December 2020 in Sweden and between 1 January 2010 and 31 December 2018 in Norway. After exclusions, 4681 children in Sweden and 1572 children in Norway were included for analysis.
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The analysis compared children whose fathers received valproate monotherapy during spermatogenesis with children whose fathers received lamotrigine or levetiracetam monotherapy. Outcomes included NDDs, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID), and disorders of psychological development. Analyses were adjusted for relevant parental and child characteristics, including parental age, psychiatric diagnoses, psychotropic medication use, epilepsy diagnosis, and, in Sweden, parental education and maternal cohabitation/marital status.
The study specifically examined paternal antiseizure medication exposure during spermatogenesis, corresponding to the approximately 3 months before conception. Dose-response analyses and analyses restricted to fathers with epilepsy were also conducted.
Among the children included in the primary comparison, 2051 were born to fathers who used valproate monotherapy during spermatogenesis. No significant association was identified between paternal valproate exposure and NDDs compared with paternal lamotrigine or levetiracetam exposure. The findings remained consistent in dose-response analyses and when the analysis was restricted to fathers with epilepsy.
During follow-up in Sweden, 406 children were diagnosed with an NDD, including 287 with ADHD, 140 with ASD, 55 with ID, and 79 with disorders of psychological development. In Norway, 60 children were diagnosed with an NDD, including 35 with ADHD, 13 with ASD, 5 with ID, and 26 with disorders of psychological development.
For ASD, the pooled adjusted hazard ratio was 1.29 (95% CI 0.89 to 1.85). The study authors noted that point estimates were slightly above 1.0 in some analyses but did not reach statistical significance.
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Source: Razaz, N., Soderling, J., Tomson, T., et al. Risk of Neurodevelopmental Disorders Associated With Paternal Use of Valproate During Spermatogenesis. Journal of Neurology, Neurosurgery & Psychiatry. 2026; 97-8: 671-679. Published: August, 2026. DOI: 10.1136/jnnp-2025-337441.
Hepatic Venous Pressure Gradient Predicts Anticoagulation Response and Prognosis in PA-HSOS
In 76 patients with PA-HSOS, HVPG independently predicted nonresponse to initial anticoagulation. An HVPG cutoff of 20.165 mmHg yielded an AUC of 0.741, increasing to 0.881 when combined with serum total bilirubin, heart rate, and blood urea nitrogen. Higher HVPG was associated with poorer survival and greater sinusoidal injury.
KEY FINDINGS: In patients with PA-HSOS, HVPG may help identify individuals at increased risk of nonresponse to initial anticoagulation and poorer survival. An HVPG threshold of 20.165 mmHg demonstrated moderate predictive performance, while a model incorporating HVPG, serum total bilirubin, heart rate, and blood urea nitrogen showed improved discrimination. The prognostic and disease-severity associations of HVPG were stronger when measurement was performed within 1 month of disease onset. These findings suggest that early HVPG assessment may support risk stratification and treatment planning, although the results require validation in larger prospective studies.
BACKGROUND: Pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) is a drug-induced liver injury characterized by rapidly progressive portal hypertension. Although hepatic venous pressure gradient (HVPG) is an established measure of sinusoidal portal hypertension, its utility in assessing disease severity, predicting response to anticoagulation, and determining prognosis in PA-HSOS remains uncertain. This retrospective study evaluated the clinical value of HVPG in patients with PA-HSOS.
DETAILS: This single-center retrospective study included 76 patients diagnosed with PA-HSOS according to the Nanjing criteria who underwent HVPG measurement between January 2016 and April 2020. All patients received anticoagulation-transjugular intrahepatic portosystemic shunt (TIPS) stepwise treatment. The investigators assessed the association of HVPG with nonresponse to initial anticoagulation, prognostic survival, Drum Tower Severity Scoring (DTSS), and histopathological findings.
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Among the 76 patients, 33 responded to initial anticoagulation, whereas 43 did not respond and subsequently underwent TIPS. The median follow-up duration was 35.42 (0.53-54.47) months. HVPG was evaluated using multivariable logistic regression and receiver operating characteristic analysis. A subgroup analysis was performed after excluding patients with disease onset more than 1 month before assessment.
HVPG was independently associated with nonresponse to initial anticoagulation (95% CI: 1.006-1.413, P=0.043). An HVPG cutoff of 20.165 mmHg predicted nonresponse with a sensitivity of 0.744, specificity of 0.697, and AUC of 0.741 (95% CI: 0.626-0.857, P<0.001). Combining HVPG >20.165 mmHg with serum total bilirubin, heart rate, and blood urea nitrogen increased the AUC to 0.881 (95% CI: 0.804-0.958, P<0.001).
Patients with HVPG >20.165 mmHg had significantly poorer survival than those with HVPG <=20.165 mmHg (P=0.022, χ2=5.285). Overall mortality was 13.16% (10/76), with 9 deaths among 42 patients in the high-HVPG group and 1 death among 34 patients in the low-HVPG group.
HVPG was positively correlated with the area of sinusoidal bleeding (P=0.008, R=0.343). After excluding patients with disease onset of more than 1 month, the predictive performance of HVPG improved, with an AUC of 0.789 (95% CI: 0.654-0.924, P=0.001). In this subgroup, HVPG also showed significant linear relationships with DTSS (P0.001, R=0.522) and sinusoidal bleeding area (P=0.001, R=0.499).
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Source: Cai, Z., Li, R., Zhang, H., et al. The Value of Hepatic Venous Pressure Gradient in Patients With Pyrrolidine Alkaloid-Induced Hepatic Sinusoidal Obstruction Syndrome. Journal of Gastrointestinal Surgery. 2026; 30(8)): 102376. Published: August, 2026. DOI: 10.1016/j.gassur.2026.102376.
Once-Weekly Oral Islatravir-Lenacapavir Maintains HIV-1 Viral Suppression at 48 Weeks
In 607 adults with virologically suppressed HIV-1, once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF at week 48. HIV-1 RNA levels of 50 copies/mL or higher occurred in 0% versus 0.3% of participants, respectively. Virologic suppression, CD4+ T-cell changes, and safety outcomes were comparable between the groups.
KEY FINDINGS: Once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF for maintaining virologic suppression through week 48 in adults with previously suppressed HIV-1. No participants receiving ISL/LEN had HIV-1 RNA levels of 50 copies/mL or higher, and virologic suppression rates remained high in both treatment groups. CD4+ T-cell changes and safety outcomes were broadly comparable. The once-weekly oral regimen may provide a less frequent treatment option for patients who prefer oral therapy but may benefit from reduced dosing frequency.
BACKGROUND: Daily single-tablet antiretroviral regimens have substantially improved HIV-1 management; however, maintaining long-term adherence remains challenging for some patients. Less frequent oral treatment schedules may provide an alternative to daily therapy while avoiding the need for injectable regimens. This phase 3 trial evaluated the efficacy and safety of once-weekly oral islatravir-lenacapavir (ISL/LEN) in adults with virologically suppressed HIV-1.
DETAILS: This phase 3, double-blind, randomized, active-controlled, noninferiority trial was conducted in 12 countries. Adults with HIV-1 viral suppression for at least 6 months while receiving once-daily bictegravir-emtricitabine-tenofovir alafenamide (B/F/TAF) were randomly assigned in a 1:1 ratio to switch to once-weekly oral ISL/LEN (2 mg/300 mg) or continue once-daily B/F/TAF for 96 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA levels of 50 copies/mL or higher at week 48, assessed using the FDA-defined snapshot algorithm. The prespecified noninferiority margin was 4 percentage points. A total of 607 participants underwent randomization, including 304 assigned to ISL/LEN and 303 assigned to B/F/TAF. At week 48, no participants in the ISL/LEN group and 1 participant (0.3%) in the B/F/TAF group had HIV-1 RNA levels of 50 copies/mL or higher (difference, -0.3 percentage points; 95.002% CI, -1.4 to 0.8), meeting the criterion for noninferiority. HIV-1 RNA levels below 50 copies/mL were observed in 284 participants (93.4%) receiving ISL/LEN and 280 participants (92.4%) receiving B/F/TAF (difference, 1.0 percentage point; 95% CI, -3.2 to 5.2). The mean change in CD4+ T-cell count was -10 cells/µL with ISL/LEN and -18 cells/µL with B/F/TAF, with a least-squares mean difference of 12 cells/µL (95% CI, -16 to 39). Treatment discontinuation due to adverse events occurred in 6 participants (2.0%) receiving ISL/LEN and 5 participants (1.7%) receiving B/F/TAF; serious adverse events occurred in 16 participants (5.3%) and 14 participants (4.6%), respectively.
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Obesity, Rather Than High Body Surface Area Alone, Predicts Clinically Significant Asparaginase Toxicity During Induction Therapy for Acute Lymphoblastic Leukemia
Among 4,925 children and young adults with ALL, obesity—not high BSA alone—was the strongest predictor of clinically significant asparaginase toxicity. Patients with obesity and high BSA had the highest risk of hepatic toxicity and thromboembolism, whereas induction toxicities were not associated with increased end-of-induction MRD positivity.
KEY FINDINGS: This large multicenter analysis demonstrates that obesity-not elevated BSA alone-is the principal patient-related risk factor for clinically significant asparaginase toxicity during induction therapy for ALL. The greatest excess risk occurred in patients with both obesity and high BSA, particularly for hepatic toxicity and thromboembolic events, while pancreatitis risk was unaffected. Older age independently increased toxicity risk, especially hyperbilirubinemia. Notably, induction-phase AAT did not compromise early treatment response, as measured by EOI MRD. These findings suggest that obesity should be prioritized when identifying patients for enhanced toxicity surveillance and future preventive strategies, whereas high BSA in the absence of obesity does not appear to justify dose modification based solely on body size.
BACKGROUND: Asparaginase remains a cornerstone of induction therapy for acute lymphoblastic leukemia (ALL), but treatment-limiting toxicities frequently interrupt therapy and may compromise long-term outcomes. Previous studies have produced conflicting evidence regarding whether older age, obesity, or high body surface area (BSA) independently increase the risk of asparaginase-associated toxicities (AAT). This large Children’s Oncology Group analysis evaluated the relative contributions of these risk factors and examined whether induction-phase AAT affected early treatment response measured by end-of-induction (EOI) minimal residual disease (MRD).
DETAILS: This retrospective analysis included 4,925 patients aged 1-30 years enrolled in the Children’s Oncology Group trials AALL0232 and AALL0434. All patients received a single induction dose of pegaspargase 2500 IU/m² without dose capping. Investigators assessed grade >=3 hyperbilirubinemia, grade >=4 alanine aminotransferase (ALT) elevation, grade >=2 thromboembolism, and grade >=3 acute pancreatitis. Multivariable analyses evaluated the independent effects of age, obesity, and BSA, while EOI MRD positivity (>=0.01%) was analyzed to determine whether AAT adversely influenced early leukemia response. Among 4,925 patients, 290 (6%) experienced at least one clinically significant AAT during induction. Toxicity rates increased with advancing age and obesity. After adjustment for confounding variables, obesity independently increased the likelihood of AAT (OR 2.5; 95% CI 1.88-3.24), whereas high BSA alone was not an independent predictor. Patients with both obesity and high BSA had the greatest risk of overall AAT (OR 3.3; 95% CI 2.22-4.77), while high BSA without obesity was not associated with increased risk (OR 1.4; 95% CI 0.94-2.04). Older patients (>=10 years) demonstrated more than a twofold increase in AAT risk compared with younger children.
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Obesity combined with high BSA significantly increased the risk of hyperbilirubinemia (OR 3.5; 95% CI 2.2-5.7), severe ALT elevation (OR 3.3; 95% CI 1.7-6.6), and thromboembolism (OR 3.1; 95% CI 1.5-6.5). Acute pancreatitis showed no significant association with obesity or BSA. Importantly, development of AAT did not increase the likelihood of EOI MRD positivity (36.6% vs 33.5%; Ps= .318), suggesting that induction toxicities did not adversely affect early disease response.
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Source: Orgel, E., Maese, L. D., Devidas, M., et al. Toxicity From Asparaginase During Acute Lymphoblastic Leukemia Induction: A Report From the Children's Oncology Group. Blood Advances. 2026; 10(14):4923-4930. Published: July 28, 2026. DOI: 10.1182/bloodadvances.2026019870
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