Medications Not Dosed Within Recommended Range for Renal Function in Patients With Chronic Kidney Disease Identified upon Hospice Admission
Hospice-eligible patients frequently have renally cleared medications prescribed and at doses too high for their renal function. Analgesics, over-the-counter antihistamines, anticoagulants, anticholinergics have potential for significant adverse effects and higher vigilance is needed.
Summary
A Retrospective Chart Review
[Posted 5/Mar/2026]
AUDIENCE: Hospice & Palliative Nursing, Nephrology
KEY FINDINGS: Hospice-eligible patients frequently have renally cleared medications prescribed and at doses too high for their renal function. Analgesics, over-the-counter antihistamines, anticoagulants, anticholinergics have potential for significant adverse effects and higher vigilance is needed.
BACKGROUND: Hospice-eligible patients are vulnerable to adverse medication effects given their advanced illnesses and general older age. It is not known how often medications are not renal dose adjusted in hospice-eligible patients and which are frequently problematic. This study aims to identify commonly prescribed medications with significant renal clearance that are dosed too high and patient characteristics that increase the likelihood of occurrence.
DETAILS: This is a retrospective chart review of adult patients admitted to hospice care. Data collected included clinical/demographic data, renally cleared medications taken at time of hospice admission, and calculated renal function using several formulas. Descriptive statistics and binomial logistic regression were used to analyze data. Of 283 included charts, 27% had >=1 medication dosed too high for renal function. The most common medications prescribed and not renal dose adjusted included tramadol, gabapentin, duloxetine, loratadine, cetirizine, famotidine, apixaban, rivaroxaban, metformin, trospium, and most antimicrobials. Increasing serum creatinine values and increasing number of renally cleared medications were associated with a higher likelihood of a medication dosed too high [OR, 1.702, 95% CI (1.257, 2.305), P < 0.001] and [OR, 1.856, 95% CI (1.517, 2.271), P < 0.001] respectively. Residing at home vs a facility was associated with a reduced likelihood of having a medication dosed too high [OR, 0.30, 95% CI (0.134, 0.673), P = 0.003.].
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Source: Latuga, N. M. and Levy, K. Medications Not Dosed Within Recommended Range for Renal Function in Patients With Chronic Kidney Disease Identified upon Hospice Admission: A Retrospective Chart Review. American Journal of Hospice and Palliative Medicine. 2026; 43(3): 234-241. Published: March, 2026. DOI: 10.1177/10499091251323284.
Long-Term Outcomes of Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia
In a phase II study of 30 patients with newly diagnosed FLT3-mutated AML, azacitidine, venetoclax, and gilteritinib produced a 96% CR/CRi rate. At a median follow-up of 41.5 months, median RFS and OS were 23.4 and 29.7 months, with 3-year rates of 43% and 46%, respectively. Baseline RAS pathway mutations were associated with poorer outcomes, while 67% of evaluable relapses lacked detectable FLT3 mutations. The triplet produced durable remissions but frequently required treatment dose or duration reductions because of myelosuppression.
KEY FINDINGS: In this phase II study, azacitidine, venetoclax, and gilteritinib produced high remission rates and encouraging long-term survival in patients with newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy. The 3-year RFS and OS rates were 43% and 46%, respectively, although outcomes were less favorable in patients with FLT3-ITD mutations and baseline RAS pathway mutations. Most evaluable relapses were FLT3-negative, suggesting that resistance may involve mechanisms beyond persistent FLT3-mutated disease. Dose or duration reductions were frequently required during consolidation, primarily reflecting the challenge of managing myelosuppression. Randomized studies are needed to establish the role of this triplet regimen relative to current standard approaches.
BACKGROUND: Relapse after frontline azacitidine and venetoclax remains a major challenge in patients with FLT3-mutated acute myeloid leukemia (AML), with relapse often associated with expansion of FLT3-mutated clones. This phase II study evaluated the long-term efficacy and safety of adding the FLT3 inhibitor gilteritinib to azacitidine and venetoclax in adults with newly diagnosed FLT3-mutated AML who were considered unfit for intensive chemotherapy.
DETAILS: Thirty patients with newly diagnosed FLT3-mutated AML were treated with the azacitidine, venetoclax, and gilteritinib triplet regimen. The median age was 71 years, and 22 (73%) patients had FLT3-ITD mutations. Fourteen patients (47%) proceeded to allogeneic hematopoietic stem cell transplantation in first remission. The median follow-up was 41.5 months.
The complete remission or complete remission with incomplete hematologic recovery rate was 96%. Eleven patients (37%) subsequently relapsed, and among evaluable relapses, the FLT3 mutation was no longer detectable in 67%, indicating that relapse mechanisms were not necessarily driven by persistent FLT3-mutated disease.
The median relapse-free survival (RFS) was 23.4 months and median overall survival (OS) was 29.7 months. At 3 years, RFS was 43% and OS was 46%. Among patients with FLT3-ITD-mutated AML, median RFS and OS were 17.0 months and 21.8 months, respectively, with 3-year RFS and OS rates of 32% and 36%. Baseline RAS pathway mutations were associated with poorer outcomes.
Survival outcomes were similar regardless of whether patients underwent allogeneic hematopoietic stem cell transplantation in first remission. Among patients receiving at least one consolidation cycle, 68% required a reduction in the dose or duration of at least one study drug, highlighting the need to manage treatment-related myelosuppression during prolonged therapy.
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Source: Short, N. J., Kantarjian, H. M., Daver, N., et al. Long-Term Outcomes of Azacitidine, Venetoclax and Gilteritinib in Newly Diagnosed FLT3-Mutated AML. Blood Advances.. 2026; 10(17): 5743–5750. Published: May 27, 2026. DOI: 10.1182/bloodadvances.2026019841.
[Posted 2/Sep/2026]
AUDIENCE: Hematology, Oncology
KEY FINDINGS: In this phase II study, azacitidine, venetoclax, and gilteritinib produced high remission rates and encouraging long-term survival in patients with newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy. The 3-year RFS and OS rates were 43% and 46%, respectively, although outcomes were less favorable in patients with FLT3-ITD mutations and baseline RAS pathway mutations. Most evaluable relapses were FLT3-negative, suggesting that resistance may involve mechanisms beyond persistent FLT3-mutated disease. Dose or duration reductions were frequently required during consolidation, primarily reflecting the challenge of managing myelosuppression. Randomized studies are needed to establish the role of this triplet regimen relative to current standard approaches.
BACKGROUND: Relapse after frontline azacitidine and venetoclax remains a major challenge in patients with FLT3-mutated acute myeloid leukemia (AML), with relapse often associated with expansion of FLT3-mutated clones. This phase II study evaluated the long-term efficacy and safety of adding the FLT3 inhibitor gilteritinib to azacitidine and venetoclax in adults with newly diagnosed FLT3-mutated AML who were considered unfit for intensive chemotherapy.
DETAILS: Thirty patients with newly diagnosed FLT3-mutated AML were treated with the azacitidine, venetoclax, and gilteritinib triplet regimen. The median age was 71 years, and 22 (73%) patients had FLT3-ITD mutations. Fourteen patients (47%) proceeded to allogeneic hematopoietic stem cell transplantation in first remission. The median follow-up was 41.5 months.
The complete remission or complete remission with incomplete hematologic recovery rate was 96%. Eleven patients (37%) subsequently relapsed, and among evaluable relapses, the FLT3 mutation was no longer detectable in 67%, indicating that relapse mechanisms were not necessarily driven by persistent FLT3-mutated disease.
The median relapse-free survival (RFS) was 23.4 months and median overall survival (OS) was 29.7 months. At 3 years, RFS was 43% and OS was 46%. Among patients with FLT3-ITD-mutated AML, median RFS and OS were 17.0 months and 21.8 months, respectively, with 3-year RFS and OS rates of 32% and 36%. Baseline RAS pathway mutations were associated with poorer outcomes.
Survival outcomes were similar regardless of whether patients underwent allogeneic hematopoietic stem cell transplantation in first remission. Among patients receiving at least one consolidation cycle, 68% required a reduction in the dose or duration of at least one study drug, highlighting the need to manage treatment-related myelosuppression during prolonged therapy.
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Source: Short, N. J., Kantarjian, H. M., Daver, N., et al. Long-Term Outcomes of Azacitidine, Venetoclax and Gilteritinib in Newly Diagnosed FLT3-Mutated AML. Blood Advances.. 2026; 10(17): 5743–5750. Published: May 27, 2026. DOI: 10.1182/bloodadvances.2026019841.
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.
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.
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.
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
Suicide Risk Peaks During the First Year After Dementia Diagnosis in Older Adults
Among 2,667,987 older adults with newly diagnosed dementia, suicide risk during the first year was significantly higher than in the general population (SMR 1.53), peaking within 90 days of diagnosis. Adults aged 65–74 years, patients with frontotemporal dementia, and those with mental illness, substance use disorders, or chronic pain had the greatest risk.
KEY FINDINGS: Older adults experience a significantly elevated risk of suicide during the first year after receiving a dementia diagnosis, particularly within the first 90 days. Individuals aged 65-74 years and those diagnosed with frontotemporal dementia represent the highest-risk groups. Coexisting mental illness, substance use disorders, chronic pain, rural residence, and recent mental health service utilization further increase suicide risk. These findings support routine suicide risk assessment, early psychiatric evaluation when appropriate, caregiver support, and discussions regarding restriction of access to lethal means immediately after a dementia diagnosis.
BACKGROUND: A new diagnosis of Alzheimer's disease or related dementias (ADRD) can be psychologically distressing and may increase vulnerability to suicidal behavior. Previous studies have reported inconsistent findings regarding suicide risk after dementia diagnosis. This nationwide U.S. cohort study evaluated suicide mortality and non-fatal suicidal events during the first year following a new ADRD diagnosis and identified patient characteristics associated with increased risk.
DETAILS: This retrospective cohort study included 2,667,987 Medicare fee-for-service beneficiaries aged >=65 years with newly diagnosed ADRD identified between 2012 and 2015. Patients were followed for up to 12 months after the initial dementia diagnosis or until death. Suicide deaths were identified through linkage with the National Death Index, while non-fatal suicidal events were captured using hospital claims. Standardized mortality ratios (SMRs) compared suicide risk with that of the general U.S. older adult population. Adjusted hazard ratios (AHRs) were calculated after controlling for age, sex, and race/ethnicity. During the first year after diagnosis, 705 suicide deaths occurred, corresponding to a suicide rate of 26.42 per 100,000 person-years, with an overall SMR of 1.53 (95% CI 1.42-1.65) compared with the general older adult population. The highest relative risk was observed among adults aged 65-74 years (SMR 3.40; 95% CI 2.94-3.86), and approximately half of all suicides occurred within the first 90 days after diagnosis. Patients with frontotemporal dementia had the highest suicide rate (124.63 per 100,000 person-years) and a significantly increased risk of suicide compared with unspecified dementia (AHR 2.91; 95% CI 1.67-5.05). Rural residence, recent mental health disorders, substance use disorders, chronic pain, and recent mental health-related healthcare utilization were independently associated with higher suicide risk. Non-fatal suicidal events were more frequent among patients with vascular dementia, personality disorders, bipolar disorder, anxiety disorders, substance use disorders, and chronic pain.
Genetic Analysis Identifies Vitamin B1 Metabolism as a Potential Therapeutic Target for Gut Motility Disorders
A multiancestry GWAS of 268,606 individuals identified 21 stool frequency loci, including 10 novel signals, and implicated vitamin B1 metabolism as a regulator of gut motility. Higher dietary thiamine intake correlated with increased stool frequency (p less than 0.0001), with effects modified by SLC35F3/XPR1 genotypes, highlighting a potential therapeutic target for IBS and dysmotility disorders.
KEY FINDINGS: This large multiancestry GWAS substantially expands the genetic architecture of gut motility by identifying 21 stool frequency-associated loci and uncovering vitamin B1 metabolism as a previously unrecognized regulator of intestinal transit. The convergence of genetic evidence on SLC35F3 and XPR1, together with the observed association between higher dietary thiamine intake and increased stool frequency, suggests that thiamine metabolism may represent a modifiable pathway for personalized nutritional or pharmacologic interventions. The findings also reinforce the importance of bile acid and cholinergic signaling in gut motility and provide a foundation for future mechanistic studies and therapeutic development for IBS and other dysmotility disorders.
BACKGROUND: Altered gastrointestinal motility is a central feature of irritable bowel syndrome (IBS) and other disorders of gut–brain interaction, yet the molecular mechanisms regulating intestinal transit remain incompletely understood. Stool frequency serves as a practical population-based surrogate for gut motility and enables large-scale genetic studies aimed at identifying biologically relevant pathways and potential therapeutic targets.
DETAILS: Investigators conducted a multiancestry genome-wide association study (GWAS) meta-analysis of stool frequency in 268,606 individuals of European (167,966) and East Asian (100,640) ancestry. Heritability, genetic correlations, Mendelian randomization, fine-mapping, and functional annotation analyses were performed to identify genes influencing gut motility. Dietary interaction analyses evaluating vitamin B1 (thiamine) intake were subsequently conducted in 98,449 UK Biobank participants to examine gene–nutrient interactions. Stool frequency demonstrated modest but consistent heritability across populations (7.0% in Europeans and 5.6% in East Asians). The analysis identified 21 independent genetic loci, including 10 novel loci, with significant genetic correlations observed between stool frequency and gastrointestinal, psychiatric, and cardiovascular traits (rg=0.12–0.47). Mendelian randomization supported a causal effect of stool frequency on IBS.
Fine-mapping highlighted two genes involved in thiamine metabolism-SLC35F3, encoding a thiamine transporter, and XPR1, which facilitates phosphate export required for activation of thiamine into thiamine pyrophosphate. Among 98,449 UK Biobank participants, higher dietary thiamine intake was associated with increased stool frequency (p<0.0001), and a combined SLC35F3/XPR1 genotype score significantly modified this relationship (p<0.0001). Additional candidate pathways implicated bile acid synthesis through KLB and cholinergic signaling through COLQ, supporting multiple biologically actionable mechanisms regulating intestinal transit. Drug-signature analyses further identified compounds targeting calcium channels, cholinergic pathways, histamine signaling, and bile acid regulation as potential candidates for therapeutic exploration.
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Source: Díaz-Muñoz, C., Bozzarelli, I., Lopera-Maya, E. A., et al. Genetic Dissection of Stool Frequency Implicates Vitamin B1 Metabolism and Other Actionable Pathways in the Modulation of Gut Motility. Gut. 2026; 75:1480-1490 Published: June 22, 2026. DOI: 10.1136/gutjnl-2025-337059.
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