Development and validation of a model to predict acute kidney injury following high-dose methotrexate in patients with lymphoma.

STUDY OBJECTIVE: To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure. DESIGN: Retrospective analysis. SETTING: Multisite integrated health system throughout Minnesota and Wisconsin. PATIENTS: Adult patients with lymphoma who received HDMTX as a 4-h infusion. MEASUREMENTS AND MAIN RESULTS: LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort. CONCLUSION: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

Glucagon prescribing and prevention of hospitalization for hypoglycemia in a large health system.

AIMS: To examine glucagon prescribing trends among patients at high risk of severe hypoglycemia and assess if a glucagon prescription is associated with lower rates of severe hypoglycemia requiring hospital care. METHODS: Retrospective analysis of electronic health records from a large integrated healthcare system between May 2019 and August 2021. We included adults (≥18 years) with type 1 diabetes or with type 2 diabetes treated with short-acting insulin and/or recent history of hypoglycemia-related emergency department visit or hospitalization. We calculated rates of glucagon prescribing overall and by patient characteristics. We then matched 1:1 those who were and were not prescribed glucagon and assessed subsequent hypoglycemia-related hospitalization. RESULTS: Of 9,200 high risk adults, 2063 (22.4%) were prescribed glucagon. Among patients more likely to be prescribed glucagon were those younger, female, White, living in urban areas, with prior severe hypoglycemia, and with a recent endocrinology specialist visit. In the matched cohort (N = 1707 per arm), 62 prescribed glucagon and 33 not prescribed glucagon were hospitalized for hypoglycemia (adjusted incidence rate ratio 1.71, 95% CI 1.10-2.66; P = 0.018). CONCLUSION: Glucagon prescribing was infrequent with significant racial and rural disparities. Patients with glucagon prescriptions did not have lower rates of hospitalization for hypoglycemia.

Infant and Maternal Vitamin D Supplementation: Clinician Perspectives and Practices.

INTRODUCTION: Rates of infant vitamin D supplementation fall short of guideline recommendations. We explored this discrepancy from the clinician perspective as they advise and affect this important intervention to prevent rickets. We compared infant and high-dose maternal vitamin D supplementation prescribing attitudes and practices between infant-only clinicians (IC) and clinicians who care for mothers and infants (MIC). METHODS: We surveyed clinicians in departments of family medicine, obstetrics/gynecology, primary care pediatrics, neonatology, newborn nursery, and members of vitamin D and rickets working groups and a social media group for lactation medicine providers about their perspectives and practices regarding vitamin D supplementation. RESULTS: 360 clinician survey responses were analyzed. In current practice, IC were more likely than MIC to recommend vitamin D supplementation to exclusively (P < .001) and partially breastfed infants (P = .005). MIC were more likely than IC to discuss infant and high-dose maternal supplementation options and let the parents/caregivers choose (34.7%, 22.0%, P = .009). If supplementing the mother with high-dose vitamin D or the infant directly each provided adequate vitamin D in the infant, MIC were more likely than IC to think that supplementation of the mother would be preferred by parents/caregivers (63.0%, 45.2%, P = .003), improve adherence (66.5%, 49.4%, P = .006), and promote breastfeeding (54.7%, 36.5%, P = .001); they were also more likely to recommend supplementation of the mother (17.7%, 8.9%, P = .04). CONCLUSIONS: MIC are more likely than IC to embrace high-dose maternal vitamin D supplementation to provide adequate vitamin D for infants. This highlights an opportunity for further education of clinicians about this option.

Evaluation of an Enhanced Primary Care Team Model to Improve Diabetes Care.

PURPOSE: Primary care practices manage most patients with diabetes and face considerable operational, regulatory, and reimbursement pressures to improve the quality of this care. The Enhanced Primary Care Diabetes (EPCD) model was developed to leverage the expertise of care team nurses and pharmacists to improve diabetes care. METHODS: Using a retrospective, interrupted-time series design, we evaluated the EPCD model's impact on D5, a publicly reported composite quality measure of diabetes care: glycemic control, blood pressure control, low-density lipoprotein control, tobacco abstinence, and aspirin use. We examined 32 primary care practices in an integrated health care system that cares for adults with diabetes; practices were categorized as staff clinician practices (having physicians and advanced practice providers) with access to EPCD (5,761 patients); resident physician practices with access to EPCD (1,887 patients); or staff clinician practices without access to EPCD (10,079 patients). The primary outcome was the percentage of patients meeting the D5 measure, compared between a 7-month preimplementation period and a 10-month postimplementation period. RESULTS: After EPCD implementation, staff clinician practices had a significant improvement in the percentage of patients meeting the D5 composite quality indicator (change in incident rate ratio from 0.995 to 1.005; P = .01). Trends in D5 attainment did not change significantly among the resident physician practices with access to EPCD (P = .14) and worsened among the staff clinician practices without access to EPCD (change in incident rate ratio from 1.001 to 0.994; P = .05). CONCLUSIONS: Implementation of the EPCD team model was associated with an improvement in diabetes care quality in the staff clinician group having access to this model. Further study of proactive, multidisciplinary chronic disease management led by care team nurses and integrating clinical pharmacists is warranted.

Association of mindfulness with female sexual dysfunction.

OBJECTIVES: Female sexual dysfunction (FSD) affects women of all ages. It is often a multifactorial problem with a strong psychosocial component. Mindfulness may help alleviate FSD with nonjudgmental, present-moment awareness and decreased emotional reactivity. The goal of this study was to assess the association between dispositional or trait mindfulness and FSD. STUDY DESIGN: In this cross-sectional study at a tertiary care women's health clinic, 1718 cisgender women (mean age, 51.9 years) completed the Mindfulness Attention Awareness Scale (MAAS), Female Sexual Function Index (FSFI), and Female Sexual Distress Scale-Revised (FSDS-R). MAIN OUTCOME MEASURES: Regression analysis was used to test the associations of mindfulness, sexual function, and sexual distress with univariate and multivariable analyses, adjusting for potential confounders. RESULTS: Within the sample, 57% of women met FSD criteria (FSFI scores ≤26.55 and FSDS-R ≥ 11). On univariate analysis, higher MAAS scores, signifying greater mindfulness, were associated with higher (better) sexual function scores, lower sexual distress scores, and lower odds of FSD. This association persisted on multivariable analysis after adjusting for potential confounders. CONCLUSIONS: Higher trait mindfulness was associated with better sexual function, lower sexual distress, and lower likelihood of FSD. Further studies are needed to assess the role of mindfulness in mitigating FSD.

Early, empiric high-dose leucovorin rescue in lymphoma patients treated with sequential doses of high-dose methotrexate.

BACKGROUND: In patients exposed to high-dose methotrexate (HDMTX; >1g/m2) with a history of elevated methotrexate (MTX) concentrations during previous doses, it is unclear whether prescribing high-dose leucovorin (HDLV) rescue limits future high levels or reduces the likelihood of acute kidney injury (AKI). METHODS: This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (>1.0 µmol/L) and incident AKI after each HDMTX dose. RESULTS: The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75-4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38-3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5-1.7, p < 0.001). CONCLUSION: Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.

Iron deficiency anemia associated with extracorporeal photopheresis: A retrospective analysis.

BACKGROUND: Extracorporeal photopheresis (ECP) is associated with few adverse effects. We have anecdotally noted patients treated with long-term ECP develop iron deficiency anemia (IDA). METHODS: We performed a retrospective chart review of adult patients who received ECP for any indication at Mayo Clinic Rochester and Mayo Clinic Arizona. The primary objective was to describe the cumulative incidence of IDA at 1 year of ECP therapy. RESULTS: A total of 123 patients were eligible for analysis. Graft-vs-host disease was the most common indication for ECP (n = 76, 61.8%). At 1 year of ECP therapy, the cumulative incidence of IDA was 24.1% (95% CI, 14.2%-32.9%). At 5 years, the cumulative incidence of IDA was 68.3% (95% CI, 38%-83.8%). Risk factors for the development of IDA included: cumulative number of ECP sessions (HR 1.34, 95% CI, 1.05-1.73 per 10 additional sessions, P = .022), an indication for ECP of solid organ transplant rejection (compared to cutaneous T-cell lymphoma, HR 5.46, 95% CI, 2.06-14.49, P < .001), and proton pump inhibitor use at baseline (HR 2.15, 95% CI, 1.1-4.21, P = .03). Iron supplementation was initiated in 29 of 37 evaluable patients who developed IDA, with a cumulative incidence of supplementation in 77.2% patients within 3 months of recognition of IDA (95% CI, 55.8%-88.3%). Hemoglobin normalized in 50.1% of patients started on iron supplementation for IDA within 7 months (95% CI, 25.2%-66.7%). CONCLUSIONS: Iron deficiency anemia is common in patients receiving long-term ECP and occurs throughout ECP therapy. IDA resolved with iron supplementation in half of patients.

A comparison of levofloxacin and oral third-generation cephalosporins as antibacterial prophylaxis in acute leukaemia patients during chemotherapy-induced neutropenia.

BACKGROUND: There is demonstrated benefit with fluoroquinolones as infection prophylaxis in neutropenic patients; however, side effects, drug interactions and increasing resistance necessitate investigation of alternative therapies. OBJECTIVES: To compare the incidence of febrile neutropenia in high-risk patients with haematological malignancy receiving a fluoroquinolone with those receiving an oral third-generation cephalosporin (OTGC) as antibacterial prophylaxis during chemotherapy-induced neutropenia. METHODS: A retrospective, matched, single-centre study comparing clinical and microbiological outcomes in acute leukaemia patients receiving fluoroquinolones versus OTGCs as antibacterial prophylaxis after chemotherapy. RESULTS: A total of 120 patients (levofloxacin n = 80, OTGC n = 40) were included and matched. The 30 day incidence of febrile neutropenia was 89.7% (95% CI = 82.4-93.9). The rates of febrile neutropenia were similar between antimicrobials (OTGC versus levofloxacin HR = 0.90, 95% CI = 0.54-1.52, P = 0.70). The most frequent site of infection was the bloodstream (line related) (n = 24, 62%) and the majority (n = 28, 72%) of infections were caused by Gram-positive organisms. Groups were similar in terms of site of infection (P = 0.91) and morphology of recovered microorganisms (P = 0.74). There were significantly more cultures positive for Enterobacter spp. in the OTGC group (P = 0.043). Three patients died during follow-up (from first dose up to 30 days after the last dose) (30 day survival = 99.2%, 95% CI = 97.5-100), with only two of the reported deaths attributable to infection. CONCLUSIONS: These findings demonstrate comparable rates of febrile neutropenia and culture positivity with an increase in cultures positive for Enterobacter spp. when OTGCs are compared with levofloxacin for antibacterial prophylaxis during chemotherapy-induced neutropenia. Further prospective, randomized investigation is warranted.

Prospective Outcomes of a Pelvic Floor Rehabilitation Program Including Vaginal Electrogalvanic Stimulation for Urinary, Defecatory, and Pelvic Pain Symptoms.

OBJECTIVES: This study evaluated our experience after implementing a pelvic floor rehabilitation program including behavioral modification, biofeedback, and vaginal electrogalvanic stimulation (EGS). METHODS: This prospective cohort study evaluated outcomes of patients with pelvic floor dysfunction (urinary or defecatory dysfunction, pelvic pain/dyspareunia) who underwent pelvic floor rehabilitation. Patients received 4 to 7 sessions (1 every 2 weeks) including biofeedback and concluded with 30 minutes of vaginal EGS. Surveys assessed subjective changes in symptoms; success was evaluated using a 10-point visual analog scale (VAS) at the final session (10 = most successful). Paired comparisons of responses at baseline and final treatment were evaluated. RESULTS: Ninety-four patients were followed up through therapy completion. Treatment indications included urinary (89.4%), defecatory (33.0%), and pelvic pain or dyspareunia (30.9%); 44.7% of patients had a combination of indications. Among women with urinary symptoms, the percentage reporting leakage decreased from 92.9% to 79.3% (P = 0.001), leakage at least daily decreased from 69.0% to 39.5% (P < 0.001), daily urgency with leakage decreased from 42.7% to 19.5% (P = 0.001), daily urgency without leakage decreased from 41.5% to 18.3% (P < 0.001), and median VAS rating (0 = not at all, 10 = a great deal) of daily life interference decreased from 5 to 1.5 (P < 0.001). The median success ratings were 8, 8, and 7 for treatment of urinary symptoms, pelvic pain/dyspareunia, and bowel symptoms, respectively. CONCLUSIONS: An aggressive pelvic rehabilitation program including biofeedback with vaginal EGS had a high rate of self-reported subjective success and satisfaction and should be considered a nonsurgical treatment option in patients with pelvic floor dysfunction.