Chemotherapy-induced febrile neutropenia (FN): healthcare resource utilization (HCRU) and costs in commercially insured patients in the US.

PURPOSE: Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data. METHODS: A retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group. RESULTS: 7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI=0: $23,095; NCI >0-2: $26,084; NCI ≥2: $26,851). CONCLUSIONS: FN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.

Impact of dietary habits on renal function in Saku, a rural Japanese town: a cohort study.

BACKGROUND: High protein intake leads to a decline in renal function in the advanced stages of chronic kidney disease (CKD). An effective diet for maintaining renal function in healthy individuals or patients in the early stages of CKD has not been established. This cohort study was conducted in Saku, Nagano Prefecture, Japan, to investigate the impact of dietary habits on renal function. METHODS: In this cross-sectional cohort study, we used the Saku Control Obesity Program (UMIN000016892), including 4,446 participants who submitted a brief-type self-administered diet history questionnaire and underwent routine physical examination. The amount of food intake was divided into quartiles. After adjusting for age and sex, multivariate logistic regression analysis was used to calculate the odds ratio (OR) for the risk of developing CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2). RESULTS: In total, 3,899 participants were analyzed. The overall prevalence of patients with eGFR < 60 mL/min/1.73 m2 was 11% (n = 434, male; 7.1%, female; 4.1%). The groups with a high intake of chicken (approximately 63.4 g/day, adjusted OR: 0.632, P = 0.003), natto (fermented bean; approximately 21.7 g/day, adjusted OR: 0.679, P = 0.01), and plant protein (approximately 0.8 g/ideal body weight/day, adjusted OR: 0.695, P = 0.042) showed a low risk of developing CKD compared to the group with the lowest intake. CONCLUSIONS: Our cross-sectional study showed that the intake of chicken meat, natto, and plant protein was associated with high eGFR levels. This information can be of value for preventing CKD incidence in healthy Japanese individuals.

An interrupted time series study of electronic health record clinical decision support for providers caring for patients with atrial fibrillation at increased stroke risk.

PURPOSE: To measure the effect of clinical decision support (CDS) on anticoagulation rates in patients with atrial fibrillation (AFib) or atrial flutter (AFlut) at high stroke risk and receiving care in outpatient settings, and to assess provider response to CDS. METHODS: This observational, quasi-experimental, interrupted time series study utilized electronic health record data at a large integrated delivery network in Texas from April to November 2020. CDS consisted of an electronic Best Practice Advisory (BPA)/alert (Epic Systems Corporation, Verona, WI) with links to 2 AFib order sets displayed to providers in outpatient settings caring for non-anticoagulated patients with AFib and elevated CHA2DS2VASc scores. Weekly outpatient anticoagulation rates were assessed in patients with high stroke risk before and after implementation of CDS. Alert actions and acknowledgment reasons were evaluated descriptively. RESULTS: Mean (SD) weekly counts of eligible patients were 8,917 (566) before and 8,881 (811) after implementation. Weekly anticoagulation rates increased during the pre-BPA study period (ß1 = 0.07%; SE, 0.02%; P = 0.0062); however, there were no significant changes in the level (ß2 = 0.60%; SE, 0.42%; P = 0.1651) or trend (ß3 = -0.01%; SE, 0.05%; P = 0.8256) of anticoagulation rates associated with CDS implementation. In encounters with the BPA/alert displayed (n = 17,654), acknowledgment reasons were provided in 4,473 (25.3%) of the encounters, with prescribers most commonly citing bleeding risk (n = 1,327, 7.5%) and fall risk (n = 855, 4.8%). CONCLUSION: There was a significant trend of increasing anticoagulation rates during the pre-BPA period, with no significant change in trend during the post-BPA period relative to the pre-BPA period.

Real-world treatment patterns and clinical outcomes after introduction of immune checkpoint inhibitors: Results from a retrospective chart review of patients with advanced/metastatic non-small cell lung cancer in the EU5.

BACKGROUND: Real-world evidence is increasingly used to guide treatment and regulatory decisions for non-small cell lung cancer (NSCLC). Real-world treatment patterns and clinical outcomes among patients with advanced/metastatic NSCLC in France, Germany, Italy, Spain, and the UK (EU5) were assessed. METHODS: This retrospective physician-completed patient chart review assessed treatment patterns (regimen, duration of treatment [DOT], time to discontinuation), and clinical outcomes (duration of response [DOR], progression-free survival [PFS], and overall survival [OS]) of patients with stage IIIB/C or IV NSCLC who received pembrolizumab-based first-line induction chemotherapy. RESULTS: Overall, 322 patients were included; at first-line maintenance (1LM), 92% had stage IV NSCLC, 68% had nonsquamous histology, and 89% had no central nervous system (CNS)/brain metastasis. The two most common 1LM regimens were pembrolizumab monotherapy (76% overall) and pembrolizumab + pemetrexed (21% overall). Docetaxel monotherapy was the most common second-line regimen in all countries except Germany (54% overall). For 1LM therapy, the overall median DOT and DOR were 5 and 10 months, respectively; PFS was 7 months and OS was 8 months. Germany had a longer duration of each outcome except for DOR which was longer in Spain. Clinical outcomes were generally poorer for patients with squamous histology and CNS/brain metastases. CONCLUSIONS: This study demonstrated differences in treatment patterns and clinical outcomes in NSCLC across the EU5 and patient subgroups. Improved survival was generally associated with response to first-line therapy, nonsquamous histology, and CNS/brain metastases absence. These real-world data provide valuable insights which may aid treatment decision-making and clinical trial design.

Real-world characteristics of patients with sickle cell disease who initiated crizanlizumab therapy.

OBJECTIVE: To provide real-word evidence of patients with SCD initiating crizanlizumab, their use of other SCD treatments, and crizanlizumab treatment patterns. METHODS: Using IQVIA's US-based, Longitudinal Patient-Centric Pharmacy and Medical Claims Databases patients with a diagnosis of SCD between November 1, 2018, and April 30, 2021, and ≥1 claim for crizanlizumab (date of first claim = index date) between November 1, 2019, and January 31, 2021 who were ≥16 years of age, and had ≥12 months of pre-index data were selected for analysis. Two cohorts were identified based on available follow-up time (3- and 6-month cohorts). Patient characteristics were reported along with pre- and post-index SCD treatments and crizanlizumab treatment patterns (e.g. total doses received, gap-days between doses, days on therapy, discontinuation, and restarts). RESULTS: 540 patients met the base inclusion criteria (345 in the 3-month cohort and 262 in the 6-month cohort. Most patients (64%) were female with a mean (SD) age of 35 (12) years overall. Concomitant hydroxyurea use was observed in 19-39% of patients, while concomitant L-glutamine use was observed for 4-8% of patients. 85% of 3-month cohort patients received at least two doses of crizanlizumab, while 66% of the 6-month cohort received at least 4 doses of crizanlizumab. The median number of gap days between doses was 1 or 2. CONCLUSIONS: 66% of patients who receive crizanlizumab receive at least 4 doses within 6-months. The low median number of gap days suggests high adherence.

Proximal-tubule molecular relay from early Protein diaphanous homolog 1 to late Rho-associated protein kinase 1 regulates kidney function in obesity-induced kidney damage.

The small GTPase protein RhoA has two effectors, ROCK (Rho-associated protein kinase 1) and mDIA1 (protein diaphanous homolog 1), which cooperate reciprocally. However, temporal regulation of RhoA and its effectors in obesity-induced kidney damage remains unclear. Here, we investigated the role of RhoA activation in the proximal tubules at the early and late stages of obesity-induced kidney damage. In mice, a three-week high-fat-diet induced proximal tubule hypertrophy and damage without increased albuminuria, and RhoA/mDIA1 activation without ROCK activation. Conversely, a 12-week high-fat diet induced proximal tubule hypertrophy, proximal tubule damage, increased albuminuria, and RhoA/ROCK activation without mDIA1 elevation. Proximal tubule hypertrophy resulting from cell cycle arrest accompanied by downregulation of the multifunctional cyclin-dependent kinase inhibitor p27Kip1 was elicited by RhoA activation. Mice overexpressing proximal tubule-specific and dominant-negative RHOA display amelioration of high-fat diet-induced kidney hypertrophy, cell cycle abnormalities, inflammation, and renal impairment. In human proximal tubule cells, mechanical stretch mimicking hypertrophy activated ROCK, which triggered inflammation. In human kidney samples from normal individuals with a body mass index of about 25, proximal tubule cell size correlated with body mass index, proximal tubule cell damages, and mDIA1 expression. Thus, RhoA activation in proximal tubules is critical for the initiation and progression of obesity-induced kidney damage. Hence, the switch in the downstream RhoA effector in proximal tubule represents a transition from normal to pathogenic kidney adaptation and to body weight gain, leading to obesity-induced kidney damage.

Home-based aerobic exercise and resistance training for severe chronic kidney disease: a randomized controlled trial.

BACKGROUND: The potential effects of aerobic and resistance training in patients with severe chronic kidney disease (CKD) are not fully elucidated. This study investigated the effects of a home-based exercise programme on physical functioning and health-related quality of life (HRQOL) in patients with Stage 4 CKD, equivalent to estimated glomerular filtration rate of 15-30 mL/min/1.73 m2 . METHODS: Forty-six patients with Stage 4 CKD (median age, 73 years; 33 men) were randomly assigned to exercise (n = 23) and control (n = 23) groups. Exercise group patients performed aerobic exercise at 40-60% peak heart rate thrice weekly and resistance training at 70% of one-repetition maximum twice weekly at home for 6 months. Control patients received no specific intervention. Primary outcomes were distance in incremental shuttle walking test and HRQOL assessed using the Kidney Disease Quality of Life-Short Form questionnaire. Secondary outcomes included kidney function assessed with combined urea and creatinine clearance, urinary biomarkers, and anthropometric and biochemical parameters associated with CKD. RESULTS: Improvement in incremental shuttle walking test was significantly greater in the exercise group compared with controls (39.4 ± 54.6 vs. -21.3 ± 46.1; P < 0.001). Among Kidney Disease Quality of Life domains, significant mean differences were observed between the exercise group and the control group in work status, quality of social interaction, and kidney disease component summary outcomes (12.76 ± 5.76, P = 0.03; 5.97 ± 2.59, P = 0.03; and 4.81 ± 1.71, P = 0.007, respectively). There were greater reductions in natural log (ln)-transformed urinary excretion of liver-type fatty acid-binding protein, ln serum C-reactive protein, and acylcarnitine to free carnitine ratio in the exercise group compared with controls, with significant between-group differences of -0.579 ± 0.217 (P = 0.008), -1.13 ± 0.35 (P = 0.003), and -0. 058 ± 0.024 (P = 0.01), respectively. CONCLUSIONS: Our 6 month home-based exercise programme improved aerobic capacity and HRQOL in patients with Stage 4 CKD, with possible beneficial effects on kidney function and CKD-related parameters.

Malignancy-associated membranous nephropathy with PLA2R double-positive for glomeruli and carcinoma.

Phospholipase A2 receptor (PLA2R) is the most common primary target antigen of idiopathic membranous nephropathy (MN) although PLA2R antibodies are also reported to be present in malignancy-associated MN. However, a case of PLA2R-positive MN secondary to PLA2R-positive carcinoma has not been reported. A 26-year-old Japanese woman presented with general fatigue, fever, and nonproductive cough. Computed tomography demonstrated a left kidney mass with pathologic diagnosis of Xp11.2 translocation renal cell carcinoma (RCC). After the second time of administration with Sunitinib, the patients exhibited significant proteinuria and hypoalbuminemia. Renal biopsy revealed a diagnosis of diffuse MN secondary to RCC. Immunofluorescence staining showed granular patterns positive for immunoglobulin (Ig) G, IgA, and C3c. PLA2R and IgG1-3 were positive, while IgG4 was negative. For the treatment of severe nephrotic syndrome, we attempted steroid therapy without any clinical improvement. Open nephrectomy was performed and surprisingly, RCC was stained for PLA2R with polarity for the basal side. At outpatient follow-up, 4 months after the operation, urinary protein had still persisted, although serum albumin was slightly increased. We report a case of PLA2R-positive MN secondary to PLA2R-positive RCC.

Patient and provider characteristics and outcomes associated with outpatient antibiotic overuse in acute adult bronchitis.

Nonbacterial acute bronchitis leads to many outpatient clinic visits in the US that result in an antibiotic prescription. Understanding antibiotic prescribing patterns and their clinical consequences will help improve antimicrobial stewardship efforts. A retrospective chart review was conducted to identify any correlations between patient and provider characteristics with antibiotic use in adult acute bronchitis (AAB) and to compare the clinical outcomes and rates of health care utilization between those who did and did not receive antibiotics. Study participants included adults with uncomplicated AAB seen by family medicine or internal medicine, specialty, and mid-level practitioners in a Baylor Scott & White Health outpatient facility. Phase 1 investigated whether prescribing rates varied by provider- or patient-level characteristics. Phase 2 compared clinical outcomes and health care utilization between patients who received an antibiotic versus those who did not receive an antibiotic for AAB. Among 35,383 visits for AAB, 81.4% resulted in a prescription for an antibiotic. Physicians >35 years of age and internal and family medicine physicians were more likely to prescribe antibiotics. Health care utilization rates did not differ between cohorts. The number of Clostridium difficile events was negligible.

A Case Report of Autosomal Dominant Polycystic Kidney Disease Under Peritoneal Dialysis With Cyst Infection and Culture-Positive Peritoneal Fluid.

BACKGROUND: Cyst infection is a complication sometimes seen in patients with autosomal dominant polycystic kidney disease (ADPKD) and often shows through a positive blood culture. However, there have been no reports of ADPKD patients whose cyst infection propagate to peritoneal fluid leading to positive peritoneal fluid culture. CASE PRESENTATION: A 74-year-old Japanese man with ADPKD under peritoneal dialysis (PD) was presented with left flank pain, fever, and chills at our hospital. He did not show any symptoms or signs suggestive of peritonitis. There were no elevated cell counts or polymorphonuclear leucocytes in his PD fluid. There were some complicated cysts found in computed tomography and magnetic resonance imaging examinations. We clinically diagnosed him as having a renal cyst infection rather than PD-related peritonitis. We initiated treatment by administering ceftriaxone with an immediate favorable response. As the possibility of accompanying prostatitis still remained, we switched to intravenous levofloxacin on the second day. On the 10th day, Helicobacter cinaedi was detected in 2 sets of blood culture as well as in PD fluid. We switched back to ceftriaxone and this treatment was entirely successful. CONCLUSIONS: This is the first report of H cinaedi cyst infection which propagates to peritoneal fluid in a patient with ADPKD.

Task difficulty modulates the impact of emotional stimuli on neural response in cognitive-control regions.

Both heightened reactivity to emotional stimuli and impaired cognitive control are key aspects of depression, anxiety, and addiction. But the impact of emotion on cognitive-control processes, and the factors that modulate this impact, are still not well understood. We examined the effects of threat and reward distracters on the neural correlates of cognitive control using functional MRI (fMRI) and the Multi-Source Interference Task (MSIT). Behaviorally, subjects were slower and less accurate on the more demanding incongruent trials compared to the easier congruent trials. In addition, both threat and reward distracters significantly impaired the speed of responding on incongruent trials relative to the no-distracter condition. At the neural level, we used the incongruent - congruent contrast to functionally define four cognitive-control regions of interest (ROIs): anterior cingulate cortex (ACC), left and right inferior frontal gyrus (IFG)/insula, and right dorsolateral prefrontal cortex (DLPFC). A repeated-measures analysis of variance on the extracted contrast values in these ROIs indicated a significant interaction of stimulus salience and task difficulty on the neural response in cognitive-control regions. Specifically, threat distracters significantly decreased the response in cognitive-control regions on incongruent trials, whereas they significantly increased that response on congruent trials, relative to the no-distracter condition. Exploratory analyses of the amygdala response showed a similar interaction of stimulus salience and task difficulty: threat distracters significantly decreased the amygdala response only on incongruent trials. Overall, our results suggest that the impact of emotional distracters on the neural response in cognitive-control regions as well as in the amygdala is modulated by task difficulty, and add to our understanding of the factors that determine whether emotion enhances or impairs cognition.

Impulsivity and inhibitory control deficits are associated with unhealthy eating in young adults.

Heightened impulsivity and inefficient inhibitory control are increasingly recognized as risk factors for unhealthy eating and obesity but the underlying processes are not fully understood. We used structural equation modeling to investigate the relationships between impulsivity, inhibitory control, eating behavior, and body mass index (BMI) in 210 undergraduates who ranged from underweight to obese. We demonstrate that impulsivity and inhibitory control deficits are positively associated with several facets of unhealthy eating, including overeating in response to external food cues and in response to negative emotional states, and making food choices based on taste preferences without consideration of health value. We further show that such unhealthy eating is, for the most part, associated with increased BMI, with the exception of Restraint Eating, which is negatively associated with BMI. These results add to our understanding of the impact of individual differences in impulsivity and inhibitory control on key aspects of unhealthy eating and may have implications for the treatment and prevention of obesity.