Red cell exchange modulates neutrophil degranulation responses in sickle cell disease.

BACKGROUND: Neutrophils in sickle cell disease (SCD) are activated, contributing to disease. Red cell exchange (RCE), with the goal of lowering hemoglobin S (HbS), is an important part of therapy for many SCD patients. Whether RCE impacts neutrophil reactivity is unknown. STUDY DESIGN AND METHODS: To determine the effect of RCE on neutrophil activation, SCD patients undergoing RCE in steady-state were enrolled. Neutrophil degranulation responses were examined before/after RCE. Kinetic studies were completed to determine the duration of the effect of RCE on neutrophil function. Degranulation results were examined in relation to white blood cell count, neutrophil count, and HbS levels. The effect of RCE on RBC phosphatidylserine (PS) exposure was examined as a possible contributor to modulation of neutrophil function by RCE. RESULTS: Twenty-two patients with SCD, genotype SS, who underwent RCE (average pre-RCE HbS 33 ± 14%) were included for the study. RCE significantly decreased neutrophil degranulation responses. The effect of RCE on neutrophil activation was unrelated to cell count and instead directly correlated with HbS. The effect of RCE on neutrophil activation was sustained over several days post-apheresis. Furthermore, while increased RBC PS exposure results in increased neutrophil degranulation, RCE decreases RBC PS exposure. DISCUSSION: To our knowledge, this is the first study demonstrating that RCE significantly decreases neutrophil activation in a sustained HbS-dependent manner. Modulation of PS exposure by RCE may be a contributing mechanism by which RCE modulates neutrophil activation. These studies raise the possibility that modulation of neutrophil activation contributes significantly to the therapeutic effect of RCE.

Evaluating prevalence and consequence of residual disease in individuals with psoriasis receiving apremilast treatment: results from a US patient survey.

Purpose: This noninterventional, cross-sectional survey estimated the prevalence and consequences of residual disease in apremilast-treated US adults with moderate to severe psoriasis. Materials and Methods: Residual disease was defined as experiencing moderate, severe, or very severe psoriasis over the past week or having ≥3% body surface area affected, despite treatment. Factors associated with residual disease and its effects on flare-ups, humanistic burden, and health care resource utilization (HCRU) were evaluated. Results: Of the 344 apremilast users (mean age, 44.9 years; female, 65.4%), 174 (50.6%) had residual disease. It was more prevalent in Black versus White participants (OR, 4.5; 95% CI, 1.6-12.2), those receiving apremilast for ≥1 versus <1 year (OR, 16.5; 95% CI, 7.9-34.4), those reporting ≥2 versus 0 to 1 flare-ups during the past 3 months (OR, 10.0; 95% CI, 5.0-20.1), and those with ≥4 versus 1 to 3 body regions affected at time of survey (OR, 8.6; 95% CI, 3.8-19.8). Participants with versus without residual disease self-reported more psoriasis flare-ups over the past 3 months (mean, 4.7 vs 0.9; p < .001) and more anxiety (89.7% vs 50.0%; p < .001) and depression (69.0% vs 23.6%; p < .001) over the past 30 days. Conclusion: Generally, participants with versus without residual disease also had significantly more comorbidities and greater HCRU.

Evaluating Treatment Choice in Patients with Moderate to Severe Psoriasis in the United States: Results from a US Patient Survey.

INTRODUCTION: While multiple treatments are available for moderate to severe psoriasis, patient preferences are rarely systematically studied. This study aims to identify factors associated with choice of a new once-daily oral psoriasis treatment, elicit patient views on treatment characteristics, and rank treatment characteristics by importance. METHODS: This noninterventional, cross-sectional survey study, conducted from December 2021 to June 2022, recruited US adults with moderate to severe psoriasis. Demographics, clinical characteristics, and perspectives on psoriasis treatment were collected. Factors associated with the choice of a new oral treatment were identified using multivariable logistic regression analysis. Treatment characteristics and reasons for treatment choice were ranked using bivariate comparisons. RESULTS: The study included 882 participants [mean (standard deviation; SD) age, 45.7 (12.8) years; female, 67.7%; White, 74.9%]; 92.7% were currently receiving treatment [mean (SD) duration, 2.9 (4.8) years]. Half of participants rated their psoriasis symptoms over the past week as mild, very mild, or nonexistent; 36.5% as moderate; and 12.7% as severe or very severe. Most (66.5%) indicated willingness to start a new oral treatment; 65.0% indicated that the new oral treatment would cause less anxiety than injections/infusions. Participants were significantly more likely to start the new oral treatment if they were currently receiving a tumor necrosis factor inhibitor [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.4-3.1] or ustekinumab (OR: 2.7, 95% CI: 1.6-5.0) versus apremilast (P < 0.001) or if they reported mild (OR: 3.2, 95% CI: 2.0-4.9), moderate (OR: 5.0, 95% CI: 3.1-8.2), or severe (OR: 7.6, 95% CI: 3.9-15.0) psoriasis symptoms compared with those who reported no symptoms in the past week (P < 0.001). CONCLUSION: Most participants indicated willingness to start a new once-daily oral treatment, viewing it as less anxiety provoking than injections/infusions. Current treatment and psoriasis severity affected participants' willingness to start a new oral treatment.

Patients with psoriasis have multiple treatment options available to them. We surveyed 882 adults with moderate to severe psoriasis in the US to assess their perspectives and the values placed on treatment characteristics that are most important to them when making treatment-related decisions. Participants were assigned to one of five groups based on their psoriasis treatment at the time of the survey: (1) apremilast (oral), (2) a tumor necrosis factor inhibitor (TNFi) treatment (injectable), (3) ustekinumab (injectable), (4) a topical therapy or phototherapy, or (5) over-the-counter medications or participants who were untreated (this group included those who were not currently using a psoriasis treatment). The extent of skin clearance associated with a drug, how a drug is taken, and a drug's safety profile were among the top-ranked treatment characteristics that are important to survey participants when they choose a psoriasis treatment. Most participants (66.5%) were willing to start a new oral treatment, with 65.0% indicating that the new oral treatment would cause less anxiety than injections or infusions. Participants were more willing to switch to a new oral psoriasis treatment if they were currently receiving an injectable treatment, such as ustekinumab or a TNFi, compared with those who were already taking an oral treatment. These findings suggest that, when prescribing treatments for psoriasis, health care providers should consider the treatment characteristics that are important to their patients and consider that patients generally prefer an oral versus injectable drug.

Neutrophil functional heterogeneity is a fixed phenotype and is associated with distinct gene expression profiles.

Differences in the ability of neutrophils to perform relevant effector functions has been identified in a variety of disease states. Although neutrophil functional heterogeneity is increasingly recognized during disease, few studies have examined neutrophil functional heterogeneity during periods of health. In this study, we systematically characterize neutrophil functional heterogeneity in a cohort of healthy human subjects using a range of biologically relevant agonists including immune complexes, bacterial ligands, and pathogens. With repeated testing over several years, we show that neutrophil functional capability represents a fixed phenotype for each individual. This neutrophil phenotype is preserved across a range of agonists and extends to a variety of effector functions including degranulation, neutrophil extracellular trap release, reactive oxygen species generation, phagocytosis, and bacterial killing. Using well-phenotyped healthy human subjects, we demonstrate that neutrophil functional heterogeneity is characterized by differences in neutrophil gene expression patterns. Altogether, our findings demonstrate that while neutrophil function is highly heterogeneous among healthy subjects, each individual's functional capability represents a fixed phenotype defined by a distinct neutrophil gene expression profile. These findings may be relevant during disease states where the ability to perform relevant neutrophil effector functions may impact disease course and/or clinical outcome.

Vaccination Capability Inventory of Community, Migrant, and Homeless Health Centers: A Survey Report.

CONTEXT: Federally funded Community, Migrant, and Homeless Health Centers provide health services to the most vulnerable communities in the United States. However, little is known about their capabilities and processes for providing vaccinations to adults. PROGRAM: We conducted the first national survey of health centers assessing their inventory, workflow, capacity for, and barriers to provision of routinely recommended adult vaccines. In addition, we asked health center leaders' perceptions regarding best practices and policy recommendations for adult vaccinations. IMPLEMENTATION: A survey was developed on the basis of domains elicited from advisory panels and focus groups and was sent electronically to leaders of 762 health centers throughout the United States and its territories; data were collected and analyzed in 2018. EVALUATION: A total of 319 survey responses (42%) were obtained. Health centers reported stocking most routinely recommended vaccines for adults; zoster vaccines were not stocked regularly due to supply and storage issues. Respondents most commonly reported adequate reimbursement for vaccination services from private insurance and Medicaid. Most vaccinations were provided during primary care encounters; less than half of health centers reported providing vaccines during specialist visits. Vaccines administered at the health center were most commonly documented in an open field of the electronic health record (96%) or in an immunization information system (72%). Recommendations for best practices related to better documentation of vaccinations and communication with immunization information systems were provided. DISCUSSION: Health centers provide most adult vaccines to their patients despite financial and technological barriers to optimal provisioning. Further studies at point of care could help identify mechanisms for system improvements.

Effectiveness of an Evidence-Based Induction Therapy Protocol Revision in Adult Kidney Transplant Recipients.

STUDY OBJECTIVE: Induction immunosuppression significantly improves graft outcomes after kidney transplantation, but protocols vary among transplant centers due to the lack of data identifying an optimal induction agent. The objective of this study was to assess the effectiveness of an evidence-based protocol change in induction therapy in adult kidney transplant recipients. DESIGN: Retrospective cohort study. SETTING: Large tertiary care academic medical center. PATIENTS: A total of 349 patients transplanted between August 2011 and December 2013 were included in the study. A protocol revision in 2012 reserved the use of lymphocyte-depleting induction therapy to a select group of traditionally high-risk patients based on the findings of a previous randomized controlled trial performed at this center. MEASUREMENTS AND MAIN RESULTS: The primary outcome was biopsy-proved acute rejection and graft loss. The use of nondepleting induction therapy increased significantly after the protocol revision, with no significant differences in rejection or infection rates identified between protocols. When comparing graft survival between the protocol cohorts, there was no significant difference. A cost-minimization analysis indicated that the revised protocol was associated with considerable medication cost savings. CONCLUSION: A protocol targeting the use of lymphocyte-depleting induction to a select group of high-risk recipients appears to have equivalent efficacy and safety and is less costly compared with a more traditional induction protocol.

Community health center provider ability to identify, treat and account for the social determinants of health: a card study.

BACKGROUND: The social determinants of health (SDH) are conditions that shape the overall health of an individual on a continuous basis. As momentum for addressing social factors in primary care settings grows, provider ability to identify, treat and assess these factors remains unknown. Community health centers care for over 20-million of America's highest risk populations. This study at three centers evaluates provider ability to identify, treat and code for the SDH. METHODS: Investigators utilized a pre-study survey and a card study design to obtain evidence from the point of care. The survey assessed providers' perceptions of the SDH and their ability to address them. Then providers filled out one anonymous card per patient on four assigned days over a 4-week period, documenting social factors observed during encounters. The cards allowed providers to indicate if they were able to: provide counseling or other interventions, enter a diagnosis code and enter a billing code for identified factors. RESULTS: The results of the survey indicate providers were familiar with the SDH and were comfortable identifying social factors at the point of care. A total of 747 cards were completed. 1584 factors were identified and 31 % were reported as having a service provided. However, only 1.2 % of factors were associated with a billing code and 6.8 % received a diagnosis code. CONCLUSIONS: An obvious discrepancy exists between the number of identifiable social factors, provider ability to address them and documentation with billing and diagnosis codes. This disparity could be related to provider inability to code for social factors and bill for related time and services. Health care organizations should seek to implement procedures to document and monitor social factors and actions taken to address them. Results of this study suggest simple methods of identification may be sufficient. The addition of searchable codes and reimbursements may improve the way social factors are addressed for individuals and populations.

Predicting and preventing readmissions in kidney transplant recipients.

A lack of research exploring post-transplant process optimization to reduce readmissions and increasing readmission rates at our center from 2009 to 2013 led to this study, aimed at assessing the effect of patient and process factors on 30-d readmission rates after kidney transplantation. This was a retrospective case-control study in adult kidney transplant recipients. Univariate and multivariate analyses were utilized to assess patient and process determinants of 30-d readmissions. 384 patients were included; 30-d readmissions were significantly associated with graft loss and death (p = 0.001). Diabetes (p = 0.049), pharmacist identification of poor understanding or adherence, and prolonged time on hemodialysis prior to transplant were associated with an increased risk of 30-d readmissions. After controlling for risk factors, readmission rates were only independently predicted by pharmacist identification of patient lack of understanding or adherence regarding post-transplant medications and dialysis exposure for more than three yr (OR 2.3, 95% CI 1.10-4.71, p = 0.026 and OR 2.1, 95% CI 1.22, 3.70, respectively), both of which were significantly modified by history of diabetes. Thirty-d readmissions are attributable to both patient and process-level factors. These data suggest that a lack of post-transplant medication knowledge in high-risk patients drives early hospital readmission.

A review of the pharmacology and clinical uses of pimobendan.

OBJECTIVE: To review the pharmacology, research developments, and clinical uses of pimobendan DATA SOURCES: Original research articles and clinical studies from 1984 to August 2011. VETERINARY DATA SYNTHESIS: Pimobendan is approved for use in dogs for the treatment of congestive heart failure (CHF) secondary to chronic valvular heart disease (CVHD) and dilated cardiomyopathy (DCM). Expert-based veterinary guidelines recommend the use of pimobendan in the management of acute, hospital-based therapy for patients with CHF attributable to CVHD. CONCLUSIONS: The use of pimobendan, an inodilator with phosphodiesterase 3 (PDE3) inhibitory and calcium-sensitizing properties, is regarded as a component of the standard of care in the management of dogs with CHF secondary to both DCM and CVHD. Further studies are warranted to confirm the safety and efficacy of pimobendan for the off-label use of this drug in asymptomatic CVHD, pulmonary arterial hypertension, asymptomatic myocardial diseases, CHF from all other causes and in cats with CHF.

Retrospective evaluation of neurotoxic rattlesnake envenomation in dogs and cats: 34 cases (2005-2010).

OBJECTIVE: To describe common physical examination findings, clinicopathologic changes, treatment, and outcome in patients with evidence of neurotoxicity secondary to rattlesnake envenomation. DESIGN: Retrospective multicenter study (2005-2010). SETTING: Three private veterinary referral centers. ANIMALS: Thirty-four client-owned cats and dogs with evidence of neurotoxicity secondary to rattlesnake envenomation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient signalment, approximate time between envenomation and presentation for veterinary evaluation, physical examination and clinicopathologic findings, treatments, serial neurologic assessment, duration of hospitalization, and outcome were recorded. Signs of neurotoxicity such as ataxia, postural deficits, muscle fasciculations, paresis, paralysis, or seizures were required for inclusion into the study. The incidence of neurotoxicity amongst the general population treated with antivenin for rattlesnake envenomation in this study was 5.4%. Crotalidae Polyvalent Immune Fab(b) and veterinary approved Antivenin (Crotalidae) Polyvalent(a) were both used in this study. There was no statistically significant difference between type of antivenin or number of vials of antivenin administered and neurologic status, length of hospitalization (LOH), or survival. Hypokalemia was a frequently identified complication, but the presence of hypokalemia did not have a statistically significant association with LOH or survival. Four of the 34 patients (11.8%) required positive pressure ventilation for signs consistent with respiratory paralysis; 2 of these patients survived to discharge. Overall mortality rate was 17.6%. Survival was not significantly different between dogs and cats. However, cats had a significantly longer LOH when compared with dogs (median LOH 3.5 d for cats, 2 d for dogs). Cats appear to be overrepresented in the subset of envenomated patients with neurotoxicity. CONCLUSION: Although the incidence of neurotoxicity secondary to rattlesnake envenomation may be relatively low, patients can have rapid progression of their clinical signs and a higher mortality rate, necessitating timely and appropriate treatment. Patients treated for neurotoxicity secondary to envenomation appear to have a fair to good prognosis.