Assessments and observations of infection prevention and control practices in US outpatient hemodialysis facilities, 2015-2018: important opportunities for improvement.

Infections cause substantial morbidity and mortality among patients receiving care in outpatient hemodialysis facilities. We describe comprehensive infection prevention assessments by US public health departments using standardized interview and observation tools. Results demonstrated how facility layouts can undermine infection prevention and that clinical practices often fall short of policies.

Human Factors Contributing to Infection Prevention in Outpatient Hemodialysis Centers: A Mixed Methods Study.

RATIONALE & OBJECTIVE: Infection prevention efforts in dialysis centers can avert patient morbidity and mortality but are challenging to implement. The objective of this study was to better understand how the design of the work system might contribute to infection prevention in outpatient dialysis centers. STUDY DESIGN: Mixed methods, observational study. SETTING & PARTICIPANTS: Six dialysis facilities across the United States visited by a multidisciplinary team over 8 months. ANALYTICAL APPROACH: At each facility, structured macroergonomic observations were undertaken by a multidisciplinary team using the SEIPS 1.0 model. Ethnographic observations were collected about staff encounters with dialysis patients including the content of staff conversations. Selective and axial coding were used for qualitative analysis and quantitative data were reported using descriptive statistics. RESULTS: Organizational and sociotechnical barriers and facilitators to infection prevention in the outpatient dialysis setting were identified. Features related to human performance, (eg, alarms, interruptions, and task stacking), work system design (eg, physical space, scheduling, leadership, and culture), and extrinsic factors (eg, patient-related characteristics) were identified. LIMITATIONS: This was an exploratory evaluation with a small sample size. CONCLUSIONS: This study used a systematic macroergonomic approach in multiple outpatient dialysis facilities to identify infection prevention barriers and facilitators related to human performance. Several features common across facilities were identified that may influence infection prevention in outpatient care and warrant further exploration.

Hepatitis C Virus Testing, Infection, and Cases Reported Through Public Health Surveillance During Expanded Screening Recommendations, United States, 2013-2021.

OBJECTIVES: Hepatitis C virus (HCV) infection is the most common bloodborne infection in the United States. We assessed trends in HCV testing, infection, and surveillance cases among US adults. METHODS: We used Quest Diagnostics data from 2013-2021 to assess trends in the numbers tested for HCV antibody and proportion of positivity for HCV antibody and HCV RNA. We also assessed National Notifiable Diseases Surveillance System 2013-2020 data for trends in the number and proportion of hepatitis C cases. We applied joinpoint regression for trends testing. RESULTS: Annual HCV antibody testing increased from 1.7 million to 4.8 million from 2013 to 2021, and the positivity proportion declined (average, 0.2% per year) from 5.5% to 3.7%. The greatest percentage-point increase in HCV antibody testing occurred in hospitals and substance use disorder treatment facilities and among addiction medicine providers. HCV RNA positivity was stable at about 60% in 2013-2015 and declined to 41.0% in 2021 (2015-2021 average, -3.2% per year). Age-specific HCV RNA positivity was highest among people aged 40-59 years during 2013-2015 and among people aged 18-39 years during 2016-2021. The number of reported hepatitis C cases (acute and chronic) declined from 179 341 in 2015 to 105 504 in 2020 (average decline, -13 177 per year). The proportion of hepatitis C cases among those aged 18-39 years increased by an average of 1.4% per year during 2013-2020; among individuals aged 40-59 years, it decreased by an average of 2.3% per year during 2013-2018. CONCLUSIONS: HCV testing increased, suggesting improved universal screening. Various data sources are valuable for monitoring elimination progress.

Incidental finding of atrial myxoma following curative treatment for paediatric neuroblastoma.

Cardiac tumours are uncommon in the general population and even more so in the paediatric population. Here we present a case of an asymptomatic 7-year-old male with history of high-risk neuroblastoma who underwent 1-year post-treatment surveillance scan with an incidental finding of intracardiac lesion found to be an atrial myxoma.

Opportunities for enhanced prevention and control of hepatitis C through improved screening and testing efforts.

An estimated 2.4 million people in the United States are living with hepatitis C virus (HCV) infection. In 2020, the Centers for Disease Control and Prevention updated hepatitis C screening recommendations to test adults aged ≥ 18 years at least once in a lifetime and pregnant persons during each pregnancy. For those with ongoing exposure to HCV, periodic testing is recommended. The recommended testing sequence is to obtain an HCV antibody test and, when positive, perform an HCV RNA test. Examination of HCV care cascades has found incomplete HCV testing occurs when a separate visit is required to obtain the HCV RNA test. Hepatitis C core antigen (HCVcAg) testing has been shown to be a useful tool for diagnosing current HCV infection is some settings. Hepatitis C testing that is completed, accurate, and efficient is necessary to achieve hepatitis C elimination goals.

Updated Operational Guidance for Implementing CDC's Recommendations on Testing for Hepatitis C Virus Infection.

Current hepatitis C virus (HCV) testing guidance recommends a two-step testing sequence for diagnosis of HCV infection. Performing an HCV RNA test whenever an HCV antibody test is reactive (complete testing) is critical to achieve national HCV elimination goals. When an HCV antibody test is reactive and no HCV RNA test is performed, testing is considered incomplete. Historically, approximately one third of patients have incomplete testing. This update clarifies that all sites performing HCV screening should ensure single-visit sample collection. This approach allows for automatic HCV RNA testing when an HCV antibody test is reactive to avoid incomplete testing. Use of strategies that require multiple visits to collect HCV testing samples should be discontinued. Automatic HCV RNA testing on all HCV antibody reactive samples will increase the percentage of patients with current HCV infection who are linked to care and receive curative antiviral therapy.

Single Nucleotide Polymorphisms in Cytokine Genes are Associated with the Susceptibility to Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of cancer among men in the Indian subcontinent. Cytokines regulate inflammation and angiogenesis in a variety of cancers. Genetic variability in the cytokine genes can potentially influence the predisposition to oral carcinogenesis. The aim of the current study was to investigate the associations of SNPs in cytokine genes with the susceptibility of oral squamous cell carcinoma. In the present study, we have analyzed the allelic frequency of 32 single nucleotide polymorphisms (SNPs) using MassArray-based iPLEX assay in 16 cytokine genes in 166 OSCC patients and 151 healthy subjects from central India. Out of 32 SNPs analyzed, five SNPs were significantly associated with the risk of OSCC. AA and GG genotypes of IL-1ß +3953 were associated with an increased and decreased risk of OSCC, respectively. In several genetic models, GG genotype and G allele in IL-12A 3'UTR G>A were found to be associated with an increased risk of OSCC. Similarly, the GG genotype of IL-12B +1188 T>G was associated with increased susceptibility to OSCC. We conclude that SNPs in the genes coding for IL-1ß, IL-12A and IL-12B are associated with increased genetic susceptibility to OSCC in the central Indian population.

Curricular changes in times of crisis: Lessons learned.

BACKGROUND AND PURPOSE: During the early months of the COVID-19 pandemic, experiential education became challenging as sites began to cancel scheduled rotations, and the University of Florida College of Pharmacy had to cancel the first advanced pharmacy practice experience (APPE) block. This was allowable given the excess number of experiential hours built into the curriculum. EDUCATIONAL ACTIVITY AND SETTING: To meet total program credit hour requirements, a six-credit virtual course was created to mimic an experiential rotation. This course was designed to bridge didactic learning with experiential learning. The course included presentation of patient cases, topic discussions, pharmaceutical calculations, self-care cases, disease state management cases, and career development. FINDINGS: Students provided feedback via a survey containing 23 Likert type questions and four open-ended questions. Most students agreed or strongly agreed that participation in self-care scenarios, small group discussions (calculations and topic discussion), and disease state management cases (preceptor dialogue and verbal defense activities) were valuable learning experiences. The verbal defense portion of the disease management case and the self-care scenarios were the most highly rated learning activities. Peer review activities in the career development assignments were seen as the least beneficial component of the course. SUMMARY: This course allowed students an opportunity to further prepare for APPEs in a unique learning environment. The college was able to identify students requiring additional support during APPEs and provide earlier intervention. Additionally, data supported exploring incorporation of new learning activities into the current curriculum.

A cluster of gram-negative bloodstream infections in Connecticut hemodialysis patients associated with contaminated wall boxes and prime buckets.

BACKGROUND: Maintenance hemodialysis (HD) patients are at increased risk of bloodstream infections (BSI). We investigated a cluster of Delftia acidovorans infections among patients undergoing HD at an outpatient unit (Facility A). METHODS: A case was defined as a Facility A HD patient with ≥1 culture positive for D acidovorans between February 1 and April 30, 2018. An investigation included review of patient records, facility policies, practice observations, and environmental cultures. RESULTS: The cluster included 2 patients with confirmed D acidovorans BSI. Both patients had recently been dialyzed at Station #2, where a wall box culture yielded D acidovorans. One patient also had a BSI due to Enterobacter asburiae, which was recovered from several other wall boxes and saline prime buckets (SPB). Observations revealed leakage of wastewater from wall boxes onto the floor, and that SPBs were not always disinfected and dried appropriately before reuse. Multiple deficiencies in hand hygiene and station disinfection were observed. No deficiencies in water treatment practices were identified, and water cultures were negative for the observed pathogens. CONCLUSIONS: The cluster of D acidovorans infections was most likely due to indirect exposures to contaminated wall boxes and possibly SPBs due to poor hand hygiene and station disinfection.

Vital Signs: Hepatitis C Treatment Among Insured Adults - United States, 2019-2020.

INTRODUCTION: Over 2 million adults in the United States have hepatitis C virus (HCV) infection, and it contributes to approximately 14,000 deaths a year. Eight to 12 weeks of highly effective direct-acting antiviral (DAA) treatment, which can cure ≥95% of cases, is recommended for persons with hepatitis C. METHODS: Data from HealthVerity, an administrative claims and encounters database, were used to construct a cohort of adults aged 18-69 years with HCV infection diagnosed during January 30, 2019-October 31, 2020, who were continuously enrolled in insurance for ≥60 days before and ≥360 days after diagnosis (47,687). Multivariable logistic regression was used to assess the association between initiation of DAA treatment and sex, age, race, payor, and Medicaid restriction status; adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: The prevalence of DAA treatment initiation within 360 days of the first positive HCV RNA test result among Medicaid, Medicare, and private insurance recipients was 23%, 28%, and 35%, respectively; among those treated, 75%, 77%, and 84%, respectively, initiated treatment within 180 days of diagnosis. Adjusted odds of treatment initiation were lower among those with Medicaid (aOR = 0.54; 95% CI = 0.51-0.57) and Medicare (aOR = 0.62; 95% CI = 0.56-0.68) than among those with private insurance. After adjusting for insurance type, treatment initiation was lowest among adults aged 18-29 and 30-39 years with Medicaid or private insurance, compared with those aged 50-59 years. Among Medicaid recipients, lower odds of treatment initiation were found among persons in states with Medicaid treatment restrictions (aOR = 0.77; 95% CI = 0.74-0.81) than among those in states without restrictions, and among persons whose race was coded as Black or African American (Black) (aOR = 0.93; 95% CI = 0.88-0.99) or other race (aOR = 0.73; 95% CI = 0.62-0.88) than those whose race was coded as White. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Few insured persons with diagnosed hepatitis C receive timely DAA treatment, and disparities in treatment exist. Unrestricted access to timely DAA treatment is critical to reducing viral hepatitis-related mortality, disparities, and transmission. Treatment saves lives, prevents transmission, and is cost saving.

Bioavailability of acalabrutinib suspension delivered via nasogastric tube in the presence or absence of a proton pump inhibitor in healthy subjects.

AIMS: Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, is approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukaemia. Many critically ill patients are unable to swallow and need oral medications to be delivered via a nasogastric (NG) tube. Furthermore, critically ill patients are typically administered proton-pump inhibitors (PPIs) to prevent stress ulcers. Concomitant administration with PPIs reduces acalabrutinib exposure and is not currently recommended. To evaluate acalabrutinib in subjects co-administered with PPIs who require NG delivery, a phase 1, open-label, randomized, crossover, single-dose study was conducted in healthy subjects. METHODS: The study assessed the relative bioavailability of an acalabrutinib suspension-in regular, degassed Coca-Cola-administered via NG tube (Acala-NG) versus the pharmacokinetics (PK) of an acalabrutinib capsule administered orally with water. In addition, the PPI effect was evaluated by comparing the PK following Acala-NG in the presence or absence of rabeprazole. RESULTS: Exposure of acalabrutinib and its active metabolite (ACP-5862) were comparable following administration of Acala-NG versus the oral capsule (Geo mean ratio, % ref [90% confidence interval, CI]: acalabrutinib AUCinf : 103 [93-113]; Cmax : 144 [120-173]). In addition, exposure was similar following administration of Acala-NG with and without a PPI (Geo mean ratio, % ref [90% CI]: acalabrutinib AUCinf : 105 [79-138]; Cmax : 95 [66-137]). No safety or tolerability concerns were observed, and all adverse events were mild and resolved without treatment. CONCLUSIONS: Acala-NG with or without a PPI is safe and well-tolerated without impeding bioavailability.

Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: pooled analysis of 762 patients.

Cardiovascular (CV) toxicities of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib may limit use of this effective therapy in patients with chronic lymphocytic leukemia (CLL). Acalabrutinib is a second-generation BTK inhibitor with greater BTK selectivity. This analysis characterizes pooled CV adverse events (AE) data in patients with CLL who received acalabrutinib monotherapy in clinical trials (clinicaltrials gov. Identifier: NCT02029443, NCT02475681, NCT02970318 and NCT02337829). Acalabrutinib was given orally at total daily doses of 100-400 mg, later switched to 100 mg twice daily, and continued until disease progression or toxicity. Data from 762 patients (median age: 67 years [range, 32-89]; median follow-up: 25.9 months [range, 0-58.5]) were analyzed. Cardiac AE of any grade were reported in 129 patients (17%; grade ≥3, n=37 [5%]) and led to treatment discontinuation in seven patients (1%). The most common any-grade cardiac AE were atrial fibrillation/flutter (5%), palpitations (3%), and tachycardia (2%). Overall, 91% of patients with cardiac AE had CV risk factors before acalabrutinib treatment. Among 38 patients with atrial fibrillation/flutter events, seven (18%) had prior history of arrhythmia or atrial fibrillation/flutter. Hypertension AE were reported in 67 patients (9%), 43 (64%) of whom had a preexisting history of hypertension; no patients discontinued treatment due to hypertension. No sudden cardiac deaths were reported. Overall, these data demonstrate a low incidence of new-onset cardiac AE with acalabrutinib in patients with CLL. Findings from the head-to-head, randomized trial of ibrutinib and acalabrutinib in patients with highrisk CLL (clinicaltrials gov. Identifier: NCT02477696) prospectively assess differences in CV toxicity between the two agents.

Exposure-response analysis of acalabrutinib and its active metabolite, ACP-5862, in patients with B-cell malignancies.

AIMS: Examine relationships between the systemic exposure of acalabrutinib, a highly selective, next-generation Bruton tyrosine kinase inhibitor, and its active metabolite (ACP-5862) vs. efficacy and safety responses in patients with B-cell malignancies who received acalabrutinib as monotherapy or in combination with obinutuzumab. METHODS: For exposure-efficacy analyses, patients with untreated chronic lymphocytic leukaemia were assessed for best overall response, progression-free survival and tumour regression. For exposure-safety analyses, incidences of grade ≥2 adverse events (AEs), grade ≥3 AEs and grade ≥2 events of clinical interest were assessed in patients with B-cell malignancies. Acalabrutinib and ACP-5862 pharmacokinetic (PK) parameter estimates were obtained from population PK modelling. Exposure calculations were based on study dosing regimens. Total active moieties were calculated to account for contributions of ACP-5862 to overall efficacy/safety. RESULTS: A total of 573 patients were included (exposure-efficacy analyses, n = 274; exposure-safety analyses, n = 573). Most patients (93%) received acalabrutinib 100 mg twice daily. Median total active area under the concentration-time curve (AUC24h,ss ) and total active maximal concentration at steady-state (Cmax,ss ) were similar for patients who received acalabrutinib as monotherapy or in combination with obinutuzumab, and for responders and nonresponders. No relationship was observed between AUC24h,ss /Cmax,ss and progression-free survival or tumour regression. Acalabrutinib AUC24h,ss and Cmax,ss were generally comparable across groups regardless of AE incidence. CONCLUSION: No clinically meaningful correlations between acalabrutinib PK exposure and efficacy and safety outcomes were observed. These data support the fixed acalabrutinib dose of 100 mg twice daily in the treatment of patients with B-cell malignancies.

Safety and Efficacy of Pembrolizumab in Combination with Acalabrutinib in Advanced Head and Neck Squamous Cell Carcinoma: Phase 2 Proof-of-Concept Study.

PURPOSE: Programmed cell death-1 (PD-1) receptor inhibitors have shown efficacy in head and neck squamous cell carcinoma (HNSCC), but treatment failure or secondary resistance occurs in most patients. In preclinical murine carcinoma models, inhibition of Bruton's tyrosine kinase (BTK) induces myeloid cell reprogramming that subsequently bolsters CD8+ T cell responses, resulting in enhanced antitumor activity. This phase 2, multicenter, open-label, randomized study evaluated pembrolizumab (anti-PD-1 monoclonal antibody) plus acalabrutinib (BTK inhibitor) in recurrent or metastatic HNSCC. PATIENTS AND METHODS: Patients received pembrolizumab 200 mg intravenously every 3 weeks, alone or in combination with acalabrutinib 100 mg orally twice daily. Safety and overall response rate (ORR) were co-primary objectives. The secondary objectives were progression-free survival (PFS) and overall survival. RESULTS: Seventy-six patients were evaluated (pembrolizumab, n = 39; pembrolizumab + acalabrutinib, n = 37). Higher frequencies of grade 3-4 treatment-emergent adverse events (AE; 65% vs. 39%) and serious AEs (68% vs. 31%) were observed with combination therapy versus monotherapy. ORR was 18% with monotherapy versus 14% with combination therapy. Median PFS was 2.7 [95% confidence interval (CI), 1.4-6.8] months in the combination arm and 1.7 (95% CI, 1.4-4.0) months in the monotherapy arm. The study was terminated due to lack of clinical benefit with combination treatment. To assess how tumor immune contexture was affected by therapy in patients with pre- and post-treatment biopsies, spatial proteomic analyses were conducted that revealed a trend toward increased CD45+ leukocyte infiltration of tumors from baseline at day 43 with pembrolizumab (monotherapy, n = 5; combination, n = 2), which appeared to be higher in combination-treated patients; however, definitive conclusions could not be drawn due to limited sample size. CONCLUSIONS: Despite lack of clinical efficacy, immune subset analyses suggest that there are additive effects of this combination; however, the associated toxicity limits the feasibility of combination treatment with pembrolizumab and acalabrutinib in patients with recurrent or metastatic HNSCC.

Acalabrutinib monotherapy for treatment of chronic lymphocytic leukaemia (ACE-CL-001): analysis of the Richter transformation cohort of an open-label, single-arm, phase 1-2 study.

BACKGROUND: Patients with chronic lymphocytic leukaemia who progress to Richter transformation (diffuse large B-cell lymphoma morphology) have few therapeutic options. We analysed data from the Richter transformation cohort of a larger, ongoing, phase 1-2, single-arm study evaluating the safety and activity of the selective, irreversible Bruton's tyrosine kinase inhibitor acalabrutinib for the treatment of chronic lymphocytic leukaemia or small lymphocytic lymphoma. METHODS: For this open-label, single-arm, phase 1-2 study, patients aged 18 years or older with biopsy-proven treatment-naive or previously treated diffuse large B-cell lymphoma (Richter transformation) or prolymphocytic leukaemia transformation (Eastern Cooperative Oncology Group performance status ≤2) were assigned to receive oral acalabrutinib 200 mg twice daily as monotherapy until disease progression or toxicity. Patients were enrolled across seven centres from four countries. Safety and pharmacokinetics were assessed as primary endpoints; secondary endpoints were overall response rate, duration of response, and progression-free survival. Safety was assessed in the all-treated population (patients who received ≥1 dose), and activity was assessed in the all-treated population (for progression-free survival) and efficacy-evaluable population (for response rate; patients in the all-treated population with ≥1 response assessment after the first dose). This trial is registered with ClinicalTrials.gov (NCT02029443). FINDINGS: Between Sept 2, 2014, and April 25, 2016, 25 patients with Richter transformation were enrolled; 12 (48%) were male and 23 (92%) were White. As of data cutoff (March 1, 2021), two (8%) of 25 patients remained on acalabrutinib. The median time on study was 2·6 months (IQR 1·8-8·4). The most common adverse events (all grades) were diarrhoea (12 [48%] of 25 patients), headache (11 [44%]), and anaemia (eight [32%]). The most common grade 3-4 adverse events were neutropenia (seven [28%] of 25) and anaemia (five [20%]). The most common reason for treatment discontinuation was disease progression (17 [68%] of 25 patients). 11 (44%) deaths were reported within 30 days of the last acalabrutinib dose; none was considered treatment-related. Acalabrutinib was rapidly absorbed and eliminated, with similar day 1 and day 8 exposures. The overall response rate was 40·0% (95% CI 21·1-61·3), with two (8%) of 25 patients having a complete response and eight (32%) having a partial response; the median duration of response was 6·2 months (95% CI 0·3-14·8). Median progression-free survival in the overall cohort was 3·2 months (95% CI 1·8-4·0). INTERPRETATION: Acalabrutinib appears to be generally well tolerated, although progression-free survival was relatively poor in this cohort of patients with Richter transformation. On the basis of these findings, the use of acalabrutinib monotherapy in this setting is limited; however, further assessment of acalabrutinib as part of combination-based regimens for patients with Richter transformation is warranted. FUNDING: Acerta Pharma, a member of the AstraZeneca Group.

Assessment of Phenobarbital Administration to Reduce Opioid and Benzodiazepine Use in the Immediate Postoperative Period Following Stage 2 Single-Ventricle Palliation.

OBJECTIVE: The Glenn procedure may lead to the development of elevated cerebral venous pressures, which is believed to result in "Glenn headaches." This manifests as excessive irritability, often requiring significant use of opioids and benzodiazepines. This study was designed to report our experience with the use of phenobarbital in the postoperative phase after the Glenn procedure. METHODS: We performed a retrospective chart review to compare Glenn patients before and after implementation of a sedation protocol using phenobarbital. The 2 groups were compared for demographics, surgical characteristics, and cumulative sedation usage. Correlation coefficients between the preoperative catheterization variables and sedation usage were also calculated. RESULTS: Groups A (pre-phenobarbital; n = 8) and B (post-phenobarbital; n = 11) were comparable in terms of demographics, cardiac anatomy, preoperative catheterization data, and hemodynamics. Patients in Group B received a median dose of 21.8 mg/kg of phenobarbital during their ICU stay. Although there was a decreased administration of morphine equivalents (2.60 mg/kg vs 2.25 mg/kg, p = 0.38), benzodiazepine (0.1 mg/kg vs 0.074 mg/kg, p = 0.43), and dexmedetomidine (47 mcg/kg vs 37.2 mcg/kg, p = 0.53) in Group B, the differences were not statistically significant. There was also no strong correlation between preoperative hemodynamic variables and the postoperative sedation requirement, and there was no statistically significant difference in overall outcomes between the 2 groups. CONCLUSIONS: While phenobarbital may have mitigated the use of opioids, benzodiazepines, and alpha-agonist agents in some postoperative Glenn patients, the overall findings for all patients were not statistically significant. Further prospective studies are needed to ascertain the role of phenobarbital in these patients.