Experiences of baccalaureate nursing students in preceptorship during the COVID-19 pandemic: a systematic review protocol.

OBJECTIVE: The objective of this review is to appraise and synthesize current evidence of the clinical experiences of baccalaureate nursing students in preceptorship during the COVID-19 pandemic. INTRODUCTION: Nursing education programs support quality clinical practice learning experiences, which are essential for preparing students for both the current and future workforce. The COVID-19 pandemic has drastically changed the health care system and, previous estimates of the global shortage of nurses have now almost doubled. Understanding nursing students' clinical experiences during the pandemic can assist with identifying the needs of the future workforce. Nursing students complete the final practicum, also known as the last clinical, internship, or preceptorship, before they are eligible to apply for licensure. This review seeks to explore these pre-transitional, unprecedented preceptorship experiences during COVID-19 to better understand how to prepare pre-licensure nurses for the altered workforce. INCLUSION CRITERIA: This review will include qualitative studies that address the clinical experiences of undergraduate nursing students in preceptorship during the COVID-19 pandemic from 2020 until the present. METHODS: The databases to be searched will include CINAHL, MEDLINE, ERIC, Google Scholar, and Embase. Reference lists of included studies will be reviewed to identify additional studies. Gray literature will be searched for via ProQuest Dissertations and Theses, Google, and GreyNet International. Unpublished studies will be searched for on websites, including those of national associations of nursing. Study selection, critical appraisal, data extraction, and data synthesis will be performed independently by 2 reviewers. The findings will be collated using meta-aggregation to produce comprehensive synthesized findings and a ConQual Summary of Findings. REVIEW REGISTRATION: PROSPERO CRD42022328303.

American Cochlear Implant Alliance Task Force Guidelines for Determining Cochlear Implant Candidacy in Children.

This article summarizes the available evidence on pediatric cochlear implantation to provide current guidelines for clinical protocols and candidacy recommendations in the United States. Candidacy determination involves specification of audiologic and medical criteria per guidelines of the Food and Drug Administration. However, recommendations for a cochlear implant evaluation also should maintain flexibility and consider a child's skill progression (i.e., month-for-month progress in speech, language, and auditory development) and quality of life with appropriately fit hearing aids. Moreover, evidence supports medical and clinical decisions based on other factors, including (a) ear-specific performance, which affords inclusion of children with asymmetric hearing loss and single-sided deafness as implant candidates; (b) ear-specific residual hearing, which influences surgical technique and device selection to optimize hearing; and (c) early intervention to minimize negative long-term effects on communication and quality of life related to delayed identification of implant candidacy, later age at implantation, and/or limited commitment to an audiologic rehabilitation program. These evidence-based guidelines for current clinical protocols in determining pediatric cochlear implant candidacy encourage a team-based approach focused on the whole child and the family system.

Cochlear Implantation Can Improve Auditory Skills, Language and Social Engagement of Children With Autism Spectrum Disorder.

OBJECTIVE: To review outcomes of cochlear implantation (CI) in children diagnosed with autism spectrum disorder (ASD). STUDY DESIGN: Retrospective case review and parent survey. SETTING: Tertiary care children's hospital. PATIENTS: Thirty children with ASD who underwent CI between 1991 and 2018. Mean age at CI = 3.5 years (0.8-11.8), mean age at diagnosis of ASD = 5.1 years (2.0-15.0) (22/30 diagnosed after CI), mean follow-up = 10.5 years (1.4-21.6). Parents of 7 children returned a survey. INTERVENTION: Unilateral or bilateral cochlear implantation. MAIN OUTCOME MEASURES: Speech perception; expressive communication mode; educational placement; social engagement; consistency of CI use; parent survey of child behavior change. RESULTS: Thirty-three percent of all and 45% of the 22 consistent device users developed measurable open-set speech perception by an average of 4.5 years of device use. Educational placement at last follow-up included 13% mainstreamed without interpreter, 50% Special Education programs, 10% therapeutic residential or day programs, 23% total communication programs, and one home schooled. Spoken language alone was used by 31% and spoken plus sign by 14%, with the remainder using sign alone, augmentative communication devices or no mode of communication. By parent report, 86% showed improvement in social engagement compared to pre-CI. Survey results showed the behaviors most frequently ranked as most affected by CI were communication and attention, while awareness of environment had the lowest (most affected) mean ranking. CONCLUSIONS: Findings support a growing body of literature that cochlear implantation has the potential to improve auditory skills, language, and enhance social engagement in some deaf children with autism spectrum disorder.

Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial.

PURPOSE: Glofitamab is a T-cell-engaging bispecific antibody possessing a novel 2:1 structure with bivalency for CD20 on B cells and monovalency for CD3 on T cells. This phase I study evaluated glofitamab in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Data for single-agent glofitamab, with obinutuzumab pretreatment (Gpt) to reduce toxicity, are presented. METHODS: Seven days before the first dose of glofitamab (0.005-30 mg), all patients received 1,000 mg Gpt. Dose-escalation steps were determined using a Bayesian continuous reassessment method with overdose control. Primary end points were safety, pharmacokinetics, and the maximum tolerated dose of glofitamab. RESULTS: Following initial single-patient cohorts, 171 patients were treated within conventional multipatient cohorts and received at least one dose of glofitamab. This trial included heavily pretreated patients with R/R B-NHL; most were refractory to prior therapy (155; 90.6%) and had received a median of three prior therapies. One hundred and twenty-seven patients (74.3%) had diffuse large B-cell lymphoma, transformed follicular lymphoma, or other aggressive histology, and the remainder had indolent lymphoma subtypes. Five (2.9%) patients withdrew from treatment because of adverse events. Cytokine release syndrome occurred in 86 of 171 (50.3%) patients (grade 3 or 4: 3.5%); two (1.2%) patients experienced grade 3, transient immune effector cell-associated neurotoxicity syndrome-like symptoms. The overall response rate was 53.8% (complete response [CR], 36.8%) among all doses and 65.7% (CR, 57.1%) in those dosed at the recommended phase II dose. Of 63 patients with CR, 53 (84.1%) have ongoing CR with a maximum of 27.4 months observation. CONCLUSION: In patients with predominantly refractory, aggressive B-NHL, glofitamab showed favorable activity with frequent and durable CRs and a predictable and manageable safety profile.

British Obesity and Metabolic Surgery Society Guidelines on perioperative and postoperative biochemical monitoring and micronutrient replacement for patients undergoing bariatric surgery-2020 update.

Bariatric surgery is recognized as the most clinically and cost-effective treatment for people with severe and complex obesity. Many people presenting for surgery have pre-existing low vitamin and mineral concentrations. The incidence of these may increase after bariatric surgery as all procedures potentially cause clinically significant micronutrient deficiencies. Therefore, preparation for surgery and long-term nutritional monitoring and follow-up are essential components of bariatric surgical care. These guidelines update the 2014 British Obesity and Metabolic Surgery Society nutritional guidelines. Since the 2014 guidelines, the working group has been expanded to include healthcare professionals working in specialist and non-specialist care as well as patient representatives. In addition, in these updated guidelines, the current evidence has been systematically reviewed for adults and adolescents undergoing the following procedures: adjustable gastric band, sleeve gastrectomy, Roux-en-Y gastric bypass and biliopancreatic diversion/duodenal switch. Using methods based on Scottish Intercollegiate Guidelines Network methodology, the levels of evidence and recommendations have been graded. These guidelines are comprehensive, encompassing preoperative and postoperative biochemical monitoring, vitamin and mineral supplementation and correction of nutrition deficiencies before, and following bariatric surgery, and make recommendations for safe clinical practice in the U.K. setting.

Safety and Effectiveness of Cochlear Implantation of Young Children, Including Those With Complicating Conditions.

OBJECTIVE: Determine safety and effectiveness of cochlear implantation of children under age 37 months, including below age 12 months. STUDY DESIGN: Retrospective review. SETTING: Tertiary care children's medical center. PATIENTS: 219 children implanted before age 37 mos; 39 implanted below age 12 mos and 180 ages 12-36 mos. Mean age CI = 20.9 mos overall; 9.4 mos (5.9-11.8) and 23.4 mos (12.1-36.8) for the two age groups, respectively. All but two ≤12 mos (94.9%) received bilateral implants as did 70.5% of older group. Mean follow-up = 5.8 yrs; age last follow-up = 7.5 yrs, with no difference between groups. INTERVENTIONS: Cochlear implantation. MAIN OUTCOME MEASURES: Surgical and anesthesia complications, measurable open-set speech discrimination, primary communication mode(s). RESULTS: Few surgical complications occurred, with no difference by age group. No major anesthetic morbidity occurred, with no critical events requiring intervention in the younger group while 4 older children experienced desaturations or bradycardia/hypotension. Children implanted under 12 mos developed open-set earlier (3.3 yrs vs 4.3 yrs, p ≤ 0.001) and were more likely to develop oral-only communication (88.2% vs 48.8%, p ≤ 0.001). A significant decline in rate of oral-only communication was present if implanted over 24 months, especially when comparing children with and without additional conditions associated with language delay (8.3% and 35%, respectively). CONCLUSIONS: Implantation of children under 37 months of age can be done safely, including those below age 12 mos. Implantation below 12 mos is positively associated with earlier open-set ability and oral-only communication. Children implanted after age 24 months were much less likely to use oral communication exclusively, especially those with complex medical history or additional conditions associated with language delay.

Vitamin D deficiency and prognostics among patients with pancreatic adenocarcinoma.

BACKGROUND: The prevalence of vitamin D deficiency among patients with cancer has been previously reported. Because vitamin D is fat soluble, patients with pancreatic adenocarcinoma may have an especially high risk of vitamin D deficiency in association with ongoing and varying degrees of malabsorption. However, little is known about the correlation between vitamin D status and prognosis in these patients. METHODS: We conducted a retrospective review of vitamin D status in patients with pancreatic adenocarcinoma who were treated at Siteman Cancer Center. Patients' demographic information, clinical staging at the time of vitamin D assessment, vitamin D levels, and survival data were collected. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25[OH]D) level of less than 20 ng/mL, and vitamin D insufficiency was defined as a 25(OH)D level of between 20 ng/mL and 30 ng/mL. RESULTS: Between December 2007 and June 2011, 178 patients with pancreatic adenocarcinoma had their vitamin D levels checked at the time of initial visit at this center. Of these 178 patients, 87 (49%) had vitamin D deficiency, and 44 (25%) had vitamin D insufficiency. The median 25(OH)D level was significantly lower among nonwhite patients and among patients with stage I and II disease. A 25(OH)D level of less than 20 ng/mL was found to be associated with poor prognosis (p = 0.0019) in patients with stage III and IV disease. CONCLUSIONS: Vitamin D insufficiency and deficiency were prevalent among patients with pancreatic adenocarcinoma. The vitamin D level appears to be prognostic for patients with advanced pancreatic adenocarcinoma, and its effects should be further examined in a prospective study.

Randomized controlled trial of danoprevir plus peginterferon alfa-2a and ribavirin in treatment-naïve patients with hepatitis C virus genotype 1 infection.

BACKGROUND & AIMS: The combination of a hepatitis C virus (HCV) protease inhibitor, peginterferon, and ribavirin is the standard of care for patients with HCV genotype 1 infection. We report the efficacy and safety of response-guided therapy with danoprevir (a potent second-generation protease inhibitor), peginterferon alfa-2a (40 KD), and ribavirin in these patients. METHODS: Treatment-naïve patients (N = 237) were randomly assigned to groups given 12 weeks of danoprevir (300 mg every 8 hours; 600 mg every 12 hours, and 900 mg every 12 hours) or placebo plus peginterferon alfa-2a and ribavirin, followed by peginterferon alfa-2a and ribavirin. Patients given danoprevir who had an extended rapid virologic response (eRVR4-20: HCV RNA <15 IU/mL during weeks 4-20) stopped therapy at week 24; those without an eRVR4-20 continued therapy to 48 weeks. Patients who were given placebo received 48 weeks of peginterferon alfa-2a and ribavirin. The primary efficacy end point was sustained virologic response (SVR: HCV RNA <15 IU/mL after 24 weeks without treatment). RESULTS: Rates of SVR were higher among patients given danoprevir 300 mg (68%), 600 mg (85%), and 900 mg (76%) than placebo (42%) (95% confidence interval: 26%-59%). Seventy-nine percent of patients given danoprevir 600 mg had an eRVR4-20; among these, 96% had an SVR. Serious adverse events were reported in 7% to 8% of patients given danoprevir and 19% given placebo. Four patients given danoprevir (1 patient in the 600-mg group and 3 in the 900-mg group) had reversible, grade 4 increases in alanine aminotransferase, which led to early discontinuation of the 900-mg arm of the study. CONCLUSIONS: The combination of danoprevir, peginterferon alfa-2a, and ribavirin leads to high rates of SVR in patients with HCV genotype 1 infection, but high doses of danoprevir can lead to grade 4 increases in alanine aminotransferase. Studies of lower doses of danoprevir with ritonavir, to reduce overall danoprevir exposure while maintaining potent antiviral activity, are underway; Clinicaltrials.gov number, NCT00963885.

Usher syndrome: characteristics and outcomes of pediatric cochlear implant recipients.

OBJECTIVE: To evaluate the characteristics and outcomes of pediatric cochlear implant recipients diagnosed with Usher syndrome (US). STUDY DESIGN: Retrospective study of consecutive pediatric cochlear implant recipients (1991-2010). SETTING: Tertiary care children's hospital. PATIENTS: Children who received a cochlear implant who were diagnosed with US either before or after implantation. MAIN OUTCOME MEASURES: Electroretinography and ophthalmologic findings, cochlear anatomy based on preoperative imaging, age of independent ambulation, age at implantation, speech perception level, and communication method. RESULTS: Approximately 26 (3.7%) of 712 cochlear implant recipients were diagnosed with US based on the results of electroretinography and/or genetic testing. Preoperative imaging revealed no evidence of cochlear malformations. Average age of independent ambulation was 21.9 months (range, 12-30). Average age at implantation was 3.3 years (range, 6 mo to 11.6 yr). Mean follow-up after implantation was 7.8 years (range, 10 mo to 15.6 yr). Open-set speech perception was present in 92% of children, with use of a primarily oral communication mode in 69.2%. CONCLUSION: In this large series of patients with the diagnosis of US who have undergone cochlear implantation, CT and MRI imaging were normal. Significant delay in independent ambulation was present in this population secondary to abnormal vestibular function associated with US Type I. A majority of children developed significant open-set speech perception and oral communication skills. Implantation of US children provides them with the opportunity to develop useful hearing and oral communication.

Auditory function in rhesus monkeys: effects of aging and caloric restriction in the Wisconsin monkeys five years later.

Caloric restriction (CR) slows aging in many species and protects some animals from age-related hearing loss (ARHL), but the effect on humans is not yet known. Because rhesus monkeys are long-lived primates that are phylogenically closer to humans than other research animals are, they provide a better model for studying the effects of CR in aging and ARHL. Subjects were from the pool of 55 rhesus monkeys aged 15-28 years who had been in the Wisconsin study on CR and aging for 8-13.5 years. Distortion product otoacoustic emissions (DPOAE) with f2 frequencies from 2211 to 8837 Hz and auditory brainstem response (ABR) thresholds from clicks and 8, 16, and 32 kHz tone bursts were obtained. DPOAE levels declined linearly at approximately 1 dB/year, but that rate doubled for the highest frequencies in the oldest monkeys. There were no interactions for diet condition or sex. ABR thresholds to clicks and tone bursts showed increases with aging. Borderline significance was shown for diet in the thresholds at 8 kHz stimuli, with monkeys on caloric restriction having lower thresholds. Because the rhesus monkeys have a maximum longevity of 40 years, the full benefits of CR may not yet be realized.

Monitoring of a pharmaceutical nanomilling process using grating light reflection spectroscopy.

An optical diagnostic method, grating light reflection spectroscopy (GLRS), has been demonstrated for the in situ monitoring of properties of heterogeneous matrices in industrial processes. The technique is based on measurements near the critical points of intensity and phase in waves reflected from a transmission diffraction grating in contact with a diagnostic sample. The features contained in the reflection spectrum near these thresholds allow for the simultaneous determination of the real and imaginary parts of the dielectric function of the sample. Using these data, the milling progress of highly concentrated fluid suspensions is observed as the material is milled from approximately 40 mm to 160 nm in diameter. A theoretical model that closely resembles experimentally determined spectra was constructed and applied in combination with principal components analysis (PCA) to demonstrate that GLRS can be used to closely monitor changes in the mean particle size of the nanomilled drug product.

Preparative-scale fractionation by isoelectric trapping under nondenaturing conditions: separation of egg white protein isoforms on a modified Gradiflow unit.

pH-biased isoelectric trapping was used to separate proteins from egg white at the preparative level (80 mg), into discrete protein fractions based on isoelectric point. The problems of isoelectric precipitation that are common for the separation of complex protein mixtures under isoelectric conditions were mitigated by using single-component isoelectric buffers within the sample separation compartments. This combined with the mild process conditions of the Gradiflow unit that was modified for binary isoelectric trapping separations, ensured that biological activity was maintained. This was verified by measurement of the trypsin protease inhibitory activity of the extract and separated fractions. Furthermore, the high resolving power of this system under preparative conditions was demonstrated by separation of three protein isoforms using isoelectric membranes with differences of 0.025 pH units from each other.

Spectroscopic approach for on-line monitoring of particle size during the processing of pharmaceutical nanoparticles.

A novel application of near-infrared (near-IR) spectroscopy for the on-line determination of nanoparticle size of a drug compound in a high solids dispersion is described. The on-line spectroscopic technique provides real-time data for process monitoring and control and overcomes the limitations that are encountered using laboratory-based instrumentation for nanoparticle size determination. Near-IR spectroscopy is capable of providing an accuracy of 2.4 nm near the endpoint of particle production, where the volume-weighted D90 particle size is determined to be 200-220 nm. The accuracy is adequate for endpoint control, which minimizes excess processing and provides control over the particle size throughout nanoparticle production.

A Janus splicing regulatory element modulates HIV-1 tat and rev mRNA production by coordination of hnRNP A1 cooperative binding.

Retroviral protein production depends upon alternative splicing of the viral transcript. The HIV-1 acceptor site A7 is required for tat and rev mRNA production. Production of the Tat transcriptional activator is highly controlled because of its apoptotic properties. Two silencer elements (ESS3 and ISS) and two enhancer elements (ESE2 and ESE3/(GAA)3) were previously identified at site A7. hnRNP A1 binds ISS and ESS3 and is involved in the inhibitory process, ASF/SF2 activates site A7 utilisation. Here, by using chemical and enzymatic probes we established the 2D structure of the HIV-1(BRU) RNA region containing site A7 and identified the RNA segments protected in nuclear extract and by purified hnRNP A1. ISS, ESE3/(GAA)3 and ESS3 are located in three distinct stem-loop structures (SLS1, 2 and 3). As expected, hnRNP A1 binds sites 1, 2 and 3 of ISS and ESS3b, and oligomerises on the polypurine sequence upstream of ESS3b. In addition, we discovered an unidentified hnRNP A1 binding site (AUAGAA), that overlaps ESE3/(GAA)3. On the basis of competition experiments, hnRNP A1 has a stronger affinity for this site than for ESS3b. By insertion of (GAA)3 alone or preceded by the AUA trinucleotide in a foreign context, the AUAGAA sequence was found to modulate strongly the (GAA)3 splicing enhancer activity. Cross-linking experiments on these heterologous RNAs and the SLS2-SLS3 HIV-1 RNA region, in nuclear extract and with recombinant proteins, showed that binding of hnRNP A1 to AUA(GAA)3 strongly competes the association of ASF/SF2 with (GAA)3. In addition, disruption of AUA(GAA)3 demonstrated a key role of this sequence in hnRNP A1 cooperative binding to the ISS and ESS3b inhibitors and hnRNP A1 oligomerisation on the polypurine sequence. Thus, depending on the cellular context ([ASF/SF2]/[hnRNP A1] ratio), AUA(GAA)3 will activate or repress site A7 utilisation and can thus be considered as a Janus splicing regulator.