Emergence of Erythromycin-Resistant and Pertactin- and Filamentous Hemagglutinin-Deficient Bordetella pertussis Strains - Beijing, China, 2022-2023.

What is already known about this topic?: Pertussis has reemerged as a significant public health threat, primarily due to variations in Bordetella pertussis strains, antimicrobial resistance, and vaccine evasion. What is added by this report?: All isolated strains were identified as ptxA1/ptxC2/ptxP3/prn150/fim2-1/fim3-1/fhaB1/tcfA2 type and exhibited resistance to erythromycin. Two strains showed a deficiency in Fha, thirty in Prn, and one strain exhibited multiple immunogen deficiencies. What are the implications for public health practice?: The emergence and spread of immunogen-deficient strains likely result from prolonged vaccine selection pressure, posing challenges to the efficacy of pertussis vaccines. Additionally, the ongoing dissemination of ptxP3 strains with high-level macrolide resistance presents a significant obstacle to clinical treatment strategies.

Unravelling the Role of Candida albicans Prn1 in the Oxidative Stress Response through a Proteomics Approach.

Candida albicans Prn1 is a protein with an unknown function similar to mammalian Pirin. It also has orthologues in other pathogenic fungi, but not in Saccharomyces cerevisiae. Prn1 highly increases its abundance in response to H2O2 treatment; thus, to study its involvement in the oxidative stress response, a C. albicans prn1∆ mutant and the corresponding wild-type strain SN250 have been studied. Under H2O2 treatment, Prn1 absence led to a higher level of reactive oxygen species (ROS) and a lower survival rate, with a higher percentage of death by apoptosis, confirming its relevant role in oxidative detoxication. The quantitative differential proteomics studies of both strains in the presence and absence of H2O2 indicated a lower increase in proteins with oxidoreductase activity after the treatment in the prn1∆ strain, as well as an increase in proteasome-activating proteins, corroborated by in vivo measurements of proteasome activity, with respect to the wild type. In addition, remarkable differences in the abundance of some transcription factors were observed between mutant and wild-type strains, e.g., Mnl1 or Nrg1, an Mnl1 antagonist. orf19.4850, a protein orthologue to S. cerevisiae Cub1, has shown its involvement in the response to H2O2 and in proteasome function when Prn1 is highly expressed in the wild type.

Comparison of measles IgG enzyme immunoassays (EIA) versus plaque reduction neutralization test (PRNT) for measuring measles serostatus: a systematic review of head-to-head analyses of measles IgG EIA and PRNT.

BACKGROUND: As countries move towards or achieve measles elimination status, serosurveillance is an important public health tool. However, a major challenge of serosurveillance is finding a feasible, accurate, cost-effective, and high throughput assay to measure measles antibody concentrations and estimate susceptibility in a population. We conducted a systematic review to assess, characterize, and - to the extent possible - quantify the performance of measles IgG enzyme-linked assays (EIAs) compared to the gold standard, plaque reduction neutralization tests (PRNT). METHODS: We followed the PRISMA statement for a systematic literature search and methods for conducting and reporting systematic reviews and meta-analyses recommended by the Cochrane Screening and Diagnostic Tests Methods Group. We identified studies through PubMed and Embase electronic databases and included serologic studies detecting measles virus IgG antibodies among participants of any age from the same source population that reported an index (any EIA or multiple bead-based assays, MBA) and reference test (PRNT) using sera, whole blood, or plasma. Measures of diagnostic accuracy with 95% confidence intervals (CI) were abstracted for each study result, where reported. RESULTS: We identified 550 unique publications and identified 36 eligible studies for analysis. We classified studies as high, medium, or low quality; results from high quality studies are reported. Because most high quality studies used the Siemens Enzygnost EIA kit, we generate individual and pooled diagnostic accuracy estimates for this assay separately. Median sensitivity of the Enzygnost EIA was 92.1% [IQR = 82.3, 95.7]; median specificity was 96.9 [93.0, 100.0]. Pooled sensitivity and specificity from studies using the Enzygnost kit were 91.6 (95%CI: 80.7,96.6) and 96.0 (95%CI: 90.9,98.3), respectively. The sensitivity of all other EIA kits across high quality studies ranged from 0% to 98.9% with median (IQR) = 90.6 [86.6, 95.2]; specificity ranged from 58.8% to 100.0% with median (IQR) = 100.0 [88.7, 100.0]. CONCLUSIONS: Evidence on the diagnostic accuracy of currently available measles IgG EIAs is variable, insufficient, and may not be fit for purpose for serosurveillance goals. Additional studies evaluating the diagnostic accuracy of measles EIAs, including MBAs, should be conducted among diverse populations and settings (e.g., vaccination status, elimination/endemic status, age groups).

PRN usage before and after discharge from a forensic inpatient unit: A series example of patients with intellectual disabilities.

Adults living with intellectual and developmental disabilities are often prescribed psychotropic medication on an "as needed" basis (PRN) in response to behavioural challenges. In the present study we conducted a retrospective analysis of medication administration records in the 6-months preceding and following discharge of 11 adults with intellectual and developmental disabilities to community settings from forensic inpatient units within a mental health hospital. We found a significant reduction in the frequency of PRN usage after discharge. We propose potential reasons for the difference in PRN administration across settings and make suggestions for future research.

YOSEMITE and RHINE: Phase 3 Randomized Clinical Trials of Faricimab for Diabetic Macular Edema: Study Design and Rationale.

Purpose: Faricimab is a novel anti-angiopoietin-2 and anti-vascular endothelial growth factor (VEGF) bispecific antibody with high affinities and specificities for both VEGF and angiopoietin-2. It is postulated that targeting angiogenic factors and inflammatory pathways in addition to the VEGF pathway will increase treatment durability and improve outcomes. The phase 3 YOSEMITE (ClinicalTrials.gov identifier, NCT03622580) and RHINE (ClinicalTrials.gov identifier, NCT03622593) trials are designed to assess efficacy, safety, and durability of faricimab compared with aflibercept in patients with diabetic macular edema (DME). The trials evaluate a personalized treatment interval (PTI) approach to address heterogeneity in treatment response among patients with DME. Design: Two identically designed, global, double-masked, randomized, controlled phase 3 trials (YOSEMITE and RHINE). Participants: Adults with center-involving DME secondary to type 1 or 2 diabetes mellitus. Methods: These studies were designed to evaluate 3 treatment groups: faricimab 6.0 mg dosed either at fixed dosing every 8 weeks after initial treatment with 6 intravitreal doses at 4-week intervals, or faricimab 6.0 mg dosed according to PTI after initial treatment with 4 every-4-week doses, compared with aflibercept 2.0 mg dosed every 8 weeks after 5 initial every-4-week doses. The primary end point of the studies was change from baseline in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Secondary end points included anatomic, durability, and patient-reported outcomes. Safety outcomes included incidence and severity of ocular and nonocular adverse events. The PTI is a protocol-defined flexible regimen based on the treat-and-extend concept, which allowed up to every-16-week adjustable dosing based on objective and standardized criteria. The PTI design aimed to maximize therapeutic results while minimizing treatment burden. Main Outcome Measures: We describe the rationale for the study design and the novel PTI (up to every-16-week adjustable dosing) approach for treatment with faricimab. Results: YOSEMITE and RHINE enrolled 940 and 951 patients, respectively. Results from each study will be reported separately. Conclusions: YOSEMITE and RHINE were the first registrational trials in retinal disease to incorporate an objective PTI regimen, allowing for up to every-16-week adjustable dosing with a dual angiopoietin-2 and VEGF-A inhibitor, faricimab 6.0 mg, for treatment of DME.

Rationalising Antipsychotic Prescribing in Dementia (RAPID) complex intervention: A mixed-methods feasibility intervention study.

Background: To help address the issue of inappropriate antipsychotic prescribing to nursing home residents with dementia, the 'Rationalising Antipsychotic Prescribing in Dementia' (RAPID) complex intervention was developed, comprising staff education and training, academic detailing and a novel resident assessment tool. Objectives: The primary objective was to assess the feasibility and acceptability of the RAPID complex intervention in a nursing home setting. The secondary objective was to describe associated trends in psychotropic prescribing, falls, and behavioural symptoms. Methods: A mixed-methods feasibility intervention study in one large nursing home in Ireland was undertaken between 07/2017 and 01/2018. Focus groups and semi-structured interviews were conducted with nursing home staff and GPs at the end of the 3-month follow up period to assess participants' experience of the intervention. Quantitative measurements included pre- and post-course evaluation and psychotropic prescribing rates. Results: Sixteen nursing home staff members attended the two education and training days (21% attendance rate), and four GPs participated in the academic detailing sessions (100% attendance rate). Participants of the focus groups and interviews (n = 18) found the education and training beneficial for their work and expressed a desire to continue educating new staff after the study's completion. However, there was limited usage of the resident assessment tool. Participants also offered recommendations to enhance the intervention.The proportion of dementia residents prescribed at least one regular antipsychotic was stable over the 3-months pre-intervention at 45% (n = 18), and at baseline at 44% (n = 19) but decreased slightly to 36% (n = 14) at 3-months post-intervention. At the same time the absolute number of 'PRN' psychotropics administered monthly to dementia residents decreased substantially from 90 at baseline to 69 at 3-months post-intervention. Conclusion: The RAPID complex intervention was broadly feasible to conduct and may be acceptable to stakeholders. However, before it can be evaluated in larger scale studies, certain protocol modifications and further exploratory work are required to improve implementation.

A Novel Satellite PRN Code Assignment Method Based on Improved RLF Algorithm.

Low Earth Orbit (LEO) satellites have stronger received signals and more rapid geometry changes than Global Navigation Satellite System (GNSS) satellites, making them attractive for positioning, navigation, and timing (PNT) applications. Due to the low altitude, the LEO constellation requires more satellites to cover the entire globe and more Pseudo Random Noise (PRN) codes to realize Code Division Multiple Access (CDMA), which means greater receiver storage resources and receiver acquisition time. In this paper, different from the traditional methods that assign a unique PRN code to each satellite, we propose a novel method in which several satellites share the same PRN code, and simply demonstrate the feasibility and benefits of this method. To determine the minimum number of PRN codes needed for a constellation, we build a mathematical model. After the algorithm comparison, we improve the recursive largest first (RLF) algorithm so that it has a higher running speed and a smaller approximate optimal solution within a certain time period. By studying polar-orbiting and walker constellations, we find that if other satellite parameters remain the same, the higher the orbital altitude is, the more PRN codes are needed, and no matter what the orbital inclination is, the minimum number of PRN codes remains the same. Overall, it is feasible and meaningful for several satellites sharing the same PRN code to save storage resources and reduce the satellite acquisition time of the receiver. If this new technology is applied, the storage resources and the average satellite acquisition time of the receiver will be, at most, one-third of previous ones.

The Influence of COVID-19 on the Stability of Patients with Neovascular Age-Related Macular Degeneration with Different Treatment Regimens.

INTRODUCTION: To explore the impact of coronavirus disease 2019 (COVID-19) on the stability of patients with neovascular age-related macular degeneration (nAMD) receiving the treat and extend (T&E) or the pro re nata (PRN) treatment regimen and to identify indicators that may predict the disease stability of nAMD. METHODS: This is a retrospective study of patients with nAMD treated at the Second Affiliated Hospital of Harbin Medical University whose treatment schedule was interrupted at least once between 1 February and 31 May 2020. The demographic and clinical characteristics, including the best corrected visual acuity (BCVA), optical coherence tomography (OCT) features, subfoveal choroidal thickness (SFCT), interval between the last injection and the beginning of the pandemic, and the number of anti-vascular endothelial growth factor (VEGF) injections, were analyzed. RESULTS: A total of 209 stable patients with nAMD (122 eyes received the T&E regimen; 87 eyes received the PRN regimen) were identified. Compared to those who received the PRN regimen, the patients who received the T&E regimen were more stable during the first visit after COVID-19 (53.3% vs. 33.3%, P = 0.004), the BCVA was significantly better (58.5 letters vs. 56 letters, P = 0.006), and the CRT fluctuated only slightly (15 µm vs. 35 µm, P = 0.001). Furthermore, a multivariate logistic regression analysis showed that stable patients with nAMD with type 1 choroidal neovascularization (CNV) (OR 2.493 [95% CI 1.179-5.272], compared with type 2 CNV; P = 0.017; OR 2.912 [95% CI 1.133-7.485], compared with retinal angiomatous proliferation; P = 0.026) or with pigment epithelial detachment (PED) were more likely to remain stable when treatment was interrupted (OR 0.392 [95% CI 0.181-0.852], compared with no PED; P = 0.018). CONCLUSION: Compared to patients who received the PRN treatment regimen, stable patients with nAMD who received the T&E treatment regimen could better maintain stability when the treatments were suddenly interrupted by the COVID-19 pandemic. In addition, patients with type 1 CNV or patients with PED were more likely to remain stable. At present, the COVID-19 pandemic is becoming increasingly normalized, and the T&E regimen can become a more advanced treatment option for patients undergoing therapy.

Older Adults Living in Sheltered Housing's Experiences of Involvement in Pro Re Nata Decisions. A Narrative Positioning Analysis.

Decisions regarding pro re nata medications might be challenging due to the complex nature of the practice. The aim of this study was to expand our understanding of the experiences of older people living in sheltered housings with regard to shared decision-making concerning pro re nata medications. In this study, we conducted in-depth interviews with residents living in Norwegian sheltered housings. The analysis was inductive, based on a narrative positioning analysis. Twelve residents were interviewed, and three narratives representing participants' variation are presented. People take different positions in shared decision-making of pro re nata medication, and they position themselves variously at different levels and situations. Prevailing master narratives affect the residents' positions in shared decision-making. Contrasts in older adults' experiences indicate that shared decision-making is not straightforward and is highly reliant on the context. Seemingly, they wish to be involved and not involved at the same time, a contradiction that healthcare providers need to consider.

Ethical Tenets of PRN Medicines Management in Healthcare Settings: A Clinical Perspective.

Prescription and administration of pro re nata (PRN) medications has remained a poorly discussed area of the international literature regarding ethical tenets influencing this type of medication practice. In this commentary, ethical tenets of PRN medicines management from the clinical perspective based on available international literature and published research have been discussed. Three categories were developed by the authors for summarising review findings as follows: 'benefiting the patient', 'making well-informed decision', and 'follow up assessment' as pre-intervention, through-intervention, and post-intervention aspects, respectively. PRN medicines management is mainly intertwined with the ethical tenets of beneficence, nonmaleficence, dignity, autonomy, justice, informed consent, and error disclosure. It is a dynamic process and needs close collaboration between healthcare professionals especially nurses and patients to prevent unethical practice.

PRN Medicines Management for Older People with Long-Term Mental Health Disorders in Home Care.

Older people with long-term mental health conditions who receive care in their own home are vulnerable to the inappropriate use of medications and polypharmacy given their underlying health conditions and comorbidities. Inappropriate use of pro re nata (PRN) medications in these older people can enhance their suffering and have negative consequences for their quality of life and well-being, leading to readmission to healthcare settings and the increased cost of health care. This narrative review on published international literature aims at improving our understanding of medicines management in home care and how to improve PRN medication use among older people with long-term health conditions in their own home. Accordingly, the improvement of PRN medicines management for these older people requires the development of an individualised care plan considering 'reduction of older people's dependence on PRN medications', 'empowerment of family caregivers', and 'support by healthcare professionals.' PRN medication use should be reduced through deprescription and discontinuation strategies. Also, older people and their family caregivers should be encouraged to prioritize the use of non-pharmacologic methods to relieve physical and psychological problems. Besides the empowerment of family caregivers through role development, education and training about PRN medications, and involvement in decision-making, they need support by the multidisciplinary network in terms of supervision, monitoring, and home visits.

Pertactin-Deficient Bordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis.

Recent reemergence of pertussis (whooping cough) in highly vaccinated populations and rapid expansion of Bordetella pertussis strains lacking pertactin (PRN), a common acellular vaccine antigen, have raised the specter of vaccine-driven evolution and potential return of what was once the major killer of children. The discovery that most circulating B. pertussis strains in the United States have acquired new and independent disruptive mutations in PRN is compelling evidence of strong selective pressure. However, the other 4 antigens included in acellular vaccines do not appear to be selected against so rapidly. We consider 3 aspects of PRN that distinguish it from other vaccine antigens, which might, individually or collectively, explain why only this antigen is being precipitously eliminated. An understanding of the increase in PRN-deficient strains should provide useful information for the current search for new protective antigens and provide broader lessons for the design of improved subunit vaccines.

Validation of the Spanish Version of the VERITAS-PRN Scale to Assess Adherence to on Demand Regimens in Patients with Hemophilia.

INTRODUCTION: The episodic or on-demand administration of clotting factor concentrates in hemophilia patients in the event of hemorrhage is employed to restore hemostasis. Adherence to on-demand treatments needs to be assessed in order to improve patient management, avoiding adverse effects and serious clinical complications. AIM: To validate the Spanish version of the treatment adherence scale in patients with hemophilia, namely, Validated Hemophilia Regimen Treatment Adherence Scale-PRN (VERITAS-PRN). METHODS: Eighty-five patients were recruited in three hemophilia patient associations in Spain. The VERITAS-PRN scale was adapted through a back-translation process from English to Spanish. A native Spanish bilingual translator translated the scale from English to Spanish, and subsequently another native English bilingual translator translated the scale from Spanish to English. The scale was applied twice (two months apart) to assess test-retest reliability. RESULTS: Internal consistency reliability was slightly lower in the VERITAS-PRN in Spanish (0.80) versus the English version (0.85). There were no differences (p > 0.05) between the means of the dimensions or in the total scores between the sample of patients in Spain and the USA. The test-retest reliability coefficient of the scores on the total scale was 0.80 [CI, 0.74-0.86]. The test-retest reliability coefficient was greater than 0.90 in all subscales. CONCLUSION: The Spanish version of VERITAS-PRN has high consistency and empirical validity. This scale is useful for assessing the degree of adherence to treatment in adult patients with hemophilia following episodic infusion treatment.

One year outcomes of treat and extend and pro re nata (PRN) treatment regimens with aflibercept for polypoidal choroidal vasculopathy.

PURPOSE: To compare the 1-year outcomes of treat-and-extend and pro re nata (PRN) treatment regimens with aflibercept for polypoidal choroidal vasculopathy (PCV), by the means of visual acuity (VA), frequency of recurrence of polypoidal lesions and developed fibrosis, and the number of intravitreal injections, and thus to determine which one is preferable in the maintenance phase in PCV. METHODS: In our prospective study, only naive and previously untreated PCV patients were included. Initially one session of photodynamic therapy (PDT) and three monthly intravitreal injections of 2.0 mg aflibercept (IAIs) were applied in 38 eyes. After this loading phase, they were re-examined and 30 PCV eyes with no exudative phenomena were included in the study. They were divided in two groups; in the first one (16 patients) the PRN treatment modality of IAIs was applied, while in the second one (14 patients) the treat-and-extend regimen was applied. RESULTS: Over a 12-month period, VA significantly improved in treat-and-extend group (logMAR BCVA 0.41 ± 0.15 vs 0.57 ± 0.24 at baseline, p = 0.044), while in the PRN group VA remained stable (logMAR BCVA 0.70 ± 0.36 vs 0.65 ± 0.18 at baseline, p = 0.61). During the maintenance phase, the patients of treat-and-extend group did not encounter development/progression of fibrosis or any recurrent episodes, whereas the patients of PRN group had significantly more recurrent episodes (0 vs 1.37 ± 0.5, p < 0.001) and the frequency of development/progression of fibrosis was significantly higher (0% vs 44%, p = 0.02). However, the treat-and-extend treatment regimen was accompanied by significantly more administered IAIs (6 ± 0 vs 5.13 ± 1.08, p = 0.006). CONCLUSION: We highlighted the superiority of treat-and-extend regime with IAIs, which seems to yield better functional outcomes by preventing recurrence and subfoveal fibrosis, although a greater number of injections is required.

Comparing Effectiveness of Three Different Anti-VEGF Treatment Regimens for Neovascular Age-Related Macular Degeneration: Two Years' Real-World Clinical Outcomes.

PURPOSE: To compare and report the 2-year treatment outcomes from 3 different anti-VEGF treatment regimens in treating neovascular aged-related macular degeneration (nAMD): Ranibizumab pro re nata (Ranibizumab-PRN); Ranibizumab treat and extend (Ranibizumab-T&E); Aflibercept fixed first year dosing (7 injections) with treat and extend in subsequent year (Aflibercept-Fixed). METHODS: All treatment-naïve nAMD patients who completed 24 months of monitoring from a single treatment center were included. Patients received the initial loading dose of three injections (4-weekly interval), followed by one of the 3 treatment regimens. Primary outcomes were changes in visual acuity (VA) and central retinal thickness (CRT). Secondary outcome was number of injections required in each year. Data analysis included last observation carried forward (LOCF) for patients with incomplete year-2 follow-up. RESULTS: A total of 249 eyes (230 patients) were studied: 121 Ranibizumab-PRN; 65 Ranibizumab-T&E, and 63 Aflibercept-Fixed. Baseline median VA (ETDRS letters) for Ranibizumab-PRN, Ranibizumab-T&E, and Aflibercept-Fixed was 53.9, 61.1, and 54.9 letters, achieving final VA of 54.9, 65.1, and 65.1 letters, respectively. Hence, the number of letters increased at the end of 24 months for each group was +1.0 (Ranibizumab-PRN), +4.0 (Ranibizumab-T&E), highest +10.2 in Aflibercept-Fixed group. Median number of injections over 2 years (year-1/year-2) was 5/1 for Ranibizumab-PRN, 9/6 for Ranibizumab-T&E, and 7/5 for Aflibercept-Fixed. Both Ranibizumab-T&E and Aflibercept-Fixed also shared the same reduction of median CRT (115 µm), higher than Ranibizumab-PRN (83 µm). CONCLUSION: We report VA improvement from all three different treatment regimens with both Aflibercept-Fixed and Ranibizumab-T&E regimens achieving the same higher final VA. Aflibercept-Fixed dosing may have more favorable efficacy with the highest VA gain and comparatively lower dosing frequency whereas Ranibizumab-T&E may be more efficient than Ranibizumab-PRN regimen, according to our study.

Impact of Intravenous Antihypertensives on Outcomes Among Hospitalized Patients.

BACKGROUND: Many hospitalized patients with acute elevations in blood pressure (BP) are treated with intravenous (IV) antihypertensive medications without evidence of benefit. This study investigated the effects of IV as-needed (PRN) antihypertensives on BP, hospital length of stay, and mortality. METHODS: We included hospitalized patients with an order for an IV PRN antihypertensive medication. We excluded patients with target organ damage. We performed multivariate analysis to assess whether the medication was independently associated with outcomes. RESULTS: 1,784 out of 5,680 patients (31%) had an administration of the PRN medication. Patients who received the medication had a longer hospital stay compared with patients with an order for the medication who did not receive it (4.9 ± 6.1 vs. 3.1 ± 4.1 days, P < 0.001). This remained statistically significant after adjusting for covariates. In-hospital mortality was higher in the group that received the medication (3.3% vs. 1.6%, P < 0.001), but this was not statistically significant on multivariate analysis. IV hydralazine caused the most significant reduction in BP and led to a shorter length of stay when compared with enalapril and labetalol. A total of 62% of patients received the medication for a systolic BP lower than 180 mm Hg. CONCLUSIONS: Treating hypertension in the in-patient setting remains complex. Rapid lowering of BP can cause harm to patients, and this study showed that antihypertensive medication increased hospital length of stay. Once assuring no target organ damage, a strategic approach should be to treat modifiable factors and gradually reduce BP.

Mindful Melody: feasibility of implementing music listening on an inpatient psychiatric unit and its relation to the use of as needed medications for acute agitation.

BACKGROUND: In this quality improvement project, we set out to study the effectiveness and feasibility of using music as an adjunct or replacement for pharmacologic agitation management on an inpatient psychiatric unit. We hypothesized music intervention would not only assist in de-escalation/calming of agitated patients, but also reduce overall administration of PRN medications on the unit. METHOD: The project included 172 volunteer participants over 6 months: Three months without music available and 3 months with a music de-escalation option. During the latter period, patients were given the option of selecting a preferred music genre and provided with wireless headphones for up to 30 min. The number of as needed (PRN) medications administered for agitation and anxiety (including oral, sublingual, and intramuscular routes) was compiled from raw data using pharmacy records. Patients and nurses were provided with self-report surveys regarding the music intervention. RESULTS: The average weekly PRN medication administrations decreased significantly during the 3 months with music for both haloperidol (8.46 [+/- 1.79, p < 0.05] to 5.00 [+/- 1.44, p < 0.05] administrations/week) and olanzapine (9.69 [+/- 2.32, p < 0.05] to 4.62 [+/- 1.51, p < 0.05] administrations/week), compared to the 3 months prior to music implementation. There was a non-significant increase in administration of lorazepam (3.23 [+/- 1.09, p < 0.05] to 6.38 [+/- 2.46, p < 0.05] average administrations/week). The patient survey responses were 96% positive (non-neutral; either agree or strongly agree with calming effect). Nurses agreed that the project was easy to implement; 56% agreed that music helped to calm patients down. Other exploratory outcomes included observed reductions in average length of hospital stay and number of seclusion events. CONCLUSION: Music may play a significant role in reducing the utilization of PRN agitation medications on acute inpatient psychiatric units. More studies are needed to expand on these findings and explore the effect of PRN music on other therapeutic outcomes. TRIAL REGISTRATION: Protocol registration NCT04514432 , retrospectively registered on 08/13/2020.

Understanding the Patient Experience of "as-Required" Medication in a Hospice In-Patient Unit.

BACKGROUND: Timely administration of 'as-required' medication is important for managing patients' symptoms in palliative care. There are no national or local standards around the maximum length of time for the process to administer 'as-required' medication and little in the literature to inform practice. Our aim was to understand the patient experience of receiving these medications in the in-patient setting of a hospice. METHODS: A survey of hospice patients who had been on the ward at least seven days was conducted over a fifteen-week period looking at current practice, the patient experience of requesting medication and how long it took to be administered. RESULTS: Thirty-one responses were obtained. Patients made their requests in a variety of ways but 33% did not use their call bell. When looking at their most recent 'as-required' medication request, 87% of patients estimated that they received it within ten minutes. When considering their longest wait, 16% of patients reported waiting longer than twenty minutes. CONCLUSION: This survey highlights the importance of there being a variety of ways for patients to request 'as-required' medication and staff being proactive with patients to facilitate these requests. Patients perceive nursing staff to be busy and do not want to bother them. Although usually patients get their medication within ten minutes, patients can be waiting more than twenty minutes. There is a need for national standards on time to administer as-required medication within a healthcare setting and a need for more data to inform such a standard.

Prospective, Longitudinal Pilot Study: Daily Self-Imaging with Patient-Operated Home OCT in Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate longitudinally the performance of the Notal Vision Home OCT (NVHO), comprising a spectral-domain OCT device for patient self-imaging at home, telemedicine infrastructure for automated data upload, and deep learning algorithm for automated OCT evaluation. The aims were to study the system's performance in daily image acquisition and automated analysis and to characterize the dynamics of retinal fluid exudation in neovascular age-related macular degeneration (nAMD). Design: Pilot prospective, observational longitudinal study. Participants: Four individuals (mean age, 73.8 years) with nAMD (one or both eyes) undergoing anti-vascular endothelial growth factor therapy in routine clinical practice. Methods: The participants performed daily self-imaging at home with the NVHO for 1 month. The macular cube scans were uploaded automatically to the Notal Health Cloud. They underwent evaluation separately by the Notal OCT Analyzer (NOA) and human expert graders for fluid presence, segmentation, and volume. Main Outcome Measures: Daily self-imaging completion, image quality, acquisition time, agreement between automated and human grading of retinal fluid, and temporal dynamics of fluid volume. Results: Of 240 self-imaging attempts initiated, the number successfully completed was 211 (87.9%). Of these, 97.6% had satisfactory quality. For fluid presence, the NOA agreed with human grading in 94.7% of cases. From a subset of 24 scans with fluid, for agreement between NOA and human fluid volume measurements, the correlation coefficient was 0.996 and mean absolute difference was 1.5 nl (vs. 0.995 and 1.2 nl, respectively, for interhuman agreement). Graphic plots of fluid volume revealed wide variation in the dynamics of fluid exudation and treatment response. Conclusions: The participants could perform daily self-imaging at home and generate macular cube scans of satisfactory quality. Automated quantitative OCT analysis achieved high agreement with human grading. Daily self-imaging with automated OCT analysis permitted detailed characterization of the dynamics of fluid exudation and revealed wide variation between eyes. Metrics describing these dynamics may become important disease biomarkers. Home OCT telemedicine systems represent an alternative paradigm of disease monitoring; they may allow highly personalized retreatment decisions, with fewer unnecessary injections and clinic visits.

Treat-and-Extend vs. Pro Re Nata Regimen of Ranibizumab for Diabetic Macular Edema-A Two-Year Matched Comparative Study.

PURPOSE: To compare 2-year treatment outcomes of ranibizumab using treat-and-extend (T&E) or pro re nata (PRN) regimens for diabetic macular edema (DME) in clinical settings. METHODS: We retrospectively enrolled 34 patients (34 eyes) with DME treated with ranibizumab using the T&E regimen, and 34 patients (34 eyes) treated with ranibizumab using the PRN regimen and matched to cases in the treat-and-extend group by baseline best-corrected visual acuity (BCVA) and central foveal thickness (CFT). BCVA and CFT changes, number of injections and recurrence of macular edema over 2 years were compared between the groups. RESULTS: The average BCVA gain in the T&E and PRN groups was 16.2 and 7.6 ETDRS letters at 2 years (p = 0.011), respectively. The mean CFT reduction was 145.5 ± 127.3 and 97.3 ± 152.5 µm in the T&E and PRN groups at 2 years (p = 0.035), respectively. The T&E group had a higher proportion of patients with BCVA gain ≥ 15 letters at months 18 (p = 0.015) and 24 (p = 0.029) than the PRN group. During the 2-year treatment periods, the T&E group received more injections than the PRN group (11.0 ± 3.2 vs. 6.2 ± 2.0; p < 0.001), while the PRN group had more recurrence of macular edema than the T&E group (71 vs. 41%; p = 0.015). CONCLUSIONS: After 2-year ranibizumab treatment for DME, better visual and anatomical improvement and less recurrence of macular edema were achieved in the T&E group, with more injections administered.