Search

Abstract Hypoxia represents one of the key factors that stimulates the growth of leukemic cells in their niche. Leukemic cells in hypoxic conditions are forced to reprogram their original transcriptome, miRNome, and metabolome. How the coupling of microRNAs (miRNAs)/mRNAs helps to maintain or progress the leukemic status is still not fully described. MiRNAs regulate practically all biological processes within cells and play a crucial role in the development/progression of leukemia. In the present study, we aimed to uncover the impact of hsa-miR-155-5p (miR-155, MIR155HG) on the metabolism, proliferation, and mRNA/miRNA network of human chronic lymphocytic leukemia cells (CLL) in hypoxic conditions. As a model of CLL, we used the human MEC-1 cell line where we deleted mature miR-155 with CRISPR/Cas9. We determined that miR-155 deficiency in leukemic MEC-1 cells results in lower proliferation even in hypoxic conditions in comparison to MEC-1 control cells. Additionally, in MEC-1 miR-155 deficient cells we observed decreased number of populations of cells in S phase. The miR-155 deficiency under hypoxic conditions was accompanied by an increased apoptosis. We detected a stimulatory effect of miR-155 deficiency and hypoxia at the level of gene expression, seen in significant overexpression of EGLN1, GLUT1, GLUT3 in MEC-1 miR-155 deficient cells. MiR-155 deficiency and hypoxia resulted in increase of glucose and lactate uptake. Pyruvate, ETC and ATP were reduced. To conclude, miR-155 deficiency and hypoxia affects glucose and lactate metabolism by stimulating the expression of glucose transporters as GLUT1, GLUT3, and EGLN1 [Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2)] genes in the MEC-1 cells.

# Background Medical oxygen is frequently used in healthcare settings. Challenges with oxygen disruption, such as oxygen tanks running out due to communication issues between staff or tanks not being set up properly, have been noted in the limited existing literature. Challenges and patient safety issues associated with oxygen disruption persist. Utilizing a human factors approach, our study aims to understand the contributing factors and context of oxygen disruption--related patient safety event reports in the inpatient setting and provide person-based and system-based solutions. # Methods Through keyword matching, we identified and then qualitatively analyzed 298 patient safety event reports to understand the factors contributing to oxygen disruption, patient location when the oxygen disruptions occurred, hand-off breakdowns by healthcare team member role, and whether high supplemental oxygen was being administered. # Results The most frequent contributing factor to oxygen disruption was the patient not being transferred to another source of oxygen (n=135 of 298, 45.3%), followed by tank found empty (n=107, 35.9%), patient connected to a functioning oxygen source, no oxygen flowing (n=25, 8.4%), oxygen delivery device malfunction (n=22, 7.4%), and no oxygen available (n=9, 3.0%). Over one-third of all oxygen disruption events occurred on the unit where the patient was admitted (n=109 of 298, 36.6%). Roughly 40% of reports involved a hand-off breakdown (n=123 of 298, 41.3%) and the most frequent breakdowns occurred between a nurse and a patient transporter (n=47 of 123, 38.2%). Almost one quarter of reports involved a patient with high supplemental oxygen requirements (n=74 of 298, 24.8%). # Conclusion Oxygen disruption events can have serious patient safety implications. Many of the oxygen disruption events we reviewed occurred due to lack of situational awareness and hand-off breakdowns. Combining person-based solutions, such as paper-based tools and checklists, with system-based solutions involving central monitoring and supervisory systems may help reduce the risk of oxygen disruption events.

# Background When placing orders into the electronic health record (EHR), prescribers often use free-text information to complement the order. However, the use of these free-text fields can result in patient safety issues. The objective of our study was to develop a deeper understanding of the conditions under which free-text information, or special instructions, are used in the EHR and the patient safety issues associated with their use, through an analysis of patient safety event (PSE) reports. # Methods We identified 847 PSE reports submitted to the Pennsylvania Patient Safety Reporting System (PA-PSRS) between January 1, 2021, and December 31, 2022; this dataset was reduced to 677 after controlling for oversampling from particular facilities. After limiting to reports that mentioned the terms "special instructions," "order instructions," "order comments," or "special comments," we analyzed a total of 329 reports. A physician and human factors expert independently reviewed the reports and assigned each a code from the following categories: general care process, medication class, information expressed in the special instruction, special instruction issue, department or staff for which special instruction was intended, and whether the error reached the patient. # Results Almost three quarters of the special instruction reports were related to Medication (n=233 of 329, 70.8%), followed by Laboratory/Blood Bank (n=54, 16.4%), and Radiology (n=23, 7.0%). Medication classes most frequently associated with special instructions included infectious disease medications (n=51 of 230, 22.2%), antithrombotic/antithrombotic reversal agents (n=32, 13.9%), and nutritional/electrolytes/intravenous fluids (n=32, 13.9%). Nearly one quarter each of medication-related special instructions were about timing (n=58 of 233, 24.9%) and dosing (n=54, 23.2%); most about laboratory/blood bank were related to the site of the blood draw (n=33 of 54, 61.1%), and many involving radiology were related to radiology/echocardiography instructions (n=16 of 23, 69.6%). The most frequent issues associated with special instructions were containing information contradictory to the order or other information (n=62 of 329, 18.8%); being confusing, incorrect, or used incorrectly (n=58, 17.6%); and not seen (n=25, 7.6%), not viewable (n=11, 3.3%), or instructions absent (n=11, 3.3%). In more than half of the reports, special instructions were intended for nursing staff (n=184 of 329, 55.9%), followed by pharmacy (n=49, 14.9%), radiology (n=21, 6.4%), and laboratory/blood bank (n=20, 6.1%). The error reached the patient in roughly three quarters (n=243 of 329, 73.9%) of the reports reviewed. # Conclusion Special instructions are frequently used to provide additional context about medication orders and laboratory and radiology procedures and are often intended for nurses and pharmacists. However, these instructions can result in errors and may cause patient harm. Based on our analysis, we provide EHR design strategies and policies and protocols to address patient safety issues associated with free text to enable safer and more resilient care delivery.

IntroductionIt is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of recipient gut lymphocyte populations in immunosuppressed conditions.MethodsUsing polychromatic flow cytometry that includes HLA allele group-specific antibodies distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients.ResultsWe confirm the early presence of naïve donor B cells in the circulation (donor age range: 1-14 years, median: 3 years) and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa (recipient age range at the time of transplant: 1-44 years, median: 3 years). Recipient B cell repopulation of the allograft was most rapid in infant (

# Background Alteplase and tenecteplase are thrombolytic agents used to treat patients with acute ischemic stroke (AIS). Despite the convenient bolus dosing of tenecteplase, its off-label use for AIS creates new patient safety challenges that are understudied. # Methods The study was conducted in two parts. In Part I, we queried the Pennsylvania Patient Safety Reporting System (PA-PSRS) database for event reports involving alteplase and tenecteplase that were submitted between 2017 and 2022. Based on results from Part I, in Part II we narrowed the query to reports submitted in 2021–2022 and applied inclusion criteria to identify reports that described a medication error involving the use of alteplase or tenecteplase to treat AIS. In Part II, all reports were reviewed and coded for stages of the medication-use process, associated factors, and event type. # Results Part I results (N=858) showed a decrease in reports of alteplase events and an increase in reports of tenecteplase events. In Part II (N=92), 52% of reports involved alteplase and 48% involved tenecteplase. Wrong dose was the most frequently coded event type for both medications at a combined 48%. Several tenecteplase-related events were attributed to unfamiliarity with the medication, confusion between indications, and incorrect use of the electronic health record (EHR) or failure to use the EHR, whereas many errors unique to alteplase occurred during the multistep calculation, preparation, and administration processes. # Conclusions Safety events involving alteplase and tenecteplase in the treatment of AIS are diverse. We present a list of potential strategies to prevent and mitigate errors involving these high-alert medications and encourage providers to adopt those that are meaningful to their workflow and practice setting.

# Background The Pennsylvania Patient Safety Reporting System (PA-PSRS) is the largest repository of patient safety data in the United States and one of the largest in the world, with over 4.7 million acute care event reports dating back to 2004. In this article, we analyze the patient safety event reports submitted to PA-PSRS in 2023. # Methods We extracted data from PA-PSRS and obtained data from the Pennsylvania Health Care Cost Containment Council (PHC4). Report counts are based on report submission date, and rates are based on event occurrence date and calculated per 1,000 patient days for hospitals or 1,000 surgical encounters for ambulatory surgical facilities (ASFs). # Results In 2023, 287,997 reports were submitted to PA-PSRS, which is a considerable increase from 2022 but very close to the 2021 total. Reports of serious and high harm events increased by 20.6% and 25.0%, respectively, representing the largest annual increases historically. Of the 287,997 reports, 96.0% were from hospitals, 3.8% were from ambulatory surgical facilities, and 0.2% were from birthing centers and abortion facilities. The vast majority (95.9%) of the 2023 reports were incidents, with the remaining 4.1% classified as serious events. The reporting rate based on event occurrence date for hospitals in the first half of 2023 was 30.0 reports per 1,000 patient days; for ASFs, the rate was 9.9 reports per 1,000 surgical encounters. For each of the past five years, the most frequently reported event type was Error Related to Procedure/Treatment/Test, which accounted for 33.1% of acute care event reports submitted in 2023. From a distribution perspective, the greatest increase in percent of total reports in 2023 occurred with event type Medication Error, and the greatest increase for serious events was with event type Complication of Procedure/Treatment/Test (P/T/T). Almost half of the increase in Complication of P/T/T was with subtype Complication following surgery or invasive procedure (48.2%; 968 of 2,009), and 54.6% (529 of 968) of reports in this subtype were due to unplanned returns to the operating room. # Conclusion The number of total reports, serious events, and high harm events, as well as preliminary reporting rates for hospitals and ASFs, all increased in 2023. Patient Safety Authority will continue working with Pennsylvania healthcare facilities to support high-quality reporting and patient safety practices.

# Background The Pennsylvania Patient Safety Reporting System (PA-PSRS) is the largest database of patient safety event reports in the United States. In addition to over 4.7 million acute care reports, the PA-PSRS database contains more than 420,000 long-term care (LTC) healthcare-associated infection (HAI) reports. # Methods LTC HAI data from PA-PSRS were extracted on March 1, 2024. Infection counts were calculated based on report submission date and rates were calculated based on infection confirmation date. Reports submitted by LTC facilities and specific care areas were included for infection rates each month if resident and device days were also entered in PA-PSRS for the facility and care area. # Results A total of 23,970 infection reports were submitted by Pennsylvania’s LTC facilities in 2023, representing an 18.6% increase from 2022. The overall infection rate increased by 11.4%, from 0.88 in 2022 to 0.98 in 2023, and all six regions of the state had an increase in infection rate. The Northeast region had the highest rate, with 1.28 reports per 1,000 resident days, and the Southeast region had the lowest rate, at 0.72. The overall rate increase was driven by rates of urinary tract infection (UTI) and skin and soft tissue infection (SSTI), which increased by 20.1% and 17.4%, respectively. Within the UTI infection type, symptomatic urinary tract infection (SUTI) rates increased by 21.1% and catheter-associated urinary tract infection (CAUTI) rates increased by 11.8%. # Conclusion There was an increase in the total number and rate of infections reported to PA-PSRS in 2023.

Summary: Background: Understanding formation of the human tissue resident memory T cell (TRM) repertoire requires longitudinal access to human non-lymphoid tissues. Methods: By applying flow cytometry and next generation sequencing to serial blood, lymphoid tissue, and gut samples from 16 intestinal transplantation (ITx) patients, we assessed the origin, distribution, and specificity of human TRMs at phenotypic and clonal levels. Findings: Donor age ≥1 year and blood T cell macrochimerism (peak level ≥4%) were associated with delayed establishment of stable recipient TRM repertoires in the transplanted ileum. T cell receptor (TCR) overlap between paired gut and blood repertoires from ITx patients was significantly greater than that in healthy controls, demonstrating increased gut-blood crosstalk after ITx. Crosstalk with the circulating pool remained high for years of follow-up. TCR sequences identifiable in pre-Tx recipient gut but not those in lymphoid tissues alone were more likely to populate post-Tx ileal allografts. Clones detected in both pre-Tx gut and lymphoid tissue had distinct transcriptional profiles from those identifiable in only one tissue. Recipient T cells were distributed widely throughout the gut, including allograft and native colon, which had substantial repertoire overlap. Both alloreactive and microbe-reactive recipient T cells persisted in transplanted ileum, contributing to the TRM repertoire. Interpretation: Our studies reveal human intestinal TRM repertoire establishment from the circulation, preferentially involving lymphoid tissue counterparts of recipient intestinal T cell clones, including TRMs. We have described the temporal and spatial dynamics of this active crosstalk between the circulating pool and the intestinal TRM pool. Funding: This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) P01 grant AI106697.

Abstract Objective: To understand early-life growth in the Middle East and North Africa (MENA) region, and how it has changed over time, we estimated the prevalence of wasting and overweight at ages under 5 years. Design: Cross-sectional data from twenty-nine Demographic and Health Surveys with direct anthropometric data and parent-reported demographic information were examined. The study utilised the WHO Child Growth Standards to classify overweight (weight-for-height z-score ≥ 2 sd above the median), wasting (weight-for-height z-score ≤ 2 sd below the median) and unhealthy weight defined as either wasting or overweight. Setting: Nationally representative for nine of the MENA countries (Armenia, Azerbaijan, Egypt, Jordan, Mauritania, Morocco, Tunisia, Turkey and Yemen). Participants: Children under age 5 from nine MENA countries between 1987 and 2016 (n 155 961). Results: Across the region, at the most recent time point, between 7·3 and 23·6 % of children experienced unhealthy weight (Jordan – 7·3 %, Egypt –23·6 %); 1·7 and 16·6 % had wasting (Turkey, Yemen) and 2·0 and 15·0 % had overweight (Yemen, Egypt). Overweight was more common than wasting in all countries except Yemen and Mauritania. Between 1987 and 2016, the prevalence of unhealthy weight in the region increased (10·0–18·4 %) due to increases in both wasting and overweight. Boys had a higher prevalence of unhealthy weight than girls. Conclusion: Undernutrition continues to be a problem in some countries in the MENA region, and overnutrition is emerging as a health concern in many countries in the region. Countries in the region must advance programmes that reduce undernutrition while not overlooking or inadvertently promoting overnutrition.

Abstract Despite recent relevant therapeutic progresses, chronic lymphocytic leukemia (CLL) remains an incurable disease. Selinexor, an oral inhibitor of the nuclear export protein XPO1, is active as single agent in different hematologic malignancies, including CLL. The purpose of this study was to evaluate the anti-tumor effects of selinexor, used in combination with chemotherapy drugs (i.e. fludarabine and bendamustine) or with the PI3Kδ inhibitor idelalisib in CLL. Our results showed a significant decrease in CLL cell viability after treatment with selinexor-containing drug combinations compared to each single compound, with demonstration of synergistic cytotoxic effects. Interestingly, this drug synergism was exerted also in the presence of the protective effect of stromal cells. From the molecular standpoint, the synergistic cytotoxic activity of selinexor plus idelalisib was associated with increased regulatory effects of this drug combination on the tumor suppressors FOXO3A and IkBα compared to each single compound. Finally, selinexor was also effective in potentiating the in vivo anti-tumor effects of the PI3Kδ inhibitor in mice treated with the drug combination compared to single agents. Our data provide preclinical evidence of the synergism and potential efficacy of a combination treatment targeting XPO1 and PI3Kδ in CLL.

Objective Heart failure remains a key public health priority across the globe. The median age of people with heart failure admitted to hospital in the UK is 81 years old. Many such patients transcend the standard interventions that are well characterised and evidenced in guidelines, into holistic aspects surrounding frailty, rehabilitation and social care. Previous published competency frameworks in heart failure have focused on the value of doctors, nurses and pharmacists. We aimed to provide an expert consensus on the minimum heart failure-specific competencies necessary for multiple different healthcare professionals, including physiotherapists, occupational therapists, dietitians and cardiac physiologists.Methods The document has been developed focussing on four main parts, (1) establishing a project working group of expert professionals, (2) a literature review of previously existing published curricula and competency frameworks, (3) consensus building, which included developing a structure to the framework with ongoing review of the contents to adapt and be inclusive for each specialty and (4) write up and dissemination to widen the impact of the project.Results The final competency framework displays competencies across seven sections; knowledge (including subheadings on heart failure syndrome, diagnosis and clinical management); general skills; heart failure-specific skills; clinical autonomy; multidisciplinary team working; teaching and education; and research and development.Conclusion People with heart failure can be complex and have needs that require input from a broad range of specialties. This publication focuses on the vital impact of wider multidisciplinary groups and should help define the generic core heart failure-specific competencies needed to support future pipelines of professionals, who regularly interact with and deliver care for patients with heart failure.

ABSTRACTPrimary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs). We characterized the phenotypic response to UDCA based on BA and bacterial profiles of PBC patients treated with UDCA. Patients from the UK-PBC cohort (n = 419) treated with UDCA for a minimum of 12-months were assessed using the Barcelona dynamic response criteria. BAs from serum, urine, and feces were analyzed using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry and fecal bacterial composition measured using 16S rRNA gene sequencing. We identified 191 non-responders, 212 responders, and a subgroup of responders with persistently elevated liver biomarkers (n = 16). Responders had higher fecal secondary and tertiary BAs than non-responders and lower urinary bile acid abundances, with the exception of 12-dehydrocholic acid, which was higher in responders. The sub-group of responders with poor liver function showed lower alpha-diversity evenness, lower abundance of fecal secondary and tertiary BAs than the other groups and lower levels of phyla with BA-deconjugation capacity (Actinobacteriota/Actinomycetota, Desulfobacterota, Verrucomicrobiota) compared to responders. UDCA dynamic response was associated with an increased capacity to generate oxo-/epimerized secondary BAs. 12-dehydrocholic acid is a potential biomarker of treatment response. Lower alpha-diversity and lower abundance of bacteria with BA deconjugation capacity might be associated with an incomplete response to treatment in some patients.

Background Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online. Objective To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders. Design Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation. Setting Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals. Participants Children aged 9–17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months. Interventions Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control). Outcome Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation. Results Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was −2.29 points (95% confidence interval −3.86 to −0.71) in favour of therapy (effect size −0.31, 95% confidence interval −0.52 to −0.10). This effect was sustained throughout to the final follow-up at 18 months (−2.01 points, 95% confidence interval −3.86 to −0.15; effect size −0.27, 95% confidence interval −0.52 to −0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval −£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval −0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes. Harms Two serious, unrelated adverse events occurred in the control group. Limitations We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services. Conclusion Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months. Future work Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice. Trial registration This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information. Plain language summary It can be difficult for children and young people with tics to access therapy. This is because there are not enough trained tic therapists. Online remote behavioural intervention for tics was a clinical trial to see whether an online platform that delivered two different types of interventions could help tics. One intervention focused on techniques to control tics; this type of therapy is called exposure and response prevention. The other intervention was psychoeducation, where participants learned about the nature of tics but not how to control them. The online remote behavioural intervention for tics interventions also involved help from a therapist and support from a parent. Participants were aged 9–17 years with Tourette syndrome/chronic tic disorder and were recruited from 16 clinics, two study sites (Nottingham and London) or via online self-referral. All individuals who were eligible for the online remote behavioural intervention for tics trial were randomised in a 50/50 split by researchers who were unaware of which treatment was being given. Participants received either 10 weeks of online exposure and response prevention or 10 weeks of online psychoeducation. A total of 224 children and young people participated: 112 allocated to exposure and response prevention and 112 to psychoeducation. Tics decreased more in the exposure and response prevention group (16% reduction) than in the psychoeducation group (6% reduction) 3 months after treatment. This difference is considered a clinically important difference in tic reduction. The treatment continued to have a positive effect on tic symptoms at 6, 12 and 18 months, showing that the effects are durable. This was achieved with minimal therapist involvement. The cost of online exposure and response prevention to treat young people with tics within this study was less when compared to the cost of face-to-face therapy. The results show that exposure and response prevention is an effective behavioural therapy for tics in this specific patient group. Delivering exposure and response prevention online with minimal therapist contact can be a successful and cost-effective treatment to improve access to behavioural therapy. Scientific summary Background Tic disorders including Tourette syndrome and chronic tic disorders are common conditions that affect approximately 1% of the population in the UK. Young people with tics often report substantial impairment, thus it is important that they have access to evidence-based treatment. Face-to-face behavioural therapy (BT) such as exposure and response prevention (ERP) may be offered to some young people. However, due to a lack of trained therapists, there are often difficulties accessing BT, and there is a better need to understand the clinical and cost-effectiveness of the online delivery of such therapy. Objectives The primary objective of this study was to evaluate the clinical effectiveness of therapist-guided, parent-assisted, internet-based ERP BT for tics in young people with tic disorders compared to online psychoeducation. Secondary objectives included (1) optimising the design of the intervention, (2) undertaking an internal pilot, (3) evaluating cost-effectiveness, (4) establishing whether the efficacy is maintained longer term, (5) understanding the mechanisms of impact of the intervention and (6) identifying barriers to implementation. Methods We conducted an individually randomised (1 : 1 ratio), multicentre trial, with an internal pilot and embedded process evaluation. Participants were assigned to either receive online, remotely delivered, therapist- and parent-supported ERP for tics or online, remotely delivered, therapist- and parent-supported psychoeducation for tics. Participants were recruited from the two study sites, 16 patient identification centres in England or could self-refer online via the study webpage or via Tourettes Action (a national charity for tics). The inclusion criteria were age between 9 and 17 years, with tics assessed on the Yale Global Tic Severity Scale (YGTSS), able to provide written informed consent (parental consent for children aged < 16 years) and with a suitable device they could use to access the internet. Exclusion criteria included receiving a therapy for tics in the past 12 months, starting or stopping tic medication within the past 2 months and intellectual disability/substance use/anorexia nervosa/psychosis/suicidality, moderate/severe intellectual disability, risk to self or others or parent or young person unable to speak or read/write English. All potential participants attended a screening/baseline appointment at one of the two study centres. Participants who were eligible and consented were randomised into one of two study groups. In the intervention group participants received 10 weeks of the remotely delivered, therapist-guided ERP behaviour therapy. In the control group participants received 10 weeks of remotely delivered, therapist-guided psychoeducation about tics. Participants completed measures at the mid-treatment point (5 weeks) and at 3 and 6 months (this formed phase 1, per-protocol design). For phase 2 (a naturalist design), follow-up measures were obtained at 12 and 18 months. The primary outcome (at 3 months) was the total tic severity score (TTSS) on the YGTSS. Secondary outcomes included measures of tics (parent tic questionnaire), general difficulties (strengths and difficulties questionnaire), mood and anxiety (moods and feelings questionnaire and Spence Child Anxiety Scale), global functioning (Children’s Global Assessment Scale, Clinical Global Impressions-Improvement), adverse events, need for further treatment, treatment credibility and satisfaction and the Child and Adolescent Version of the Gilles de la Tourette Syndrome Quality of Life Scale. Quality of life [child health utility 9D (CHU9D)] and resource use (modified child and adolescent service use schedule) data were also collected for the economic evaluation. Follow-up assessments were completed online or via telephone/Webex videoconferencing (YGTSS). The trial internal pilot evaluated recruitment rate, engagement with the intervention and retention to the primary outcome at 9 months into the trial and the results were reported to the relevant oversight committees (Trial Steering Committees and Data Monitoring Committee). A sub-sample of parents and young people in the intervention arm, clinicians and therapists were interviewed to explore barriers/facilitators to implementation and refine the intervention for future use, which formed part of the mixed-methods process evaluation. The quantitative data for the process evaluation included intervention usage metrics, clinical and demographic trial data and therapist contacts. Intervention The intervention was delivered via Barninternetprojektet (Child Internet Project; Swedish digital platform) (BIP), a Swedish web-based digital platform. The BT intervention (ERP) was translated from the Swedish original intervention (BIP TIC), refined and adapted for UK use by our trial team. The active control intervention (psychoeducation) was created by our trial team. Both interventions consisted of 10 web-based chapters, designed to last 10 weeks. Participants had regular contact with a therapist during this time via messages that could be sent inside the treatment platform (resembling an email). The therapist’s role was to give specific feedback to motivate the patient and not to deliver therapeutic content. The young person and the parent/carer were provided with their own separate logins to the BIP platform. For both the intervention and the comparator, treatment completion was defined as completion of the first four child chapters. Results The trial recruited and retained participants exceeding the pre-specified criteria for the internal pilot and therefore proceeded to the full trial. In total 445 candidates signed up to the study and were assessed for eligibility, of which 221 potential participants were excluded (90 did not meet inclusion criteria, 84 declined to participate and 47 were unable to contact family). This meant 224 participants were enrolled and randomly assigned (1 : 1) to either the ERP BT group (n = 112) or psychoeducation group (n = 112). The characteristics of the two groups were similar at baseline. The enrolled patients were mostly male (n = 177; 79%) and of white ethnicity (n = 195; 87%). Only 13% of participants were receiving tic medication. Adherence to the intervention was good in 99 (88%) of the 112 participants in the ERP group, and 105 (94%) of the 112 participants in the psychoeducation group were classified as treatment completers (i.e. completing at least the first four chapters). Retention to the primary outcome at the 3-month primary end point (90%) and 6-month follow-up (> 80%) was excellent. Retention to the primary outcome measure remained high at 12 months (81% in both arms) and 18 months (> 79% in both arms). The primary analysis showed that participants in the ERP group [16% reduction, standard deviation (SD) 1.1] had a greater decrease in tics than those in the psychoeducation group (6% reduction, SD 1.0) at 3 months (primary end point). The estimated mean difference in YGTSS-TTSS change between the groups adjusted for baseline and site was −2.29 points [95% confidence interval (CI) −3.86 to −0.71] in favour of ERP, with an effect size of −0.31 (95% CI −0.52 to −0.10). This effect was sustained at 6 months, with a mean decrease of 6.9 points (24%, SD 1.2) in the ERP group versus 3.4 points (12%, SD 1.0) in the psychoeducation group. For phase 2, participants in the ERP group continued to have a greater decrease in tics than the control group. The estimated mean difference in YGTSS-TTSS between groups adjusting for baseline and site at 12 months was −2.64 points (95% CI −4.48 to −0.79), with an effect size of −0.36 (95% CI −0.61 to −0.11), at 18 months it was −2.01 points (95% CI −3.86 to −0.15), with an effect size of −0.27 (95% CI −0.52 to −0.02), in favour of the ERP group. In addition, extended follow-up showed those receiving online ERP compared with online psychoeducation had reduced scores for low mood and anxiety at 12 and 18 months and superior tic-specific quality of life, with the largest effects seen at 18 months. The direct cost of the intervention was £155 per person, including £104.57 for the online platform, supervision and training and a mean variable cost of £50.43 per participant for therapist time in the trial. At 18 months, using proxy parent-completed CHU9D responses, there were a mean additional 0.040 (95% CI −0.004 to 0.083) quality-adjusted life-years (QALYs) per participant in the ERP group compared with psychoeducation, with an addition mean cost per participant of £662 (95% CI −£59 to £1384). The incremental cost-effectiveness ratio in the primary analysis was £16,708 per QALY gained from a health and social care cost perspective at 18 months. In the 10-year long-term decision model, online ERP cost £537 less per participant than face-to-face BT and resulted in 0.02 fewer QALYs. Two serious adverse events (SAEs) occurred (hospital attendance due to one ‘collapse’ and one ‘tic attack’), both in the active control psychoeducation group, neither of which were related to the study intervention. The process evaluation found that the ERP intervention was implemented with high fidelity, and participants found the intervention acceptable and satisfactory. Engagement was high, with child participants completing an average of 7.5/10 chapters and 99/112 (88.4%) participants completing the minimum of the first four chapters (the predefined threshold for effective dose). Parental engagement was the only significant independent predictor of child engagement. Improvement in tic severity and overall clinical condition was not moderated by the relationship between demographic or baseline clinical factors and engagement and no mediators were found. However, level of parental engagement was associated with overall clinical improvement, and this relationship was illuminated by the qualitative data. Conclusion Implications for health care The findings demonstrate that online, therapist-supported ERP for young people with chronic tic disorders is clinically effective at reducing tic severity. Therefore, this is an efficient public mental health approach to supporting young people with tics. The intervention can be delivered at lower cost than standard face-to-face BT and may also result in improved service efficiencies, allowing a greater number of young people to access evidence-based care. Future research implications Further ‘field trials’ should be conducted to explore the clinical and service implications of delivering the intervention in real-world settings. Given that online interventions are context dependent, exploring the validity of these findings in different cultures/countries is important. Future research should explore where online, therapist-supported ERP best fits in the tic disorder care pathway and how online and face-to-face therapy can be best combined (e.g. non-responders to online ERP are ‘stepped up’ to face-to-face therapy). Trial registrations This trial is registered as ISRCTN70758207 and ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.

Abstract Background Cognitive Behavioural Therapy for psychosis (CBTp) has an established evidence base and is recommended by clinical guidelines to be offered during the acute phases of psychosis. However, few research studies have examined the efficacy of CBTp interventions specifically adapted for the acute mental health inpatient context with most research trials being conducted with white European community populations. Aims The aim of this study is to conduct a pilot randomised controlled trial (RCT), which incorporates the examination of feasibility markers, of a crisis-focused CBTp intervention adapted for an ethnically diverse acute mental health inpatient population, in preparation for a large-scale randomised controlled trial. The study will examine the feasibility of undertaking the trial, the acceptability and safety of the intervention and the suitability of chosen outcome measures. This will inform the planning of a future, fully powered RCT. Methods A single-site, parallel-group, pilot RCT will be conducted examining the intervention. Drawing on principles of coproduction, the intervention has been adapted in partnership with key stakeholders: service users with lived experience of psychosis and of inpatient care (including those from ethnic minority backgrounds), carers, multi-disciplinary inpatient clinicians and researchers. Sixty participants with experience of psychosis and in current receipt of acute mental health inpatient care will be recruited. Participants will be randomly allocated to either the crisis-focused CBTp intervention or treatment as usual (TAU). Discussion Findings of this pilot RCT will indicate whether a larger multi-site RCT is needed to investigate the efficacy of the intervention. If the initial results demonstrate that this trial is feasible and the intervention is acceptable, it will provide evidence that a full-scale effectiveness trial may be warranted. Trial registration This trial has been prospectively registered on the ISRCTN registry ( ISRCTN59055607 ) on the 18th of February 2021.

The purpose of this exercise was to consider how language teaching changed in response to the teaching conditions imposed by the pandemic (e.g., distanced online learning, face-to-face teaching with restrictions on activities, a hybrid situation where some pupils were present and some online, synchronous or asynchronous teaching) both during the pandemic (especially during lockdowns) and post-pandemic. Eight practitioners described their experiences honestly and openly through an asynchronous conversation, each giving an answer to six questions and then engaging with the answers given by others. Key points that emerged • All types of distanced learning magnified the challenges of regular teaching • Examples of very positive use of technology to meet the challenges of distanced learning • Departments tended to divide up responsibility for lesson planning to make this more efficient • Assessment of routine language was made more engaging and easier to monitor via technology • Stark differences between schools regarding teacher and pupil access to and expertise in technology The contributions provide a rich source of information which could provide the basis for research into effective language teaching pedagogy generally.

# Background The Pennsylvania Patient Safety Reporting System (PA-PSRS) is the largest database of patient safety event reports in the United States. In addition to over 4.5 million acute care reports, the PA-PSRS database contains more than 396,000 long-term care (LTC) healthcare-associated infection (HAI) reports. # Methods LTC HAI data from PA-PSRS were extracted on March 1, 2023. Reports submitted by LTC facilities and specific care areas were included for infection rates each month if resident and device days were also entered in PA-PSRS for the facility and care area. # Results A total of 20,216 infections were reported in 2022, representing a 12.5% increase from 2021. Overall, the reporting rate from LTC facilities increased from 0.77 in 2021 to 0.87 in 2022. Over half (56%) of the increase in overall rate is due to an increase in the respiratory tract infection rate, with another 27% due to an increase in the gastrointestinal infection rate. All six regions of the state had an increase in overall infection rate from 2021 to 2022. The North Central region of the state had the highest overall rate, as well as the largest increase in rate, with 1.14 reports per 1,000 resident days in 2022, which is an increase of 21.3% over the 2021 rate of 0.94. The Southeast region had the lowest overall rate, at 0.67, which is an 8.1% increase from 2021. The number of reports increased for all five infection types from 2021 to 2022, with gastrointestinal infections increasing the most percentagewise, by 67.7%. Of the 14 infection subtypes, 11 had an increase in number of reports from 2021 to 2022, with influenza showing the largest increase of 857 reports. Norovirus had a larger percentage increase of 942.9%, going from 70 reported infections in 2021 to 730 in 2022. The three subtypes that decreased in number had relatively smaller changes than the increases, with the largest of the decreases occurring with *C. diff*, which dropped by 29 reports from 2021 to 2022. # Conclusions There was an increase in the total number and rate of infections reported to PA-PSRS in 2022. Patient Safety Authority infection preventionists continue to note operational challenges in LTC facilities and are providing ongoing education and guidance to enhance infection prevention and surveillance strategies and improve reporting of HAIs.

# Background Pennsylvania is the only state that requires acute care facilities to report all events of harm or potential for harm. The Pennsylvania Patient Safety Reporting System (PA-PSRS) is the largest repository of patient safety data in the United States and one of the largest in the world, with over 4.5 million acute care event reports dating back to 2004. Herein, we examine patient safety event reports submitted to the PA-PSRS acute care database in 2022 and compare them to prior years. # Methods We extracted data from PA-PSRS and obtained data from the Pennsylvania Health Care Cost Containment Council (PHC4). Counts of reports were calculated based on report submission date, and rates were calculated based on event occurrence date and calculated per 1,000 patient days for hospitals or 1,000 surgical encounters for ambulatory surgical facilities (ASFs). # Results A total of 256,679 reports were submitted to PA-PSRS in 2022, representing an 11.1% decrease from 2021. Three facilities collectively submitted 18,601 fewer reports in 2022 compared to 2021, which accounted for 57.8% of the overall decrease. Reports of serious and high harm events increased by 7.7% and 11.1%, respectively. Of the 256,679 reports submitted, 95.9% were from hospitals, 3.9% were from ambulatory surgical facilities, and 0.2% were from birthing centers and abortion facilities. The vast majority of the 2022 reports were incidents (96.2%) as opposed to serious events (3.8%). For each of the past five years, the most frequently reported event type was Error Related to Procedure/Treatment/Test, accounting for 32.8% of all submitted acute care event reports in 2022. The second, third, and fourth most frequently reported event types in 2022 were Complication of Procedure/Treatment/Test, Medication Error, and Fall, accounting for 15.6%, 13.2%, and 12.8% of submitted reports, respectively. The reported event rate based on occurrence date for hospitals in the first half of 2022 was 27.5 reports per 1,000 patient days. For ASFs, the reported event rate for the first half of 2022 was 9.4 reports per 1,000 surgical encounters. # Conclusions There was a decrease in the number of incident reports submitted to PA-PSRS in 2022 and an increase in serious and high harm event reports. PSA will continue to work with facilities, monitor reporting, and take further action as needed.

# Background Medical equipment, supplies, and devices (ESD) serve a critical function in healthcare delivery and how they function can have patient safety consequences. ESD-related safety issues include malfunctions, physically missing ESDs, sterilization, and usability. Describing ESD-related safety issues from a human factors perspective that focuses on user interactions with ESDs can provide additional insights to address these issues. # Methods We manually reviewed ESD patient safety event reports submitted to the Pennsylvania Patient Safety Reporting System to identify ESD-related safety issues using a taxonomy that was informed by the Food and Drug Administration Manufacturer and User Facility Device Experience taxonomy. This taxonomy consisted of the following high-level categories: malfunctions, physically missing, sterilization, and usability. The type of ESD and associated components or ESD subtypes, event classification, and care area group were noted for each report. # Results Of the 450 reports reviewed, the most frequent ESD-related safety issue coded was malfunction (n=365 of 450, 81.1%) followed by sterilization (n=40 of 450, 8.9%), usability (n=36 of 450, 8.0%), and physically missing (n=9 of 450, 2.0%). Among the coded malfunctions, software/output problem (n=122 of 365, 33.4%) was the most frequent, followed by general malfunction (n=103 of 365, 28.2%); material integrity (n=72 of 365, 19.7%); and activation, positioning, or separation (n=68 of 365, 18.6%). The most frequent ESDs noted were infusion pump, instrument set, and intravenous, and the most frequent components/subtypes noted were alarm/alert, tubing, and tray. # Conclusions ESD-related patient safety issues, especially malfunctions, impact patient care despite current policies and practices to address these issues. Healthcare facilities may be able to address some ESD-related patient safety issues during procurement through use of the accompanying procurement assessment tool.

# Background Alarms are signals intended to capture and direct human attention to a potential issue that may require monitoring, assessment, or intervention and play a critical safety role in high-risk industries. Healthcare relies heavily on auditory and visual alarms. While there are some guidelines to inform alarm design and use, alarm fatigue and other alarm issues are challenges in the healthcare setting. Automotive, aviation, and nuclear industries have used the science of human factors to develop alarm design and use guidelines. These guidelines may provide important insights for advancing patient safety in healthcare. # Methods We identified documents containing alarm design and use guidelines from the automotive, aviation, and nuclear industries that have been endorsed by oversight agencies. These guidelines were reviewed by human factors and clinical experts to identify those most relevant to healthcare, qualitatively analyze the relevant guidelines to identify meaningful topics, synthesize the guidelines under each topic to identify key commonalities and differences, and describe how the guidelines might be considered by healthcare stakeholders to improve alarm design and use. # Results A total of 356 guidelines were extracted from industry documents (2012–present) and 327 (91.9%) were deemed relevant to healthcare. A qualitative analysis of relevant guidelines resulted in nine distinct topics: Alarm Reduction, Appropriateness, Context-Dependence, Design Characteristics, Mental Model, Prioritization, Specificity, Urgency, and User Control. There were several commonalities, as well as some differences, across industry guidelines. The guidelines under each topic were found to inform the auditory or visual modality, or both. Certain guidelines have clear considerations for healthcare stakeholders, especially technology developers and healthcare facilities. # Conclusion Numerous guidelines from other high-risk industries can inform alarm design and use in healthcare. Healthcare facilities can use the information presented as a framework for working with their technology developers to appropriately design and modify alarming technologies and can evaluate their clinical environments to see how alarming technologies might be improved.

Objective: US women exhibit racial disparities in the lifetime risk of diabetes and related outcomes. Identifying heterogeneity in clinical presentation may assist with reducing racial disparities in diabetes outcomes. We identified clinical phenotypes of diabetes and examined their racial and ethnic distribution in US women. Research design and methods: We conducted cluster analysis based on five factors in US women with diagnosed diabetes assessed in the National Health and Nutrition Examination Surveys 1999–2018 (n = 825). Multinomial logistic regression analysis was performed to identify racial and ethnic differences in the distribution of phenotypes. Results: We identified four distinct clinical phenotypes. Two phenotypes, mild age-related and severe insulin-deficient diabetes, each included approximately a third of women. Mild insulin-resistant and severe insulin-resistant diabetes phenotypes accounted for 19.9% and 13.7%, respectively. The distribution of clusters did not differ by race and ethnicity. Conclusions: The prevalence of four clinically distinct diabetes phenotypes identified in US women did not differ by race and ethnicity.

Background: Firefighters may experience high environmental temperatures or carry out intensive physical tasks, or both, which leads to increased core body temperature and risk of fatalities. Hence there is a need to remotely and non-invasively monitor core body temperature. Methods: Estimated (heart rate algorithm) and actual core body temperature (ingested telemetric pill) measures were collected simultaneously for comparison during training exercises on 44 firefighter volunteers. Results: Prediction of core body temperature varied, with no specific identifiable pattern between the algorithm values and directly measured body core temperatures. Group agreement of Lin's Concordance of 0.74 (95% Upper 0.75, lower CI 0.73), was deemed poor. Conclusion: From individual agreement data Lin's Concordance was variable (Min 0.11, CI 0.13–0.01; Max 0.83, CI 0.86–0.80), indicating that the heart rate algorithm approach was not suitable for core body temperature monitoring in this population group, especially at the higher more critical core body temperatures seen.

Abstract Effective physical activity messaging plays an important role in the pathway towards changing physical activity behaviour at a population level. The Physical Activity Messaging Framework (PAMF) and Checklist (PAMC) are outputs from a recent modified Delphi study. This sought consensus from an international expert panel on how to aid the creation and evaluation of physical activity messages. In this paper, we (1) present an overview of the various concepts within the PAMF and PAMC, (2) discuss in detail how the PAMF and PAMC can be used to create physical activity messages, plan evaluation of messages, and aid understanding and categorisation of existing messages, and (3) highlight areas for future development and research. If adopted, we propose that the PAMF and PAMC could improve physical activity messaging practice by encouraging evidence-based and target population-focused messages with clearly stated aims and consideration of potential working pathways. They could also enhance the physical activity messaging research base by harmonising key messaging terminologies, improving quality of reporting, and aiding collation and synthesis of the evidence.

IntroductionThe effects of the SARS-CoV-2 virus on the body, and why the effects are more severe in certain patients, remain incompletely understood. One population of special interest is transplant recipients because of their immunosuppressed state. Understanding the pathophysiology of graft dysfunction in transplant patients with the COVID-19 viral syndrome is important for prognosticating the risk to the graft as well as understanding how best to prevent and, if necessary, treat graft injury in these patients.MethodsWe analyzed multiple types of solid organ transplant recipients (liver, kidney, heart or lung) at our institution who died from SARS-CoV-2 and underwent autopsy (n = 6) or whose grafts were biopsied during active SARS-CoV-2 infection (n = 8). Their serum inflammatory markers were examined together with the histological appearance, viral load, and TCR repertoire of their graft tissue and, for autopsy patients, several native tissues.ResultsHistology and clinical lab results revealed a systemic inflammatory pattern that included elevated inflammatory markers and diffuse tissue damage regardless of graft rejection. Virus was detected throughout all tissues, although most abundant in lungs. The TCR repertoire was broadly similar throughout the tissues of each individual, with greater sharing of dominant clones associated with more rapid disease course. There was no difference in viral load or clonal distribution of overall, COVID-associated, or putative SARS-CoV-2-specific TCRs between allograft and native tissue. We further demonstrated that SARSCoV-2-specific TCR sequences in transplant patients lack a donor HLArestricted pattern, regardless of distribution in allograft or native tissues,suggesting that recognition of viral antigens on infiltrating recipient cells can effectively trigger host T cell anti-viral responses in both the host and graft.DiscussionOur findings suggest a systemic immune response to the SARS-CoV-2 virus in solid organ transplant patients that is not associated with rejection and consistent with a largely destructive effect of recipient HLA-restricted T cell clones that affects donor and native organs similarly.

Abstract Background There is evidence of geographical variation in the use of mental health services in the UK and in international settings. It is important to understand whether this variation reflects differences in the prevalence of mental disorders, or if there is evidence of variation related to other factors, such as population socioeconomic status and access to primary care services. Methods This is a cross-sectional ecological study using Public Health England data. The unit of analysis was the population served by clinical commissioning groups (CCGs), National Health Service (NHS) catchment areas. The analysis explored associations between area characteristics and the number of people in contact with mental health services using regression modelling. Explanatory variables included age, gender, prevalence of severe mental illness (SMI), prevalence of common mental disorder (CMD), index of multiple deprivation (IMD), unemployment, proportion of the population who are Black and Minority Ethnic (BAME), population density, access to and recovery in primary care psychological therapies. Unadjusted results are reported, as well as estimates adjusted for age, prevalence of CMD and prevalence of SMI. Results The populations of 194 CCGs were included, clustered within 62 trusts (NHS providers of mental health services). The number of people in contact with mental health services showed wide variation by area (range from 1131 to 5205 per 100,000 population). Unemployment (adjusted IRR 1.11; 95% CI 1.05 to 1.17; p

Background: National policy recommends intensive support teams for all areas of England for adults with intellectual disabilities who display challenging behaviour. However, to the best of our knowledge, there has not been a systematic evaluation of intensive support teams to date. Objectives: Our objectives were to identify and describe the geographical distribution and characteristics of intensive support teams in England; to create a typology of intensive support teams; to investigate clinical and cost outcomes of intensive support team models and factors associated with those outcomes; and to explore professionals’, service users’ and carers’ experiences and describe the wider system context in which they operate. Design: This was a two-phase mixed-methods study. In phase 1, a national survey examined the intensive support team models in operation in England. In phase 2, an observational study of adults with intellectual disabilities investigated the clinical effectiveness and cost-effectiveness of the two intensive support team models. Semistructured interviews with intensive support team managers and professionals, carers, and adults with intellectual disabilities explored their experiences of intensive support team care. In parallel, we examined service-level outcomes related to the function of intensive support teams. Setting: Phase 1 included 80 intensive support teams serving 242 community intellectual disability services in England. Phase 2 included 21 intensive support teams, half of which were in the enhanced intensive support teams model and half of which were in the independent model. Participants: In phase 1, a total of 73 intensive support team managers provided data. In phase 2, a total of 226 participants with intellectual disabilities from 21 intensive support teams (enhanced: teams, n = 11; participants, n = 115; independent: teams, n = 10; participants, n = 111) were enrolled in the study. A total of 42 stakeholders were interviewed. Main outcome measure: The main outcome measure was the Aberrant Behaviour Checklist-Community, version 2, total score. Additional data sources were the carer and self-reported questionnaires, qualitative interviews and focus groups. Results: Two intensive support team models were identified in England – enhanced and independent. Challenging behaviour at 9 months was reduced in both intensive support team models (β 3.08, 95% confidence interval –7.32 to 13.48; p = 0.561), but the observed Aberrant Behaviour Checklist-Community, version 2, score reduction appeared larger in the independent model than in the enhanced model (21% vs. 13%, respectively). No statistically significant differences were found in the secondary outcomes [Psychiatric Assessment Schedule for Adults with Developmental Disabilities Clinical Interview organic condition (odds ratio 1.09, 95% confidence interval 0.39 to 3.02), affective or neurotic disorder (odds ratio 0.91, 95% confidence interval 0.32 to 2.59), or psychotic disorder score (odds ratio 1.08, 95% confidence interval 0.21 to 5.50); risk score (β 1.12, 95% confidence interval –0.44 to 2.68); or quality of life questionnaire score (β –2.63, 95% confidence interval –5.65 to 0.40)]. Similarly, no differences were observed between models in relation to cost-effectiveness (health and social care costs mean difference £3409.95, 95% confidence interval –£9957.92 to £4039.89; societal costs mean difference –£4712.30, 95% confidence interval –£11,124.85 to £2106.36). The experiences of stakeholders did not differ between the intensive support team models, with carers and adults with intellectual disabilities valuing service accessibility, person-centred care and engagement. All stakeholders reported a range of barriers to intensive support team care. Service-level data and the operational policies from intensive support teams showed variation in organisational function and the roles of intensive support teams. The most commonly delivered intervention was positive behaviour support. Conclusions: The study describes the operation of intensive support teams in England and identified two distinct models. We did not find advantages or disadvantages associated with clinical outcomes between models, nor did we find cost differences. On this basis, we recommend that local services decide which model best suits their circumstances. Limitations: This was not a randomised controlled trial. It is possible that confounding factors have not been controlled for as there was no matching between intensive support teams. Last, there was no comparison with usual care. Future work: There is need to develop model fidelity and investigate clinical effectiveness and cost-effectiveness in a randomised controlled evaluation of intensive support teams against treatment as usual. Study registration: This study is registered as ClinicalTrials.gov NCT03586375, Integrated Research Application System (IRAS) 239820 and National Institute for Health and Care Research (NIHR) Central Portfolio Management System (CPMS) 38554. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 33. See the NIHR Journals Library website for further project information.

Background: Duplicate medication orders are a prominent type of medication error that in some circumstances has increased after implementation of health information technology. Duplicate medication orders are commonly defined as two or more active orders for the same medication or medications within the same therapeutic class. While there have been several studies that have identified contributing factors and described potential solutions, duplicate medication order errors continue to impact patient safety. Methods: We analyzed 377 reports from 95 healthcare facilities to more granularly define the types of duplicate medication order errors and the context under which these errors occurred, as well as potential contributing factors. Results: Of the 377 reports reviewed, 304 (80.6%) met the criteria to be defined as a duplicate medication order error. The most frequent duplicate medication order error type was same order (n=131, 43.1%), followed by same therapeutic class (n=98, 32.2%) and same medication (n=70, 23.0%). Errors were identified during different medication process tasks and most commonly during medication reconciliation during the patient’s stay in the hospital (n=72, 23.7%) and during pharmacy verification (n=36, 11.8%). Factors contributing to these errors included health information technology issues (n=63, 20.7%), gaps in care coordination (n=44, 14.5%), and a prior dose or medication order not being discontinued (n=52, 17.1%). Conclusion: Our results highlight specific areas for practice improvement, and we make recommendations for how healthcare facilities can better address duplicate medication order errors.

Background: The Pennsylvania Patient Safety Reporting System (PA-PSRS) is the largest repository of patient safety data in the United States. In addition to over 4.2 million acute care reports, the PA-PSRS database contains more than 375,000 long-term care (LTC) healthcare-associated infection (HAI) reports. Methods: LTC HAI data from PA-PSRS were extracted on February 10, 2022. Reports submitted by LTC facilities and specific care areas were included for infection rates each month if resident and device days were also entered in PA-PSRS for the facility and care area. Results: A total of 17,971 infections were reported in 2021, representing a 31.7% decrease from the prior year. Overall, the reporting rate from LTC facilities decreased notably, from 1.06 in 2020 to 0.78 in 2021, due in large part to a drop in respiratory tract infections, which had an infection rate of 0.431 in 2020 and 0.191 in 2021. The North Central region of the state had the highest overall infection rate, with 0.94 reports per 1,000 resident days, and the Southeast region had the lowest rate at 0.62. The number of reports decreased for all five infection types from 2020 to 2021, with respiratory tract infections decreasing the most, by 58.4%. The number of reports for all infection subtypes decreased as well, with the exception of scabies, which increased by 7.1%. Among all infection subtypes, the number of reports for lower respiratory tract infections decreased the most, with 2,553 fewer reports in 2021 than in 2020. In terms of percentage, influenza-like illness decreased the most, dropping 93.9% from 2020 to 2021. In terms of infection rate, catheter-associated urinary tract infections showed the greatest decrease, and infections involving cellulitis, soft tissue, and wounds showed the greatest increase. Conclusions: In 2021, there were notable decreases in both the infection rate and the number of infection reports submitted by Pennsylvania LTC facilities. Currently, it is unknown whether these decreases are reflective of fewer infections in LTC facilities or a lack of identifying and reporting infections, or a combination of both. Patient Safety Authority infection preventionists (IPs) continue to work with LTC IPs to provide support, education, and tools to assist them in their role.

Background: Pennsylvania is the only state that requires acute care facilities to report all events of harm or potential for harm. With over 4.2 million acute care event reports, the Pennsylvania Patient Safety Reporting System (PA-PSRS) is the largest repository of patient safety data in the United States and one of the largest in the world. This study examines patient safety event reports submitted to the PA-PSRS acute care database in 2021. Methods: We queried PA-PSRS for all event reports submitted by Pennsylvania acute care facilities during calendar year 2021. We also obtained the most current data from the Pennsylvania Health Care Cost Containment Council (PHC4) to calculate rates based on patient days for hospitals and surgical encounters for ambulatory surgical facilities (ASFs). For the Other (specify) subtype within the Other/Miscellaneous event type, we identified the words occurring most frequently in the required free-text response field and calculated the increase in associated reports for each of the words from 2020 to 2021. Results: Of the 288,882 patient safety event reports submitted by Pennsylvania’s acute care facilities in 2021, 96.8% were from hospitals and 3.1% were from ASFs. The remaining 0.1% were from birthing centers and abortion facilities. The vast majority of the 2021 reports were Incidents (96.9%) rather than Serious Events (3.1%). For each of the past five years, the most frequently reported event type was Error Related to Procedure/Treatment/Test, accounting for 31.3% of all submitted acute care event reports in 2021. The second, third, and fourth most frequently reported event types were Medication Error, Complication of Procedure/Treatment/Test, and Fall, accounting for 16.9%, 15.3%, and 12.3% of submitted reports in 2021, respectively. The reporting rate for hospitals in 2021 (Q1 and Q2) was 30.9 reports per 1,000 patient days. For ASFs, the reporting rate in 2021 (Q1 and Q2) was 8.6 reports per 1,000 surgical encounters. Conclusions: There was an increase in the total number of patient safety event reports submitted in 2021, yet the percentage of high harm reports remained steady. Four event types—Error Related to Procedure/Treatment/Test, Medication Error, Complication of Procedure/Treatment/Test, and Fall—accounted for more than three-quarters of all reports submitted to PA-PSRS in 2021. Readers can use the longitudinal and categorical insights shared in this article to focus patient safety improvement efforts.

Background: Previous research has shown that visitors can decrease the risk of patient harm; however, the potential to increase the risk of patient harm has been understudied. Methods: We queried the Pennsylvania Patient Safety Reporting System database to identify event reports that described visitor behaviors contributing to either a decreased or increased risk of patient harm. Event reports from January 1 to June 30, 2019, were searched for keywords and reviewed for inclusion criteria. Event reports were manually coded to identify visitor influence on risk of patient harm (e.g., increase or decrease), visitor behavior, and event type. Results: A total of 427 event reports were analyzed and we identified five categories of visitor behavior that influenced patient safety by either decreasing or increasing the risk of patient harm. We found that 63.7% (272 of 427) of event reports described a visitor behavior that decreased the risk of patient harm and the remaining 36.3% (155 of 427) of reports described behavior that increased the risk of harm. There was a greater variety of visitor behaviors that contributed to an increased risk of patient harm, as opposed to a decreased risk of harm. The visitor behavior most frequently associated with a decreased risk of patient harm was communicating with staff (91.2%, 248 of 272); for example, to inform staff of deterioration of a patient’s condition. The visitor behavior most frequently associated with an increased risk of patient harm was moving a patient (63.2%, 98 of 155). Across the 427 event reports, we found that visitor behavior was associated with seven event types; the falls event type (61.6%, 263 of 427) and medication-related event type (14.8%, 63 of 427) occurred most frequently. Conclusion: The current study provides insight into which visitor behaviors are contributing to a decreased risk of patient harm and adds to the literature by identifying behaviors that can increase the risk of patient harm, across multiple event types. Table 6 and Table 7 outline potential safety strategies that staff and facilities may consider using to target visitor behavior. As outlined in Table 6, the use of warning and instructional signage can be a relatively low-effort and effective strategy to influence visitor behavior and address multiple behavior categories and event types.

Background: Dose calculation errors are one of the most common types of medication errors impacting children and they can result in significant harm. Technology-based solutions, such as computerized provider order entry, can effectively reduce dose calculation issues; however, these technologies are not always optimized, resulting in potential benefits not being fully realized. Methods: We analyzed pediatric dose-related patient safety event reports submitted to the Pennsylvania Patient Safety Reporting System using a task-analytic approach that focused on information being used in the dose calculation, calculation errors during ordering, and errors during dose preparation or administration. From these reports, we identified whether the patient was impacted by the error, the type of medication involved, and whether a technology optimization could have mitigated the issue. Results: Of the 356 reports reviewed, 326 (91.6%) met the criteria for a dose calculation issue. The 326 reports meeting criteria had the following dose calculation issue types: wrong information used in the calculation (49 of 326, 15.0%), incorrect calculation during ordering (97 of 326, 29.8%), and calculated dose was not properly used or incorrect calculation during preparation/administration (180 of 326, 55.2%). Most of these dose calculation issues impacted the patient (219 of 326, 67.2%). Analysis of these issues by patient age group and drug class also revealed interesting patterns. Technology optimizations potentially could have addressed 81.6% of the dose calculation issues identified. Conclusion: While many healthcare facilities have adopted health information technology and other devices to support the medication process, these technologies are not always optimized to address dose calculation issues. Human factors–informed recommendations, a safety checklist, and test cases for optimizing technology are provided in the context of these findings.

Two main variants of Richter syndrome (RS) are recognized, namely, the diffuse large B-cell lymphoma (DLBCL) and the Hodgkin’s lymphoma (HL) variant. Clonal relationship, defined as an identity of the immunoglobulin heavy chain variable (IGHV) region sequence between chronic lymphocytic leukemia (CLL) and RS clones, characterizes patients with a poor prognosis. Due to method sensitivity, this categorization is performed without considering the possibility of small-size ancillary clones, sharing the same phenotype with the preexisting predominant CLL clone, but with different IGHV rearrangements. Here we describe and molecularly profile the peculiar case of a patient with a CLL-like monoclonal B-cell lymphocytosis (MBL), who sequentially developed a DLBCL, which occurred concomitantly to progression of MBL to CLL, and a subsequent HL. Based on standard IGHV clonality analysis, DLBCL was considered clonally unrelated to the concomitantly expanded CLL clone and treated as a de novo lymphoma, achieving a persistent response. Three years later, the patient further developed a clonally unrelated HL, refractory to bendamustine, which was successfully treated with brentuximab vedotin and radiotherapy, and later with pembrolizumab. We retrospectively performed additional molecular testing, by applying next-generation sequencing (NGS) of immunoglobulin repertoire (Ig-rep) techniques and a more sensitive allele-specific oligonucleotide-droplet digital PCR (ASO-ddPCR) strategy, in order to quantitatively investigate the presence of the rearranged IGHV genes in tumor specimens collected during the disease course. In this highly complex case, the application of modern and sensitive molecular technologies uncovered that DLBCL, initially considered as a de novo lymphoma, was instead the result of the transformation of a preexisting ancillary B-cell clone, which was already present at the time of first MBL diagnosis. A similar approach was also applied on the HL sample, showing its clonal unrelatedness to the previous MBL and DLBCL.

Summary: Background: Uncertainty exists about how best to identify primary biliary cholangitis (PBC) patients who would benefit from second-line therapy. Existing, purely clinical, ursodeoxycholic acid (UDCA) response criteria accept degrees of liver biochemistry abnormality in responding patients, emerging data, however, suggest that any degree of ongoing abnormality may, in fact, be associated with an increased risk of adverse outcomes. This cohort study explores the link between response status, the biology of high-risk disease and its implications for clinical practice. Methods: Proteomics, exploring 19 markers previously identified as remaining elevated in PBC following UDCA therapy, were performed on 400 serum samples, from participants previously recruited to the UK-PBC Nested Cohort between 2014 and 2019. All participants had an established diagnosis of PBC and were taking therapeutic doses of UDCA for greater than 12 months. UDCA response status was assessed using Paris 1, Paris 2 and the POISE criteria, with additional analyses using normal liver blood tests stratified by bilirubin level. Statistical analysis using parametric t tests and 1-way ANOVA. Findings: Disease markers were statistically significantly higher in UDCA non-responders than in responders for all the UDCA response criteria, suggesting a meaningful link between biochemical disease status and disease mechanism. For each of the criteria, however, marker levels were also statistically significantly higher in responders with ongoing liver function test abnormality compared to those who had normalised their liver biochemistry. IL-4RA, IL-18-R1, CXCL11, 9 and 10, CD163 and ACE2 were consistently elevated across all responder groups with ongoing LFT abnormality. No statistically significant differences occurred between markers in normal LFT groups stratified by bilirubin level. Interpretation: This study provides evidence that any ongoing elevation in alkaline phosphatase levels in PBC after UDCA therapy is associated with some degree of ongoing disease activity. There was no difference in activity between patients with normal LFT when stratified by bilirubin. These findings suggest that if our goal is to completely control disease activity in PBC, then normalisation of alkaline phosphatase and bilirubin should be the treatment target. This would also simplify messaging around goals of therapy in PBC, benefiting both patients and clinicians. Funding: Funding by the UK Medical Research Council (Stratified Medicine Programme) and an independent research grant by Pfizer. The study funders played no role in the study design, data collection, data analyses, data interpretation or manuscript writing.

Background: Although serious medication errors are uncommon, accounting for only 0.4% (166 of 46,568) of medication errors reported to the Pennsylvania Patient Safety Reporting System (PA-PSRS) in 2020, their effects can be devastating for patients and their loved ones. Methods: We queried PA-PSRS for reports of serious events classified as medication errors that occurred in the emergency department (ED) from January 1, 2011, to December 31, 2020. We performed a descriptive analysis to identify trends among patient sex, patient age, event harm score, event day of the week, and event time of day. We also manually coded and analyzed events based on the prescribed medication(s) and medication class(es), stage of the medication-use process at which the error occurred, and medication error type. Results: We identified 250 reports of serious medication error events in PA-PSRS that occurred in the ED from 2011 to 2020. Reports more often specified that the patient was female (61.2%; 153 of 250), and patients ranged in age from 8 months to 96 years, with a median patient age of 55 years. Events were significantly more likely to occur Friday through Sunday versus Monday through Thursday (p = .0214) and in the p.m. hours versus a.m. hours, (p = .0007). The most common prescribed medications mentioned in reports were epinephrine, insulin, hydromorphone, sodium chloride, heparin, propofol, diltiazem, ketamine, and morphine. Events occurred most often at the prescribing stage of the medication-use process (42.0%; 105 of 250), and the most common medication error type was a wrong dose (42.0%; 105 of 250). Conclusion: Potential safety strategies to consider to reduce the risk of medication errors in the ED include stocking epinephrine autoinjectors, using clinical decision support at the ordering/prescribing stage of the process, and adding an emergency medicine pharmacist as part of an interdisciplinary emergency medicine team.

Background: Tracheostomy- and laryngectomy-related airway safety events can lead to life-threatening situations, permanent harm, or death. We conducted a statewide population-based study to learn about these events and the relationship with associated factors, interventions, and outcomes to identify potential areas for improvement. Methods: We queried the Pennsylvania Patient Safety Reporting System (PA-PSRS) to find tracheostomy- and laryngectomy-related airway safety event reports involving adults age 18 years and older that occurred between January 1, 2018, and December 31, 2020. Results: Reports related to tracheostomies and laryngectomies accounted for 97.3% and 2.7% of the total, respectively. The four most frequent tracheostomy-related complications were unplanned decannulations, 71.4%; uncontrolled bleeding/hemorrhage, 9.2%; and partial/total occlusion and mucus plug/thick secretions, which each accounted for 6.9%. Conclusions: Safe airway management for patients with a tracheostomy or laryngectomy requires staff who are knowledgeable and confident, and have the necessary skills and equipment to provide immediate attention when complications arise. We discuss potential safety strategies to reduce the risk of unplanned decannulations, uncontrolled bleeding/hemorrhage, and partial/total occlusions, as well as issues related to equipment, knowledge/training, and communication.

BackgroundRandom acts of kindness can improve wellbeing. However, less is known about the impacts of giving and receiving acts of kindness with strangers on wellbeing and loneliness. Therefore, this study’s objectives were to evaluate a participatory public mental health project involving sending and receiving a card with goodwill messages, to understand how such acts of kindness influence wellbeing and loneliness, and to investigate the potential mechanisms underlying the project’s impacts.Materials and MethodsThis study was an analysis of anonymized service evaluation data collected in the ‘Kindness by Post’ (KBP) project in 2020. It used a mixed-methods single-group design and data from 289 participants. Changes in wellbeing, loneliness, sense of belonging and hope from baseline (12th–14th February) to follow-up (26th February–2nd March) were analyzed using linear or multinomial logistic regression. Regression models also examined the associations between changes in wellbeing and baseline loneliness or participation level. Free text responses about experiences and suggestions for the project were analyzed using thematic analysis.ResultsParticipants had a small, but statistically significant improvement, in wellbeing equating to 0.21 standard deviations (95% CI: 0.12–0.30) after taking part in the project, as well as improvements in loneliness, sense of belonging and hope. How lonely a participant was at baseline and whether participants both sent and received a kindness card were not associated with improvements in wellbeing. In the qualitative analysis, a desire to help others emerged as the main motivator to take part in the card exchange. Participants reported enhanced personal fulfillment, leading to improvements in wellbeing. Receiving a card could make people feel special and cherished, which was reported to establish a sense of connection with others, with potential benefits for reducing loneliness.ConclusionThis study provided preliminary evidence that the KBP project might improve wellbeing, loneliness, sense of belonging and hope. Sending a kindness card in this project played a predominant role in wellbeing enhancement, and receiving a kindness card could reduce loneliness. This study suggests that the KBP project can be replicated in more contexts in the future, and might improve wellbeing and loneliness in large communities.

Immune-based therapeutic strategies have drastically changed the landscape of hematological disorders, as they have introduced the concept of boosting immune responses against tumor cells. Anti-CD20 monoclonal antibodies have been the first form of immunotherapy successfully applied in the treatment of CLL, in the context of chemoimmunotherapy regimens. Since then, several immunotherapeutic approaches have been studied in CLL settings, with the aim of exploiting or eliciting anti-tumor immune responses against leukemia cells. Unfortunately, despite initial promising data, results from pilot clinical studies have not shown optimal results in terms of disease control - especially when immunotherapy was used individually - largely due to CLL-related immune dysfunctions hampering the achievement of effective anti-tumor responses. The growing understanding of the complex interactions between immune cells and the tumor cells has paved the way for the development of new combined approaches that rely on the synergism between novel agents and immunotherapy. In this review, we provide an overview of the most successful and promising immunotherapeutic modalities in CLL, including both antibody-based therapy (i.e. monoclonal antibodies, bispecific antibodies, bi- or tri- specific killer engagers) and adoptive cellular therapy (i.e. CAR T cells and NK cells). We also provide examples of successful new combination strategies and some insights on future perspectives.

We examine whether social data can be used to predict how members of Major League Baseball (MLB) and members of the National Basketball Association (NBA) transition between teams during their career. We find that incorporating social data into various machine learning algorithms substantially improves the algorithms' ability to correctly determine these transitions in the NBA but only marginally in MLB. We also measure the extent to which player performance and team fitness data can be used to predict transitions between teams. This data, however, only slightly improves our predictions for players for both basketball and baseball players. We also consider whether social, performance, and team fitness data can be used to infer past transitions. Here we find that social data significantly improves our inference accuracy in both the NBA and MLB but player performance and team fitness data again does little to improve this score.

Background & Aims: Treatment options remain limited for patients with autoimmune hepatitis (AIH), while there are still concerns over the consequences of long-term corticosteroid use. A few studies have suggested a role for B cell-driven autoimmune liver injury in AIH. This multicentre, international retrospective cohort study from the International Autoimmune Hepatitis Group aims to evaluate the clinical efficacy and safety of rituximab in difficult-to-manage AIH. Methods: Clinical data from 22 patients who received rituximab between 2007 and 2017 were collected from centres in the United Kingdom, Germany and Canada. Clinical response was assessed using changes in biochemical and immunological parameters up to 24 months post-rituximab infusion. In addition, we compared the doses of prednisolone used 3 months before and 12 months after treatment, and assessed freedom from AIH flares over the post-treatment period. Results: Twenty-two patients with type-1 AIH were included, with a median age of 40 years at diagnosis (range 19–79); 15/22 (68%) were female and 18/22 (82%) were Caucasian. The median period from diagnosis to the end of follow-up in these patients was 11 years (range 3–28). Values of alanine aminotransferase, aspartate aminotransferase and albumin improved significantly following rituximab therapy, and were sustained for up to 2 years (all p ≪0.001). Prednisolone doses were significantly reduced by 12 months post-treatment (p = 0.003), with 13/21 (62%) patients having a dose reduction. Over a median post-treatment follow-up period of 6 years (range 1–10), 5 patients developed AIH flares at a median of 22 months post-treatment, giving an estimated 71% freedom from AIH flare at 2 years. Four of these patients received a second course of treatment, of whom 2 had subsequent further flares. No serious adverse events attributable to rituximab were recorded. Conclusion: In patients with difficult-to-manage AIH, rituximab appears to be clinically effective and well tolerated. Rituximab was associated with sustained improvements in serum liver tests, an absence of clinical disease flares, and a reduction in prednisolone dose. Controlled trials are warranted to further evaluate B cell-targeting therapies in patients with AIH. Lay summary: Autoimmune hepatitis is an autoimmune condition of the liver, usually treated with medications that suppress the immune system, such as steroids. However, some patients do not respond to this treatment. We analysed the safety and efficacy of rituximab in patients who were not responding to first- or second-line therapies. Rituximab was safe and improved liver blood tests in 70% of patients over a 2-year follow-up period, while enabling steroid doses to be reduced in two-thirds of patients, which is a very positive clinical outcome. Keywords: Autoimmune hepatitis, Prednisolone, Difficult-to-manage, B cell depletion therapy, Rituximab

Atrial fibrillation (AF) is a cardiac arrhythmia characterized by an irregular rhythm and often rapid heart rate. People with AF can be symptomatic or asymptomatic and are at increased risk for stroke. In this study, we used two data sources—a survey and Pennsylvania Patient Safety Reporting System (PA-PSRS) reports—to examine new-onset AF in Pennsylvania ambulatory surgical facilities (ASFs). The survey was developed and conducted to learn more about new-onset AF–related cancellations and transfers in Pennsylvania ASFs and to update the Patient Safety Authority ASF Cancellation and Transfer Tracking Tool. The survey response rate was 53.1%, with 50.9% of respondents indicating new-onset AF–related cancellations in the last year. A five-year review of PA-PSRS data revealed an increase in the number of new-onset AF–related cancellation and transfer events that occurred in the last two years. In 70.9% of the reports, patients were 65 years of age and older. A paucity of research on this patient safety issue led us to identify areas for future research.

Background: Little is known about the effectiveness of befriending for people with intellectual disability and whether or not befriending improves depressive symptoms and social outcomes. Objective: This pilot trial aimed to assess the feasibility and acceptability of conducting a future full-scale randomised controlled trial of one-to-one befriending for people with intellectual disability who had depressive symptoms. Design: This was a parallel-group, two-armed randomised controlled trial incorporating an exploratory economic analysis and a mixed-methods process evaluation. Outcome assessments were conducted at baseline and at 6 months post randomisation by a research assistant who was blind to allocation. We aimed to approach 50 participants, with a view to recruiting 40. Setting: Participants with intellectual disability were recruited from one NHS trust and from referrals to two community befriending services. The intervention was delivered by community befriending services. Participants: Adults with mild or moderate intellectual disability with a score on the Glasgow Depression Scale for people with a Learning Disability of ≥ 5 were included. Those attending a day service/college for ≥ 3 days a week were excluded. Volunteers were aged ≥ 18 years and had no history of prior convictions. Intervention: Participants in the intervention group were matched with a volunteer befriender and were expected to meet once per week for 1 hour, over 6 months. Volunteers recorded activities in a logbook. Volunteers received training and regular supervision. Both groups received usual care and a resource booklet of local activities. Main outcome measures: The feasibility outcomes and progression criteria were recruitment of at least 70% of participants approached; matching of at least 70% of participants in the intervention group to a volunteer; a dropout rate of

Background: Generalised anxiety disorder, characterised by excessive anxiety and worry, is the most common anxiety disorder among older people. It is a condition that may persist for decades and is associated with numerous negative outcomes. Front-line treatments include pharmacological and psychological therapy, but many older people do not find these treatments effective. Guidance on managing treatment-resistant generalised anxiety disorder in older people is lacking. Objectives: To assess whether or not a study to examine the clinical effectiveness and cost-effectiveness of acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder is feasible, we developed an intervention based on acceptance and commitment therapy for this population, assessed its acceptability and feasibility in an uncontrolled feasibility study and clarified key study design parameters. Design: Phase 1 involved qualitative interviews to develop and optimise an intervention as well as a survey of service users and clinicians to clarify usual care. Phase 2 involved an uncontrolled feasibility study and qualitative interviews to refine the intervention. Setting: Participants were recruited from general practices, Improving Access to Psychological Therapies services, Community Mental Health Teams and the community. Participants: Participants were people aged ≥ 65 years with treatment-resistant generalised anxiety disorder. Intervention: Participants received up to 16 one-to-one sessions of acceptance and commitment therapy, adapted for older people with treatment-resistant generalised anxiety disorder, in addition to usual care. Sessions were delivered by therapists based in primary and secondary care services, either in the clinic or at participants’ homes. Sessions were weekly for the first 14 sessions and fortnightly thereafter. Main outcome measures: The co-primary outcome measures for phase 2 were acceptability (session attendance and satisfaction with therapy) and feasibility (recruitment and retention). Secondary outcome measures included additional measures of acceptability and feasibility and self-reported measures of anxiety, worry, depression and psychological flexibility. Self-reported outcomes were assessed at 0 weeks (baseline) and 20 weeks (follow-up). Health economic outcomes included intervention and resource use costs and health-related quality of life. Results: Fifteen older people with treatment-resistant generalised anxiety disorder participated in phase 1 and 37 participated in phase 2. A high level of feasibility was demonstrated by a recruitment rate of 93% and a retention rate of 81%. A high level of acceptability was found with respect to session attendance (70% of participants attended ≥ 10 sessions) and satisfaction with therapy was adequate (60% of participants scored ≥ 21 out of 30 points on the Satisfaction with Therapy subscale of the Satisfaction with Therapy and Therapist Scale-Revised, although 80% of participants had not finished receiving therapy at the time of rating). Secondary outcome measures and qualitative data further supported the feasibility and acceptability of the intervention. Health economic data supported the feasibility of examining cost-effectiveness in a future randomised controlled trial. Although the study was not powered to examine clinical effectiveness, there was indicative evidence of improvements in scores for anxiety, depression and psychological flexibility. Limitations: Non-specific therapeutic factors were not controlled for, and recruitment in phase 2 was limited to London. Conclusions: There was evidence of high levels of feasibility and acceptability and indicative evidence of improvements in symptoms of anxiety, depression and psychological flexibility. The results of this study suggest that a larger-scale randomised controlled trial would be feasible to conduct and is warranted. Trial registration: Current Controlled Trials ISRCTN12268776. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 54. See the NIHR Journals Library website for further project information.

Previous research has shown that patients in infectious-agent isolation are at greater risk for certain types of safety-related events. We conducted a study to explore the relationship between the various types of events that occur in an isolation environment and the associated factors, which may have implications for the likelihood of the event and severity of patient harm. We conducted a query of the Pennsylvania Patient Safety Reporting System (PA-PSRS) database to identify event reports submitted by acute care hospitals between January 1 and September 30, 2020. We identified 484 relevant event reports from 94 hospitals for inclusion in our descriptive study (excluding near-miss events). We measured the frequency of relationship between categories of safety-related event types and 18 categories of associated factors. Among the seven categories of event types, the most frequently identified were skin integrity (141 of 484, 29%), falls (129 of 484, 27%), and medication-related (78 of 484, 16%). Across all 18 categories of associated factors, which had or may have had an influence on the event type, the most frequent were patient’s mental status (80 of 484, 17%), staff’s time to don personal protective equipment (62 of 484, 13%), and patient’s interference with equipment/supplies (45 of 484, 9%). Overall, our results revealed that the frequency of certain associated factors varied considerably from one event type to another, which indicates that the relation between event types and associated factors should guide selection of risk mitigation strategies. We encourage readers to leverage our results along with Table 9, which provides a list of challenges identified in an isolation environment and potential solutions. We envision hospital staff proactively and systematically using the information in our manuscript to facilitate their evaluation of the isolation environment and prioritization of risk mitigation strategies.

A nonpunitive approach to safety event reporting and analysis is an important dimension of healthcare organization safety culture. A system-based safety event review process, one focused on understanding and improving the conditions in which individuals do their work, generally leads to more effective and sustainable safety solutions. On the contrary, the more typical person-based approach, that blames individuals for errors, often results in unsustainable and ineffective safety solutions, but these solutions can be faster and less resource intensive to implement. We sought to determine the frequency of system-based and person-based approaches to adverse event reviews through analysis of the recommendation text provided by a healthcare organization in response to an event report. Human factors and clinical safety science experts developed a taxonomy to describe the content of the recommendation text, reviewed 8,546 event report recommendations, and assigned one or more taxonomy category labels to each recommendation. The taxonomy categories aligned with a system-based approach, aligned with a person-based approach, did not provide an indicator of the approach, or indicated the review/analysis was pending. A total of 9,848 category labels were assigned to the 8,546 event report recommendations. The most frequently used category labels did not provide an indicator of the approach to event review (4,145 of 9,848 category labels, 42.1%), followed by a person-based approach (2,327, 23.6%), review/analysis pending (1,862 ,18.9%), and a system-based approach (1,514, 15.4%). Analyzing the data at the level of each recommendation, 23.2% (1,979 of 8,546) had at least one person-based and no system-based category, 13.3% (1,133) had at least one system-based and no person-based category, and 3% (254) had at least one person-based and one system-based category. There was variability in the event review approach based on the general event type assigned to the safety event (e.g., medication, transfusion, etc.) as well as harm severity. Results suggest improvements in applying system-based approaches are needed, especially for certain general event type categories. Recommendations for improving safety event reviews are provided.

The Pennsylvania Patient Safety Reporting System (PA-PSRS) is the largest repository of patient safety data in the United States. In addition to over 3.9 million acute care records, PA-PSRS has collected more than 357,000 long-term care (LTC) healthcare-associated infection reports since 2009. A total of 26,331 infections were reported in 2020, representing a 7.0% decrease from the prior year. The Northeast region of the state had the highest overall infection rate, with 1.29 reports per 1,000 resident days, and the Southeast region had the largest increase in infection rate from the prior year (increased from 0.87 to 1.02). There was a 10.2% increase in respiratory tract infections from 2019 to 2020; however, the other four main infection types decreased (gastrointestinal by 44.6%, device-related bloodstream by 17.0%, skin and soft tissue by 16.5%, and urinary tract by 1.8%). Additionally, of the four infection subtypes that comprise the respiratory tract infections category, all increased from 2019 to 2020 except for pneumonia. The most frequently reported infection subtype in 2020 was cellulitis, soft tissue, or wound infection, although it had the second largest decrease from 2019. The infection rate for catheter-associated urinary tract infections (CAUTI) had the largest increase from 2019 to 2020, and the rate for norovirus had the largest decrease from 2019 to 2020. Infection rates also differed across the various nursing unit types. The seasonal peak for respiratory infections in 2020 occurred in the second quarter, with the exception of influenza, which peaked in the first quarter. Overall, this analysis demonstrates areas in which continued education and infection prevention measures can be applied to further enhance the safety for residents in long-term care facilities.

Pennsylvania is the only state that requires acute healthcare facilities to report all events of harm or potential for harm. With over 3.9 million acute care event reports, the Pennsylvania Patient Safety Reporting System (PA-PSRS) is the largest repository of patient safety data in the United States and one of the largest in the world. Of the 278,548 patient safety event reports submitted by Pennsylvania’s acute care facilities in 2020, 97.2% were from hospitals and 2.7% were from ambulatory surgical facilities (ASFs). The remaining 0.1% were from birthing centers and abortion facilities. The vast majority of the 2020 reports were Incidents (97.0%) rather than Serious Events (3.0%). For each of the last five years, the most frequently reported event type was Error Related to Procedure/Treatment/Test, accounting for 32.1% of all submitted acute care event reports in 2020. The second, third, and fourth most frequently reported event types were Medication Error, Complication of Procedure/Treatment/Test, and Fall, accounting for 16.7%, 16.2%, and 11.8% of submitted reports in 2020, respectively. The reporting rates for hospitals in Q1 and Q2 2020 were 32.8 and 31.5 reports per 1,000 patient days, respectively. For ASFs, the reporting rates for Q1 and Q2 2020 were 9.8 and 8.4 reports per 1,000 surgical encounters, respectively.

Durable ventricular assist devices (VAD), despite being a standard therapy for adults in end-stage heart failure, are not so extended among the paediatric population for some reasons. These may include the complex underlying congenital heart disease in some cases, but also due to the lack of small medical devices available. In most of the cases, left ventricular assist devices are implanted as a bridge to transplant therapy, with a high success rate.Great Ormond Street Hospital in London, being one of the two centres in the UK implanting VAD in children, has a wide experience in VAD management in infants, children and adolescents. So far, 98 Berlin Heart devices and 18 HeartWare have been implanted, with a successful bridging to transplant (80.6% and 72.2%, respectively). This is a consequence of a large and well-trained multidisciplinary team, involved in the whole process: from the indication to the subsequent follow-up of the patients in their local facilities. However, the incidence of adverse events is still high, with 30.61% of neurological vascular complications for Berlin Heart and 22.22% for HeartWare. Hence, it is essential to give the patient and family sufficient information regarding possible risks and benefits of long-term mechanical circulation support, and referring these patients to a centre with an expert and trained multidisciplinary team to get the best results. Resumen: El uso de asistencias de larga duración (VAD) en adultos es una práctica estandarizada que, por el contrario, no se encuentra muy extendida en la población pedátrica: tanto por la complejidad de las cardiopatías, como por el tamaño disponible de los dispositivos. En la mayoría de los casos estas se implantan como puente a trasplante, con un alta tasa de éxito.El Great Ormond Street Hospital, en Londres, siendo uno de los 2 centros en el Reino Unido que implantan este tipo de dispositivos, dispone de una gran experiencia en el manejo de asistencias en niños y adolescentes. Hasta el momento actual se han implantado 98 dispositivos Berlin Heart® y 18 HeartWare®, con un alta tasa de puente a trasplante (80,6 y 72,22%, respectivamente). Esto es a consecuencia de un gran y experto equipo multidisciplinar, implicado desde el momento de la indicación hasta el seguimiento del paciente en su centro local. Aún así, la tasa de complicaciones asociadas sigue siendo alta: 30,61% de accidentes cerebrovasculares (isquémicos o hemorrágicos) para Berlin Heart® y 22,22% para HeartWare®. Por ello, es fundamental educar tanto a los pacientes como a las familias en los posibles riesgos y beneficios del soporte mecánico circulatorio a largo plazo, y tener disponible un equipo multidisciplinar con la adecuada formación y experiencia para conseguir los mejores resultados. Keywords: Mechanical circulatory support, Heart failure, Paediatric, Palabras clave: Asistencia circulatoria, Insuficiencia cardíaca, Pediátrica