Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. METHODS: This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. FINDINGS: Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. INTERPRETATION: To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).

Evaluation of a COVID-19 fundamental nursing care guideline versus usual care: The COVID-NURSE cluster randomized controlled trial.

AIM: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness. DESIGN: Parallel two-arm, cluster-level randomized controlled trial. METHODS: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses. RESULTS: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup. CONCLUSION: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. IMPACT: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care. REPORTING METHOD: CONSORT and CONSERVE. PATIENT OR PUBLIC CONTRIBUTION: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.

Fecal Immunoglobulin A Against a Sporozoite Antigen at 12 Months Is Associated With Delayed Time to Subsequent Cryptosporidiosis in Urban Bangladesh: A Prospective Cohort Study.

In this prospective cohort study of Bangladeshi children, greater fecal immunoglobulin A, but not plasma immunoglobulin G, directed against the Cryptosporidium sporozoite-expressed antigen Cp23 at 12 months of age was associated with delayed time to subsequent cryptosporidiosis. This finding suggests a protective role for mucosal antibody-mediated immunity in naturally exposed children.

Long-term Impact of Pneumococcal Conjugate Vaccines on Invasive Disease and Pneumonia Hospitalizations in Indigenous and Non-Indigenous Australians.

BACKGROUND: Universal pneumococcal conjugate vaccine (PCV) programs began in Indigenous Australian children in 2001 and all children in 2005, changing to 13-valent PCV (PCV13) in 2011. We used laboratory data for invasive pneumococcal disease (IPD) and coded hospitalizations for noninvasive pneumococcal community-acquired pneumonia (PnCAP) to evaluate long-term impact. METHODS: Annual incidence (per 100 000 population) was calculated for age-specific total IPD, PCV13 non-7-valent PCV (PCV7) serotypes, and PnCAP by Indigenous status. Incidence in the pre-universal PCV7 (2002-2004), early PCV7 (2005-2007), pre-PCV13 (2008 to mid-2011), and post-PCV13 (mid-2011 to 2016) periods was used to calculate incidence rate ratios (IRRs). RESULTS: In the total population, all-age incidence of IPD declined from 11.8 pre-PCV7 to 7.1 post-PCV13 (IRR, 0.61 [95% confidence interval {CI}, .59-.63]) but for PnCAP declined among ages <1 year (IRR, 0.34 [95% CI, .25-.45]) and 1-4 years (IRR, 0.50 [95% CI, .43-.57]) but increased significantly among age ≥5 years (IRRs, 1.08-1.14). In Indigenous people, baseline PCV13 non-PCV7 IPD incidence was 3-fold higher, amplified by a serotype 1 epidemic in 2011. By 2015-2016, although incidence of IPD and PnCAP in children aged <5 years decreased by 38%, neither decreased in people aged ≥5 years. CONCLUSIONS: Fifteen years post-PCV and 5 years post-PCV13, direct and indirect impact on IPD and PnCAP differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.Fifteen years after pneumococcal conjugate vaccine (PCV) introduction and 5 years post-PCV13, direct and indirect impact on invasive pneumococcal disease and pneumococcal community-acquired pneumonia differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.

Identifying Potential Medication Discrepancies During Medication Reconciliation in the Post-Acute Long-Term Care Setting.

Medication reconciliation has been an area with increased focus among transitions of care due to associations with error rates and risk of patient harm. Chart reviews were performed to evaluate the discrepancies between the initial physician order sheet (POS), hospital discharge summary, electronic health record (EHR), health information exchange (HIE), and the patient interview/home medication list. The objectives were to determine which medication information source provided the least number of discrepancies and describe the different types of discrepancies among sources. Of all orders, 30% contained a discrepancy. The average number of discrepancies per medication source per patient included: 5.6 for the hospital discharge summary, 7.6 for the EHR, and 9.6 for the home medication list/interview. The most frequent types of discrepancies included: omission of medication orders between lists (42.7%), additional medications not included on the initial POS (24.6%), and discrepancies in frequency (11.8%). The hospital discharge summary proved to be the medication source that provided the least number of discrepancies, compared to the initial POS. [Journal of Gerontological Nursing, 45(7), 5-10.].

Species of Cryptosporidia Causing Subclinical Infection Associated With Growth Faltering in Rural and Urban Bangladesh: A Birth Cohort Study.

Background: Cryptosporidiosis is a major cause of childhood diarrhea in low- and middle-income countries and has been linked to impairment of child growth. This study investigated the burden of cryptosporidiosis and its impact on child growth in both a rural and an urban site in Bangladesh. Methods: Pregnant women in the second trimester were identified at 2 sites in Bangladesh, 1 urban and 1 rural. Their offspring were enrolled at birth into the study (urban, n = 250; rural, n = 258). For 2 years, the children were actively monitored for diarrhea and anthropometric measurements were obtained every 3 months. Stool samples were collected monthly and during diarrheal episodes with Cryptosporidium infection and causative species determined by quantitative polymerase chain reaction assays. Results: Cryptosporidium infections were common at both sites and mostly subclinical. In the urban site, 161 (64%) children were infected and 65 (26%) had ≥2 infections. In the rural site, 114 (44%) were infected and 24 (9%) had multiple infections. Adjusted for potential confounders, cryptosporidiosis was associated with a significantly greater drop in the length-for-age z score (LAZ) at 24 months from LAZ at enrollment (Δ-LAZ), an effect greatest in the children with multiple episodes of cryptosporidiosis. The most common species in Mirpur was Cryptosporidium hominis, whereas Cryptosporidium meleagridis predominated in Mirzapur. Conclusions: Cryptosporidiosis is common in early childhood and associated with early growth faltering in Bangladeshi children. Predominant Cryptosporidium species differed between the 2 sites, suggesting different exposures or modes of transmission but similar consequences for child growth. Clinical Trials Registration: NCT02764918.

Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial.

BACKGROUND: IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in 20-40% of patients within 10-20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy of a novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy. METHODS: We did a randomised, double-blind, placebo-controlled phase 2b trial, comprised of 6-month run-in, 9-month treatment, and 3-month follow-up phases at 62 nephrology clinics across ten European countries. We recruited patients aged at least 18 years with biopsy-confirmed primary IgA nephropathy and persistent proteinuria despite optimised renin-angiotensin system (RAS) blockade. We randomly allocated patients with a computer algorithm, with a fixed block size of three, in a 1:1:1 ratio to 16 mg/day TRF-budesonide, 8 mg/day TRF-budesonide, or placebo, stratified by baseline urine protein creatinine ratio (UPCR). Patients self-administered masked capsules, once daily, 1 h before breakfast during the treatment phase. All patients continued optimised RAS blockade treatment throughout the trial. Our primary outcome was mean change from baseline in UPCR for the 9-month treatment phase, which was assessed in the full analysis set, defined as all randomised patients who took at least one dose of trial medication and had at least one post-dose efficacy measurement. Safety was assessed in all patients who received the intervention. This trial is registered with ClinicalTrials.gov, number NCT01738035. FINDINGS: Between Dec 11, 2012, and June 25, 2015, 150 randomised patients were treated (safety set) and 149 patients were eligible for the full analysis set. Overall, at 9 months TRF-budesonide (16 mg/day plus 8 mg/day) was associated with a 24·4% (SEM 7·7%) decrease from baseline in mean UPCR (change in UPCR vs placebo 0·74; 95% CI 0·59-0·94; p=0·0066). At 9 months, mean UPCR had decreased by 27·3% in 48 patients who received 16 mg/day (0·71; 0·53-0·94; p=0·0092) and 21·5% in the 51 patients who received 8 mg/day (0·76; 0·58-1·01; p=0·0290); 50 patients who received placebo had an increase in mean UPCR of 2·7%. The effect was sustained throughout followup. Incidence of adverse events was similar in all groups (43 [88%] of 49 in the TRF-budesonide 16 mg/day group, 48 [94%] of 51 in the TRF-budesonide 8 mg/day, and 42 [84%] of 50 controls). Two of 13 serious adverse events were possibly associated with TRF-budesonide-deep vein thrombosis (16 mg/day) and unexplained deterioration in renal function in follow-up (patients were tapered from 16 mg/day to 8 mg/day over 2 weeks and follow-up was assessed 4 weeks later). INTERPRETATION: TRF-budesonide 16 mg/day, added to optimised RAS blockade, reduced proteinuria in patients with IgA nephropathy. This effect is indicative of a reduced risk of future progression to end-stage renal disease. TRF-budesonide could become the first specific treatment for IgA nephropathy targeting intestinal mucosal immunity upstream of disease manifestation. FUNDING: Pharmalink AB.

Chronic Obstructive Pulmonary Disease in Older Adults: Part I: Case Study.

Chronic obstructive pulmonary disease (COPD) is a distressing respiratory disease that may greatly impact a patient's quality of life. Although many treatment options exist, the Global Initiative for Chronic Obstructive Lung Disease Guidelines outline management strategies based on severity of daily symptoms and exacerbations. Although it is important to weigh the risks and benefits of medication use, involvement of patients in their overall care plan is imperative to optimal outcomes. According to recent studies, the prevalence of COPD in older adults is increasing, along with the complexity of care due to comorbidities, drug interactions, and side effects. A thorough evaluation of a patient case provides insight into the everyday challenges of COPD management. [Journal of Gerontological Nursing, 44(7), 10-14.].

Surveillance of pneumococcal serotype 1 carriage during an outbreak of serotype 1 invasive pneumococcal disease in central Australia 2010-2012.

BACKGROUND: An outbreak of serotype 1 invasive pneumococcal disease (IPD) occurred in Central Australia from October 2010 to the latter part of 2012. Surveillance of serotype 1 carriage was conducted to determine epidemiological features of asymptomatic carriage that could potentially be driving the outbreak. METHODS: 130 patients and accompanying persons presenting at Alice Springs Hospital Emergency Department consented to nasopharyngeal swab (NPS) collection. NPS were processed by standard methods, including culture, pneumococcal lytA quantitative real-time PCR, serotype 1-specific real-time PCR and multi-locus sequence typing (MLST). RESULTS: Pneumococcal carriage was detected in 16% of participants. Carriage was highest in the under 10 year olds from remote communities surrounding Alice Springs (75%). Four NPS were positive for serotype 1 DNA by PCR; 3 were also culture-positive for serotype 1 pneumococci. Serotype 1 isolates had atypical colony morphology on primary culture. All serotype 1 carriers were healthy children 5 to 8 years of age from remote communities. By MLST, serotype 1 isolates were ST306, as were IPD isolates associated with this outbreak. CONCLUSIONS: During an outbreak of serotype 1 ST306 IPD, carriage of the outbreak strain was detected in 3% NPS collected. All carriers were healthy children 5 to 8 years of age.

Low utilization of extra embryos in donor oocyte in vitro fertilization cycles: an ethical dilemma to donor management.

PURPOSE: To explore outcomes of donor In Vitro Fertilization (IVF) cycles with regards to cryopreservation and utilization of extra embryos after fresh transfer. METHODS: A database search was performed to identify all consecutive fresh donor oocyte cycles from January 1, 2000 to December 31, 2010 at a private fertility laboratory. Parameters analyzed included: number of oocytes retrieved, number of patients choosing embryo cryopreservation, number of patients returning for frozen embryo transfer (FET), and pregnancy outcomes. RESULTS: A total of 1070 fresh oocyte donor cycles were identified. Average number of oocytes retrieved was 16.9 ± 7.9, and average number of embryos transferred was 2.3 ± 0.96. Sixty-six percent of patients cryopreserved excess embryos following fresh transfer, and only 40 % of these patients ultimately returned for FET. Patients who conceived in their fresh cycle were much less likely to return for FET than those who did not (25 % v 65 %, p < 0.001), however chance of conceiving with FET was no different between these two groups (38 % v 38 %, NS). CONCLUSIONS: An unexpectedly low number of patients undergoing a donor oocyte IVF cycle will ultimately return to utilize extra embryos from their fresh cycle. This is concerning considering the high numbers of oocytes retrieved and the known complications from hyperstimulation, especially in light of the relatively high pregnancy rates associated with donor cycles. This raises concerns not only for donor management, but also raises ethical dilemmas when considering the large numbers of remaining embryos that will never be utilized.

Evaluation of Peak Inspiratory Flow Rate in Hospitalized Palliative Care Patients with COPD.

Dry powder inhalers are an effective yet costly COPD medication-delivery device. Patients must possess a minimum peak inspiratory flow rate (PIFR) for inhaled medication to be properly deposited into the lungs. Hospitalized palliative-care patients with diminished lung function due to advanced COPD may not possess the minimum PIFR (30 L/min) for adequate drug delivery. This study aims to quantify PIFR values for hospitalized palliative-care patients with advanced COPD to evaluate whether these patients meet the minimum PIFR requirements. Hospitalized patients ≥18 years old with a palliative-care consultation were eligible if they had a diagnosis of advanced COPD (GOLD C or D). Patients were excluded if they lacked decision-making capacity or had a positive COVID-19 test within the previous 90 days. Three PIFR values were recorded utilizing the In-CheckTM device, with the highest of the three PIFR attempts being utilized for statistical analysis. Eighteen patients were enrolled, and the mean of the highest PIFR readings was 72.5 L/min (±29 L/min). Post hoc analysis indicated 99.9% power when comparing the average best PIFR to the minimum PIFR (30 L/min) but only 51.4% power when compared to the optimal PIFR (60 L/min). This study found that palliative-care patients possess the minimum PIFR for DPI drug delivery.

The role of elagolix in the suppression of ovulation in donor oocyte cycles.

Objective: To study the clinical use of elagolix in ovarian stimulation and its effect on premature ovulation in a cohort of women undergoing oocyte donation. Design: A prospective cohort study with the use of historical controls. Setting: A private reproductive endocrinology and infertility clinic. Patients: Seventy-five oocyte donors and 75 historical donors, aged 21-30 years, who had each passed Food and Drug Administration and American Society for Reproductive Medicine-approved oocyte donor screening. Interventions: Administration of elagolix 200 mg orally every night at bedtime with development of a follicular size of ≥14 mm for ovulation suppression compared with ganirelix 250 µg every night at bedtime. Main Outcome Measures: Premature ovulation rate, total oocytes, mature oocytes, maximum estradiol, luteinizing hormone, and progesterone levels. Results: Oocytes were available in all retrievals because there were no instances of premature ovulation in either the elagolix or ganirelix groups. There were no statistically significant differences between the groups in baseline demographics. Both groups had the same amounts of gonadotropins consumed and days of stimulation. The average number of total oocytes was similar between the control group and elagolix group (30.55 vs. 30.31). Furthermore, the average number of mature oocytes was similar between the control and study groups (25.42 vs. 24.73). An analysis of the 580 fresh oocytes in the elagolix group and the 737 fresh oocytes in the ganirelix group showed similar outcomes with fertilization rates of 79.7% and 84.6%, respectively. Blastocyst development rates were also similar: 62.9% in the elagolix group and 57.3% in the ganirelix group. Conclusions: Compared with a historical control group using ganirelix, patients receiving elagolix demonstrated a similar number of oocytes and mature oocytes with on average 4.2 fewer injections per cycle and average per-cycle patient savings of $289.10. Clinical Trial Registration Number: Western IRB Pr. No.: 20191163, April 11, 2019. First enrollment June 20, 2019.

Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response.

Small repeat-associated siRNAs (rasiRNAs) mediate silencing of retrotransposons and the Stellate locus. Mutations in the Drosophila rasiRNA pathway genes armitage and aubergine disrupt embryonic axis specification, triggering defects in microtubule polarization as well as asymmetric localization of mRNA and protein determinants in the developing oocyte. Mutations in the ATR/Chk2 DNA damage signal transduction pathway dramatically suppress these axis specification defects, but do not restore retrotransposon or Stellate silencing. Furthermore, rasiRNA pathway mutations lead to germline-specific accumulation of gamma-H2Av foci characteristic of DNA damage. We conclude that rasiRNA-based gene silencing is not required for axis specification, and that the critical developmental function for this pathway is to suppress DNA damage signaling in the germline.

Invasive pneumococcal disease in Australia 2007 and 2008.

Enhanced surveillance for invasive pneumococcal disease (IPD) was conducted in all Australian states and territories in 2007 and 2008 with comprehensive comparative data available since 2002. There were 1,477 cases of IPD notified to the National Notifiable Diseases Surveillance System in Australia in 2007; a notification rate of 7.0 cases per 100,000 population. In 2008 there were 1,628 cases; a notification rate of 7.6 cases per 100,000 population. The overall rate of IPD in Indigenous Australians was almost 6 times the rate in non-Indigenous Australians in 2007 and almost 5 times in 2008. By 2008, the 4th year of a funded universal infant 7-valent pneumococcal conjugate vaccine (7vPCV) program in Australia with a 3+0 schedule, vaccine serotype IPD notification rates in those identified as non-Indigenous decreased in all age groups compared with 2002 levels, most significantly by 96% in children aged less than 5 years. However, rates of disease in non-vaccine serotypes increased by 168% in children aged less than 5 years, including a four-fold increase in the number of cases due to serotype 19A. For the Aboriginal and Torres Strait Islander population, national pre-vaccination data are not available, as the vaccine program was funded for this group from 2001. From 2002 to 2008, the proportion of disease due to 7vPCV serotypes in children aged less than 5 years decreased by 77%, while disease due to non-7vPCV serotypes increased by 76%. In Indigenous adults (≥50 years), rates of 23vPPV serotypes increased by 92%. There were 120 deaths attributed to IPD in 2007 and 113 in 2008, although it should be noted that deaths may be under-reported. The number of invasive pneumococcal isolates with reduced penicillin susceptibility remains low and reduced susceptibility to third-generation cephalosporins is rare.

Deprescribing Interventions by Palliative Care Clinical Pharmacists Surrounding Goals of Care Discussions.

Background: Palliative care (PC) pharmacists can play an important role in optimizing medications for patients with serious illnesses by aligning patients' goals with their treatment regimens. Objectives: The objectives of this study were to (1) quantify successful pharmacist deprescribing interventions incorporated in the hospital discharge plan and (2) describe deprescribing interventions by medication class, reason for discontinuation, and perception of patient/caregiver understanding and acceptance. Methods: This pilot study included 45 inpatient PC consultations and collected data on deprescribing interventions performed by PC clinical pharmacists in Maryland and Washington, D.C., U.S. Descriptive statistics were used to analyze outcomes. Results: Eighty-two percent of recommendations were successfully implemented during hospitalization and included in the discharge plan. Medication classes recommended for discontinuation included vitamins/supplements (20%), antidiabetics (13%), antiplatelets (10%), anticoagulants (10%), statins (10%), antihypertensives (7%), proton pump inhibitors/H2 blockers (7%), antibiotics (5%), dementia medications (1%), and antidepressants (1%). Top reasons for discontinuation included pill burden, unacceptable treatment burden, and potential harm outweighs potential benefit. Conclusions: Results of this study demonstrate PC pharmacists' deprescribing recommendations have a high rate of successful implementation by the primary inpatient care team.

Communication Gaps Between Providers and Caregivers of Patients in a Pediatric Emergency Department.

Communication gaps between the healthcare team and caregivers of pediatric patients can result in negative consequences. This study aims to identify specific words and phrases used in a pediatric emergency department (ED) that are unclear or confusing to caregivers. Research assistants at the Primary Children's Hospital recorded caregivers' responses to the question, "What words or phrases have been used during this visit that are unclear or don't make sense to you?" Across all steps in the care process, 62 of 220 participants (28.2%) reported unclear words and phrases used by the healthcare team. Responses recorded after the discharge step had the highest proportion of communication problems, followed by the initial evaluation and then the update step (χ2 [2, N = 220] = 6.30, P = .043). Themes among responses included ED logistics, signs/symptoms, the diagnostic process, treatment/procedures, general confusion, and language barriers. These results provide feedback to pediatric emergency medicine providers about potential communication gaps and point to a need for further efforts to train providers in the practice of high-quality communication.

A Brief Online Implicit Bias Intervention for School Mental Health Clinicians.

Clinician bias has been identified as a potential contributor to persistent healthcare disparities across many medical specialties and service settings. Few studies have examined strategies to reduce clinician bias, especially in mental healthcare, despite decades of research evidencing service and outcome disparities in adult and pediatric populations. This manuscript describes an intervention development study and a pilot feasibility trial of the Virtual Implicit Bias Reduction and Neutralization Training (VIBRANT) for mental health clinicians in schools-where most youth in the U.S. access mental healthcare. Clinicians (N = 12) in the feasibility study-a non-randomized open trial-rated VIBRANT as highly usable, appropriate, acceptable, and feasible for their school-based practice. Preliminarily, clinicians appeared to demonstrate improvements in implicit bias knowledge, use of bias-management strategies, and implicit biases (as measured by the Implicit Association Test [IAT]) post-training. Moreover, putative mediators (e.g., clinicians' VIBRANT strategies use, IAT D scores) and outcome variables (e.g., clinician-rated quality of rapport) generally demonstrated correlations in the expected directions. These pilot results suggest that brief and highly scalable online interventions such as VIBRANT are feasible and promising for addressing implicit bias among healthcare providers (e.g., mental health clinicians) and can have potential downstream impacts on minoritized youth's care experience.

How low can you go? Examining the effects of brief online training and post-training consultation dose on implementation mechanisms and outcomes for measurement-based care.

BACKGROUND: Initial training and ongoing post-training consultation (i.e., ongoing support following training, provided by an expert) are among the most common implementation strategies used to change clinician practice. However, extant research has not experimentally investigated the optimal dosages of consultation necessary to produce desired outcomes. Moreover, the degree to which training and consultation engage theoretical implementation mechanisms-such as provider knowledge, skills, and attitudes-is not well understood. This study examined the effects of a brief online training and varying dosages of post-training consultation (BOLT+PTC) on implementation mechanisms and outcomes for measurement-based care (MBC) practices delivered in the context of education sector mental health services. METHODS: A national sample of 75 clinicians who provide mental health interventions to children and adolescents in schools were randomly assigned to BOLT+PTC or control (services as usual). Those in BOLT+PTC were further randomized to 2-, 4-, or 8-week consultation conditions. Self-reported MBC knowledge, skills, attitudes, and use (including standardized assessment, individualized assessment, and assessment-informed treatment modification) were collected for 32 weeks. Multilevel models were used to examine main effects of BOLT+PTC versus control on MBC use at the end of consultation and over time, as well as comparisons among PTC dosage conditions and theorized mechanisms (skills, attitudes, knowledge). RESULTS: There was a significant linear effect of BOLT+PTC over time on standardized assessment use (b = .02, p < .01), and a significant quadratic effect of BOLT+PTC over time on individualized assessment use (b = .04, p < .001), but no significant effect on treatment modification. BOLT + any level of PTC resulted in higher MBC knowledge and larger growth in MBC skill over the intervention period as compared to control. PTC dosage levels were inconsistently predictive of outcomes, providing no clear evidence for added benefit of higher PTC dosage. CONCLUSIONS: Online training and consultation in MBC had effects on standardized and individualized assessment use among clinicians as compared to services as usual with no consistent benefit detected for increased consultation dosage. Continued research investigating optimal dosages and mechanisms of these established implementation strategies is needed to ensure training and consultation resources are deployed efficiently to impact clinician practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT05041517 . Retrospectively registered on 10 September 2021.

Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment (The ATLANTIS trial): protocol for a randomised double-blind placebo-controlled trial in primary care.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional bowel disorder that has a considerable impact on patient quality of life and substantial societal and health care resource costs. Current treatments are often ineffective. Tricyclic antidepressants have shown promise in secondary care populations but their effectiveness in a primary care setting remains unclear. METHODS: ATLANTIS is a randomised, multi-centre, parallel-group, two-arm, double-blind, placebo-controlled trial of low-dose amitriptyline as a second-line treatment for IBS in primary care. Participants will be invited by letter, or recruited opportunistically, from general practices in three regions of England (West Yorkshire, Wessex, and West of England) and screened for eligibility. A total of 518 adult patients with IBS, who are symptomatic despite first-line therapies, will be randomised 1:1 to amitriptyline or identical placebo for 6 months. Treatment will commence at a dose of 10 mg (or one placebo tablet) daily at night, with dose titration up to a maximum of 30 mg at night, depending on side effects and response to treatment. Participant-reported assessments will be conducted at baseline and 3, 6, and 12 months post-randomisation. The primary objective is to determine the effectiveness of amitriptyline, compared with placebo, in improving participant-reported global symptoms of IBS at 6 months (using the IBS Severity Scoring System). Secondary outcomes include relief of IBS symptoms, effect on IBS-associated somatic symptoms (Patient Health Questionnaire-12), anxiety and depression (Hospital Anxiety and Depression Scale), ability to work and participate in other activities (Work and Social Adjustment Scale), acceptability and tolerability of treatment, self-reported health care use, health-related quality of life (EQ-5D-3L), and cost-effectiveness. A nested, qualitative study will explore patient and general practitioner experiences of treatments and trial participation, including acceptability, adherence, unanticipated effects, and implications for wider use of amitriptyline for IBS in primary care. DISCUSSION: Determining the clinical and cost-effectiveness of low-dose amitriptyline as a second-line treatment for IBS in primary care will provide robust evidence to inform management decisions. TRIAL REGISTRATION: ISRCTN ISRCTN48075063 . Registered on 7th June 2019.

Individuals lacking ridge detail: A case study in adermatoglyphia.

Adermatoglyphia is a very rare autosomal-dominant condition that is genetically inherited and causes an individual to be born without conventional ridge detail on either their palmar or plantar surfaces (the fingers and palms of the hands and the toes and the soles of the feet). While adermatoglyphia has been the focus of medical and genetic research, no previous research has been conducted with regard to the forensic recovery and identification of marks from an adermatoglyphic individual. By observation of ridge detail donated by an adermatoglyphic subject, the study uses different methods in order to capture fingermarks (methods include: inked capture, livescan (biometric) capture, cyanoacrylate fuming, ninhydrin enhancement, and physical developer). Unusually, the purpose of this paper ends up presenting a number of examples of an absence of evidence; unsuccessful attempts made to capture and enhance fingerprint ridge detail. This is determined over a range of standard means including "live" donations by the adermatoglyphic subject onto the Livescan system, and enhancements of latent donations. The subject shows to leave either insubstantial fingermarks with no detail, or no mark whatsoever.