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Su Jung Lee,1 Hyun-Ju Seo,2 IL Han Choo,3 Seong Min Kim,4 Jeong Min Park,5 Eun-Young Yang,4 Yu Mi Choi6 1College of Nursing, Inje University, Gimhae, South Korea; 2College of Nursing, Chungnam National University, Daejeon, South Korea; 3Department of Neuropsychiatry, Chosun University and Chosun University Hospital, Gwangju, South Korea; 4Department of Nursing, Donggang University, Gwangju, South Korea; 5Department of Nursing, Nambu University, Gwangju, South Korea; 6College of Nursing, Graduate School of Chungnam National University, Daejeon, South KoreaCorrespondence: Hyun-Ju Seo, College of Nursing, Chungnam National University, Daejeon, 35015, South Korea, Tel +82-42-580-8320, Fax +82-42-580-8309, Email shj5th@korea.ac.krObjective: Accumulating evidence of the effects of dementia caregiving on individuals, society, and health has generated intervention studies to reduce the stress among family caregivers of people with dementia. This study aims to evaluate the effectiveness of a family support program, community-based dementia caregiver intervention (CDCI), among family caregivers of people with dementia compared with a control group (no intervention).Patients and Methods: This study is a quasi-experimental, non-randomized controlled trial conducted in six dementia relief centers of a community healthcare center in Korea. Family caregivers of 83 patients with dementia were recruited; of these 78 were included in the final study, with 40 in the intervention group and 38 in the control group. Analysis of covariance (ANCOVA) was used to compare the mean difference in the scores of the total short-form Zarit Burden Interview (SZBI), personal strain, role strain, depression, and attitude between the groups.Results: Compared with controls, in the intervention group, the adjusted mean score of personal strain (F = 4.353, t = 0.041) and attitude toward dementia (F = 10.284, t = 0.002) differed significantly after the intervention, with a small to moderate effect. There was no significant difference in the total SZBI, role strain, or depression mean score.Conclusion: The findings suggest that CDCI may be an effective intervention strategy to reduce personal strain and enhance the attitudes of family caregivers of people with dementia.Keywords: community-based intervention, caregiver burden, dementia, family support program, family caregiver

Jung-Hyun Kim,1 Sung-Min Kim,2 Yong-Chan Kim,2,* Byung-Kwan Seo3,* 1Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, 05278, Republic of Korea; 2Department of Orthopaedic Surgery, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Seoul, 05278, Republic of Korea; 3Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, 02447, Republic of Korea*These authors contributed equally to this workCorrespondence: Byung-Kwan Seo, Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea, Tel +82-2-440-6239, Fax +82-2-440-7143, Email seohbk@hanmail.netIntroduction: Efforts are necessary to promote postoperative patient management to reduce complications or side effects, particularly those adapted to spinal surgery. Considering compatible medical system in Korea, the study objective is to report the opinions of Korean medical doctors regarding integrative enhanced recovery after spine surgery.Methods: From December 2020 to January 2021, members of the Korean Medical Association were asked to complete an online questionnaire regarding an integrative enhanced recovery program after spine surgery. A total of 726 participants responded to the survey.Results: Approximately half of the respondents had more than 10 years of medical experience in the Korean health-care system, and 58.29% were affiliated with primary Korean medical clinics. The majority of respondents were not aware of the ERAS program (N = 412, 79.08%) but said that patient management would be advanced from the establishment of a postoperative medical program that reflected an integrated medical perspective (N = 505, 96.92%). Furthermore, Korean medical professionals believe that Korean medical interventions should play a major role in the pain management and digestive improvement sections of the upcoming postoperative program. Moreover, respondents claimed that Korean traditional medical modalities such as acupuncture, moxibustion, cupping, and herbal decoction should be included in the program.Discussion/Conclusion: Responses collected from the present study can be used as a spadework for future studies. A study on the development of a comprehensive postoperative program that reflects the perspectives of patients and conventional medical doctors is needed.Keywords: enhanced recovery after surgery, web-based survey, Korean medical doctors, spinal surgery

Sang-Mi Kim,1 Hyun-Seung Lee,1 Na-Young Hwang,2 Kyunga Kim,2 Hyung-Doo Park,1 Soo-Youn Lee1,3,4 1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea; 3Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Health Science and Technology, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, KoreaCorrespondence: Soo-Youn LeeDepartment of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-ro, Gangnam-gu, Seoul, 06351, KoreaTel +82-2-3410-1834Fax +82-2-3410-2719Email suddenbz@skku.eduBackground: To date, outcome data with a large sample size and data regarding the clinical outcomes of pharmacokinetic-guided (PK) dosing of vancomycin are limited.Aim: We evaluated the pharmacokinetic and clinical outcomes of a PK-guided dosing advisory program, pharmacokinetic consultation service (PKCS), in vancomycin treatment.Methods: We investigated vancomycin therapeutic drug monitoring (TDM) and PKCS use through a retrospective review of patients who had serum vancomycin trough concentration data from October 2017 to November 2018. Among these patients, we selected non-critically ill adult patients satisfying our selection criteria to evaluate the effect of PKCS. Target trough attainment rate, time to target attainment, vancomycin-induced nephrotoxicity (VIN), vancomycin treatment failure rate, and duration of vancomycin therapy were compared between patients whose dosing was adjusted according to PKCS (PKCS group), and those whose dose was adjusted at the discretion of the attending physician (non-PKCS group).Results: A total of 280 patients met the selection criteria for the VIN analysis (PKCS, n=134; non-PKCS, n=146). The incidence of VIN was similar between the two groups (PKCS, n=5; non-PKCS, n=5); however, the target attainment rate was higher in the PKCS group (75% vs 60%, P = 0.012). The time to target attainment was similar between the two groups. Further exclusions yielded 112 patients for the clinical outcome evaluation (PKCS, n=51; non-PKCS, n=61). The treatment failure rate was similar, and the duration of vancomycin therapy was longer in the PKCS group (12 vs 8 days, P = 0.008).Conclusion: In non-critically ill patients, an increase in target trough achieved by PKCS did not lead to decreased vancomycin treatment failures, shorter vancomycin treatment, or decreased nephrotoxicity in vancomycin treatment. Considering the excessive amount of effort currently put into vancomycin dosing and monitoring, more selective criteria for individualized pharmacokinetic-guided dosing needs to be applied.Keywords: vancomycin, pharmacokinetics, dosing, therapeutic drug monitoring, trough concentration, nephrotoxicity

Seong Min Kim,1,2 Masashi Ueki,1 Xueli Ren,3 Jun Akimoto,1 Yasuyuki Sakai,2 Yoshihiro Ito1,3 1Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan; 2Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan; 3Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, Wako, Saitama 351-0198, JapanCorrespondence: Yoshihiro ItoNano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, JapanTel +81 48 467 5809Fax +81 48 467 9300Email y-ito@riken.jpBackground: Nerve regeneration is important for the treatment of degenerative diseases and neurons injured by accidents. Nerve growth factor (NGF) has been previously conjugated to materials for promotion of neurogenesis.Materials and methods: Photoreactive gelatin was prepared by chemical coupling of gelatin with azidobenzoic acid (P-gel), and then NGF was immobilized on substrates in the presence or absence of micropatterned photomasks. UV irradiation induced crosslinking reactions of P-gel with itself, NGF, and the plate for immobilization.Results: By adjustment of the P-gel concentration, the nanometer-order height of micropatterns was controlled. NGF was quantitatively immobilized with increasing amounts of P-gel. Immobilized NGF induced neurite outgrowth of PC12 cells, a cell line derived from a pheochromocytoma of the rat adrenal medulla, at the same level as soluble NGF. The immobilized NGF showed higher thermal stability than the soluble NGF and was repeatedly used without loss of biological activity. The 3D structure (height of the formed micropattern) regulated the behavior of neurite guidance. As a result, the orientation of neurites was regulated by the stripe pattern width.Conclusion: The micropattern-immobilized NGF nanolayer biochemically and topologically regulated neurite formation.Keywords: nerve growth factor, photoreactive gelatin, micropatterned immobilization, PC12 cell, neurite outgrowth

Jae Hee Won,1 Sung Min Kim,1 Jong Wan Kim,1 Jun Ho Park,2 Jeong Yeon Kim1 1Department of Surgery, Dongtan Sacred Hospital, Hallym University College of Medicine, KyungKee, Korea; 2Department of Surgery, Kangdong Sacred Hospital, Hallym University College of Medicine, KyungKee, KoreaCorrespondence: Jeong Yeon KimDepartment of Surgery, Dongtan Sacred Hospital, Hallym University College of Medicine, Seokwoodong 42, kyungkee 18450, Republic of KoreaTel +82 031 8 086 2430Fax +82 031 8 086 2029Email imanisia@hallym.or.krBackground: Colorectal mucosa-associated lymphoid tissue (MALT) lymphoma (cMALToma) is rare and comprises only 2.5% of the MALT lymphomas. Its etiology and treatment have not been well established. The aim of this systematic literature review was to try to characterize cMALToma and analyze the risk factors for treatment failure with various therapeutic strategies.Methods: We retrospectively reviewed 50 case reports from 1993 to 2017 through a PubMed search of English medical literature, describing cMALToma. We included 67 patients from previous case reports and we added 6 patients treated for cMALToma in our multicenter institutes. Risk factor analysis was done for treatment failure, defined as remission failure and recurrence.Results: Of 73 patients diagnosed with cMALToma, tumors were located in 54 patients (74.0%) in the rectum, in 10 patients (13.6%) in the right colon, in 3 patients (4.1%) in the transverse colon, and in 6 patients (8.2%) in the sigmoid colon. In first-line treatment, patients achieved complete remission (CR) with surgery (18/19 cases), local resection (18/19 cases), chemotherapy (12/13 cases), radiation therapy (4/5 cases), antibiotics therapy including Helicobacter pylori eradication (12/15 cases), and no treatment (1/2 cases). Among these, eight cases (10.9%) needed second-line treatment, and there was overall remission failure in 3 cases (4.1%). Of the remaining 70 patients with CR, the tumor recurred in 5 patients (6.8%). The multivariable analysis showed that male sex, multiple tumors, and first-line treatment failure were significantly related to treatment failure (p=0.03, p=0.05, p=0.03, respectively).Conclusion: CR of primary cMALToma was achieved using various therapeutic strategies. First-line treatment failure and multiple tumors were associated with treatment failure, although the numbers of cases that failed are too small to draw definitive conclusions.Keywords: MALT-associated lymphoma, colon, rectum, prognosis

Sun Mi Kim,1 Sung Yong Park,1 Young In Kim,1 Young Don Son,2 Un-Sun Chung,3,4 Kyung Joon Min,1 Doug Hyun Han1 1Department of Psychiatry, School of Medicine, Chung-Ang University, Seoul, 2Department of Biomedical Engineering, Gachon University of Medicine and Science, Incheon, 3Department of Psychiatry, School of Medicine, Kyungpook National University, 4School Mental Health Resources and Research Center, Kyungpook National University Children’s Hospital, Daegu, South Korea Aim: Disruptive behaviors are thought to affect the progress of major depressive disorder (MDD) in adolescents. In resting-state functional connectivity (RSFC) studies of MDD, the affective network (limbic network) and the default mode network (DMN) have garnered a great deal of interest. We aimed to investigate RSFC in a sample of treatment-naïve adolescents with MDD and disruptive behaviors.Methods: Twenty-two adolescents with MDD and disruptive behaviors (disrup-MDD) and 20 age- and sex-matched healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). We used a seed-based correlation approach concerning two brain circuits including the affective network and the DMN, with two seed regions ­including the bilateral amygdala for the limbic network and the bilateral posterior cingulate cortex (PCC) for the DMN. We also observed a correlation between RSFC and severity of depressive symptoms and disruptive behaviors.Results: The disrup-MDD participants showed lower RSFC from the amygdala to the orbitofrontal cortex and parahippocampal gyrus compared to HC participants. Depression scores in disrup-MDD participants were negatively correlated with RSFC from the amygdala to the right orbitofrontal cortex. The disrup-MDD participants had higher PCC RSFC compared to HC participants in a cluster that included the left precentral gyrus, left insula, and left parietal lobe. Disruptive behavior scores in disrup-MDD patients were positively correlated with RSFC from the PCC to the left insular cortex.Conclusion: Depressive mood might be correlated with the affective network, and disruptive behavior might be correlated with the DMN in adolescent depression. Keywords: resting-state functional connectivity, major depressive disorder, disruptive behaviors, limbic network, default mode network

Seong Muk Kim,1 Chang Hyun Jeong,2 Ji Sun Woo,2 Chung Heon Ryu,1 Jeong-Hwa Lee,3 Sin-Soo Jeun1,21Postech-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Department of Neurosurgery, Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea; 3Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, KoreaAbstract: Mesenchymal stem cell (MSC)-based gene therapy is a promising tool for the treatment of various neurological diseases, including brain tumors. However, the tracking of in vivo stem cell migration, distribution, and survival need to be defined for their clinical application. The systemic routes of stem cell delivery must be determined because direct intracerebral injection as a cure for brain tumors is an invasive method. In this study, we show for the first time that near-infrared (NIR) imaging can reveal the distribution and tumor tropism of intravenously injected MSCs in an intracranial xenograft glioma model. MSCs were labeled with NIR fluorescent nanoparticles, and the effects of the NIR dye on cell proliferation and migratory capacity were evaluated in vitro. We investigated the tumor-targeting properties and tissue distribution of labeled MSCs introduced by intravenous injection and followed by in vivo imaging analysis, histological analysis, and real-time quantitative polymerase chain reaction. We observed no cytotoxicity or change in the overall growth rate and characteristics of labeled MSCs compared with control MSCs. NIR fluorescent imaging showed the organ distribution and targeted tumor tropism of systemically injected human MSCs. A significant number of MSCs accumulated specifically at the tumor site in the mouse brain. These results suggest that NIR-based cell tracking is a potentially useful imaging technique to visualize cell survival, migration, and distribution for the application of MSC-mediated therapies in the treatment of malignant gliomas.Keywords: mesenchymal stem cells, near-infrared nanoparticles, glioma, systemic delivery, in vivo imaging

Jinuk Song,1 Doug Hyun Han,1 Sun Mi Kim,1 Ji Sun Hong,1 Kyung Joon Min,1 Jae Hoon Cheong,2 Bung Nyun Kim3 1Department of Psychiatry, Chung Ang University Hospital, 2Uimyung Research Institute for Neuroscience, Samyook University, 3Department of Psychiatry, Seoul National Hospital, Seoul, South Korea Background: Although schizophrenia and bipolar disorder (BD) are classified as different disease entities, they share critical pathognomonic symptoms in terms of hallucination and delusion. Because the characteristics of clinical symptoms are not sufficient to differentiate schizophrenia from BD, several studies have applied brain imaging methods to provide biological evidence of differences. We compared gray matter (GM) volume differences in schizophrenia and BD patients and examined volumetric differences associated with hallucination and delusion in these two groups.Methods: Ninety-three schizophrenia patients and 75 BD patients who were followed for at least 3 years in an outpatient department were recruited for this study. Magnetic resonance data from 71 schizophrenia patients and 44 BD patients were obtained using a 3.0 T scanner. Volumetric differences were analyzed using Matlab 8.0.0 and SPM8 software.Results: The results showed that delusion symptoms were negatively correlated with GM volume within both frontal and both temporal cortices in the schizophrenia group and were negatively correlated with GM volume within the bilateral frontal cortices in the BD group. Hallucination symptoms were negatively correlated with GM volume within the bilateral frontal, bilateral temporal, and left parietal cortices in the schizophrenia group and were negatively correlated with GM volume within the bilateral frontal, right parietal, occipital, and insular cortices in the BD group.Conclusion: Delusions in schizophrenia were correlated with GM volume in multiple brain regions, including the frontal, temporal, and parietal cortices, compared to those in patients with BD. Hallucination was associated with temporal lobe GM volume in patients with schizophrenia and with insular cortex GM volume in patients with BD. Keywords: schizophrenia, bipolar disorder, delusion, hallucination, voxel-based morphometry

The frequency of poor outcomes in relapsed leukemia patients underscores the need for novel therapeutic approaches. The Food and Drug Administration-approved immunosuppressant FTY720 limits leukemia progression by activating protein phosphatase 2A and restricting nutrient access. Unfortunately, FTY720 cannot be re-purposed for use in cancer patients due to on-target toxicity associated with S1P receptor activation at the elevated, anti-neoplastic dose. Here we show that the constrained azacyclic FTY720 analog SH-RF-177 lacks S1P receptor activity but maintains anti-leukemic activity in vitro and in vivo. SH-RF-177 was not only more potent than FTY720, but killed via a distinct mechanism. Phosphorylation is dispensable for FTY720's anti-leukemic actions. However, chemical biology and genetic approaches demonstrated that the sphingosine kinase 2 (SPHK2)-mediated phosphorylation of SH-RF-177 led to engagement of a pro-apoptotic target and increased potency. The cytotoxicity of membrane-permeant FTY720 phosphonate esters suggests that the enhanced potency of SH-RF-177 stems from its more efficient phosphorylation. The tight inverse correlation between SH-RF-177 IC50 and SPHK2 mRNA expression suggests a useful biomarker for SH-RF-177 sensitivity. In summary, these studies indicate that FTY720 analogs that are efficiently phosphorylated but fail to activate S1P receptors may be superior anti-leukemic agents compared to compounds that avoid cardiotoxicity by eliminating phosphorylation.

The internal state of an organism influences its perception of attractive or aversive stimuli and thus promotes adaptive behaviors that increase its likelihood of survival. The mechanisms underlying these perceptual shifts are critical to our understanding of how neural circuits support animal cognition and behavior. Starved flies exhibit enhanced sensitivity to attractive odors and reduced sensitivity to aversive odors. Here, we show that a functional remodeling of the olfactory map is mediated by two parallel neuromodulatory systems that act in opposing directions on olfactory attraction and aversion at the level of the first synapse. Short neuropeptide F sensitizes an antennal lobe glomerulus wired for attraction, while tachykinin (DTK) suppresses activity of a glomerulus wired for aversion. Thus we show parallel neuromodulatory systems functionally reconfigure early olfactory processing to optimize detection of nutrients at the risk of ignoring potentially toxic food resources.

Abstract Sickle cell disease (SCD) is an inherited blood disorder marked by homozygosity of hemoglobin S, which is a defective hemoglobin caused by a missense mutation in the β-globin gene. However, clinical phenotypes of SCD vary among patients. To investigate genetic variants associated with various clinical phenotypes of SCD, we genotyped DNA samples from 520 SCD subjects and used a genome-wide association study (GWAS) approach to identify genetic variants associated with phenotypic features of SCD. For HbF levels, the previously reported 2p16.1 locus (BCL11A) reached genome significance (rs1427407, P = 8.58 × 10–10) in our GWAS as expected. In addition, we found a new genome-wide significance locus at 15q14 (rs8182015, P = 2.07 × 10–8) near gene EMC7. GWAS of acute chest syndrome (ACS) detected a locus (rs79915189, P = 3.70 × 10–8) near gene IDH2 at 15q26.1. The SNP, rs79915189, is also an expression quantitative trait locus (eQTL) of IDH2 in multiple tissues. For vasoocclusive episode (VOE), GWAS detected multiple significant signals at 2p25.1 (rs62118798, P = 4.27 × 10–8), 15q26.1 (rs62020555, P = 2.04 × 10–9) and 15q26.3 (rs117797325, P = 4.63 × 10–8). Our findings provide novel insights into the genetic mechanisms of SCD suggesting that common genetic variants play an important role in the presentation of the clinical phenotypes of patients with SCD.

Abstract Background Half of mental health problems are established by the age of 14 years and 75% by 24 years. Early intervention and prevention of mental ill health are therefore vitally important. However, increased demand over recent years has meant that access to child mental health services is often restricted to those in severest need. Watch Me Play! (WMP) is an early intervention designed to support caregiver attunement and attention to the child to promote social-emotional well-being and thereby mental health resilience. Originally developed in the context of a local authority mental health service for children in care, it is now also delivered online as a low intensity, scalable, preventative intervention. Although WMP shows promise and is already used in some services, we do not yet know whether it is effective. Methods A non-randomised single group feasibility study with embedded process evaluation. We propose to recruit up to 40 parents/carers of children aged 0–8 years who have been referred to early years and children’s services in the UK. WMP involves a parent watching the child play and talking to their child about their play (or for babies, observing and following signals) for up to 20 min per session. Some sessions are facilitated by a trained practitioner who provides prompts where necessary, gives feedback, and discusses the child’s play with the caregiver. Services will offer five facilitated sessions, and parents will be asked to do at least 10 additional sessions on their own with their child in a 5-week period. Feasibility outcomes examined are as follows: (i) recruitment, (ii) retention, (iii) adherence, (iv) fidelity of delivery, (v) barriers and facilitators of participation, (vi) intervention acceptability, (vii) description of usual care, and (viii) data collection procedures. Intervention mechanisms will be examined through qualitative interview data. Economic evaluation will be conducted estimating cost of the intervention and cost of service use for child and parents/carers quality-adjusted life years. Discussion This study will address feasibility questions associated with progression to a future randomised trial of WMP. Trial registration ISRCTN13644899 . Registered on 14th April 2023.

Objective: This paper outlines the design and implementation of iManage SCD, a self-management mobile health application for adolescents and young adults (AYA) with sickle cell disease (SCD) during transition from pediatric to adult health care. Methods: The Integrate, Design, Assess, Share (IDEAS) framework, emphasizing user insights, iterative design, rigorous assessment, and knowledge sharing, guided the development process. The design team consisted of researchers, psychologists, physicians, social workers, AYA with SCD, and parents of AYA with SCD (n = 16) across three states. Qualitative focus groups and interviews were conducted and analyzed using thematic analysis across the integrate and design phases. Point of use feedback from AYA with SCD was used to assess feasibility and acceptability. Results: The development process was centered around tenants of the Social-ecological Model of Adolescent and Young Adult Readiness to Transition. Development integrated multidisciplinary perspectives, fostering a person-centered approach. The iterative design process involved collaboration with a digital health firm, Agency39A. Health equity and implementation considerations were addressed at individual, community, and healthcare system levels. Themes that emerged from focus groups with AYA, clinicians, and researchers in the integrate and design phases of development included recommendations for content and user experience features. Conclusions: iManage SCD emerges as a comprehensive, user-friendly mobile health application, incorporating theoretical principles and direct user input. The development process demonstrated feasibility and acceptability, and the paper discusses dissemination strategies for the Community Health Workers and Mobile Health Programs to Help Young Adults with SCD Transition to Using Adult Healthcare Services (COMETS) study.

Objective: To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. Design: A multicentre, randomised, open‐label, equivalence trial and a meta‐analysis. Setting: Tertiary referral hospitals in South Korea. Population: Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). Methods: Eligible women were screened and randomised at 16‒22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α‐hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). Main outcome measure: Preterm birth (PTB) before 37 weeks of gestation. Results: A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention‐to‐treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI −7.6 to 13.8%), which was within the equivalence margin of 15%. The meta‐analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. Conclusion: Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation. Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation. [ABSTRACT FROM AUTHOR]

Background Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs. Objective To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event. Design Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance. Setting Primary and secondary mental health settings across the United Kingdom’s National Health Service. Participants One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation. Interventions Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60–90 minutes, or to guided self-help using Spring, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions. Main outcome measures Primary outcome: the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment. Results Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [mean difference 1.01 (one-sided 95% CI −∞ to 3.90, non-inferiority p = 0.012)]. Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural therapy with a trauma focus at this timepoint [mean difference 3.20 (one-sided 95% confidence interval −∞ to 6.00, non-inferiority p = 0.15)]. Guided self-help using Spring was not shown to be more cost-effective than face-to-face cognitive-behavioural therapy with a trauma focus although there was no significant difference in accruing quality-adjusted life-years, incremental quality-adjusted life-years −0.04 (95% confidence interval −0.10 to 0.01) and guided self-help using Spring was significantly cheaper to deliver [£277 (95% confidence interval £253 to £301) vs. £729 (95% CI £671 to £788)]. Guided self-help using Spring appeared to be acceptable and well tolerated by participants. No important adverse events or side effects were identified. Limitations The results are not generalisable to people with post-traumatic stress disorder to more than one traumatic event. Conclusions Guided self-help using Spring for mild to moderate post-traumatic stress disorder to a single traumatic event appears to be non-inferior to individual face-to-face cognitive-behavioural therapy with a trauma focus and the results suggest it should be considered a first-line treatment for people with this condition. Future work Work is now needed to determine how best to effectively disseminate and implement guided self-help using Spring at scale. Trial registration This trial is registered as ISRCTN13697710. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information. Plain language summary Post-traumatic stress disorder is a common, disabling condition that can occur following major traumatic events. Typical symptoms include distressing reliving, avoidance of reminders and feeling a current sense of threat. First-choice treatments for post-traumatic stress disorder are individual, face-to-face talking treatments, of 12–16 hours duration, including cognitive behavioural therapy with a trauma focus. If equally effective treatments could be developed that take less time and can be largely undertaken in a flexible manner at home, this would improve accessibility, reduce waiting times and hence the burden of disease. RAPID was a randomised controlled trial using a web-based programme called Spring. The aim was to determine if trauma-focused guided self-help provided a faster and cheaper treatment for post-traumatic stress disorder than first-choice face-to-face therapy, while being equally effective. Guided self-help using Spring is delivered through eight steps. A therapist provides a 1-hour introductory meeting followed by four further, fortnightly sessions of 30 minutes each and four brief (around 5 minutes) telephone calls or e-mail contacts between sessions. At each session, the therapist reviews progress and guides the client through the programme, offering continued support, monitoring, motivation and problem-solving. One hundred and ninety-six people with post-traumatic stress disorder to a single traumatic event took part in the study. Guided self-help using Spring was found to be equally effective to first-choice face-to-face therapy at reducing post-traumatic stress disorder symptoms at 16 weeks. Very noticeable improvements were maintained at 52 weeks post-randomisation in both groups, when most results were inconclusive but in favour of face-to-face therapy. Guided self-help using Spring was significantly cheaper to deliver and appeared to be well-tolerated. It is noteworthy that not everyone benefitted from guided self-help using Spring, highlighting the importance of considering it on a person-by-person basis, and personalising interventions. But, the RAPID trial has demonstrated that guided self-help using Spring provides a low-intensity treatment option for people with post-traumatic stress disorder that is ready to be implemented in the National Health Service. Scientific summary Background Post-traumatic stress disorder (PTSD) is a common mental health condition that may develop following exposure to traumatic events that involve threatened or actual death, serious injury or sexual violence. PTSD causes significant distress to those affected by it, often co-occurs with other physical and mental health conditions and is associated with a large economic burden. Face-to-face, trauma-focused psychological treatments (TFPT) have been found to be the most effective currently available treatments for PTSD and are recommended first line by treatment guidelines across the world. Unfortunately, the limited number of suitably trained therapists available to deliver TFPT in the National Health Service often prevents timely access to treatment and some people find accessing and fully engaging with face-to-face TFPT difficult for other reasons, including work commitments, travel and childcare. Guided self-help (GSH) provides an alternative approach to the delivery of treatment by combining the use of self-help materials with regular guidance from a trained professional and requires less therapist time than recommended face-to-face TFPT. GSH has been shown to be effective for other mental conditions and, if effective for PTSD, GSH would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and intervention costs. Objectives The main aim of the RAPID trial was to determine the likely clinical and cost-effectiveness of GSH using Spring, an internet-based programme based on cognitive behavioural therapies with a trauma focus (CBT-TF), for mild to moderate PTSD. RAPID also aimed to describe the experience of receiving GSH using Spring from the recipient’s perspective, and the delivery of GSH using Spring from the therapist’s perspective. The objectives were to determine if: GSH using Spring was at least equivalent in effectiveness and cost-effective relative to individual face-to-face CBT-TF for people with PTSD, as judged by reduced symptoms of PTSD and improved quality of life. GSH using Spring improved functioning and reduced symptoms of depression, symptoms of anxiety, alcohol use and perceived social support. Specific factors may impact effectiveness and successful roll-out of GSH for PTSD in the NHS. Methods RAPID was a multicentre pragmatic randomised controlled non-inferiority trial with assessors masked to treatment allocation. Individual randomisation was used. Economic evaluation was undertaken to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that may influence outcome (including context, acceptability, and facilitators and barriers, measured qualitatively). GSH using Spring was not expected to be more effective than face-to-face CBT-TF, and therefore, a non-inferiority design was chosen. Participants were recruited from NHS Improving Access to Psychological Therapy services based in primary care in England, and NHS psychological treatment settings based in primary and secondary care in Scotland and Wales. Wide eligibility criteria were used to ensure good external validity. Participants were aged 18 or over, had mild to moderate PTSD as their primary diagnosis, had regular access to the internet and gave informed consent to take part. Exclusion criteria were inability to read and write fluently in English, previous completion of a course of TFPT for PTSD, current PTSD symptoms to more than one traumatic event, current engagement in psychological therapy, psychosis, substance dependence, active suicide risk and change in psychotropic medication in the past 4 weeks. Participants were randomised to receive up to 12 face-to-face, manualised, individual CBT-TF sessions, each lasting 60–90 minutes, or to GSH using Spring. Spring is a manualised, eight-step online GSH programme based on CBT-TF. An initial meeting of 1 hour between the therapist and the person with PTSD is followed by four subsequent fortnightly meetings of 30 minutes, with four brief telephone calls or e-mail contacts between sessions. The primary outcome was the severity of symptoms of PTSD over the previous week as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 16 weeks post-randomisation. Secondary outcomes included severity of PTSD symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use, and perceived social support at both 16 and 52 weeks post-randomisation. Resource use was also collected to support the health economic evaluation. Semistructured interviews were conducted with 19 participants and 10 therapists as part of the process evaluation, to gather perspectives of receiving and delivering the interventions, to examine underlying mechanisms and factors influencing future implementation. Results One hundred and ninety-six participants were randomised with 82% retention at 16 weeks and 71% at 52 weeks. There were no serious imbalances observed in the baseline data between the two groups. Non-inferiority (margin of 5 points) was demonstrated at the primary endpoint of 16 weeks on the CAPS-5 using the intention to treat principle [mean difference 1.0, 95% one-sided confidence interval (CI) (−∞, 3.9, non-inferiority p = 0.012)]. This was also the case for all secondary outcomes at this time point, except for client satisfaction that was inconclusive but in favour of CBT-TF. At 52 weeks post-randomisation, non-inferiority was shown for Multidimensional Scale for Perceived Social Support (MSPSS), Alcohol Use Disorders Test and GSES; non-inferiority was not shown for the other outcomes but the results, which were inconclusive, were in favour of CBT-TF. Further examination of the Impact of Event Scale-Revised (IES-R) longitudinal measurements indicated that while the GSH group maintained their reduction (improvement) in IES-R scores between the 16- and 52-week assessments, the CBT-TF group continued to improve at a slow rate over the same period. There were no subgroup effects that showed any evidence of difference between the interventions including gender (pre-specified), mode of data collection or assessments conducted after the introduction of the COVID-19 lockdown. Spring was cheaper to deliver than face-to-face CBT TF [£277 (95% CI £253 to £301) vs. £729 (95% CI £671 to £788)]. When total costs were included, Spring was £572 (95% CI £64.96 to £1080.14) cheaper and produced but derived fewer quality-adjusted life-years (QALYs) compared to CBT-TF, −0.04 (95% CI −0.10 to 0.01). At a willingness-to-pay threshold of £30,000 per QALY gained, the probability of GSH being cost-effective was 29.74%. The process data provided evidence of acceptability of the overall trial methodology, although key points were identified for consideration in future randomised controlled design, especially concerning burden and impact of outcome measures on participants and how they are delivered and explained. Intervention acceptability was indicated for both GSH and CBT-TF interventions, although there was a preference for face-to-face treatment. Therapeutic relationship was an important factor highlighted in the acceptability of the interventions. Flexibility identified with GSH was seen as positive and some activities within Spring were described as more helpful than others. Conclusions Implications for health care GSH using Spring was found to be non-inferior to face-to-face CBT-TF at treating people with mild to moderate PTSD. Significant gains were maintained in the GSH using Spring group at 52 weeks but some ongoing improvements in the CBT-TF group appeared to result in largely inconclusive findings with respect to non-inferiority at 52 weeks. The additional benefits of GSH using Spring with respect to time, cost and convenience, and having another evidence-based treatment option could be argued as outweighing what appear to be minor differences at 52 weeks. The results of the RAPID trial should herald a step change in the approach of services to the provision of evidence-based treatment to people with mild to moderate PTSD. There is now an urgent need to make GSH using Spring available as a low-intensity treatment option for people with PTSD. Future research implications How best to effectively disseminate and implement GSH using Spring at scale, to maximise its impact, is a key research question. This includes identification of the specific skill set and competencies required by a guiding clinician to foster effective alliance and engagement, and the optimal level of training and supervision required for the provision of GSH using Spring. The optimal amount of guidance is unclear. The quantitative and qualitative results strongly suggest that the current number of facilitation sessions is right for most people but that some people could probably benefit with more. Research into the impact of increased flexibility in delivery and more personalised adaptations is desirable. Research is also required to understand the extent to which individuals may or may not be excluded from internet-based treatments due to language and literacy issues, and online access issues, and how best to address these. Trial registration This trial is registered as ISRCTN13697710. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information.

Background: Guided internet-based, cognitive behavioural therapy with a trauma-focus (i-CBT-TF) is recommended in guidelines for post-traumatic stress disorder (PTSD). There is limited evidence regarding its acceptability, with significant dropout from individual face-to-face CBT-TF, suggesting non-acceptability at least in some cases. Objective: To determine the acceptability of a guided internet-based CBT-TF intervention, ‘Spring’, in comparison with face-to-face CBT-TF for mild to moderate PTSD. Method: Treatment adherence, satisfaction, and therapeutic alliance were measured quantitatively for participants receiving ‘Spring’ or face-to-face CBT-TF as part of a Randomised Controlled Trial. Qualitative interviews were conducted with a purposive sample of therapists and participants. Results: ‘Spring’ guided internet-based CBT-TF was found to be acceptable, with over 89% participants fully or partially completing the programme. Therapy adherence and alliance for ‘Spring’ and face-to-face CBT-TF did not differ significantly, apart from post-treatment participant-reported alliance, which was in favour of face-to-face CBT-TF. Treatment satisfaction was high for both treatments, in favour of face-to-face CBT-TF. Interviews with participants receiving, and therapists delivering ‘Spring’ corroborated its acceptability. Conclusions: Guided internet-based CBT-TF is acceptable for many people with mild to moderate PTSD. Findings provide insights into future implementation, highlighting the importance of personalising guided self-help, depending on an individual’s presentation, and preferences.

Objective: The skull vibration-induced-nystagmus test (SVINT) is a noninvasive and effective screening tool for the function of the otolith and canal structures in children. It can instantaneously assess vestibular asymmetry. This study aimed to analyze the SVINT results of healthy children vs. children with hearing loss (HL) and to correlate it with sensory organization test (SOT) results as a functional balance evaluation tool. Design: This case-controlled study compared the results of SVINT to the results of the SOT of the computerized dynamic posturography (CDP) in a control group of 120 healthy normal-hearing children (i.e., NH group) vs. hearing loss (HL) group of 60 children, including 30 children with hearing aids (HAs) and 30 children with a unilateral cochlear implant (CI). The SVINT results were compared to the caloric test (CaT) and video head impulse test (vHIT) and associated with SOT scores. Results: Thirty-one children in the HL group had normal SVINT and normal SOT results. A total of 21 children in the HL group had SVINT-negative and abnormal results in the SOT (possibly due to bilateral vestibular loss (BVL)). Eight children in the HL group had positive SVINT and abnormal SOT results. However, none of the children had only positive SVINT with normal SOT findings. Moreover, 52% of children had a normal result on both the SOT and CaT, whereas 27% had abnormal results on both tests (17% bilateral weakness and 10% unilateral), and 22% had the only result of the SOT suggesting a functional abnormality. Similarly, when associating the result to vHIT, 51% had normal results on both tests, and 25% had abnormal results (13% bilateral and 12% unilateral weakness). Conclusions: SVINT findings can be correlated with SOT findings in the case of the unilateral vestibular lesion (UVL), which adds a diagnostic value in these pediatric cases but may differ in the case of the bilateral vestibular lesion (BVL). However, SVINT findings need to be cautiously interpreted in light of other test findings such as the SOT, CaT, and vHIT.

Abstract Background It is estimated that around 160,000 households in Britain experience homelessness each year, although no definitive statistics exist. Between March and September 2020, as part of the initial ‘Everyone In’ government response to COVID-19 in England, 10,566 people were living in emergency accommodation and nearly 18,911 people had been moved into settled accommodation. However, some forms of temporary accommodation may not be suitable as shared facilities make it impossible for people to adhere to government guidelines to reduce the spread of COVID-19. Methods This is parallel group, pilot randomised controlled trial. The target is to recruit three local authorities, each of which will recruit 50 participants (thus a total of approximately 150 participants). Individuals are eligible if they are aged 18 and over, in a single-person homeless household, temporarily accommodated by the LA with recourse to public funds. Participants will be randomised to receive settled accommodation (intervention group) or temporary accommodation (control group). The intervention group includes settled housing such as Private Rented Sector (low and medium support), Social Housing (low and medium support), and Housing First (High support). The control group will maintain treatment as usual. The follow-up period will last 6 months. The primary outcome is to assess the feasibility of recruitment, retention, and acceptability of trial processes against progression criteria laid out in a traffic light system (green: all criteria are met, the trial should progress as designed in this pilot; amber: the majority of criteria are met and with adaptations to methods all criteria could be met; red: the minority of criteria are met and the pilot RCT should not proceed). Secondary outcomes include assessment of completeness of data collection at 3 and 6 months and percentage of participants consenting to data linkage, as well as a process evaluation and economic evaluation. Discussion This trial will address feasibility questions associated with progression to a fully powered effectiveness trial of models of housing to reduce risk of COVID-19 infection and homelessness. Trial registration ISRCTN69564614 . Registered on December 16, 2020.

Geographic information systems (GIS) can be used to map mosquito larval and adult habitats and human populations at risk for mosquito exposure and possible arbovirus transmission. Along with traditional methods of surveillance-based targeted mosquito control, GIS can help simplify and target efforts during routine surveillance and post-disaster (e.g., hurricane-related flooding) to protect emergency workers and public health. A practical method for prioritizing areas for emergency mosquito control has been developed and is described here. North Carolina (NC) One Map was used to identify state-level data layers of interest based on human population distribution and mosquito habitat in Brunswick, Columbus, Onslow, and Robeson Counties in eastern NC. Relevant data layers were included to create mosquito control treatment areas for targeted control and an 18-step protocol for map development is discussed. This protocol is expected to help state, territorial, tribal, and/or local public health officials and associated mosquito control programs efficiently create treatment area maps to improve strategic planning in advance of a disaster. This protocol may be applied to any NC county and beyond, thereby increasing local disaster preparedness.