Efficacy of occlusal splint versus sleep hygiene and progressive muscle relaxation on perceived stress and sleep bruxism: A randomized clinical trial.

PURPOSE: The objective was the comparison of an occlusal device (OD), and sleep hygiene and progressive muscle relaxation (SH & PMR) on perceived stress and sleep bruxism activity (burst/episode and episode/hour) in participants with sleep bruxism. MATERIAL AND METHODS: Sixty-six participants with self-reported sleep bruxism were selected and randomly allocated into two groups: OD group or SH & PMR group. Assessment of perceived stress and sleep bruxism activity were the primary outcomes. The Perceived Stress Scale-10 (PSS-10 scale) was used to measure perceived stress and bruxism episodes/hour and bursts/episode recorded by electromyography of masseter and temporalis. These outcomes were assessed at baseline, 1 month, 6 months, and 1 year. The paired t-test assessed changes in PSS-10 scores and sleep bruxism activity within the same group over different time points (baseline, 1 month, 6 months, and 1 year). The unpaired t-test compared scores between two groups (OD and SH & PMR) at each time point to evaluate intervention differences. The chi-square test compared gender distribution between both groups. RESULTS: PSS-10 scores were found to decrease with the OD at 1 month and 6 months compared to baseline and SH & PMR at all subsequent follow-ups. This decrease was not statistically significant (p > 0.05) between the OD and SH & PMR groups at all follow-ups. OD and SH & PMR significantly reduced bruxism episodes/hour and bursts/episode at all follow-ups (p < 0.05). There were no adverse effects related to any intervention. CONCLUSIONS: The OD and SH & PMR both effectively reduced PSS-10 scores over 6 months and significantly decreased bruxism episodes and bursts per episode. Both methods are safe and effective for managing sleep bruxism and reducing stress.

Active follow-up of patients identified with multidrug-resistant gram-negative bacteria to discontinue contact precautions and isolation measures.

It is essential to refrain from unnecessary isolation measures indicated for patients identified with multidrug-resistant gram-negative bacteria (MDR-GNB) and therefore, this study aimed to evaluate whether a pro-active follow-up strategy to discontinue isolation measures of patients identified with MDR-GNB (without carbapenemase production) resulted in reduced isolation days during hospitalization, compared to passive follow-up. A comparison was made between active and passive follow-up strategies over a two-year period after first MDR-GNB identification. Patients could be declared negative after 2 consecutive negative screening cultures. Active follow-up patients received a questionnaire for screening cultures within six months of MDR-GNB identification. Of the 2208 patients included, 1424 patients (64.5%) underwent passive follow-up and 784 patients (35.5%) underwent active follow-up. A significantly higher proportion of active follow-up patients who had sufficient (at least two) screening cultures, were declared MDR-GNB negative compared to those with passive follow-up; 66.9% vs. 20.6% (P<0.001) for adult patients and 76.0% vs. 17.1% (P<0.001) for paediatric patients. A comparison between active follow-up patients with sufficient versus those with active follow-up but insufficient cultures revealed a reduction of isolation days for paediatric patients (median 10.6 vs. 1.6 days; P = 0.031). While this difference was not statistically significant for adults (median 5.3 vs 4.2 isolation days), there was a valuable decrease in the number of isolation days for both adult and paediatric patients under active follow-up with sufficient (≥2) cultures, indicating clinical relevance. Therefore, we recommend an active follow-up strategy of patients identified with an MDR-GNB, to prevent further unneeded infection prevention measures.

Long Term Outcomes After Renal Revascularization for Atherosclerotic Renovascular Disease in the ASTRAL Trial.

BACKGROUND: The ASTRAL trial (Angioplasty and Stenting for Renal Artery Lesions) recruited 806 patients between 2000 and 2007. Patients with atherosclerotic renal artery stenosis (RAS) and clinician uncertainty about the benefit of revascularization were randomized 1:1 to medical therapy with or without renal artery stenting. The initial results were presented in 2009 at a median 33.6-month follow-up, with no benefit of revascularization on renal or cardiovascular outcomes. Surviving patients remained under follow-up until the end of 2013, and the long-term results are presented in this study. METHODS: Data were analyzed to assess whether there was a later impact of revascularization on renal function, cardiovascular events, and survival, including a composite outcome of renal and cardiovascular outcomes and death (as in the CORAL trial [Cardiovascular Outcomes in Renal Atherosclerotic Lesions]). Prespecified subgroup analyses included different categories of renal function, rapid deterioration in kidney function, and degree of RAS. Post hoc analyses of patients with severe RAS (bilateral 70% or >70% in a solitary kidney), those with or without proteinuria, and a per-protocol analysis were performed. RESULTS: The mean age of the entry population was 70.5 years, the mean estimated glomerular filtration rate was 40 mL/min/1.73 m2, the mean RAS was 76%, and the mean blood pressure was 150/76 mm Hg; 83% of the revascularization group underwent attempted stenting. The median follow-up was 56.4 months, with 108 patients lost to follow-up. By the end of follow-up, 50% of the evaluable population had died, 18% had suffered a first renal event, and 40% had suffered a first cardiovascular event. No statistical difference was observed for any outcome in the intention-to-treat and per-protocol analyses. CONCLUSIONS: The long-term follow-up of the ASTRAL trial showed no overall benefit of renal revascularization to renal and cardiovascular outcomes. It has been highlighted that a proportion of the population had lower-risk RAS, and there is likely to be merit in further study in a higher-risk population. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN59586944.

Combination of neoadjuvant and adjuvant chemotherapy with FOLFOX compared with adjuvant chemotherapy in management of locally advanced rectal cancers: a randomized trial of a promising therapeutic approach.

BACKGROUND: Colorectal cancer (CRC) is a significant malignancy with widespread implications. Despite progress in surgical interventions for rectal cancer, improvements in overall prognosis remain disproportionate. Standard preoperative chemoradiation, while established as the standard treatment for the majority of rectal cancers, exhibits limited effectiveness in enhancing disease-free survival (DFS) and mitigating distant metastases, particularly in cases of locally advanced rectal cancer (LARC). METHODS: This randomised clinical trial assessed 286 patients with LARC in two paralleled groups. Group A underwent six courses of neoadjuvant MFOLFOX chemotherapy, chemoradiation, surgery, and six adjuvant chemotherapy cycles. Group B received concurrent chemoradiation, surgery, and twelve adjuvant chemotherapy cycles. Patient evaluations were achieved at multiple stages of treatment and follow-up. RESULTS: Group A had significantly lower local recurrence (11.64%) than Group B (21.74%, P = 0.025). The distant metastasis rate in Group A (8.90%) was lower than in Group B (20.29%) but was not significant (p = 0.143). More patients in Group A experienced downstaging (80.82% vs. 60.87%, p < 0.001). Specifically, 72.60% demonstrated downstaging of tumour invasion and 54.79% downstaging of lymph node involvement, compared to 57.25% and 41.30% in Group B (p = 0.009 and p = 0.025, respectively) as well as higher pCR rate (26.03% vs. 15.25%, p = 0.030) and three-year DFS rate (82.19% vs. 71.01%, p = 0.035) in group A compare to group B. CONCLUSION: This innovative strategy for LARC showed promising results with lower local recurrence and higher rates of downstaging and pCR. Treatment side effects were similar in both groups but less frequent in Group A. Anaemia was the most common haematological side effect (A: 58%, B: 68%), and peripheral sensory neuropathy was the most common non-haematological complication (A: 63%, B: 64%). These findings suggest this regimen could be a valuable therapeutic approach for LARC. TRIAL REGISTRATION: This trial was registered on 2023-12-08 within the IRCT.IR database under the number IRCT20210308050628N1.

Symptoms, work situation and work functioning 10 years after rehabilitation of stress-induced exhaustion disorder.

BACKGROUND: Stress-induced exhaustion disorder (SED) is the most common reason for long-term sick leave in Sweden and the recovery process may be long and troublesome. This study explores the symptoms of burnout, depression and anxiety among patients with SED 10 years after termination of a multimodal rehabilitation program. Another aim of the study was to investigate work situation, work functioning, and any remaining exhaustion and sleeping disorders among those who were gainfully employed at the 10-year follow-up. METHODS: This longitudinal study included 107 patients (91 women and 16 men), who had been diagnosed with SED 10 years prior to the study. After establishing the diagnosis they all underwent and completed an multimodal rehabilitation program. Data on symptoms of burnout, anxiety and depression were collected before and after the multimodal rehabilitation program, and at follow-ups after additional 1 year and an additional 10 years. At the 10-year follow-up, work situation, work functioning, and symptoms of exhaustion and sleep disorders were assessed in those who were gainfully employed (89 patients). RESULTS: Symptoms of burnout, anxiety, and depression remained stable from the 1- to the 10-year follow-up after completed rehabilitation. Among participants who were gainfully employed, 73% had changed workplaces, and 31.5% had reduced their working hours. Common reasons for these changes were lack of energy or because they had chosen to prioritise their lives differently. Work functioning was rated as moderate, one third self-reported SED to some extent, and one fifth reported moderate-to-severe insomnia. CONCLUSION: A relatively large proportion of former patients with SED have residual health problems 10 years after rehabilitation and some have not been able to return to full-time work. Preventive and early rehabilitative interventions with adjustments and measures at the organisational level are probably needed to achieve a more sustainable working life.

Future Needs in Nursing Informatics - Preliminary Findings from the Global Nursing Informatics Survey.

This study investigates the evolving landscape of nursing informatics by conducting a follow-up survey initiated by the International Medical Informatics Association (IMIA) Students and Emerging Professionals (SEP) Nursing Informatics (NI) group in 2015 and 2019. The participants were asked to describe what they thought should be done in their institutions and countries to advance nursing informatics in the next 5-10 years. For this paper, responses in English acquired by December 2023 were analysed using inductive content analysis. Identified needs covered a) recognition and roles, b) educational needs, c) technological needs, and d) research needs. The initial findings indicate that, despite significant progress in nursing informatics, the current needs closely mirror those identified in the 2015 survey.

Long-Term Outcomes and a Radiological Assessment of Hydroxyapatite-Tricalcium Phosphate-Coated Total Hip Arthroplasty (Trilogy/Zimmer): A Long-Term Follow-Up Study.

Background and Objectives: Favorable short- and mid-term results for hydroxyapatite (HA)-tricalcium phosphate (TCP)-coated total hip arthroplasty (THA) (Trilogy/Zimmer) have been reported in the literature; however, the long-term results beyond 15 years have not been documented. Therefore, this study evaluated the long-term postoperative results, radiological bone changes, and implant fixation of the acetabular component of HA-TCP-coated THA. Materials and Methods: This is a retrospective cohort study of 212 patients who underwent primary HA-TCP-coated THA (Trilogy/Zimmer) at our institution between 1 October 2002, and 31 March 2008; 166 who were available for follow-up at least 15 years postoperatively were included (capture rate: 78.3%). All implants were Trilogy/Zimmer. We investigated the survival rate, with aseptic loosening as the endpoint. Clinical evaluations included the presence of dislocation and a modified Harris Hip Score (mHHS) preoperatively and at the final observation. Results: The mean age at surgery and at the follow-up period were 57.7 ± 9.6 and 17.1 ± 1.5 years, respectively. The survival rate was 99.4% (165/166), with aseptic loosening as the endpoint. Dislocation was observed in 4/166 (2.4%) patients. The mHHS improved significantly from 46.1 points preoperatively to 82.2 points during the last survey (p < 0.05). The results revealed that fixation was favorable in all cases except for one case of aseptic loosening. The Trilogy implant coated with HA-TCP was highly effective in bone induction, and bone ingrowth was considered to have occurred without failure, further indicating its usefulness. The long-term results of cementless THA using an HA-TCP coating (Trilogy/Zimmer), with a mean follow-up period of 17.1 years, revealed a commendable survival rate of 99.4%, considering aseptic loosening as the endpoint. Conclusions: HA-TCP-coated THA (Trilogy/Zimmer) had good long-term results. However, further long-term observation is required in patients who have undergone this surgery, and the stem side should be evaluated and investigated, including comorbidities.

Saliva Is a Sensitive and Accessible Sample Both for SARS-CoV-2 Detection and for the Evaluation of Treatment Effectiveness in Follow-Up Studies.

Despite emerging evidence indicating that molecular SARS-CoV-2 tests performed on saliva have diagnostic sensitivity and specificity comparable to those observed with nasopharyngeal swabs (NPSs), most in vivo follow-up studies on the efficacy of drugs against SARS-CoV-2 have been performed on NPSs, not considering saliva as a possible alternative matrix. For this reason, in this study, we used, in parallel, saliva and NPS samples for the detection of SARS-CoV-2 by real-time RT-PCR in patients receiving Tixagevimab/Cilgavimab, Nirmatrelvir/Ritonavir, or Sotrovimab as a treatment against SARS-CoV-2. Our results showed a good correlation between the NPS and saliva samples for each drug; moreover, comparable changes in the cycle threshold (Ct) levels in saliva and NPSs were observed both 7 days and 30 days after treatment, thus confirming that the saliva represents a good matrix for in vivo follow-up studies verifying the effectiveness of treatments against SARS-CoV-2.

Effects of training oncology physicians advising patients on complementary and integrative therapies on patient-reported outcomes: 2-year follow-up of the multi-center, cluster-randomized KOKON-KTO study.

PURPOSE: Many cancer patients wish for complementary and integrative medicine (CIM) consultations led by their oncology physician. Within the KOKON-KTO study, oncology physicians in the intervention group were trained in a blended learning to provide CIM consultations to their cancer patients in addition to distributing a leaflet about CIM websites. Control oncology physicians only distributed the leaflet. The training showed positive effects on the patient-level. As of now, no consistent evidence exists on the long-term effects of such one-time-only CIM consultation during cancer treatment. METHODS: In the KOKON-KTO follow-up study, cancer patients previously participating in the KOKON-KTO study (intervention group:IG and control group: CG) received, at least 24 months later, a follow-up questionnaire by post, evaluating long-term effects of the KOKON-KTO consultation using the measures provided in the original study (patient-physician communication (EORTC-QLQ-COMU2), satisfaction with cancer treatment (PS-CaTE), CIM disclosure with healthcare provider (HCP), and need for CIM consultation during cancer therapy). RESULTS: In total, 102 cancer patients participated in the follow-up study (IG n = 62; CG n = 40). The overall reponse rate was around 36% (IG: 48.4%; CG: 23.7%). In the follow-up study, differences between groups had increased and were still shown (EORTC-QLQ-COMU26, 0-100 point scale, ≥10-point-group difference) in some subscales: patient's active behavior (in means; IG:73.6 (95% CI, 63.8-83.5); CG:61.1 (95% CI, 52.4-69.8)); clinician-patient relationship (IG:80.9 (95% CI, 71.8-90.0); CG:68.7 (95% CI, 59.3-78.0)). For some outcomes, differences decreased over time (e.g., EORTC-QLQ-COMU26 subscales "takes into account patient's preference" and "corrects misunderstandings"). More patients in the CG used CIM without oncology physicians' knowledge (IG: 13.7%, CG: 24.0%). CONCLUSION: This study presents first findings that one-time-only CIM consultations may enhance patient-physican relationship and CIM disclosure long-term. To further support cancer patients' in their wish for CIM consultations, training programs should provide oncology physicians with CIM competencies for different cancer stages including cancer survivors.

Time to resolution of symptoms and recovery after mild traumatic brain injury: protocol for a systematic review and meta-analysis.

INTRODUCTION: Mild traumatic brain injury (mTBI) is a leading cause of morbidity and mortality, with approximately 1 out of 200 people each year sustaining an mTBI in Europe. There is a growing awareness that recovery may take months or years. However, the exact time frame of recovery remains ill-defined in the literature. This systematic review aims to record the range of outcome measures used for mTBI and understand the time to recovery for different outcomes. METHODS AND ANALYSIS: This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guideline. A prespecified literature search for articles in the English language will be conducted from database inception to the date of searches using MEDLINE and EMBASE. A trial search was conducted on 5 October 2023 with refinement of the search criteria following this. For each study, screening of the title, abstract and full text, as well as data extraction, will be done by two reviewers, with an adjudicating third reviewer if required. The risk of bias will be assessed using the Cochrane risk of bias tool for clinical trials and the Newcastle Ottawa score for cohort studies. The primary outcome is the time to resolution of symptoms in mTBI patients who have a full recovery, using any validated outcome measure. Results will be categorised by symptom groups, including but not limited to post-concussive symptoms, mental health, functional recovery and health-related quality of life. For mTBI patients who do not recover, this review will also explore the time to the plateau of symptoms and the sequelae of these symptoms. Where possible, meta-analysis will be undertaken, with a narrative review undertaken when this is not possible. Subgroup analyses of patients aged over 64 years, and patients with repetitive head injury, are planned. ETHICAL REVIEW AND DISSEMINATION: Ethical review is not required, as no original data will be collected. Results will be disseminated through peer-reviewed publications and academic conferences. PROSPERO REGISTRATION NUMBER: CRD42023462797.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Onset of Prolonged High-Potency Benzodiazepine Use Among ICU Survivors: A Nationwide Cohort Study.

OBJECTIVES: Exposure to critical illness and intensive care may lead to long-term psychologic and physical impairments. To what extent ICU survivors become prolonged users of benzodiazepines after exposure to critical care is not fully explored. This study aimed to describe the extent of onset of prolonged high-potency benzodiazepine use among ICU survivors not using these drugs before admission, identify factors associated with this use, and analyze whether such usage is associated with increased mortality. DESIGN: Retrospective cohort study. SETTING: Sweden, including all registered ICU admissions between 2010 and 2017. PATIENTS: ICU patients surviving for at least 3 months, not using high-potency benzodiazepine before admission, were eligible for inclusion. INTERVENTIONS: Admission to intensive care. MEASUREMENTS AND MAIN RESULTS: A total of 237,904 patients were screened and 137,647 were included. Of these 5338 (3.9%) became prolonged users of high-potency benzodiazepines after ICU discharge. A peak in high-potency benzodiazepine prescriptions was observed during the first 3 months, followed by sustained usage throughout the follow-up period of 18 months. Prolonged usage was associated with older age, female sex, and a history of both somatic and psychiatric comorbidities, including substance abuse. Additionally, a longer ICU stay, a high estimated mortality rate, and prior consumption of low-potency benzodiazepines were associated with prolonged use. The risk of death between 6 and 18 months post-ICU admission was significantly higher among high-potency benzodiazepine users, with an adjusted hazard ratio of 1.8 (95% CI, 1.7-2.0; p < 0.001). No differences were noted in causes of death between users and nonusers. Conclusions: Despite the lack of evidence supporting long-term treatment, prolonged usage of high-potency benzodiazepines 18 months following ICU care was notable and associated with an increased risk of death. Considering the substantial number of ICU admissions, prevention of benzodiazepine misuse may improve long-term outcomes following critical care.

Computed tomography diagnosis of pulmonary infarction in acute pulmonary embolism.

INTRODUCTION: Pulmonary infarction is a common sequela of pulmonary embolism (PE) but lacks a diagnostic reference standard. CTPA in the setting of acute PE does not reliably differentiate infarction from other consolidations, such as reversible alveolar hemorrhage or atelectasis. We aimed to assess the diagnostic accuracy for recognizing pulmonary infarction on CT in the acute phase of PE, with follow-up CT as reference. MATERIALS AND METHODS: Initial and follow-up CT scans of 33 patients with acute PE were retrospectively assessed. Two radiologists independently evaluated the presence and size of suspected pulmonary infarction on the initial CT. Confirmation of infarction was established by detection of residual densities on follow-up CT. Sensitivity, specificity and interobserver variability were calculated. RESULTS: In total, 60 presumed infarctions were found in 32 patients, of which 34 infarctions in 21 patients could be confirmed at follow-up. On patient-level, observers' sensitivity/specificity were 91 %/9 %, and 73 %/46 %, respectively, with interobserver agreement by Kappa's coefficient of 0.17. Confirmed infarctions were usually larger than false positive lesions (median approximate volume of 6.6 mL [IQR 0.84-21.3] vs. 1.3 mL [IQR 0.57-6.5], p = 0.040), but still small. An occluding thrombus in a supplying vessel was predictive for confirmed infarction (OR 11, 95%CI 2.1-55), but was not discriminative. CONCLUSIONS: Pulmonary infarction is a common finding in acute PE, and generally small. Radiological identification of infarction was challenging, with considerable interobserver variability. Complete obstruction of the supplying (sub)segmental pulmonary artery was found as the strongest predictor for pulmonary infarction but was not demonstrated to be discriminative.

Long-term follow-up in outpatients with mildly elevated pulmonary artery systolic pressure on echocardiography: a single-centre retrospective cohort study in Shanghai, China.

OBJECTIVE: To investigate the correlation between mildly elevated pulmonary artery systolic pressure (PASP) on echocardiography and mortality, as well as long-term changes in PASP. DESIGN: Retrospective cohort study. SETTING: Shanghai, China, a single centre. PARTICIPANTS: A total of 910 patients were enrolled in this study. From January to June 2016, 1869 patients underwent echocardiography at the Zhongshan Hospital affiliated with Fudan University. Patients with malignant tumours, previous heart or other solid organ transplantation, previous or scheduled ventricular assist device implantation, severe kidney dysfunction (uraemia and patients on dialysis) and a life expectancy of less than 1 year for any medical condition were excluded. INTERVENTIONS: No interventions were done. PRIMARY AND SECONDARY OUTCOME MEASURES: The predictors of death in patients with mild echocardiographic pulmonary hypertension were analysed using univariate and multivariate Cox regression analyses. Paired t-tests were used to calculate changes in the PASP values at baseline and follow-up for different patient groups. RESULTS: The 5-year survival of patients was 93.2%. Patients were grouped according to whether they had combined organic heart disease (OHD). The PASP value was an independent predictor of all-cause mortality in patients with OHD, with each 1 mm Hg increase associated with an HR of 1.02 (95% CI: 1.01-1.03, p=0.038) but not in patients without OHD. Of the total, 46% (419/910) of the patients with 5-6 years of echocardiography were investigated for changes in the PASP value. We found significant PASP reduction in patients without OHD (42.8±2.4 mm Hg vs 39.3±8.2 mm Hg, p<0.001), but no significant change was observed for patients with OHD (42.8±2.5 mm Hg vs 42.4±8.8 mm Hg, p=0.339). CONCLUSIONS: The PASP was associated with all-cause mortality in patients with OHD and mildly elevated PASP compared with patients without OHD. After 5-6 years of follow-up, the PASP on echocardiography was not further elevated in patients without OHD.

Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up.

INTRODUCTION: Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child's neurodevelopment and behaviour development, overall health and mortality. METHODS AND ANALYSIS: This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of <15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or Actim-Partus test or (4) ruptured membranes, are randomised to atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Children born to mothers who participated in the APOSTEL 8 study (n=760) will be eligible for follow-up at 4 years of corrected age and assessed using four parent-reported questionnaires. Primary outcomes are neurodevelopment and behaviour problems. Secondary outcomes are on child growth and general health. All outcomes will be compared between the atosiban and placebo group with OR and corresponding 95% CI. Analyses will be performed using the intention-to-treat approach. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee from Amsterdam UMC confirmed that de Medical Research Involving Human Subjects Act (Dutch WMO-law) did not apply to our study (W21_386 # 21.431). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results.

Hybrid developmental follow-up for preterm infants in Brazil: A feasibility study.

INTRODUCTION: The low attendance of families in child developmental follow-up programs for at-risk preterm children is a challenge in Brazil. OBJECTIVE: This study evaluates the feasibility of implementing a developmental follow-up program for Brazilian preterm infants in a hybrid format. METHODS: This is an observational, prospective cohort study, involving preterm infants. Longitudinal developmental test results, the participation frequency in the program, and the number of referrals to early intervention programs were used to assess feasibility. The General Movements (GMs) assessment, Alberta Infant Motor Scale (AIMS) and, Survey of Wellbeing of Young Children (SWYC) Milestones were administered via telehealth. The Bayley-III was administered in-person. RESULTS: Thirty-four preterm infants attended the follow-up until 12 months of corrected age and 18 (52.9 %) concluded all follow-up assessments. Twenty-six (76.5 %) attended all assessments via telehealth, and 26 (76.5 %) attended the in-person assessment. Eighteen (52.9 %) infants showed at least one altered result in development tests. Infants exhibiting abnormal results in the GMs assessment, motor developmental delay according to the AIMS, or developmental delay based on Balley-III were promptly referred to early intervention services. CONCLUSION: This study demonstrated high participation rate and low dropout in a developmental follow-up program employing a hybrid format. The substantial number of identified infants with developmental delay emphasizes the importance of timely detection of motor delays to referral to early intervention services.

Association between bronchopulmonary dysplasia severity and its risk factors and long-term outcomes in three definitions: a historical cohort study.

OBJECTIVE: To compare the association of the severity categories of the 2001-National Institutes of Health (NIH), the 2018-NIH and the 2019-Jensen bronchopulmonary dysplasia (BPD) definitions with neurodevelopmental and respiratory outcomes at 2 and 5 years' corrected age (CA), and several BPD risk factors. DESIGN: Single-centre historical cohort study with retrospective data collection. SETTING: Infants born between 2009 and 2015 at the Amsterdam University Medical Centers, location Amsterdam Medical Center. PATIENTS: Preterm infants born at gestational age (GA) <30 weeks and surviving up to 36 weeks' postmenstrual age. INTERVENTIONS: Perinatal characteristics, (social) demographics and comorbidities were collected from the electronic patient records. MAIN OUTCOME MEASURES: The primary outcomes were neurodevelopmental impairment (NDI) or late death, and respiratory morbidity at 2 and 5 years' CA. Using logistic regression and Brier scores, we investigated if the ordinal grade severity is associated with incremental increase of adverse long-term outcomes. RESULTS: 584 preterm infants (median GA: 28.1 weeks) were included and classified according to the three BPD definitions. None of the definitions showed a clear ordinal incremental increase of risk for any of the outcomes with increasing severity classification. No significant differences were found between the three BPD definitions (Brier scores 0.169-0.230). Respiratory interventions, but not GA, birth weight or small for GA, showed an ordinal relationship with BPD severity in all three BPD definitions. CONCLUSION: The severity classification of three BPD definitions showed low accuracy of the probability forecast on NDI or late death and respiratory morbidity at 2 and 5 years' CA, with no differences between the definitions.

Natural History of Coronary Atherosclerosis in Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement: The Role of Quantitative Flow Ratio.

BACKGROUND: The prognostic impact of functionally significant coronary artery disease, as assessed with quantitative flow ratio (QFR), in patients with severe aortic stenosis treated with transcatheter aortic valve replacement is unknown. METHODS: This is a retrospective study with blind analysis of angiographic data, enrolling consecutive patients with severe aortic stenosis treated with transcatheter aortic valve replacement at 4 Italian centers. None of the patients enrolled received pre-transcatheter aortic valve replacement or concomitant coronary revascularization, either for the absence of significant coronary stenoses or by clinical decision. Visual estimation of diameter stenosis and QFR analysis were performed in all coronary arteries. The end point was all-cause mortality at a 3-year follow-up. RESULTS: A total of 318 patients were enrolled. At visual estimation, 140 patients (44%) presented a diameter stenosis ≥50% in at least 1 coronary artery, whereas 78 patients (24.5%) had at least 1 vessel with QFR <0.80 and, therefore, included in the positive QFR group. Overall, 69 (21.7%) patients died during the follow-up. In the Kaplan-Meier analysis, patients with positive QFR experienced significantly higher rates of death during follow-up compared with those without (51.1% versus 12.1%; P<0.001), whereas no significant difference was evident in terms of death between patients with or without significant coronary artery disease according to angiographic evaluation (24.3% versus 19.7%; P=0.244). In a multivariate regression model, positive QFR was an independent predictor of all-cause death during follow-up (hazard ratio, 5.31 [95% CI, 3.21-8.76]). CONCLUSIONS: Coronary QFR can predict mortality in patients with severe aortic stenosis treated with transcatheter aortic valve replacement without revascularization.

Strengthening health visitors' breastfeeding support: Results from a cluster randomised study.

AIMS: To assess the effect of the education programme on three constructs of health visitors' breastfeeding support: knowledge, self-efficacy and action competence. Furthermore, the study aimed to confirm the factor structure of these three constructs. BACKGROUND: Health professionals are key in supporting breastfeeding women but studies report gaps in health professionals' breastfeeding support knowledge and competences. The present intervention study aimed to strengthen the breastfeeding support of families to improve breastfeeding rates. Health visitors received an interactive education programme to enhance their breastfeeding support knowledge, self-efficacy and action competence, including e-learning and a two-day course of lectures, role plays and discussions. DESIGN: A pre- and post-test study was applied in a cluster randomised trial METHODS: Cluster units were Danish municipal health visiting programmes, randomised by stratifying for region and annual births per cluster. Health visitors from 21 clusters (11 intervention, 10 control) participated. The knowledge, self-efficacy and action competence were assessed in self-reported questionnaires before and after education (n=368; intervention n=176, control n=196). To analyse the effects, the intention-to-treat principle and linear mixed models were applied. Confirmatory Factor Analysis was used to confirm the factor structures of the hypothesised knowledge, self-efficacy and action competence constructs. RESULTS: 158 health visitors in the control arm and 157 in the intervention arm completed the baseline questionnaire and were analysed in intention-to-treat analyses. 125 and 116, respectively, completed the follow-up questionnaire and were analysed in sensitivity analyses. Health visitors in both trial arms had high levels of self-efficacy and action competence at baseline. Mean treatment effect of the education programme was 0.5 points (CI95 % 0.1-0.8) for knowledge, 2.4 points (CI95 % 1.6-3.3) for self-efficacy and 1.4 points (CI95 % 0.7-2.0) for action competence. The factor structure of the items used to measure knowledge, self-efficacy and action competence were confirmed. CONCLUSIONS: The education programme improved the self-reported breastfeeding support knowledge, self-efficacy and action competence of health visitors. The factor structures of the instruments used to measure effects were confirmed by confirmatory factor analysis. TRIAL REGISTRATION: Clinical Trials: NCT05311631. First posted April 5, 2022.

Effect of glucose variability on the mortality of adults aged 75 years and over during the first year of the COVID-19 pandemic.

BACKGROUND: To our knowledge, only one study has examined the association between glucose variability (GV) and mortality in the elderly population with diabetes. GV was assessed by HbA1c, and a J-shaped curve was observed in the relationship between HbA1c thresholds and mortality. No study of GV was conducted during the COVID-19 pandemic and its lockdown. This study aims to evaluate whether GV is an independent predictor of all-cause mortality in patients aged 75 years or older with and without COVID-19 who were followed during the first year of the COVID-19 pandemic and its lockdown measures. METHODS: This was a retrospective cohort study of 407,492 patients from the AGED-MADRID dataset aged 83.5 (SD 5.8) years; 63.2% were women, and 29.3% had diabetes. GV was measured by the coefficient of variation of fasting plasma glucose (CV-FPG) over 6 years of follow-up (2015-2020). The outcome measure was all-cause mortality in 2020. Four models of logistic regression were performed, from simple (age, sex) to fully adjusted, to assess the effect of CV-FPG on all-cause mortality. RESULTS: During follow-up, 34,925 patients died (14,999 women and 19,926 men), with an all-cause mortality rate of 822.3 per 10,000 person-years (95% confidence interval (CI), 813.7 to 822.3) (739 per 10,000; 95% CI 728.7 to 739.0 in women and 967.1 per 10,000; 95% CI 951.7 to 967.2 in men). The highest quartile of CV-FPG was significantly more common in the deceased group (40.1% vs. 23.6%; p < 0.001). In the fully adjusted model including dementia (Alzheimer's disease) and basal FPG, the odds ratio for mortality ranged from 1.88 to 2.06 in patients with T2DM and from 2.30 to 2.61 in patients with normoglycaemia, according to different sensitivity analyses. CONCLUSIONS: GV has clear implications for clinical practice, as its assessment as a risk prediction tool should be included in the routine follow-up of the elderly and in a comprehensive geriatric assessment. Electronic health records can incorporate tools that allow its calculation, and with this information, clinicians will have a broader view of the medium- and long-term prognosis of their patients.