Multicenter Prospective Observational Cohort Study Research Articles

Quantitative Ultrasound Measurement of Endometrial Waves in Adenomyosis Versus Women with Normal Uteri - the Waves Study

<h3>Study Objective</h3> Measurement and analysis of uterine contractions by quantitative 2D transvaginal ultrasound measurements in women with abnormal uteri due to adenomyosis versus women with normal uteri. <h3>Design</h3> Multi-centre prospective observational cohort study. <h3>Setting</h3> Outpatient gynaecology department of participating centres. <h3>Patients or Participants</h3> 29 women with adenomyosis with a natural menstrual cycle were compared to 70 women with normal uteri and regular menstrual cycles. Patients were included from September 2014 up to January 2022. <h3>Interventions</h3> Patients underwent a 4-minute 2D transvaginal ultrasound of the uterus in mid-sagittal section. Uterine motion analysis was implemented by a dedicated speckle tracking and strain analysis algorithm; with frequency, amplitude, coordination and velocity -related features extracted from the derived signals to characterise the uterine contractions. Measurements were carried out at different points of the menstrual cycle (menstrual, early follicular, periovulatory and early and late luteal phases. <h3>Measurements and Main Results</h3> Results differed most significantly between groups in the periovulatory phase, with women with adenomyosis showing lower frequency (1.44 vs. 1.79 contractions/minute, p=0.025), higher amplitude (0.09 vs. 0.04, p=0.000) and lower velocity of uterine contractions (0.62 vs. 0.83 mm/sec, p=0.0008). In the menstrual phase, women with adenomyosis showed a trend toward higher contraction frequency (1.37 vs, 1.33 contractions/minute, p=0.592), amplitude (0.05 vs. 0.04, p=0.259) and velocity (0.72 vs. 0.67, p=0.456). Across all phases, women with adenomyosis showed a trend towards reduced contraction coordination (0.23-0.34 vs. 0.15-0.26). This being statistically significant in the late luteal phase (p=0.018). <h3>Conclusion</h3> Our results confirm differences in uterine movement in abnormal versus healthy uteri. This could add to the aetiological understanding of clinical symptoms of these conditions (i.e. dysmenorrhoea or infertility). The notable difference between groups regarding coordination identifies this feature as a potential prognostic or therapeutic marker. Further research in women with (other) benign uterine disorders will hopefully lead to a better understanding of the clinical implications of abnormal uterine contractility.

Association between Renal Function at Admission and COVID-19 in-Hospital Mortality in Southern Italy: Findings from the Prospective Multicenter Italian COVOCA Study.

Background. Evidence has shown a close association between COVID-19 infection and renal complications in both individuals with previously normal renal function and those with chronic kidney disease (CKD). Methods. The aim of this study is to evaluate the in-hospital mortality of SARS-CoV-2 patients according to their clinical history of CKD or estimated glomerular filtration rate (eGFR). This is a prospective multicenter observational cohort study which involved adult patients (≥18 years old) who tested positive with SARS-CoV-2 infection and completed their hospitalization in the period between November 2020 and June 2021. Results. 1246 patients were included in the study, with a mean age of 64 years (SD 14.6) and a median duration of hospitalization of 15 days (IQR 9–22 days). Cox’s multivariable regression model revealed that mortality risk was strongly associated with the stage of renal impairment and the Kaplan–Meier survival analysis showed a progressive and statistically significant difference (p < 0.0001) in mortality according to the stage of CKD. Conclusion. This study further validates the association between CKD stage at admission and mortality in patients hospitalized for COVID-19. The risk stratification based on eGFR allows clinicians to identify the subjects with the highest risk of intra-hospital mortality despite the duration of hospitalization.

Multicentric Study to Assess Helicobacter pylori Incidence, Patient Reported Adverse Events, Compliance and Effectiveness, in Real-World Setting.

Helicobacter pylori ( H. pylori) plays an important role in chronic gastritis and globally it is estimated to be present in half of the world’s population. In Portugal, prevalence reaches 85% and its eradication is recommended using quadruple antibiotic therapy, with or without bismuth. We intended to characterize the prescribed treatments evaluating effectiveness, adverse outcomes and compliance in a real-world setting in a primary care unit. A prospective multicenter observational cohort study was developed in five primary care units of Braga, Portugal. Patients diagnosed with H. pylori infection from August 2021 to January 2022 were included. Data were collected by interview (3 weeks after treatment) and review of medical records. Comparison between two groups of treatment and multivariable analysis was conducted. We estimated 13.4 cases per 1000 adults/year from 185 diagnoses. Therapy with bismuth was the most prescribed (83.8%) with a 96.7% eradication rate. There were no significant differences between treatments. Adverse events were reported in 73.8% of inquiries and female patients were associated with higher reports of nausea (p = 0.03) and metallic taste (p = 0.02). Both eradication schemes were effective and secure. The higher rate of adverse outcomes should be validated but it could influence the debate concerning treating all patients, especially in low gastric cancer-prevalence regions.

Impact of myocardial injury on mortality and adverse events in hospitalized patients with influenza: a prospective cohort study

Abstract Background and aim Myocardial injury (MINJ) defined as elevated high-sensitivity cardiac troponin level (hs-cTnT) above normal values is a well-recognized prognostic marker in different clinical conditions, nonetheless, its relevance in Influenza remains poorly defined. We aimed to analyse incidence, predictors, short and mid-term prognostic role of MINJ in hospitalized patients (pts) with Influenza. Material and methods During 2018–2019 Influenza epidemic, a prospective multicentre observational cohort study was conducted enrolling all hospitalized adult patients with laboratory confirmed Influenza infection. MINJ was prospectively assessed at admission and defined as hs-cTnT &amp;gt;14 ng/L. Primary endpoint was all-cause death at 28-days. Secondary endpoints were all-cause death at 28-days or intensive care unit (ICU) admission/mechanical ventilation and all-cause death at follow up. Results 145 consecutive pts were enrolled. MINJ was evident in 94 (65.5%) pts. At a 28-days follow up, 7 deaths (4.8%) occurred, all in patients with MINJ at admission (log rank p=0.048). MINJ showed a strong association with the occurrence of death, ICU admission or mechanical ventilation (OR 5.74, 95% CI 1.28–53.29; p=0.015). At a median follow-up of 32.7 months, 15 (10.3%) deaths occurred, all among patients with MINJ at index hospitalization leading to a significantly high mortality rate at follow-up among patients with MINJ (log-rank p=0.003). Conclusions Influenza related MINJ is common and identifies patients at higher likelihood of short-term adverse events and midterm mortality. Funding Acknowledgement Type of funding sources: None.

Determinants of Low Bone Turnover in Type 2 Diabetes-the Role of PTH

Determinants of low bone turnover in type 2 diabetes (T2DM) are poorly understood. To investigate the relationship between markers of bone turnover, glycaemic control, disease duration and calciotropic hormones in T2DM we assessed baseline biochemical data from the DiabOS Study, a prospective multicenter observational cohort study. In a cross-sectional study-design data from 110 postmenopausal women and men aged 50–75 years diagnosed with T2DM for at least 3 years and 92 non-diabetic controls were evaluated. Biochemical markers of bone formation (N-terminal propeptide of type I procollagen [PINP]), bone-specific alkaline phosphatase [BAP]) and resorption (C-terminal cross-linking telopeptide of type I collagen [CTX]), measures of calcium homeostasis (intact parathormone [iPTH], 25-Hydroxyvitamin D, calcium, magnesium) and glycaemic control were assessed. After adjustment for age, gender and body mass index (BMI), patients with T2DM had lower serum levels of PINP (p < 0.001), CTX (p < 0.001), iPTH (p = 0.03) and magnesium (p < 0.001) compared to controls. Serum calcium, creatinine, 25-Hydroxyvitamin D and sclerostin did not differ between both groups. In multivariate linear regression analyses only serum iPTH remained an independent determinant of bone turnover markers in T2DM (PINP: p = 0.02; CTX: p < 0.001 and BAP: p < 0.01), whereas glycated haemoglobin (HbA1c), disease duration, age and BMI were not associated with bone turnover. In conclusion low bone turnover in T2DM is associated with low iPTH. The underlying mechanism remains to be elucidated.

Bone morphogenetic protein 10 as predictor for adverse outcomes in patients with atrial fibrillation

Abstract Background Patients with atrial fibrillation (AF) face an increased risk of death and major adverse cardiovascular events (MACE). Bone morphogenetic protein 10 (BMP10) is a novel atrial-specific biomarker, but data about its prognostic value in AF patients are lacking. Purpose We aimed to assess the predictive value of BMP10 for death and MACE in AF patients in comparison to N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). Methods Baseline concentrations of BMP10 and NT-proBNP were measured in stable patients with AF enrolled in Swiss-AF, a prospective multicenter observational cohort study. Primary outcomes were all-cause death and MACE (composite of heart failure hospitalization, cardiovascular death, stroke, systemic embolism, myocardial infarction). Measures of discriminative power were used to compare multivariable Cox proportional hazard models using the different biomarkers. Results A total of 2219 AF patients were included with a median follow-up of 4.3 years (IQR 3.9, 5.1). Mean age was 73±9 years and 27% were women. Incidence rate per 100 patient-years of all-cause death and MACE increased across BMP10 quartiles (Figure 1). In the multivariable adjusted Cox proportional hazard model, the hazard ratio (HR) and 95% confidence interval (CI) of BMP10 was 1.60 (1.37; 1.87) to predict all-cause death, and 1.54 (1.35; 1.76) to predict MACE. For all-cause death, the C-index (95% CI) was 0.783 (0.763; 0.809) for BMP10, 0.784 (0.765; 0.810) for NT-proBNP, and 0.789 (0.771; 0.815) for both biomarkers combined. For MACE, the C-index (95% CI) was 0.732 (0.715; 0.754) for BMP10, 0.747 (0.731; 0.768) for NT-proBNP, and 0.750 (0.734; 0.771) for both biomarkers combined. When grouping patients according to clinical used NT-proBNP categories (&amp;lt;300, 300–900, &amp;gt;900 ng/l), higher incidence rates and adjusted HRs were observed for the primary outcomes in patients with high BMP10 in the categories of low NT-proBNP (all-cause death aHR 2.28 [1.15; 4.52], MACE aHR 1.88 [1.07; 3.28]) and high NT-proBNP (all-cause death aHR 1.61 [1.14; 2.26], MACE aHR 1.38 [1.07; 1.80]) (Figure 2). Conclusion The novel atrial-specific biomarker BMP10 strongly predicts all-cause death and MACE in patients with AF. BMP10 provides additional prognostic information in low- and high-risk patients according to NT-proBNP stratification. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation

Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 1: a multicentre prospective observational cohort study in patients without planned compression.

There is no agreed treatment pathway following excision of keratinocyte cancer (KC). Compression therapy is considered beneficial for secondary intention healing on the lower leg; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed. We report a multicentre prospective observational cohort study in this patient population with the intention of informing a future trial design. To estimate the time to healing in wounds healing by secondary intention without planned postoperative compression, following excision of KC on the lower leg; to characterize the patient population, including factors affecting healing; and to assess the incidence of complications. This was a multicentre prospective observational cohort study. Inclusion criteria were age ≥ 18 years with planned excision of KC on the lower leg and healing by secondary intention, an ankle-brachial pressure index (ABPI) of ≥ 0.8; and written informed consent. Exclusion criteria included planned excision with primary closure, skin graft or flap; compression therapy for another indication; planned compression; inability of patient to receive, comply with or tolerate high compression; or a suspected diagnosis other than KC. This study recruited 58 patients from 9 secondary care dermatology clinics. In the analysis population (n = 53), mean age was 81 years (range 25-97 years), median time to healing was 81 days (95% CI 73-92) and 45 patients (84.9%) had healing of the wound at the 6-month follow-up. The healing prognostic factors were wound parameters and ABPI. Wound infections occurred in 16 participants (30.2%). Four patients (7.5%) were admitted to hospital; three because of an infection and one because of a fall. The collected data have informed the RCT preparation. A relatively high proportion (7.5-15%) of unhealed wounds, infection and hospital admissions demonstrate the need for clearly establishing potentially effective treatments to improve outcomes for this population.

Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 2: feasibility data from a multicentre prospective observational cohort study to inform a future randomized controlled trial.

Compression therapy is considered beneficial for postsurgical lower leg wound healing by secondary intention; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed. To determine the feasibility of recruitment and estimate recruitment rate; to understand the standard postoperative wound management pathway; to determine uptake of optional additional clinic visits for healing confirmation; and to explore patient acceptability of compression bandaging and plan a future RCT. Participant recruitment was performed from secondary care dermatology clinics, during a period of 22 months. Inclusion criteria were age ≥ 18 years, planned excision of keratinocyte cancer on the lower leg with healing by secondary intention and an ankle-brachial pressure index of ≥ 0.8. Exclusion criteria were planned primary closure/graft or flap; inability to receive, comply with or tolerate high compression; planned compression; or suspected melanoma. Patients were followed up weekly (maximum 6 months) in secondary care clinics and/or by telephone. Information was collected on healthcare resource use, unplanned compression, wound healing and an optional clinic visit to confirm healing. This study recruited 58 patients from 9 secondary care dermatology clinics over 22 months. Mean recruitment/centre/month was 0.8 (range 0.1-2.3). Four centres had dedicated Research Nurse support. The analysis population (n = 53) had weekly follow-up assessments. Standard care clinical contacts were: general practitioner (7 visits; 1.2%), community nurse (169; 28.5%), practice nurse visits (189; 31.8%) and dermatology clinic visits (138; 23.2%). Participants whose wounds healed (34 of 45; 75.6%) attended an optional clinic visit. Data were obtained to inform a future RCT. Recruitment rates were found to be higher in centres with dedicated research support. People would be willing to take part in a trial and attend a confirmation of healing visit.

I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators. I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment. A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia. I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Functional status in older patients with cancer and a frailty risk profile: A multicenter observational study

IntroductionFunctional status (FS) and frailty are significant concerns for older adults, especially those with cancer. Data on FS (Activities of Daily Living [ADL]; Instrumental Activities of Daily Living [IADL]) and its evolution during cancer treatment in older patients and a frailty risk profile are scarce. Therefore, this study examines FS and its evolution in older patients with cancer and a frailty risk profile and investigates characteristics associated with functional decline. Material and MethodsThis secondary data-analysis, focusing on FS, uses data from a large prospective multicenter observational cohort study. Patients ≥70 years with a solid tumor and a frailty risk profile based on the G8 screening tool (score ≤ 14) were included. A geriatric assessment was performed including evaluation of FS based on ADL and IADL. At approximately three months of follow-up, FS was reassessed. Univariable and multivariable logistic regression analyses were used to identify predictive factors for functional decline in ADL and IADL. ResultsData on ADL and IADL were available at baseline and follow-up in 3388 patients. At baseline 1886 (55.7%) patients were dependent for ADL, whereas 2085 (61.5%) patients were dependent at follow-up. Functional decline was observed in 23.6% of patients. For IADL 2218 (65.5%) patients were dependent for IADL, whereas 2591 (76.5%) patients were dependent at follow-up. Functional decline in IADL was observed in 41.0% of patients. In multivariable analysis, disease stage III or IV, comorbidities, falls history in the past twelve months, and FS measured by IADL were predictive factors for functional decline in both ADL and IADL. Other predictive factors for functional decline in ADL were polypharmacy, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) score 2–4, and cognitive impairment, and for functional decline in IADL were female sex, fatigue, and risk for depression. DiscussionFunctional impairments are frequent in older persons with cancer and a frailty risk profile, and several characteristics are identified that are significantly associated with functional decline. Therefore, FS is an essential part of the geriatric assessment which should be standard of care for this patient population. Next step is to proceed with directed interventions with the aim to limit the risk of functional decline as much as possible.

OS07.2.A Evaluation of Intraoperative Surgical Adjuncts and Resection of Glioblastoma (ELISAR GB): A UK and Ireland multicentre, prospective observational cohort study

Abstract Background Despite operative and adjuvant therapies, glioblastoma remains incurable, with the extent of resection being one of few treatments that can improve survival. To improve resection, operative adjuncts are used, with neuronavigation and 5-aminolevulinic acid (5-ALA) recommended as a standard of care in those aimed for maximal safe resection. Despite the standards, meta-analysis concluded that the impact of 5-ALA on the extent of surgical resection is of low quality due to bias in reporting tumour location and additional image guidance used, factors impacting on extent of resection as well as short-term neurological outcomes being uncertain. Therefore we aimed to evaluate the availability and use of 5-ALA and other adjuncts and compare surgical outcomes of 5-ALA-guided versus non-5-ALA-guided resections. Material and Methods A multicenter prospective observational cohort study was conducted across 27 out of 31 available centres in the UK and Ireland from 6 January until 19 March 2020. Inclusion criteria included adults with first diagnosis, supratentorial glioblastoma undergoing resection. Primary outcomes included: i) the availability and use of surgical adjuncts and ii) complete resection of enhancing tissue (CRET). Secondary outcomes included adverse events, new onset of postoperative neurological deficit and post-operative neurological function. Descriptive and inferential statistics were used for analysis with a p-value &amp;lt;0.05 deemed significant. Results 232 consecutive cases were identified. 142/232 cases were aimed for maximal safe resection subsequently divided into 5-ALA-guided (n=92) versus non-5-ALA-guided (n=50) resections. 5-ALA and neuronavigation were available across all centres. Neuronavigation and 5-ALA were used in 91% (n=129/142) and 65% (n=92/142) of cases aimed for maximal safe resection whereas 83% (n=75/90) and 49% (n=44/90) for debulk surgery. 35 unique combinations of surgical adjuncts were used in 232 operations. 5-ALA-guided resection yielded a higher percentage of CRET than without (55% versus 28%, p &amp;lt; 0.01). The two groups showed no difference in adverse events (p=0.98), new onset of neurological deficit (p=0.88) nor neurological function (p=0.7). A logistic regression analysis showed that 5-ALA was an important predictor of CRET regardless of additional adjuncts used (OR 2.4, CI 0.96-5.97, P = 0.05), tumour location and molecular characterisation (OR 3.48, CI 1.61-7.51, P &amp;lt;0.01). Conclusion Firstly, we showed that 5-ALA is not always used for glioblastoma aimed for CRET. Secondly, we report a great heterogeneity of adjuncts used for resection, possibly explained by a lack of high-quality evidence and surgeon training. Thirdly we demonstrate that 5-ALA-guided resection leads to higher percentage of CRET regardless of other adjuncts used, tumour location and molecular characterisation.

Improving prediction of response to neoadjuvant treatment in patients with breast cancer by combining liquid biopsies with multiparametric MRI: protocol of the LIMA study – a multicentre prospective observational cohort study

IntroductionThe response to neoadjuvant chemotherapy (NAC) in breast cancer has important prognostic implications. Dynamic prediction of tumour regression by NAC may allow for adaption of the treatment plan before completion,...

Adherence to antidepressant therapy: clinical experience on the example of agomelatine

The review article provides data on the prevalence and treatment problems of depression, highlights the issues of adherence to antidepressant therapy, investigation of the safety and efficacy of agomelatine in real clinical settings. The results of a prospective observational multicenter cohort study of agomelatine in clinical practice are analyzed in detail, taking into account the effect of treatment on the social functioning of patients. The results obtained in a sample representative for depression, including patients with comorbidities, confirm the long-term efficacy and good tolerability of agomelatine in daily practice, which is the basis for adherence to therapy and achievement of the goal of depression treatment

Prospective Cohort Study of Depression During Pregnancy and the Postpartum Period in Women With Epilepsy vs Control Groups.

Assess the incidence and factors associated with major depressive episodes (MDEs) and symptoms of depression and anxiety during pregnancy and postpartum periods in pregnant women with epilepsy (PWWE) compared with healthy pregnant women (HPW) and nonpregnant women with epilepsy (NPWWE) in comparable timeframes. Previous studies have reported higher rates of postpartum depression in women with epilepsy compared with women without epilepsy. However, the incidence of MDE using a structured interview during pregnancy and postpartum has not been directly compared with control groups, and the comparison of depression and anxiety symptoms and the role of associated factors remain ambiguous. The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational parallel group cohort study of PWWE and their children. This report examines mood disorders. Unlike previous epilepsy pregnancy studies, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV (SCID) provided lifetime diagnoses, and repeated SCID mood modules assessed for MDE, the a priori primary outcome. Symptoms of depression (Beck Depression Inventory [BDI] and Edinburg Postnatal Depression Scale [EPDS]) and anxiety (Beck Anxiety Inventory [BAI]) were also assessed along with multiple clinical factors. This study included PWWE (n = 331) and HPW (n = 102) during pregnancy and postpartum and NPWWE (n = 102) at comparable times. No difference in SCID-diagnosed MDE incidence was found across groups, but BDI depressive symptoms were worse during pregnancy in PWWE vs NPWWE and during postpartum vs HPW and NPWWE. BAI anxiety symptoms were worse during pregnancy in PWWE vs HPW and NPWWE and during postpartum vs HPW. Factors associated with MDE during pregnancy/postpartum for PWWE included >1 seizure/90 days, anticonvulsant polytherapy, unplanned pregnancy, and lifetime history of mood disorder. Suicidal ideation from BDI or EPDS was related to BAI anxiety symptoms. Although SCID-based MDE did not differ across groups, this prospective study confirms higher rates of psychiatric symptoms in patients with epilepsy during pregnancy and postpartum, provides new data on associated factors, and underscores the importance of anxiety in risk for depression and thoughts of death/dying or suicide. Given the risks, PWWE should be routinely assessed and symptomatic patients should be offered treatment. This study is registered at ClinicalTrials.gov as NCT01730170.

A Pragmatic Study on Nurse-Led Home Phototherapy

BACKGROUND Narrowband ultraviolet phototherapy is a safe and effective treatment option for chronic skin conditions. The requirements of clinic-based phototherapy can be burdensome, with home-based phototherapy as a reasonable alternative. OBJECTIVE This study aimed to analyze the effects of a nurse-led home phototherapy program and describe the clinical resources required. METHODS A pragmatic multicenter prospective observational cohort study was conducted from 2019 to 2021. Eighteen participants were enrolled in the program and followed for 9 months. Outcome measures included clearance rates, erythema incidence, Dermatology Life Quality Index, the burden of treatment scores, dermatologic medication usage, and clinic contacts. RESULTS Fourteen of the 18 patients (77.8%) reported high skin clearance. Mild erythema was common, moderate erythema was rare, and two episodes of severe erythema were recorded overall. Dermatology Life Quality Index and burden of treatment impact were minimal. Adjunct topical medications decreased by half. Nurses successfully reached participants up to the 3-month time point, with completed contacts decreasing over time. Unplanned contacts included phone calls and emails. CONCLUSION Dermatology nurses possess the skills needed to lead safe and effective home phototherapy programs. Although this pragmatic study was small, results are optimistic for the future of nurse-led home phototherapy.

Cerebral small vessel disease and perihematomal edema formation in spontaneous intracerebral hemorrhage

ObjectiveBlood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of cerebral small vessel disease (cSVD)-related intracerebral hemorrhage (ICH). The formation of perihematomal edema (PHE) is presumed to reflect acute BBB permeability following ICH. We aimed to assess the association between cSVD burden and PHE formation in patients with spontaneous ICH.MethodsWe selected patients with spontaneous ICH who underwent 3T MRI imaging within 21 days after symptom onset from a prospective observational multicenter cohort study. We rated markers of cSVD (white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds) and calculated the composite score as a measure of the total cSVD burden. Perihematomal edema formation was measured using the edema extension distance (EED). We assessed the association between the cSVD burden and the EED using a multivariable linear regression model adjusting for age, (log-transformed) ICH volume, ICH location (lobar vs. non-lobar), and interval between symptom onset and MRI.ResultsWe included 85 patients (mean age 63.5 years, 75.3% male). Median interval between symptom onset and MRI imaging was 6 days (IQR 1–19). Median ICH volume was 17.0 mL (IQR 1.4–88.6), and mean EED was 0.54 cm (SD 0.17). We found no association between the total cSVD burden and EED (B = −0.003, 95% CI −0.003–0.03, p = 0.83), nor for any of the individual radiological cSVD markers.ConclusionWe found no association between the cSVD burden and PHE formation. This implies that mechanisms other than BBB dysfunction are involved in the pathophysiology of PHE.

Association of Nasopharyngeal and Serum Glutathione Metabolism with Bronchiolitis Severity and Asthma Risk: A Prospective Multicenter Cohort Study.

Infants hospitalized for bronchiolitis are at high risk for asthma. Glutathione-related metabolites may antagonize oxidative stress, which induces airway injuries in respiratory infection and subsequent airway remodeling. However, little is known about the relationship of glutathione-related metabolites with bronchiolitis severity and the risk of asthma. In a multicenter prospective observational cohort study of infants hospitalized for bronchiolitis, we measured nasopharyngeal and serum glutathione-related metabolites by using liquid chromatography–tandem mass spectrometry. We then examined their association with bronchiolitis severity (defined by positive pressure ventilation (PPV) use). We also identified severity-related glutathione-related metabolite signatures and examined their association with asthma at age 6 years. In 1013 infants, we identified 12 nasopharyngeal and 10 serum glutathione-related metabolites. In the multivariable models, lower relative abundances of seven metabolites, e.g., substrates of glutathione, including cysteine (adjOR 0.21, 95%CI 0.06–0.76), glycine (adjOR 0.25, 95%CI 0.07–0.85), and glutamate (adjOR 0.25, 95%CI 0.07–0.88), were significantly associated with PPV use (all FDR < 0.05). These associations were consistent with serum glutathione-related metabolites. The nasopharyngeal glutathione-related metabolite signature was also associated with a significantly higher risk of asthma (adjOR 0.90, 95%CI 0.82–0.99, p = 0.04). In infants hospitalized for bronchiolitis, glutathione-related metabolites were associated with bronchiolitis severity and asthma risk.

The HeMoVal study protocol: a prospective international multicenter cohort study to validate cerebrospinal fluid hemoglobin as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury

IntroductionPreclinical studies provided a strong rationale for a pathophysiological link between cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) and secondary brain injury after subarachnoid hemorrhage (SAH-SBI). In a single-center prospective observational clinical study, external ventricular drain (EVD) based CSF-Hb proved to be a promising biomarker to monitor for SAH-SBI. The primary objective of the HeMoVal study is to prospectively validate the association between EVD based CSF-Hb and SAH-SBI during the first 14 days post-SAH. Secondary objectives include the assessment of the discrimination ability of EVD based CSF-Hb for SAH-SBI and the definition of a clinically relevant range of EVD based CSF-Hb toxicity. In addition, lumbar drain (LD) based CSF-Hb will be assessed for its association with and discrimination ability for SAH-SBI.MethodsHeMoVal is a prospective international multicenter observational cohort study. Adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH) are eligible. While all patients with aSAH are included, we target a sample size of 250 patients with EVD within the first 14 day after aSAH. Epidemiologic and disease-specific baseline measures are assessed at the time of study inclusion. In patients with EVD or LD, each day during the first 14 days post-SAH, 2 ml of CSF will be sampled in the morning, followed by assessment of the patients for SAH-SBI, co-interventions, and complications in the afternoon. After 3 months, a clinical follow-up will be performed. For statistical analysis, the cohort will be stratified into an EVD, LD and full cohort. The primary analysis will quantify the strength of association between EVD based CSF-Hb and SAH-SBI in the EVD cohort based on a generalized additive model. Secondary analyses include the strength of association between LD based CSF-Hb and SAH-SBI in the LD cohort based on a generalized additive model, as well as the discrimination ability of CSF-Hb for SAH-SBI based on receiver operating characteristic (ROC) analyses.DiscussionWe hypothesize that this study will validate the value of CSF-Hb as a biomarker to monitor for SAH-SBI. In addition, the results of this study will provide the potential base to define an intervention threshold for future studies targeting CSF-Hb toxicity after aSAH.Study registrationClinicalTrials.gov Identifier NCT04998370. Date of registration: August 10, 2021.

SARS-CoV-2 Genomic Characteristics and Clinical Impact of SARS-CoV-2 Viral Diversity in Critically Ill COVID-19 Patients: A Prospective Multicenter Cohort Study.

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3–8] vs. 3 [2–4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.

Comparison of diagnostic criteria for acute kidney injury in critically ill children: a multicenter cohort study

BackgroundSubstantial interstudy heterogeneity exists in defining acute kidney injury (AKI) and baseline serum creatinine (SCr). This study assessed AKI incidence and its association with pediatric intensive care unit (PICU) mortality under different AKI and baseline SCr definitions to determine the preferable approach for diagnosing pediatric AKI.MethodsIn this multicenter prospective observational cohort study, AKI was defined and staged according to the Kidney Disease: Improving Global Outcome (KDIGO), modified KDIGO, and pediatric reference change value optimized for AKI (pROCK) definitions. The baseline SCr was calculated based on the Schwartz formula or estimated as the upper normative value (NormsMax), admission SCr (AdmSCr) and modified AdmSCr. The impacts of different AKI definitions and baseline SCr estimation methods on AKI incidence, severity distribution and AKI outcome were evaluated.ResultsDifferent AKI definitions and baseline SCr estimates led to differences in AKI incidence, from 6.8 to 25.7%; patients with AKI across all definitions had higher PICU mortality ranged from 19.0 to 35.4%. A higher AKI incidence (25.7%) but lower mortality (19.0%) was observed based on the Schwartz according to the KDIGO definition, which however was overcome by modified KDIGO (AKI incidence: 16.3%, PICU mortality: 26.1%). Furthermore, for the modified KDIGO, the consistencies of AKI stages between different baseline SCr estimation methods were all strong with the concordance rates > 90.0% and weighted kappa values > 0.8, and PICU mortality increased pursuant to staging based on the Schwartz. When the NormsMax was used, the KDIGO and modified KDIGO led to an identical AKI incidence (13.6%), but PICU mortality did not differ among AKI stages. For the pROCK, PICU mortality did not increase pursuant to staging and AKI stage 3 was not associated with mortality after adjustment for confounders.ConclusionsThe AKI incidence and staging vary depending on the definition and baseline SCr estimation method used. The modified KDIGO definition based on the Schwartz method leads AKI to be highly relevant to PICU mortality, suggesting that it may be the preferable approach for diagnosing AKI in critically ill children and provides promise for improving clinicians’ ability to diagnose pediatric AKI.