Multicenter Prospective Observational Cohort Study Research Articles

Can Presepsin Be Valuable in Reducing Unnecessary Antibiotic Exposure after Birth?

Due to a lack of rapid, accurate diagnostic tools for early-onset neonatal sepsis (EOS) at the initial suspicion, infants are often unnecessarily given antibiotics directly after birth. We aimed to determine the diagnostic accuracy of presepsin for EOS before antibiotic initiation and to investigate whether presepsin can be used to guide clinicians' decisions on whether to start antibiotics. In this multicenter prospective observational cohort study, all infants who started on antibiotics for EOS suspicion were consecutively included. Presepsin concentrations were determined in blood samples collected at the initial EOS suspicion (t = 0). In addition to this, samples were collected at 3, 6, 12 and 24 h after the initial EOS suspicion and from the umbilical cord directly after birth. The diagnostic accuracy of presepsin was calculated. A total of 333 infants were included, of whom 169 were born preterm. We included 65 term and 15 preterm EOS cases. At the initial EOS suspicion, the area under the curve (AUC) was 0.60 (95% confidence interval (CI) 0.50-0.70) in the term-born infants compared to 0.84 (95% CI 0.73-0.95) in the preterm infants. A cut-off value of 645 pg/mL resulted in a sensitivity of 100% and a specificity of 54% in the preterm infants. The presepsin concentrations in cord blood and at other time points did not differ significantly from the concentrations at the initial EOS suspicion. Presepsin is a biomarker with an acceptable diagnostic accuracy for EOS (culture-proven and clinical EOS) in preterm infants and might be of value in reducing antibiotic exposure after birth when appended to current EOS guidelines. However, the small number of EOS cases prevents us from drawing firm conclusions. Further research should be performed to evaluate whether appending a presepsin-guided step to current EOS guidelines leads to a safe decrease in antibiotic overtreatment and antibiotic-related morbidity.

Feasibility, safety, and acceptability of intranasal heroin-assisted treatment in Switzerland: protocol for a prospective multicentre observational cohort study

BackgroundHeroin-assisted treatment (HAT) is a proven effective treatment option for individuals with severe opioid use disorder (OUD). In Switzerland, pharmaceutical heroin (diacetylmorphine, DAM) is available in tablet form or as injectable liquid. This creates a large barrier for individuals who require the rapid onset of effect but are either unable or do not want to inject, or who primarily snort opioids. Early experimental data has demonstrated that intranasal DAM administration can be a viable alternative to the intravenous or intramuscular route of administration. The purpose of this study is to assess the feasibility, safety, and acceptability of intranasal HAT.MethodsThis study will assess intranasal DAM using a prospective multicentre observational cohort study design in HAT clinics across Switzerland. Patients will be offered to switch from oral or injectable DAM to intranasal DAM. Participants will be followed-up over 3 years, with assessments at baseline, and after 4, 52, 104 and 156 weeks. The primary outcome measure (POM) is retention in treatment. Secondary outcomes (SOM) include prescriptions and routes of administration of other opioid agonists, illicit substance use, risk behaviour, delinquency, health and social functioning, treatment adherence, opioid craving, satisfaction, subjective effects, quality of life, physical health, and mental health.ConclusionsThe results derived from this study will generate the first major body of clinical evidence on the safety, acceptability, and feasibility of intranasal HAT. If proven to be safe, feasible and acceptable, this study would increase the accessibility of intranasal OAT for individuals with OUD globally as a critical improvement in risk reduction.

High incidence rate of postoperative sore throat in intubated children at Northwest Amhara Comprehensive Specialized Hospitals, Ethiopia. Amulticenter study.

Postoperative sore throat is the most frequent complication in pediatric patients after general anesthesia. This study aimed to investigate the incidence of postoperative sore throat in patients undergoing general anesthesia with tracheal intubation or laryngeal mask airway. A hospital-based multicenter prospective observational cohort study was conducted. Proportional allocation was done with a total of 424 patients from March 1 to June 30, 2022. The information was entered into the Epi-Data software version 4.6 and analyzed with Stata 14. Socio-demographic, surgical, and anesthetic-related characteristics were analyzed using descriptive statistics. A p-value of less than 0.2 was the cutpoint of bivariate logistic regression analysis, and p-values of less than 0.05 were regarded as statistically significant in multivariate logistic regression to determine the presence and strength of association between independent variables and postoperative sore throat. A total of 411 patients were included in this study, with a response rate of 96.9%. The overall proportion of patients who developed postoperative sore throat was 45% (95% CI: 40.18-49.84). Patients who had anesthesia for more than two hours (AOR = 8.23: 95% CI = 4.08-16.5), those who were intubated by undergraduate anesthesia students (AOR = 2.67: 95% CI = 1.53-4.67), and those who had been intubated using tracheal tube (AOR = 2.38: 95% CI = 1.15-4.92) were significantly associated with the level of postoperative sore throat. We concluded that intubated children with ETT have a high incidence of post-operative sore throat. Tracheal tube usage, intubation by undergraduate students, and more than two hours of anesthesia duration were associated factors. The incidence of sore throat can be decreased with the use of a laryngeal mask airway, intubation by a senior anesthetist, and shortening of anesthesia time.

Diabetes mellitus is associated with 90-day mortality in old critically ill COVID-19 patients: a multicenter prospective observational cohort study

BackgroundSeveral studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age.MethodsThis multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan–Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality.ResultsThis study included 3420 patients with a median age of 76 years were included. Among these, 37.3% (n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06–1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis.ConclusionDiabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19.Study registrationNCT04321265, registered March 19th, 2020.

Association of preoperative COVID-19 and postoperative respiratory morbidity during the Omicron epidemic wave: the DROMIS-22 multicentre prospective observational cohort study

Preoperative COVID-19 has been associated with excess postoperative morbi-mortality. Consequently, guidelines were developed that recommended the postponement of surgery for at least 7 weeks after the infection. We hypothesised that vaccination against the SARS-CoV-2 and the large predominance of the Omicron variant attenuated the effect of a preoperative COVID-19 on the occurrence of postoperative respiratory morbidity. We conducted a prospective cohort study in 41 French centres between 15 March and 30 May 2022 (ClinicalTrials NCT05336110), aimed at comparing the postoperative respiratory morbidity between patients with and without preoperative COVID-19 within 8 weeks prior to surgery. The primary outcome was a composite outcome combining the occurrence of pneumonia, acute respiratory failure, unexpected mechanical ventilation, and pulmonary embolism within the first 30 postoperative days. Secondary outcomes were 30-day mortality, hospital length-of-stay, readmissions, and non-respiratory infections. The sample size was determined to have 90% power to identify a doubling of the primary outcome rate. Adjusted analyses were performed using propensity score modelling and inverse probability weighting. Of the 4928 patients assessed for the primary outcome, of whom 92.4% were vaccinated against the SARS-CoV-2, 705 had preoperative COVID-19. The primary outcome was reported in 140 (2.8%) patients. An 8-week preoperative COVID-19 was not associated with increased postoperative respiratory morbidity (odds ratio 1.08 [95% CI 0.48-2.13]; p=0.83). None of the secondary outcomes differed between the two groups. Sensitivity analyses concerning the timing between COVID-19 and surgery, and the clinical presentations of preoperative COVID-19 did not show any association with the primary outcome, except for COVID-19 patients with ongoing symptoms the day of surgery (OR 4.29 [1.02-15.8]; p=0.04). In our Omicron-predominant, highly immunised population undergoing general surgery, a preoperative COVID-19 was not associated with increased postoperative respiratory morbidity. The study was fully funded by the French Society of Anaesthesiology and Intensive Care Medicine (SFAR).

P614 Reduction of bowel wall thickness and doppler signals as early as 36 hours predicts corticosteroid response in a multi-centre prospective cohort of Acute Severe Ulcerative Colitis: USUC Study including the GENIUS cohort

Abstract Background Gastrointestinal ultrasound (GIUS) can accurately assess disease activity in atients with ulcerative colitis (UC). The aim of this study was to determine the accuracy of GIUS in predicting IV corticosteroid (CS) failure in patients with Acute Severe Ulcerative Colitis (ASUC) and the requirement for rescue therapy. Methods We conducted a multi-centre prospective observational cohort study of adult ASUC admitted to hospital between November 2019 to July 2022. GIUS was performed at six time points for each patient: at hospital admission (SV1), day 3 (SV2), at discharge (SV3), and thereafter during outpatient review in the 10 months of follow-up. Medical rescue therapy was given at the discretion of treating physician according to best clinical practice. Results A total of 32 consecutive patients with ASUC were recruited with a median follow-up duration of 8.9 months: median age 32 years, 38% male and median duration of disease 19 months. Seven patients had newly diagnosed UC and six patients (19%) were biologic experienced. Sixteen patients (50%) were CS responders and the remainder required medical rescue therapy; two patients required colectomy. The median time to rescue therapy and colectomy was 3.5 and 11 days from admission, respectively. At SV1, the median BWT of the worst affected segment was similar between CS responders and non-responders (5.50mm vs 5.85mm, p=0.66), however at SV2, responders had a significantly lower BWT (3.85mm vs 5.05mm, p=0.02). CS responders demonstrated a significant reduction in width of the muscularis propria (p=0.02) and submucosal (p=0.006) layer, but not the mucosal (p=0.61) layer (Figure 1). CS non-responders had a smaller absolute and relative reduction in median BWT at SV2. Receiver operating characteristic curve analysis showed that an absolute reduction of &amp;lt;1.40mm (Sn 63%, Sp 75%, AUROC 0.76) or a relative BWT reduction of &amp;lt;20% (Sn 81%, Sp 75%, AUROC 0.78) predicted CS non-response and need for rescue therapy well. A reduction in BWT and the absence of doppler activity at SV2 further enhanced the predictive capability of GIUS (Sn 81.3%, Sp 87.5%, AUROC 0.91) (Figure 2). Conclusion This study demonstrates the predictive utility of early GIUS in the management of ASUC. A reduction in absolute BWT of &amp;lt;1.40mm or relative BWT of &amp;lt;20% at 36-48 hours of admission identifies CS non-responders with good sensitivity and specificity. BWT reduction at SV2 in responders was driven mainly by decreased muscularis propria and submucosal thickness. Accuracy is further augmented when reduction in BWT and resolution of doppler signal are combined. This study suggests GIUS may allow clinicians to expedite initiation of rescue therapy for patients requiring salvage treatment.

P663 Post-ustekinumab induction IL12, IL23, and ustekinumab levels are associated with clinical response in a multi-centre prospective cohort study of Crohn’s disease patients: results from the AURORA Study including ANZIBDC Cohort

Abstract Background Ustekinumab (UST) is a monoclonal antibody targeting IL-12 and IL-23 through their shared p40 subunit. This study aimed to determine the clinical outcomes after UST treatment in Crohn’s disease (CD) patients in a real-world setting, and to investigate the association of clinical outcomes with IL-12, IL-23 and UST levels. Methods A multi-centre prospective observational cohort study of UST for moderate to severe CD was conducted. Patients were recruited from 19 Australian centres between Sep 2019 and Apr 2022. Clinical assessments were performed at baseline study visit (SV) 1 and post-induction (SV2). Patients were assessed every 6 months during maintenance therapy to 18 months (SV4). Clinical response and remission rates were determined using PRO2 definitions (STRIDE II guidelines). Logistic regression analyses were performed to identify predictors of clinical response and remission. UST levels were measured post induction and interleukin levels including IL12p40 and IL-23p19 were measured at SV1 and SV2 using ProQuantum ELISA assays. Results A total of 198 patients were recruited: median age 40.7 years, 54.3% male, median duration of disease 90.5 months, 12.8% active smokers, and 49.7% on concomitant immunomodulatory therapy. The majority (58.4%) were biologic-naïve and 82 patients were previously exposed to biologics (51.9%; IFX n=42, ADA n=50, VDZ n=9). Clinical response was achieved in 137 patients (75.7%), and remission in 84 (46.4%) with higher rates of response (85.2% vs 61.6%, p=0.001) and remission (54.6% vs 34.2%, p=0.006) in biologic naïve patients compared to biologic-exposed. For the 114 patients with 18 months (SV4) of follow-up, durable clinical response was maintained in 66.8% and remission in 50.0%. Dose escalation (90mg 4 weekly) was administered to 13 patients (6.6%) during induction, 48 (42.1%) in maintenance, and 15 patients (13.2%) received IV re-induction during maintenance. There was a significant reduction in IL-12 and IL-23 levels from SV1 to SV2 in responders (p=0.0001), but no significant reduction in non-responders (Figure 1). Clinical response at SV4 (n=101) was associated with higher post-induction UST levels (p=0.03) (Table 1). The combination of IL-12. IL-23 and UST level at SV2 predicted long-term response at SV4 (Sn 73%, Sp 71%, AUROC 0.765), but not at SV2 (Figure 2). Conclusion This large real-world study confirms that UST is most effective in bio-naïve CD patients with significantly higher response and remission rates than bio-experienced patients. The combination of post-induction IL-12, IL-23, and UST levels was associated with response at 18 months and could represent a novel predictor of long-term clinical outcomes.

What is changing in the treatment of acute coronary syndrome in the Russian Federation?

The work of the national network of vascular centers of the Russian Federation (RF), based on the Clinical recommendations of the Russian Society of Cardiology and the procedure for providing medical care to patients with cardiovascular diseases, has led to significant positive results in the treatment of patients with acute coronary syndrome (ACS) in the country, although a number of targets have not yet been reached. The purpose of the publication is to demonstrate the trend in therapeutic approaches to the management of patients with ACS in 2020-2022. in Russia and analysis of their effectiveness. Quantitative and qualitative indicators of the treatment of patients with ACS for the presented analysis were obtained on the basis of monitoring data from the Russian Ministry of Health for 2018-2021. presented: Monitoring of measures to reduce mortality from coronary heart disease, letters of the Ministry of Health of Russia dated March 13, 2015 No. 17-6 / 10 / 1-177 and dated July 24, 2015 No. 17-9 / 10 / 2-4128, within which data collection carried out monthly, on the portal of the Federal State Budgetary Institution "TsNIIOIZ" of the Ministry of Health of Russia - Automated system for monitoring medical statistics and the register REGION-IM (Russian Register of Acute Myocardial Infarction) - a multicenter prospective observational cohort study for 2020-2022, organized by the Federal State Budgetary Institution "National Medical Research Center of Cardiology named after Academician E.I. Chazov" of the Ministry of Health of Russia. In Russia with a diagnosis of ACS in 2020 and 2021 403,931 and 397,930 patients were hospitalized, respectively. The decrease in the number of patients diagnosed with ACS admitted to Russian hospitals by 22.32% was mainly due to a significant decrease in hospital admissions of patients diagnosed with non-ST elevation ACS (non-STE-ACS) (by 29.03%). At the same time, the admission of patients with ST elevation myocardial infarction (STEMI) decreased only by 6.02%. Compared to 2018-2019, in 2020-2022. increased mortality in primary percutaneous coronary intervention (PCI) (by 9.6%) and in the general STEMI group (by 12.3%); significantly increased mortality both in the general group of NSTE-ACS (by 48%) and during PCI for patients with non-STE-ACS (by 28.6%); there was an increase in the average annual number of primary PCI (by 12.6%); an absolute and relative increase in the number of PCI in non-STE-ACS was revealed (by 2.7 and 37.1%, respectively). In the country's hospitals, by the time of discharge, 95% of patients receive statins, beta-blockers – 87%, ACE inhibitors – 80%, acetylsalicylic acid – 82%, P2Y12 inhibitors – 98% of patients, regardless of the type of ACS. In Russia in 2020-2022 unfavorable tendencies in the provision of care to patients with ACS include: increased mortality in primary PCI and in the general STEMI group; increased mortality both in the general group of non-STE-ACS and during PCI for patients with non-STE-ACS. The positive results of the work of the national network of vascular centers include: absolute, relative and estimated increase in the number of primary PCI; absolute and relative increase in the number of PCI in non-STE-ACS; a high level of prescribing drugs with a proven positive effect on the prognosis.

PREDICT-juvenile-stroke: PRospective evaluation of a prediction score determining individual clinical outcome three months after ischemic stroke in young adults – a study protocol

BackgroundAlthough of high individual and socioeconomic relevance, a reliable prediction model for the prognosis of juvenile stroke (18–55 years) is missing. Therefore, the study presented in this protocol aims to prospectively validate the discriminatory power of a prediction score for the 3 months functional outcome after juvenile stroke or transient ischemic attack (TIA) that has been derived from an independent retrospective study using standard clinical workup data.MethodsPREDICT-Juvenile-Stroke is a multi-centre (n = 4) prospective observational cohort study collecting standard clinical workup data and data on treatment success at 3 months after acute ischemic stroke or TIA that aims to validate a new prediction score for juvenile stroke. The prediction score has been developed upon single center retrospective analysis of 340 juvenile stroke patients. The score determines the patient’s individual probability for treatment success defined by a modified Rankin Scale (mRS) 0–2 or return to pre-stroke baseline mRS 3 months after stroke or TIA. This probability will be compared to the observed clinical outcome at 3 months using the area under the receiver operating characteristic curve. The primary endpoint is to validate the clinical potential of the new prediction score for a favourable outcome 3 months after juvenile stroke or TIA. Secondary outcomes are to determine to what extent predictive factors in juvenile stroke or TIA patients differ from those in older patients and to determine the predictive accuracy of the juvenile stroke prediction score on other clinical and paraclinical endpoints. A minimum of 430 juvenile patients (< 55 years) with acute ischemic stroke or TIA, and the same number of older patients will be enrolled for the prospective validation study.DiscussionThe juvenile stroke prediction score has the potential to enable personalisation of counselling, provision of appropriate information regarding the prognosis and identification of patients who benefit from specific treatments.Trial registrationThe study has been registered at https://drks.de on March 31, 2022 (DRKS00024407).

Presentation, management, and outcomes of cauda equina syndrome up to one year after surgery, using clinician and participant reporting: A multi-centre prospective cohort study.

Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1-8) with 32% (175/545) undergoing surgery within 48h. Earlier surgery was associated with catheterisation (OR:2.2, 95%CI:1.5-3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8-20.4) and one-year ODI was associated with presentation ODI (r=0.3, 95%CI:0.2-0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. DCN Endowment Fund funded study administration. Castor EDC provided database use. No other study funding was received.

PS-BPC01-6: BRACHIAL-ANKLE PULSE WAVE VELOCITY IS USEFUL FOR CARDIOVASCULAR RISK ASSESSMENT IN WELL-TREATED HYPERTENSIVE PATIENTS WITH CORONARY HEART DISEASE

Objective: Measurement of brachial-ankle pulse wave velocity (baPWV) has been performed for the assessment of arterial stiffness. The purpose of this study was to determine whether baPWV is useful for cardiovascular risk assessment in treated hypertensive patients with a history of coronary heart disease (CHD). Design and method: This study was a post hoc analysis of Flow-mediated Dilation Japan Study A, which is a prospective multicenter observational cohort study. A total of 447 treated hypertensive patients with a history of CHD were enrolled to assess predictive value of baPWV for future cardiovascular events. The primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. Results: The primary outcome occurred in 64 patients during a median follow-up period of 47.6 months. When using a blood pressure ≧ 130/80 mmHg as a reference, blood pressure &lt; 130/80 mmHg was significantly associated with a lower risk of the primary outcome after adjustments for other cardiovascular risk factors in treated hypertensive patients with CHD (hazard ratio, 0.59; 95% confidence interval [CI], 0.35–0.99; P = 0.04). In well-treated patients with CHD who had a blood pressure &lt; 130/80 mmHg, baPWV ≧ 1736 cm/s, that was derived from receiver-operator characteristic curve analysis, was significantly associated with a higher risk of the primary outcome after adjustments for traditional cardiovascular risk factors (hazard ratio, 2.83; 95% CI, 1.02–7.91; P = 0.04). Conclusions: The achievement of the target blood pressure is important to reduce the risk of cardiovascular events in treated hypertensive patients with a history of CHD. In well-treated hypertensive patients with CHD, baPWV is useful for cardiovascular risk assessment.

Mainstream germline genetic testing in men with metastatic prostate cancer: design and protocol for a multicenter observational study

BackgroundIn international guidelines, germline genetic testing is recommended for patients with metastatic prostate cancer. Before undergoing germline genetic testing, these patients should receive pre-test counseling. In the standard genetic care pathway, pre-test counseling is provided by a healthcare professional of a genetics department. Because the number of patients with metastatic prostate cancer is large, the capacity in the genetics departments might be insufficient. Therefore, we aim to implement so-called mainstream genetic testing in the Netherlands for patients with metastatic prostate cancer. In a mainstream genetic testing pathway, non-genetic healthcare professionals discuss and order germline genetic testing. In our DISCOVER study, we will assess the experiences among patients and non-genetic healthcare professionals with this new pathway.MethodsA multicenter prospective observational cohort study will be conducted in 15 hospitals, in different regions of the Netherlands. We developed an online training module on genetics in prostate cancer and the counseling of patients. After completion of this module, non-genetic healthcare professionals will provide pre-test counseling and order germline genetic testing in metastatic prostate cancer patients. Both non-genetic healthcare professionals and patients receive three questionnaires. We will determine the experience with mainstream genetic testing, based on satisfaction and acceptability. Patients with a pathogenic germline variant will also be interviewed. We will determine the efficacy of the mainstreaming pathway, based on time investment for non-genetic healthcare professionals and the prevalence of pathogenic germline variants.DiscussionThis study is intended to be one of the largest studies on mainstream genetic testing in prostate cancer. The results of this study can improve the mainstream genetic testing pathway in patients with prostate cancer.Trial registrationThe study is registered in the WHO’s International Clinical Trials Registry Platform (ICTRP) under number NL9617.

COVID-19 patients’ clinical profile and outcome with respect to their vaccination status: A prospective observational multicentre cohort study during third wave in Western India

PurposeTo understand the benefits of COVID-19 vaccination (Covishield, Covaxin) on clinical features and outcome of COVID-19 during the third wave in India. Materials and methodsThe primary study aim was to describe the clinical profile and outcome of COVID-19 regarding their vaccination and to identify risk factors for disease progression in vaccinated patients. This was a prospective observational multicentric study of COVID-19 attended by Infectious Disease physicians during January 15, 2022 to February 15, 2022. Adult patients with positive RT-PCR or rapid antigen test for COVID-19 were enrolled. Patient received treatment as per local institutional protocol. Chi square test for categorical and Mann Whitney test for continuous variables were applied for the analysis. Logistic regression was used to calculate adjusted odds ratios. ResultsA total of 788 patients were included in analysis out of 883 enrolled patients from 13 centers across Gujarat. By the end of two weeks’ follow up, 22 patients (2.8%) had expired. The Median age of subjects was 54 years, with a (55.8%) male. 90% of the subjects were vaccinated, majority (77%) of them had received 2 doses of vaccine with Covishield (659, 93%). Mortality among the non-vaccinated was significantly (11.4%) higher than vaccinated (1.8%). Logistic regression analysis showed numbers of comorbidities (p ​= ​0.027), baseline higher WBC count (p ​= ​0.02), higher NLR (p ​= ​0.016), and Ct value (p ​= ​0.046) were associated with mortality while vaccination was associated with survival (p ​= ​0.001). The factors associated with mortality among vaccinated were age, comorbidities, baseline higher WBC, NLR, and CRP. ConclusionsOmicron variant was associated with mild symptoms. Clinical and laboratory risk factors for getting severe disease with Omicron variant were the same with previous SARS CoV-2 strain. Two doses of vaccine protect people against severe disease and death. Age, comorbidities, baseline leucocytosis, high NLR, elevated CRP are the risk factors for poor outcome in vaccinated patients.

Treatment decision-making and care among older adults with kidney failure: protocol for a multicentre, prospective observational cohort study with nested substudies and linked qualitative research (the Elderly Advanced CKD Programme)

IntroductionShared treatment decision-making and planning of care are fundamental in advanced chronic kidney disease (CKD) management. There are limited data on several key outcomes for the elderly population including survival,...

Validation of Prediction Rules for Computed Tomography Use in Children With Blunt Abdominal or Blunt Head Trauma: Protocol for a Prospective Multicenter Observational Cohort Study.

Traumatic brain injuries (TBIs) and intra-abdominal injuries (IAIs) are 2 leading causes of traumatic death and disability in children. To avoid missed or delayed diagnoses leading to increased morbidity, computed tomography (CT) is used liberally. However, the overuse of CT leads to inefficient care and radiation-induced malignancies. Therefore, to maximize precision and minimize the overuse of CT, the Pediatric Emergency Care Applied Research Network (PECARN) previously derived clinical prediction rules for identifying children at high risk and very low risk for IAIs undergoing acute intervention and clinically important TBIs after blunt trauma in large cohorts of children who are injured. This study aimed to validate the IAI and age-based TBI clinical prediction rules for identifying children at high risk and very low risk for IAIs undergoing acute intervention and clinically important TBIs after blunt trauma. This was a prospective 6-center observational study of children aged <18 years with blunt torso or head trauma. Consistent with the original derivation studies, enrolled children underwent routine history and physical examinations, and the treating clinicians completed case report forms prior to knowledge of CT results (if performed). Medical records were reviewed to determine clinical courses and outcomes for all patients, and for those who were discharged from the emergency department, a follow-up survey via a telephone call or SMS text message was performed to identify any patients with missed IAIs or TBIs. The primary outcomes were IAI undergoing acute intervention (therapeutic laparotomy, angiographic embolization, blood transfusion, or intravenous fluid for ≥2 days for pancreatic or gastrointestinal injuries) and clinically important TBI (death from TBI, neurosurgical procedure, intubation for >24 hours for TBI, or hospital admission of ≥2 nights due to a TBI on CT). Prediction rule accuracy was assessed by measuring rule classification performance, using standard point and 95% CI estimates of the operational characteristics of each prediction rule (sensitivity, specificity, positive and negative predictive values, and diagnostic likelihood ratios). The project was funded in 2016, and enrollment was completed on September 1, 2021. Data analyses are expected to be completed by December 2022, and the primary study results are expected to be submitted for publication in 2023. This study will attempt to validate previously derived clinical prediction rules to accurately identify children at high and very low risk for clinically important IAIs and TBIs. Assuming successful validation, widespread implementation is then indicated, which will optimize the care of children who are injured by better aligning CT use with need. RR1-10.2196/43027.

Incidence of falls and fall-related injuries and their predictive factors in frail older persons with cancer: a multicenter study

BackgroundFalls and fall-related injuries are a major public health problem. Data on falls in older persons with cancer is limited and robust data on falls within those with a frailty profile are missing. The aim of this study is to investigate the incidence and predictive factors for falls and fall-related injuries in frail older persons with cancer.MethodsThis study is a secondary data analysis from data previously collected in a large prospective multicenter observational cohort study in older persons with cancer in 22 Belgian hospitals (November 2012–February 2015). Patients ≥70 years with a malignant tumor and a frailty profile based on an abnormal G8 score were included upon treatment decision and evaluated with a Geriatric Assessment (GA). At follow-up, data on falls and fall-related injuries were documented.ResultsAt baseline 2141 (37.2%) of 5759 included patients reported at least one fall in the past 12 months, 1427 patients (66.7%) sustained an injury. Fall-related data of 3681 patients were available at follow-up and at least one fall was reported by 769 patients (20.9%) at follow-up, of whom 289 (37.6%) fell more than once and a fall-related injury was reported by 484 patients (62.9%). Fear of falling was reported in 47.4% of the patients at baseline and in 55.6% of the patients at follow-up. In multivariable analysis, sex and falls history in the past 12 months were predictive factors for both falls and fall-related injuries at follow-up. Other predictive factors for falls, were risk for depression, cognitive impairment, dependency in activities of daily living, fear of falling, and use of professional home care.ConclusionGiven the high number of falls and fall-related injuries and high prevalence of fear of falling, multifactorial falls risk assessment and management programs should be integrated in the care of frail older persons with cancer. Further studies with long-term follow-up, subsequent impact on cancer treatment and interventions for fall prevention, and integration of other important topics like medication and circumstances of a fall, are warranted.Trial registrationB322201215495.

A multicenter prospective study validated a nomogram to predict individual risk of dependence in ambulation after rehabilitation

ObjectivesTo develop the Functional Risk Index for Dependence in Ambulation (FRIDA) score, a nomogram to predict individual risk of dependence in ambulation at discharge from postacute rehabilitation and validate its performance temporally and spatially. Study Design and SettingWe analyzed the database of a multicenter prospective observational quality cohort study conducted from January 2012 to March 2016, including data from 8,796 consecutive inpatients who underwent rehabilitation after stroke, hip fracture, lower limb joint replacement, debility, and other neurologic, orthopedic, or miscellaneous conditions. ResultsA total of 3,026 patients (34.4%) were discharged dependent in ambulation. In the training set of 5,162 patients (58.7%), Lasso-regression selected advanced age, premorbid disability, and eight indicators of medical and functional adverse syndromes at baseline to establish the FRIDA score. At the temporal validation obtained on an external set of 3,234 patients (41.3%), meta-analyses showed that the FRIDA score had good and homogeneous discrimination (summary area under the curve 0.841, 95% confidence interval = 0.826–0.855, I2 = 0.00%) combined with accurate calibration (summary Log O/E ratio 0.017, 95% confidence interval −0.155 to 0.190). These performances remained stable at spatial validation obtained on 3,626 patients, with substantial heterogeneity of estimates across nine facilities. Decision curve analyses showed that a FRIDA score–supported strategy far outperformed the usual “treat all” approach in each impairment categories. ConclusionThe FRIDA score is a new clinically useful tool to predict an individual risk for dependence in ambulation at rehabilitation discharge in many different disabilities, and may also reflect well the case-mix composition of the rehabilitation facilities.

Performance of D-Dimers in Patients with Prior History of Venous Thromboembolism Based on Anticoagulation Status

Background: D-dimers frequently stay elevated in patients with prior history of venous thromboembolism (VTE). Moreover, D-dimers seem to have lower diagnostic yield in patients presenting with a suspicion of recurrent VTE and it is not clear how D-dimers perform in patients on anticoagulation. Aim: To evaluate the performance of D-dimers in patients with a history of VTE based on anticoagulation status. Methods: The PREDICTORS study is an international prospective multicenter observational cohort study of outpatients with suspected VTE recurrence. The aim is to improve the performance of diagnostic strategies in patients with a suspicion of recurrent VTE. Pre-test clinical probability was assessed, and D-dimers were performed based on local clinical practices. Negative D-dimers were determined based on the manufacturer's threshold for every commercial assay used in each center. Recurrent VTE events (defined as proximal deep venous thrombosis or segmental or more proximal pulmonary embolism) at enrollment and during the 3-month follow-up were assessed and all suspected recurrent events were independently adjudicated. Results: D-dimer measurements were used in the diagnostic management of 482 patients, of which, 168 patients were on anticoagulation and 314 were not on anticoagulation. At enrollment, the prevalence of recurrent VTE was 29.9% (144/482). Moreover, at the index suspicion, 35.1% (169/482) had negative D-dimers. Amongst patients on anticoagulation, 4/90 (4.4%; 95%CI 1.2%-11.0%) and 21/78 (26.9%) had recurrent VTE at enrollment in patients with negative and positive D-dimers, respectively. During follow-up, no recurrent VTE occurred in patients with negative D-dimers. Amongst patients without anticoagulation, 2/79 (2.5%; 95%CI 0.3%-8.9%) and 117/235 (49.8%) had recurrent VTE at enrollment in patients with negative and positive D-dimers, respectively. One recurrent VTE occurred during follow-up amongst patients with initial negative D-dimers (1.3%; 95%CI 0.0-7.0%). Conclusion: In patients presenting with a suspected recurrent VTE, the prevalence of VTE was high, including in patients receiving anticoagulant therapy. Prevalence of VTE based on D-dimers positivity was comparable between patients on anticoagulation and patients without anticoagulation. False negative rate of D-dimers appears to be higher in patients with a suspicion of recurrent VTE than in patients with a suspected first thromboembolic event. Further studies are needed to assess if a change in the D-dimers cut-off could improve diagnostic yield.

Influence of CYP3A4*22 and CYP3A5*3 combined genotypes on tacrolimus dose requirements in Egyptian renal transplant patients.

Tacrolimus is a widely prescribed immunosuppressant agent for kidney transplantation. However, optimal dosing is challenging due to its narrow therapeutic index, potentially serious adverse effects, and wide inter-individual variability in pharmacokinetics. Cytochrome P450 3A (CPY3A) enzymes metabolize tacrolimus, so allelic variants such as CYP3A4*22 and CYP3A5*3 may contribute to individual differences in pharmacokinetics and therapeutic efficacy of tacrolimus. This study assessed the frequency and influences of CYP3A4*22 and CYP3A5*3 genotypes, alone and combined, on tacrolimus pharmacokinetics and dose requirements in Egyptian kidney transplant patients. This is a prospective multicenter observational cohort study. Patients were genotyped for the CYP3A4*22 (rs35599367), and CYP3A5*3 (rs776746). Tacrolimus dose (mg), through blood level (ng/ml), and dose-adjusted trough concentration (C0/D) (ng/ml per mg/kg) were recorded during the first and third months post-transplantation and compared among genotype groups. The CYP3A4*22 allele was rare (3.2% of subjects) while the CYP3A5*3 allele was widespread (90.38%) in this cohort. At the third month post-transplantation, median C0/D was significantly higher among CYP3A4*22 carriers than CYP3A4*1/*1 (146.25 [100-380] versus 85.57 [27-370] ng/ml per mg/kg, p= 0.028). Patients harbouring the one copy of the CYP3A4*22 allele and the CYP3A5*3/*3 genotype (n= 5) were classified as poor tacrolimus metabolizers, the CYP3A5*3/*3 plus CYP3A4*1/*1 genotype as intermediate metabolizers (n= 60), and the CYP3A4*1/*1 plus CYP3A5*1/*1 genotype as normal metabolizers (n= 13). During the first month post-transplantation, C0/D was significantly greater in poor metabolizers (113.07 ng/ml per mg/kg) than intermediate and normal metabolizers (90.380 and 49.09 ng/ml per mg/kg) (p< 0.0005). This rank order was also observed during the third month. Acute rejection rate and renal function at discharge did not differ among genotypes. Pharmacogenetics testing for CYP3A4*22 and CYP3A5*3 before renal transplantation may help in the adjustment of tacrolimus starting dose and identify patients at risk of tacrolimus overexposure or underexposure.

Opioid PrEscRiptions and usage After Surgery (OPERAS): protocol for a prospective multicentre observational cohort study of opioid use after surgery

IntroductionPostoperative pain is common and frequently addressed through opioid analgesia. This practice must balance the benefits of achieving adequate pain relief against the harms of adverse effects such as opioid-induced...