Adult Acute Patients Research Articles

Undergraduate acute care clinical competencies for managing acute care cases in adult patients within a South African in-hospital environment: A modified Delphi Study

IntroductionWith the increase of global population, there has been an increased demand for acute care services both locally and globally. In the absence of an acute care competency-based curriculum in South Africa, this study sought to identify the core competencies required by undergraduate medical students to safely manage adult patients within an acute care setting in a South African hospital environment. MethodologyThe modified Delphi study comprised of three rounds. The traditional Delphi method, which uses the same participants across various rounds, was modified by using different stakeholders across the three rounds. Emergency Medicine (EM) specialist trainees (registrars) generated competencies in round one, which were provided to a multi-disciplinary team with expertise in undergraduate curriculum development in round two, using a 5-point Likert scale for rating their agreement-disagreement. Round three entailed inviting the round one contributors to anonymously comment, via online survey, on the competencies generated in round two. ResultsA total of 34 EM registrars participated during round one and 7 curriculum development experts participated during round two. A total of 120 competencies were identified from the 3-round Delphi study; of these 103 (85.8%) were reached by “Strong Agreement”; 16 (13.3%) reached by “Agreement”; and 1 (0.8%) was undecided. DiscussionThe results of the modified Delphi study contributed to developing a comprehensive list of undergraduate acute care clinical competencies set in a South African context. The value of engaging with medical practitioners at the forefront of delivering acute care in a South African healthcare environment who are exposed on a daily basis to the healthcare needs of society, became evident. The findings of this study highlight and reinforce the importance of contextual relevance during the curriculum development process. ConclusionThe modified Delphi method, based on three iterative rounds and feedback from experts, was effective in reaching consensus on the competencies required by undergraduate medical students to manage acute care adult patients safely within a South African hospital environment.

AML-284 Feasibility of Outpatient Induction in Adolescent and Adult Acute Patients With Myeloid Leukemia in a High-Volume Centre

AML-284 Feasibility of Outpatient Induction in Adolescent and Adult Acute Patients With Myeloid Leukemia in a High-Volume Centre

Feasibility of Outpatient Induction in Adolescent and Adult Acute Patients With Myeloid Leukemia in a High-Volume Centre

Feasibility of Outpatient Induction in Adolescent and Adult Acute Patients With Myeloid Leukemia in a High-Volume Centre

Incidence and outcomes of in-hospital nutritional decline: A prospective observational cohort study in adult patients

Background and AimsHospital malnutrition is associated with higher healthcare costs and worse outcomes. Only a few prospective studies have evaluated trends in nutritional status during an acute stay, but these studies were limited by the short timeframe between nutrition assessments. The aim of this study was to investigate changes in nutritional status, incidence of hospital-acquired malnutrition (HAM), and the associated risk factors and outcomes in acute adult patients admitted for >14 days. MethodsA prospective observational cohort study was conducted in two medical and two surgical wards in a tertiary hospital in Brisbane, Australia. Nutrition assessments were performed using the Subjective Global Assessment at baseline (day eight) and weekly until discharge. Nutritional decline was defined as a change from well-nourished to moderate/severe malnutrition (HAM) or from moderate to severe malnutrition (further decline) >14 days after admission. ResultsOne hundred and thirty patients were included in this study (58.5% male; median age 67.0 years (IQR 24.4), median length of stay 23.5 days (IQR 14)). At baseline, 70.8% (92/130) of patients were well-nourished. Nutritional decline occurred in 23.8% (31/130), with 28.3% (26/92) experiencing HAM. Of the patients with moderate malnutrition on admission (n = 30), 16% (5/30) continued to decline to severe malnutrition. Improvement in nutritional status from moderate and severe malnutrition to well-nourished was 18.4% (7/38). Not being prescribed the correct nutrition care plan within the first week of admission was an independent predictor of in-hospital nutritional decline or remaining malnourished (OR 2.3 (95% CI 1.0–5.1), p = 0.039). In-hospital nutritional decline was significantly associated with other hospital-acquired complications (OR 3.07 (95% CI 1.1–8.9), p = 0.04) and longer length of stay (HR 0.63 (95% CI 0.4–0.9), p=0.044). ConclusionThis study found a high rate of nutritional decline in acute patients, highlighting the importance of repeated nutrition screening and assessments during hospital admission and proactive interdisciplinary nutrition care to treat or prevent further nutritional decline.

What is the existing evidence base for adult medical same day emergency care in UK NHS hospitals? A scoping review protocol

ObjectivesSame day emergency care (SDEC) is a new model of care, which has emerged over the past 5 years, building on prior ambulatory care services. The National Health Service (NHS)...

An open-label randomized controlled trial of leflunomide in patients with acute SARS-CoV-2 omicron variant infection.

To evaluate the efficacy and safety of leflunomide for the treatment of acute, symptomatic COVID-19. A single-center, open-label, randomized controlled trial was performed during an outbreak of SARS-CoV-2 Omicron variant in December 2022. Symptomatic patients within 5 days of COVID-19 onset were randomly allocated to receive 5 days of either symptomatic treatment with leflunomide or symptomatic treatment alone. The primary endpoint was time to sustained clinical recovery. Fifty-seven participants were randomized into two groups: 27 received leflunomide plus symptomatic treatment and 30 were assigned to symptomatic treatment alone. Participants treated with leflunomide had a shorter fever duration [3.0 interquartile range (IQR, 2.0-4.0) days and 4.0 (IQR, 3.0-6.0) days, respectively (p = 0.027)] and reduced viral shedding [7 (IQR, 6-9.5) days and 9.0 (IQR, 7.5-12.0) days, respectively (p = 0.044)] compared with individuals treated with symptomatic treatment alone. However, there were no significant differences in time to sustained clinical recovery between the two groups [hazard ratio, 1.329 (95% confidence interval, 0.878-2.529); p = 0.207]. In acute adult COVID-19 patients presenting within 5 days of symptom onset, leflunomide combined with symptomatic treatment reduced fever duration and viral shedding time. https://www.chictr.org.cn/about.html, ChiCTR2100051684.

Photodynamic therapy (pdt) in early stages of acute adult covid-19 patients: effects on viral load measured by qpcr

Background: The Covid-19 pandemic has negatively impacted Global Health and the world’s economy dramatically since early 2020. Although the development of vaccines has made fast progress, there are currently only a few effective medications and treatment options available for infected patients available. Objectives: The objective of this study was to evaluate the efficacy and safety of Photodynamic Therapy (PDT) with Riboflavin and a specially designed light treatment kit with blue and UVA light as a treatment tool for reducing viral load and clinical symptoms in patients with early stage Covid-19 infection. Methods: This interventional, non-randomized study involved 140 adult subjects. Participants were allocated to receive either PDT plus daily testing for 5 days or to receive conventional care plus testing. The viral load in the oral and nasal cavity and clinical symptoms were measured at the start of the study and after 24,48,72,96,120 and 168 hours. Results: The mean CT value in the treatment group was 29.63 at day 1 and 36.3 at day 5, for a difference of 6.68 threshold cycles and a confidence interval of [5.2;8.72]. Based on Welch’s t-test for two samples, this difference was significant (p<0.01). The same test showed no difference in the means of the control group. Further analysis showed a significant difference between the treatment and control group in the clinical symptoms after 5 days as well, when controlled for the differences at the beginning. Conclusion: PDT decreases viral load and improves clinical symptoms in patients in early stages of Covid-19 significantly. It could be a promising tool for treatment of acutely infected patients in early stages to prevent progression of disease.

The Neurobiology of Anorexia Nervosa and Abnormal Reward Learning Processes: A Systematic Review

Abstract
 Objective: Given the array of neuroimaging studies examining the neurobiology of anorexia nervosa, the purpose of this paper was to further highlight localized neurobiological abnormalities when examining reward learning pathways in patients suffering from AN.
 Methods: Literature searches using PsycINFO, EMBASE, and MEDLINE were conducted in March of 2022 using search terms relating to AN, reward learning, and neuroimaging. Relevant studies that were included must be written in English, have at least one clinical sample of either acute and/or recovered adult and/or adolescent female patients with anorexia nervosa, be controlled studies with a healthy female control group, be published in a peer-reviewed journal, and containing a neuroimaging component.
 Results: For this systematic review, 20 relevant studies were included to elucidate the brain regional and functional differences with respect to reward learning pathways in individuals with AN when compared to healthy controls. These differences include dopamine neuron and cortisol release abnormalities in relation to dopaminergic pathways, as well as regional differences involved in reward learning subconstructs that include reward expectancies, punishment sensitivity, social reward, and body dissatisfaction and body image distortion.
 Conclusion: In examining the brain regional and functional differences across individuals with AN with respect to the reward learning construct, further research efforts that focus on these important reward learning abnormalities might help inform the development of new clinical interventions aimed at these particular pathways.

Efficacy and safety of sacubitril valsartan in heart failure compared to renin angiotensin aldosterone system inhibitors: a systematic review and meta analysis of randomised controlled trials

Abstract Background Benefits and harms of the use of LCZ696 (sacubitril/valsartan, S/V), a combination of a neprilysin inhibitor and an angiotensin receptor blocker (ARB), in heart failure (HF) are unknown. Purpose To systematically assess benefits and harms of S/V as compared to angiotensin converting enzyme inhibitors (ACEI) or ARB in patients with HF. Methods We searched for randomised controlled trials (RCTs) evaluating S/V vs. ACEI or ARB in acute or chronic HF adult patients. Primary outcomes were HF hospitalisation and cardiovascular [CV] mortality; secondary outcomes were all-cause mortality, decline in renal function, myocardial dysfunction, quality of life (QoL), systolic blood pressure (SBP), diastolic blood [DBP], and adverse events (AEs) including worsening renal function (SCr≥2 mg/dL), hyperkalaemia (K+≥5.5 mmol/L), symptomatic hypotension (SBP<100 mmHg), and angio-oedema. Inverse variance random-effects meta-analyses were conducted and effects expressed as hazard ratios (HR), relative risks (RR) or mean difference (MD) and their 95% confidence intervals (CI). GRADE methodology was used to assess the certainty of evidence (CoE). Results We selected 11 RCTs (n=18766). Follow-up times ranged between 2 and 48 months; the average age of participants was 61 to 73 years-old. Five RCTs had ACEIs as control, five RCTs had ARBs as control, and one RCT had both ACEI and ARB as control. Six RCTs had low risk of bias; five RCTs had unclear risk of bias. S/V reduced the hazard of HF hospitalisations by 20% (HR 0.80, 95% CI 0.68–0.94; 3 RCTs; I2=65%; high CoE), CV mortality by 14% (HR 0.86, 95% CI 0.73 to 1.01; 2 RCTs; I2=57%; high CoE) and all-cause mortality by 11% (HR 0.89, 95% CI 0.78–1.00; 3 RCTs; I2=36%; high CoE) compared to ACEI or ARB control (Figure 1). S/V slightly improved KCCQ-QoL scores (MD 1.36 points, 95% CI 0.49 to 2.24; 6 RCTs; I2=54%). S/V did not affect LVEF and E/E' but reduced NTproBNP (SMD −0.34, 95% CI −0.52 to −0.16; 3 RCTs; I2=62%), and hs-TNT (Ratio of differences 0.84, 95% CI 0.79–0.88; 2 RCTs; I2=0%). SBP and DBP were reduced by 4 mmHg and 3 mmHg, respectively, and hypotension was increased (RR 1.69, 95% CI 1.33–2.15; 9 RCTs; I2=65%; high CoE) with S/V. Also, S/V reduced the hazard of decline in renal function by 33% (HR 0.67, 95% CI 0.39–1.14; 2RCTs; I2=78%; high CoE); hyperkalaemia and angioedema events were similar between S/V and controls. Conclusions Sacubitril/valsartan had better clinical and intermediate outcomes in HF in comparison to ACEI or ARB. Decline of renal function was less frequent with S/V in comparison to controls, and there was no difference in decline of renal function or angioedema and hyperkalaemia events. However, sacubitril/valsartan was associated with more symptomatic hypotension events vs. controls. Funding Acknowledgement Type of funding sources: None.

Efficacy and safety of Tanreqing oral liquid in treatment of acute bronchitis: study protocol for a randomized controlled trial

BackgroundApproximately 5% of adults have an episode of acute bronchitis each year, accounting for more than 10 million medical visits yearly. The primary goal of treatment is reduction of symptoms. Currently, available medications are questionable in effectiveness and safety and are not recommended for routine use in clinical practice. Although Chinese herbal medicine has been widely used in the management of acute bronchitis in China, evidence-based data is lacking. This trial aims to evaluate the efficacy and safety of Tanreqing oral liquid in the treatment of acute bronchitis with phlegm-heat obstructing lungs syndrome.Methods/designThis study is a prospective, multi-center, randomized, double-blinded, parallel-group, placebo-controlled trial. A total of 270 acute bronchitis adult patients with phlegm-heat obstructing lungs syndrome will be enrolled from outpatients and emergency departments at nine study centers across China. All included patients will be randomly allocated to receive Tanreqing oral liquid or placebo oral liquid, 20 mL three times daily for seven consecutive days. The primary outcome will be cough resolution rate. Secondary outcomes will include change of bronchitis symptoms scores from baseline to post-treatment, cough relief rate, time to cough resolution, time to cough relief, resolution rate of a single symptom, combination medicine use, change of traditional Chinese medicine syndrome score from baseline to post-treatment, and adverse events.DiscussionThis trial may provide an alternative treatment option for acute bronchitis patients, especially those in outpatients and emergency departments. It may also add evidence to Chinese herbal medicine for treating acute bronchitis.Trial registrationChinese Clinical Trial Registry ChiCTR2000040264. Registered on 26 November 2020

Pilot implementation of the competence of Czech paramedics to administer sufentanil for the treatment of pain in acute trauma without consulting a physician: observational study

BackgroundThe use of intravenous opioids in the traumatic pain in pre-hospital care in the Czech Republic is based primarily on the indication of a physician. If the paramedic crew arrives at the site earlier or only on their own, analgesia is given after phone-call consultation with the physician or after his arrival at the site. The objective of this study was to evaluate the safety and efficacy of the indication and administration of sufentanil by paramedics in the treatment of pain in acute trauma adult patients without the physician’s control.MethodsParamedics underwent voluntarily the simulation training aimed at administering intravenously sufentanil to treat pain in acute trauma in adults without physician’s indication. Subsequently, the adverse events and efficacy were monitored for a six-month period and compared in two groups: administration of sufentanil by paramedics without this competence, who further consulted the administration by telephone with physicians (group Consultation) and those with this competence (group Competence).ResultsA total number of sufentanil administration in group Consultation was 88 and in group Competence 70. There was no respiratory arrest, bradypnea, or need for oxygen therapy reported in any of the study groups. The incidence of nausea was 3% in both groups – Consultation (n = 3) and in Competence (n = 2). Vomiting was not reported in the Consultation group and in 6% in the Competence group (n = 4). Intravenous antiemetic drugs were used in the Consultation group only in 1% (n = 1) and in the Competence group in 7% of patients (n = 5) (p < 0,05). In both groups there was observed a decrease in the pain numeric rating scale (Consultation: M =—3,2; SD = 1,2 points vs. Competence: M =—3,9; SD = 1,8 points).ConclusionIntravenous administration of sufentanil by properly trained paramedics without consultation with a physician in acute trauma can be considered safe.

Perioperative antibiotic prophylaxis in Australian burns patients

Background: Perioperative antibiotic prophylaxis is perceived to reduce intraoperative bacteraemia and prevent surgical site infections, however, the evidence for its use in burns surgery is limited. Excessive use of perioperative antibiotics has become a growing concern. The authors aimed to audit the prescribing practices of perioperative antibiotic prophylaxis at the Victorian Adult Burns Service and determine whether the duration of antibiotic prophylaxis influenced the risk of postoperative wound infection, bacte-raemia and antibiotic resistance. Methods: This retrospective chart review included all acute adult burns patients who had an operation between November 2018 and November 2019. Basic demographic data, burn specific data and data on perioperative antibiotic use were collected. The outcome measures were wound infection, bacteraemia, other infections and presence of resistant organisms. Results: Results demonstrated that almost all patients (98.6%) received perioperative antibiotic prophylax-is. In comparison, there was no significant difference between the rate of postoperative wound infection, bacteraemia or antibiotic resistance between patients receiving a short or long course of antibiotics. Conclusion: The results of our study demonstrate variable use of perioperative antibiotic prophylaxis with-in one burns unit. There were many cases of unsubstantiated use of long courses of antibiotics without apparent benefit for clinical outcomes of wound infection or bacteraemia. With the growing concern over antibiotic overuse and development of resistance, there is an increasing need for development of clear guidelines for antibiotic use in burns surgery.

Frontline Consolidation with Blinatumomab for High-Risk Philadelphia-Negative Acute Lymphoblastic Adult Patients. Early Results from the Graall-2014-QUEST Phase 2

Introduction: Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) with high-risk genetics and/or measurable residual disease (MRD) are at high-risk of disease recurrence. In the previous GRAALL-2005 study, we identified KMT2A rearrangements (KMT2A-r), IKZF1 intragenic deletion (IKZF1del) and post-induction (TP1, week 6) MRD ≥ 0.01% as independent factors to predict relapse in Ph-negative B-cell precursor (BCP) ALL (Beldjord K, Blood 2014). In the GRAALL-2014 trial, high-risk (HR) patients were thus defined by the presence of at least one of these three factors. Among them, only those with higher MRD levels defined as TP1-MRD ≥ 0.1% and/or week 12 (TP2) MRD ≥ 0.01% were considered at very high risk (VHR) and proposed allogeneic hematopoietic stem cell transplant (alloSCT) in first remission (Dhedin et al., Blood 2015). Since October 2018, all these patients were eligible to be included in the GRAALL-2014-QUEST phase 2 study to receive blinatumomab as part of consolidation and maintenance phases or as a bridge to transplant.Methods: From October 2018 to December 2020, 95 patients with high-risk Ph-negative BCP-ALL without central nervous system involvement at diagnosis and in continuous complete remission after induction and consolidation 1, were prospectively included to start blinatumomab at week 12. One patient was excluded because of T-ALL phenotype (with CD19 aberrant expression). Patients with alloSCT indication and a stem cell source received blinatumomab 28 microg/d administered by continuous intravenous infusion (cIV) until transplant. A minimum of 4 weeks blinatumomab was recommended before proceeding to transplantation. All other patients received 5 cycles of blinatumomab 28 microg/day cIV (for 28 days), during consolidation 2 and 3 and at months 1/3/5 of the maintenance phase respectively. The primary objective was disease-free survival (DFS). Secondary objectives included post-blinatumomab MRD response at TP3 (after consolidation 2 or before alloSCT), overall survival (OS), and safety. Early results are reported here.Results: Median age was 35 years old (range, 18-60). Median white blood cell count (WBC) at diagnosis was 12 G/L (range, 1-449). Oncogenetic analyses allowed classifying ALL as Ph-like (18%), KMT2A-r (17%), DUX4/ERGdel (13%), ZNF384-r (11%), low hypodiploidy/near triploidy (7%), B-other (26%) or unknown (9%). An IKZF1del was found in 37/93 (40%). A TP1-MRD ≥ 0.01% was found in 46/94 patients (49%). Final risk group was HR for 45 patients and VHR for 49 patients. Last pre-blinatumomab MRD was <0.01% in 49/88 (56%) of evaluable patients. A total of 40 patients (42%) received an alloSCT. The median number of blinatumomab cycles received in patients not proceeding to alloSCT was 4 cycles (range, 1-5). Thirty-nine severe adverse events (SAEs) were reported: 1 CRS (grade 2), 8 neurotoxicities (1 grade 2, 3 grade 3, 3 grade 4, 1 grade 5), 19 infections, and 11 others. The only grade 5 SAE occurred after alloSCT (seizures). After blinatumomab, a complete MRD response (with at least 0.01% sensitivity) was achieved in 61/82 (74%) evaluable patients and in evaluable patients with pre-blinatumomab detectable MRD. MRD response to blinatumomab was lower in patients with high pre-blinatumomab MRD level, while not impacted by age, WBC, or oncogenic subgroup. With a median follow-up of 20 months, 18-month DFS and OS was 78.8% (95% CI [66.9-86.8]) and 92.1% (95% CI [83.2-96.4]) respectively (Figure 1). Patients with VHR diseases had a worse DFS (68.8%, 95% CI [51.1-81.2]) as compared to other patients (90.6%, 95% CI [72.1-97.1]); p=0.018). This difference of DFS was abrogated by censoring patients at transplant (VHR 88.1%, 95% CI [65.5-96.3] versus others 90.6%, 95% CI [72.1-97.1%], p=0.10). Other factors significantly associated with better DFS were DUX4/ERGdel subgroup, low pre-blinatumomab MRD, and complete MRD response after blinatumomab.Conclusion. In patients wih high-risk BCP-ALL, blinatumomab added to consolidation is safe and gives promising results. A comparison to similar patients treated in the same GRAALL-2014 study before October 2018 is planned with a longer follow-up. [Display omitted] DisclosuresBoissel: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; SANOFI: Honoraria; Servier: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; CELGENE: Honoraria; JAZZ Pharma: Honoraria, Research Funding; PFIZER: Consultancy, Honoraria. Huguet: Novartis: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Celgene: Other: Advisor; BMS: Other: Advisor; Amgen: Other: Advisor; Pfizer: Other: Advisor. Rousselot: Incyte, Pfizer: Consultancy, Research Funding. Chalandon: Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Amgen: Other: Advisory Board; Incyte: Speakers Bureau; Incyte, BMS, Pfizer, Abbie, MSD, Roche, Novartis, Gilead, Amgen, Jazz, Astra Zenec: Other: Travel EXpenses, Accomodation. Delabesse: Astellas: Consultancy; Novartis: Consultancy. Dombret: Abbvie: Honoraria; Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; NOVARTIS: Research Funding; pfizer: Honoraria, Research Funding; servier: Research Funding; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. OffLabel Disclosure:Blinatumomab in frontline high-risk acute lymphoblastic leukemia

Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma

AbstractTisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; we examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 validated assays. Data were pooled from the ELIANA (registered at www.clinicaltrials.gov as #NCT02435849) and ENSIGN (#NCT02228096) trials in r/r B-ALL (N = 143) and the JULIET trial (#NCT02445248) in r/r DLBCL (N = 115). Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum. Cellular responses were determined using T-cell production of interferon-γ in response to 2 different pools of mCAR19 peptides. Pretreatment anti-mCAR19 antibodies were detected in 81% of patients with r/r B-ALL and 94% of patients with r/r DLBCL. Posttreatment anti-mCAR19 antibodies were higher than patient-specific baseline in 42% of r/r B-ALL and 9% of r/r DLBCL patients. Pretreatment and posttreatment anti-mCAR19 antibodies did not affect tisagenlecleucel cellular kinetics, including maximum concentration and persistence (r2 < 0.05), clinical response (day-28 response, duration of response, and event-free survival), and safety. T-cell responses were consistent over time, with net responses <1% at baseline and posttreatment time points in a majority of patients and no effect on transgene expansion or persistence or outcomes. Presence of baseline and/or posttreatment anti-mCAR19 antibodies or T-cell responses did not alter the activity of tisagenlecleucel in patients with r/r B-ALL or r/r DLBCL.

Organ failure, aetiology and 7-day all-cause mortality among acute adult patients on arrival to an emergency department: a hospital-based cohort study.

Organ failure is both a frequent and dangerous condition among adult patients on arrival to an emergency department (ED). The risk of an unfavourable outcome could depend on the underlying aetiology. Knowledge of the relation between aetiology and prognosis could improve the risk stratification at arrival. To describe the relation between organ failure, aetiology and prognosis through 7-day all-cause mortality. An observational three-year cohort study at the ED at Odense University Hospital, Denmark, including all acute adult patients.First-measured vital signs and laboratory values were included to evaluate the presence of the following organ failures: respiratory, coagulation, hepatic, circulatory, cerebral or renal.The primary outcome was 7-day all-cause mortality. Aetiological disease categories were based on primary discharge diagnoses. We described the association between 7-day mortality, aetiology category, site of organ failures and number of patients at risk. Of 40 423 patients with a first-time visit at the ED, 5883(14.6%) had an organ failure on arrival. The median age was 69 (IQR 54-80), and 50% were men. The most frequent aetiology was infection (1495, 25.4%). Seven-day all-cause mortality ranged between aetiologies from 0.0% (95% confidence interval [CI], 0.0-14.2) allergy) to 45.6% (95% CI, 41.3-50.0) (cardiac). Combining aetiology and site of organ failure, 7-day all-cause mortality was the highest in the cardiac category, from 14.8% (95% CI, 4.2-3.7) with hepatic failure to 79.2% (95% CI, 73.6-84.1) with cerebral failure. The combination of infection and respiratory failure characterised most patients (n = 949). Infection was the most prevalent aetiology, and 7-day all-cause mortality was highly associated with the site of organ failure and aetiology.

HESTER: A Phase II Study Evaluating Efficacy and Safety of Tisagenlecleucel Reinfusion in Pediatric and Young Adult Patients with Acute Lymphoblastic Leukemia Experiencing Loss of B-Cell Aplasia

Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR)-T cell therapy approved for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma. The ELIANA trial showed efficacy (81% overall remission rate [ORR]; 60% complete remission [CR]) and safety of tisagenlecleucel in r/r B-ALL (Maude et al. N Engl J Med. 2018). In the ELIANA trial, sustained remissions were associated with B-cell aplasia, an expected on-target effect of tisagenlecleucel and a pharmacodynamic marker for tisagenlecleucel persistence. In some patients who demonstrated short CAR-T cell persistence, reinfusion with 1 or more additional doses of tisagenlecleucel has restored B-cell aplasia and produced a 60% CR rate in patients who were reinfused with humanized CD19-targeted CAR-T cell therapy (Maude et al. J Clin Oncol. 2016). This prolongs the period of tisagenlecleucel activity and immunosurveillance and may therefore prolong durable remission. We introduce a trial in progress investigating the efficacy and safety of tisagenlecleucel reinfusion in pediatric and young adult patients with B-ALL experiencing a loss of B-cell aplasia. Study Design and Methods: HESTER (NCT04225676) is a phase II, open-label, multicenter trial to determine the efficacy and safety of tisagenlecleucel reinfusion in pediatric and young adult patients with B-ALL experiencing loss of B-cell aplasia. Eligible patients must be ≤25 years of age with a confirmed diagnosis of CD19(+) leukemia. Patients must have been previously infused with commercial tisagenlecleucel and have at least 1 additional dose of commercial tisagenlecleucel prescribed to them in the course of medical practice. Commercial tisagenlecleucel must be given for reinfusion within 9 months of the initial manufacturing date. Patients must have loss of B-cell aplasia defined as peripheral blood (PB) absolute B lymphocyte count ≥50/μL or PB B lymphocyte ≥10% of the total lymphocytes; patients are not required to be minimal residual disease negative (MRD)(-). Karnofsky (age ≥16 years) or Lansky (age &amp;lt;16 years) performance status must be ≥50 at screening. Patients treated with prior gene/adoptive T-cell therapy other than tisagenlecleucel and patients with active central nervous system involvement by malignancy are excluded. The primary efficacy endpoint is the proportion of patients who reestablish B-cell aplasia within 12 months of reinfusion as measured by circulating B lymphocytes (&amp;lt;50/μL) and presence of tisagenlecleucel cells by quantitative polymerase chain reaction (qPCR) in the PB. Secondary outcomes include the ORR (CR + CR with incomplete blood count recovery) during the 12 months post reinfusion, event-free survival, overall survival, MRD status, and safety; immunogenicity and tisagenlecleucel persistence (by qPCR) are exploratory endpoints. Subgroup analysis of efficacy outcomes will include patients with a loss of B-cell aplasia within 9 months of first infusion who are MRD(+) at time of enrollment, as well as patients with very early (&amp;lt;3 mo), early (≤3 to &amp;lt;6 mo), and later (≥6 mo) loss of B-cell aplasia following first infusion. Safety will be assessed throughout the trial. For the primary analysis, a minimum of 10% of patients reestablishing B-cell aplasia within 12 months after reinfusion is expected with an estimated true rate of 25%. All secondary and exploratory variables will be summarized descriptively. Estimated enrollment is about 54 patients in the United States. Clinical Trial Information: NCT04225676 Disclosures Boyer: Thunder Biotech Inc: Consultancy. Grupp:Servier: Research Funding; Cellectis: Other; Roche: Consultancy; Adaptimmune: Other: SAB; Jazz: Other: SSC; TCR2: Other: SAB; GlaxoSmithKline: Consultancy; CRISPR Therapeutics/Vertex Pharmaceuticals: Other; Juno/BMS: Other; Janssen/JnJ: Consultancy; Humanigen: Consultancy; CBMG: Consultancy; Kite/Gilead: Research Funding; Allogene: Other; Novartis: Consultancy, Other: SSC, Research Funding. Hermiston:Novartis: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees. Kovacs:Novartis: Current Employment. Magley:Novartis: Current Employment. Myers:Novartis: Consultancy, Honoraria, Other: ELIANA trial Steering Committee, Speakers Bureau. Phillips:Novartis: Membership on an entity's Board of Directors or advisory committees. Pulsipher:Bellicum: Honoraria; Mesoblast: Honoraria; Miltenyi: Honoraria, Research Funding; Adaptive: Research Funding; Novartis: Honoraria; Jasper: Honoraria. Purkayastha:Novartis: Current Employment. Willert:Novartis: Current Employment.

Level of vital and laboratory values on arrival, and increased risk of 7-day mortality among adult patients in the emergency department: a population-based cohort study

ObjectivesThe aim of the study was to provide evidence for, at which vital and laboratory values, increased risk of 7-day mortality in acute adult patients on arrival to an emergency...

Crucial role of physiotherapy in treating COVID-19 patients

The emergence in China of 2019 of severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) previously provisionally names 2019-nCoV disease (COVID19) caused major global outbreak and is a major public health problem. On 30 January 2020, the WHO declared COVID19 to be the sixth international public health emergency. This present pandemic has engrossed the globe with a high rate of mortality. As a front line practitioner, physiotherapists are expected to be getting in direct contact with patients infected with the virus. That’s why it is necessary for understanding the many aspects of their role in the identification, contains, reduces and treats the symptoms of this disease. The main presentation is the involvement of respiratory system with symptoms like fever, cough, sore throat, sneezing and characteristics of pneumonia leads to ARDS(Acute respiratory distress syndrome) also land up in multiorgan dysfunction syndrome. This text describes and suggests physiotherapy management of acute COVID-19 patients. It also includes recommendations and guidelines for physiotherapy planning and management. It also covers the guidelines regarding personal care and equipment used for treatment which can be used in the treatment of acute adult patients with suspected or confirmed COVID-19.

Evaluation of C-reactive protein and myxovirus resistance protein A to guide the rational use of antibiotics among acute febrile adult patients in Northwest Ethiopia

ObjectivesIn low-resource settings, treatment is often given empirically without knowledge of the aetiology due to a lack of diagnostics. In the search for reliable rapid tests to guide treatment work-up, this study was performed to determine whether two biomarkers could differentiate bacterial from non-bacterial infections in acute febrile patients. MethodsAdults with acute fever were recruited at a referral hospital in Ethiopia. The QuikRead Go test was used to quantify C-reactive protein (qCRP) and the FebriDx test was used for combined qualitative detection of the bacterial CRP marker with myxovirus resistance protein A (MxA), a viral biomarker. ResultsOf the 200 patients included in this study, most presented with 2–3 days of fever, headache, and joint pain. Antibiotics were prescribed for 83.5% and antimalarials for 36.5%, while a bacterial infection was only confirmed in 5% and malaria in 11%. The median qCRP level for confirmed bacterial infections was 128 mg/l. The FebriDx and QuikRead Go test had an overall agreement of 72.0%. ConclusionsAn over-prescription of antibiotics for febrile patients was observed, even for those with low CRP levels and without a confirmed bacterial infection. The added value of the FebriDx was limited, while the combined use of rapid tests for qCRP and malaria should be considered for the management of acute febrile illness and antibiotic stewardship.

Analysis of Time-Course, Dose-Effect, and Influencing Factors of Antidepressants in the Treatment of Acute Adult Patients With Major Depression.

ObjectiveModel-based meta-analysis was used to describe the time-course and dose-effect relationships of antidepressants and also simultaneously investigate the impact of various factors on drug efficacy.MethodsThis study is a reanalysis of a published network meta-analysis. Only placebo-controlled trials were included in this study. The change rate in depression rating scale scores from baseline was used as an efficacy indicator because a continuous variable is more likely to reflect subtle differences in efficacy between drugs.ResultsA total 230 studies containing 64 346 patients were included in the analysis. The results showed that the number of study sites (single or multi-center) and the type of setting (inpatient or noninpatient) are important factors affecting the efficacy of antidepressants. After deducting the placebo effect, the maximum pure drug efficacy value of inpatients was 18.4% higher than that of noninpatients, and maximum pure drug efficacy value of single-center trials was 10.2% higher than that of multi-central trials. Amitriptyline showed the highest drug efficacy. The remaining 18 antidepressants were comparable or had little difference. Within the approved dose range, no significant dose-response relationship was observed. However, the time-course relationship is obvious for all antidepressants. In terms of safety, with the exception of amitriptyline, the dropout rate due to adverse events of other drugs was not more than 10% higher than that of the placebo group.ConclusionThe number of study sites and the type of setting are significant impact factors for the efficacy of antidepressants. Except for amitriptyline, the other 18 antidepressants have little difference in efficacy and safety.