Exclusive Oral Antibiotic Treatment for Hospitalized Community-Acquired Pneumonia: A Post-Hoc Analysis of a Randomized Clinical Trial.

OBJECTIVES: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). METHODS: In this post-hoc analysis of a RCT on patients hospitalized for CAP (PTC trial) comparing 3-day versus 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). Choice of route and molecule was left to the physician in charge. The main outcome was failure at 15 days after first antibiotic intake, defined as temperature>37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to route of administration was evaluated through logistic regression. Inverse probability treatment weighting (IPTW) with a propensity score model was used to adjust for non-randomization of treatment route and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC versus 3GC treatments, or intravenous versus oral AMC, patients with multi-lobar infection, patients aged ≥ 65 years old, and patients with CURB65 scores of 3-4). RESULTS: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. Failure rate at Day 15 was not significantly different among patients treated with initial intravenous versus oral treatment (25/93 (26.9%) versus 28/107 (26.2%), aOR 0.973 (95%CI 0.519-1.823), p=0.932). Failure rates at Day 15 were not significantly different among the subgroup populations. CONCLUSIONS: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT01963442.

Severe asthma exacerbation: Changes in patient characteristics, management, and outcomes from 1997 to 2016 in 40 ICUs in the greater Paris area.

Background: Despite advances in asthma treatments, severe asthma exacerbation (SAE) remains a life-threatening condition in adults, and there is a lack of data derived from adult patients admitted to intensive care units (ICUs) for SAE. The current study investigated changes in adult patient characteristics, management, and outcomes of SAE over a 20-year period in 40 ICUs in the greater Paris area. Methods: In this retrospective observational study, admissions to 40 ICUs in the greater Paris area for SAE from January 1, 1997, to December 31, 2016 were analyzed. The primary outcome was the proportion of ICU admissions for SAE during 5-year periods. Secondary outcomes were ICU and hospital mortality, and the use of mechanical ventilation and catecholamine. Multivariate analysis was performed to assess factors associated with ICU mortality. Results: A total of 7049 admissions for SAE were recorded. For each 5-year period, the proportion decreased over time, with SAE accounting for 2.84% of total ICU admissions (n=2841) between 1997 and 2001, 1.76% (n=1717) between 2002 and 2006, 1.05% (n=965) between 2007 and 2011, and 1.05% (n=1526) between 2012 and 2016. The median age was 46 years (interquartile range [IQR]: 32-59 years), 55.41% were female, the median Simplified Acute Physiology Score II was 20 (IQR: 13-28), and 19.76% had mechanical ventilation. The use of mechanical ventilation remained infrequent throughout the 20-year period, whereas the use of catecholamine decreased. ICU and hospital mortality rates decreased. Factors associated with ICU mortality were renal replacement therapy, catecholamine, cardiac arrest, pneumothorax, acute respiratory distress syndrome, sepsis, and invasive mechanical ventilation (IMV). Non-survivors were older, had more severe symptoms, and were more likely to have received IMV. Conclusion: ICU admission for SAE remains uncommon, and the proportion of cases decreased over time. Despite a slight increase in symptom severity during a 20-year period, ICU and hospital mortality decreased. Patients requiring IMV had a higher mortality rate.

Risk of cardiovascular disease decreases over time in psoriatic arthritis but not in spondylarthritis: meta-analysis of longitudinal studies.

OBJECTIVES: Spondyloarthritis (SpA) and psoriatic arthritis (PsA) represent two frequent inflammatory rheumatic disorders, characterized by an increased burden on quality of life, due to the association of several comorbidities, especially cardiovascular diseases (CVD). The estimated prevalence of CVD ranges from 12-19% and differ between the two diseases, however, its incidence is not completely known. We aimed to systematically review the literature (SLR) and perform a meta-analysis of controlled observational studies to assess the incidence rate of CVD over time, separately in SpA and PsA. METHODS: We performed a SLR of longitudinal studies with a study period of at least 5 years, including SpA/PsA patients and general population. The main outcome was the occurrence of CVD, including ischemic heart disease, stroke, and death from CV cause. We then performed a random-effect model for meta-analysis. RESULTS: The SLR included 34 articles, mainly focused on the association between SpA/PsA and CVD. Twenty-four articles were then selected for the meta-analysis. The overall incidence of CVD was increased in PsA (HR: 1.28, 95%CI: 1.15-1.43), and in SpA (HR: 1.45, 95%CI: 1.22-1.72) compared with the general population, with consistency across the different types of CVD; Interestingly the incidence tended to decrease over time in PsA, but not in SpA. CONCLUSION: The SLR and meta-analysis confirmed the increased incidence of CVD in both SpA and PsA patients compared with the general population during the last years, although such increase seems to be less prominent in PsA than in SpA. Future studies are needed to confirm such tendence.

Development and initial validation of a screening tool for visual ability/performance of people with polyhandicap.

BACKGROUND: Visual impairments are common in people with polyhandicap although they are poorly assessed. However, evaluation of the visual abilities of these people is critical to determining treatment for impairments. OBJECTIVES: To develop and validate an easy-to-use visual-behavioural scale for assessing the visual abilities of people with polyhandicap. METHODS: The development of the Visual Assessment for People with Polyhandicap (VA-PLH) involved 2 steps: i) construction of the scale and ii) field validation. Participant selection criteria were aged > 3 years, age at onset of cerebral lesion < 3 years, a combination of motor impairment and profound intellectual impairment associated with restricted mobility (Gross Motor Function Classification System levels [GMFCS] III, IV or V), and everyday life dependence (Functional Independency Measure [FIM] <55). Vision assessment by both an orthoptist and an ophthalmologist was the reference against which were analysed the items of the scale completed by local health care workers. Acceptability, validity, and reliability were analysed. RESULTS: Amongst the 232 participants included, 217 had a complete assessment, and 33% were < 18 years of age. Ocular abnormalities were reported in 83% of participants. Visual ability was altered or insufficient in 60% of participants. The final version of the VA-PLH included 3 items related to visual reaction (Area Under Curve Receiver Operating Characteristic = 0.83). Participants were considered at-risk if they had at ≥ 1 of 3 signs present (sensitivity 83% and specificity 73%). The scale's reliability was satisfactory CONCLUSION: The VA-PLH scale provides an easy-to-use, reliable and valid measure of visual status for people with polyhandicap and may be used both in clinical practice and clinical research. In addition, this study provides an overview of the diversity of visual impairments in a large population of people with polyhandicap, showing that most experience visual challenges.

Construction of reference criteria to admit patients to intermediate care units in France: a Delphi survey of intensivists, anaesthesiologists and emergency medicine practitioners (first part of the UNISURC project).

OBJECTIVES: No consensus criteria describe the medical eligibility of the patients to intermediate care units (IMCUs). In this first part of the UNISURC project, we aimed to develop criteria based on a consensus of physicians from the main specialties involved in IMCU admission decisions. DESIGN: We selected criteria from IMCU literature, scoring systems and intensive care unit nursing workload. We submitted these criteria to a panel of experts in a Delphi survey. We used a two-round Delphi survey procedure to assess the validity and feasibility of each criterion. SETTING: Medical practitioners in either public or private French institutions and proposed by the national scientific societies of anaesthesiology, emergency medicine and intensive care. The Delphi rounds took place in 2015-2016. OUTCOME MEASURES: Validity and feasibility of the proposed criteria; uniformity of the judgement across the primary specialty and the hospital category of the responders. RESULTS: The criteria submitted to vote were classified as one of: chronic factor (CF); acute factor (AF); specific pathway (SP); nursing activity (NA) and hospital environment (HE). Of 189 experts invited, 81 (41%) responded to the first round and 62 of them (76%) responded to the second round. A definite selection of 63 items was made, distributed across 6 CF, 18 AF, 31 SP, 3 NA and 5 HE. Validity and feasibility were influenced by the specialty or the public/private status of the institution of the responders for a few items. CONCLUSION: We created a set of 63 consensus criteria with acceptable validity and feasibility to assess the medical eligibility of the patients to IMCUs. The second part of the UNISURC project will assess the distribution of each criterion in a prospective multicentre national cohort. TRIAL REGISTRATION NUMBER: NCT02590172.

Effect of needle orientation during arteriovenous access puncture on needed compression time after hemodialysis: A randomized controlled trial.

BACKGROUND: There are two techniques for puncturing an arteriovenous fistula: one where the needle is inserted bevel up and then rotated to a bevel down position, and another where the needle is inserted bevel down. The aim of this study was to compare these two methods of needle insertion on minimum compression time required for hemostasis after needle removal. METHODS: This was a prospective, randomized, cross-over, blinded, single-center, routine care study. Each patient's average post-dialysis puncture site compression time was determined during a 2-week baseline period while using bevel-up access puncture. Subsequently, minimum post-dialysis puncture-site compression time was determined during each of two sequential follow-up periods, during which fistula puncture was done with needles inserted bevel up or down, respectively. The order of treatments (bevel up or bevel down insertion) was randomized. During each follow-up period, the minimum compression time necessary to avoid bleeding on needle removal was determined by progressively shortening the compression time. Puncture-associated pain was also assessed as prepump and venous pressures and ability to achieve desired blood flow rate during the dialysis session. RESULTS: Forty-two patients were recruited. The baseline compression time after needle removal averaged 9.99 ± 2.7 min During the intervention periods, the minimum compression time was on average 10.8 min (9.23-12.4) when the access needles had been inserted bevel down versus 11.1 min (9.61-12.5) when the access needles had been inserted bevel up (p = 0.72). There was no difference in puncture-associated pain between the two insertion techniques, and no difference in prepump or venous pressures or ability to achieve the desired blood flow rate during the dialysis session. CONCLUSION: Bevel-up and bevel-down needle orientation during arteriovenous fistula puncture are equivalent techniques in terms of achieving hemostasis on needle removal, and puncture-associated pain.

Correction: Impact of a Postintensive Care Unit Multidisciplinary Follow-up on the Quality of Life (SUIVI-REA): Protocol for a Multicenter Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/30496.].

Assessing the implementation and effectiveness of early integrated palliative care in long-term care facilities in France: an interventional mixed-methods study protocol.

BACKGROUND: Majority of residents in long-term care facilities (LTCF) have limited and delayed access to palliative care even though many suffer from incurable chronic illnesses that will likely require the provision of palliative care. We present the study protocol of "PADI-Palli", an intervention aims to advance early integrated palliative care into standard care delivered in LTCF. This study will assess the effectiveness of early integrated palliative care on palliative care accessibility for older persons in LTCF, and identify the key factors for the successful implementation of early integrated palliative care and its sustainability in the LTCF context. METHODS: This multicentre interventional study utilises a pragmatic research design with a convergent parallel mixed-methods approach. The qualitative study will use a case study design and the quantitative study will use a stepped wedge cluster randomised trial. In total, 21 participating LTCF from three French regions will be randomly allocated to one of seven clusters. The clusters will cross over from the usual care to the active intervention condition over the course of the study. The primary outcome relates to the accurate identification of palliative care needs and early access to palliative care for LTCF residents. Secondary outcomes are quality of care, quality of life for residents and their families, and quality of life at work for professionals. Measurements will be performed before and after the intervention. Implementation and evaluation of PADI-Palli intervention is grounded in the Consolidated Framework for Implementation Research. DISCUSSION: Existing evidence demonstrates that early integrated palliative care in cancer care leads to a significant improvement in patient outcomes and processes of care. Little is known, however, about early integrated palliative care in the context of LTCF for older persons. This study has the potential to fill this gap in the literature by providing evidence on the effectiveness of early integrated palliative care for older persons in LTCF. Moreover, this study will provide a better understanding of the relevant contextual elements that facilitate or hinder early integrated palliative care implementation and transferability. If proven effective, this intervention can be scaled to other care settings in which older persons require palliative care. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04708002; National registration: ID-RCB number: 2020-A01832-37.

Impact of corticosteroids on the duration of ventilatory support during severe acute exacerbations of chronic obstructive pulmonary disease in patients in the intensive care unit: a study protocol for a multicentre, randomized, placebo-controlled, double-blind trial.

BACKGROUND: Patients who are admitted to the intensive care unit (ICU) for severe acute exacerbations of chronic obstructive pulmonary disease (COPD) have poor outcomes. Although international clinical practice guidelines cautiously recommend the routine use of systemic corticosteroids for COPD exacerbations, data are scarce and inconclusive regarding their benefit for most severe patients who require mechanical ventilation in the ICU. Furthermore, corticosteroids may be associated with an increased risk of infection, ICU-acquired limb weakness, and metabolic disorders. METHODS AND ANALYSIS: This study is an investigator-initiated, multicentre, randomized, placebo-controlled, double-blind trial comparing systemic corticosteroids to placebo during severe acute exacerbations of COPD in patients who require mechanical ventilation in French ICUs. A total of 440 patients will be randomized 1:1 to methylprednisolone (1 mg/kg) or placebo for 5 days, and stratified according to initial mechanical ventilation (non-invasive or invasive), pneumonia as triggering factor, and recent use of systemic corticosteroids (< 48 h). The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without mechanical invasive and/or non-invasive ventilation between randomization and day 28. Secondary outcomes include non-invasive ventilation (NIV) failure rate, duration of mechanical ventilation (invasive and/or NIV), circulatory support (vasopressor), outcomes related to corticosteroid adverse events (severe hyperglycaemia, gastrointestinal bleeding, uncontrolled arterial hypertension, ICU-acquired weakness, ICU-acquired infections, and delirium), lengths of ICU and hospital stay, ICU and hospital mortality, day 28 and day 90 mortality, number of new exacerbation(s)/hospitalization(s) between hospital discharge and day 90, and dyspnoea and comfort at randomization, ICU discharge, and day 90. Subgroup analyses for the primary outcome are planned according to stratification criteria at randomization.

Imatinib Optimized Therapy Improves Major Molecular Response Rates in Patients with Chronic Myeloid Leukemia.

The registered dose for imatinib is 400 mg/d, despite high inter-patient variability in imatinib plasmatic exposure. Therapeutic drug monitoring (TDM) is routinely used to maximize a drug's efficacy or tolerance. We decided to conduct a prospective randomized trial (OPTIM-imatinib trial) to assess the value of TDM in patients with chronic phase chronic myelogenous treated with imatinib as first-line therapy (NCT02896842). Eligible patients started imatinib at 400 mg daily, followed by imatinib [C]min assessment. Patients considered underdosed ([C]min < 1000 ng/mL) were randomized in a dose-increase strategy aiming to reach the threshold of 1000 ng/mL (TDM arm) versus standard imatinib management (control arm). Patients with [C]min levels ≥ 1000 ng/mL were treated following current European Leukemia Net recommendations (observational arm). The primary endpoint was the rate of major molecular response (MMR, BCR::ABL1IS ≤ 0.1%) at 12 months. Out of 133 evaluable patients on imatinib 400 mg daily, 86 patients had a [C]min < 1000 ng/mL and were randomized. The TDM strategy resulted in a significant increase in [C]min values with a mean imatinib daily dose of 603 mg daily. Patients included in the TDM arm had a 12-month MMR rate of 67% (95% CI, 51−81) compared to 39% (95% CI, 24−55) for the control arm (p = 0.017). This early advantage persisted over the 3-year study period, in which we considered imatinib cessation as a censoring event. Imatinib TDM was feasible and significantly improved the 12-month MMR rate. This early advantage may be beneficial for patients without easy access to second-line TKIs.

Impact of a Postintensive Care Unit Multidisciplinary Follow-up on the Quality of Life (SUIVI-REA): Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Critically ill patients are at risk of developing a postintensive care syndrome (PICS), which is characterized by physical, psychological, and cognitive impairments and which dramatically impacts the patient's quality of life (QoL). No intervention has been shown to improve QoL. We hypothesized that a medical, psychological, and social follow-up would improve QoL by mitigating the PICS. OBJECTIVE: This multicenter, randomized controlled trial (SUIVI-REA) aims to compare a multidisciplinary follow-up with a standard postintensive care unit (ICU) follow-up. METHODS: Patients were randomized to the control or intervention arm. In the intervention arm, multidisciplinary follow-up involved medical, psychological, and social evaluation at ICU discharge and at 3, 6, and 12 months thereafter. In the placebo group, patients were seen only at 12 months by the multidisciplinary team. Baseline characteristics at ICU discharge were collected for all patients. The primary outcome was QoL at 1 year, assessed using the Euro Quality of Life-5 dimensions (EQ5D). Secondary outcomes were mortality, cognitive, psychological, and functional status; social and professional reintegration; and the rate of rehospitalization and outpatient consultations at 1 year. RESULTS: The study was funded by the Ministry of Health in June 2010. It was approved by the Ethics Committee on July 8, 2011. The first and last patient were randomized on December 20, 2012, and September 1, 2017, respectively. A total of 546 patients were enrolled across 11 ICUs. At present, data management is ongoing, and all parties involved in the trial remain blinded. CONCLUSIONS: The SUVI-REA multicenter randomized controlled trial aims to assess whether a post-ICU multidisciplinary follow-up improves QoL at 1 year. TRIAL REGISTRATION: Clinicaltrials.gov NCT01796509; https://clinicaltrials.gov/ct2/show/NCT01796509. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30496.

Rheumatoid arthritis, as a clinical disease, but not rheumatoid arthritis-associated autoimmunity, is linked to cardiovascular events.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by increased cardiovascular (CV) mortality. CV events are particularly high in patients with RA-specific autoimmunity, including rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), raising the question whether RA-specific autoimmunity itself is associated with CV events. METHODS: New CV events (myocardial infarction, stroke or death by CV cause) were recorded in 20,625 subjects of the Electricité de France - Gaz de France (GAZEL) cohort. Self-reported RA cases in the GAZEL cohort were validated by phone interview on the basis of a specific questionnaire. In 1618 subjects, in whom plasma was available, RF and ACPA were measured. A piecewise exponential Poisson regression was used to analyze the association of CV events with presence of RA as well as RA-specific autoimmunity (without RA). RESULTS: CV events in GAZEL were associated with age, male sex, smoking, hypertension, hyperlipidemia, and diabetes mellitus (HR from 1.06 to 1.87, p < 0.05). Forty-two confirmed RA cases were identified. Confirmed RA was significantly associated with CV risk increase (HR of 3.03; 95% CI: 1.13-8.11, p = 0.03) independently of conventional CV risk factors. One hundred seventy-eight subjects showed RF or ACPA positivity without presence of RA. CV events were not associated with ACPA positivity (HR: 1.52, 95% CI: 0.47-4.84, p = 0.48) or RF positivity (HR: 1.15, 95% CI: 0.55-2.40, p = 0.70) in the absence of RA. CONCLUSIONS: RA, as a clinical chronic inflammatory disease, but not mere positivity for RF or ACPA in the absence of clinical disease is associated with increased CV risk.

Treatment for multiple myeloma in hospital at home: clinical characteristics and patient care pathways.

While most patients receive anticancer injection in a conventional hospital, some are treated in hospital at home. Given the lack of data, we seek to determine the clinical characteristics and care pathways of patients benefiting from hospital at home (HAH) for anticancer injection. A longitudinal scheme was conducted about patients with multiple myeloma (MM) starting bortezomib-based regimens in HAH in 2015 with a follow-up to September 2019. 154 patients received bortezomib at home with a mean age of 70.6 years, 72.7% over 65y-old and, a median Karnofsky Performans Status of 70. One-third of the elderly lived alone, 16.1% required domestic help. After a 24-month follow-up, 77.9% of patients were alive. The median overall survival was not reached at 4 years. Between 42.1% and 48.1% of patients returned to HAH for a new line of treatment. Patients were mainly independent and "fit." The involvement of HAH was achieved without safety issues nor compromise long-term outcomes. However, the real-world patterns highlighted that only a small proportion of patients returned to HAH for a new treatment line.

Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury. METHODS: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580. FINDINGS: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089). INTERPRETATION: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. FUNDING: Programme Hospitalier de Recherche Clinique.

Cluster analysis in early axial spondyloarthritis predicts poor outcome in the presence of peripheral articular manifestations.

OBJECTIVES: To assess whether two cluster analysis-based axial SpA (axSpA) endotypes (A for purely axial; B for both axial and peripheral) are stable over time and are associated with different long-term disease outcomes. METHODS: K-means cluster analysis was performed at each visit (until 5 years) on 584 patients from the DESIR cohort, who completed all planned visits, and validated in 232 consecutive axSpA patients from the BeGiant cohort. Cluster stability overtime was assessed by kappa statistics. A generalized linear mixed-effect analysis was applied to compare outcomes between clusters. Classification and regression tree (CART) analysis was performed to determine a decision rule able to assign a given patient to a definite cluster at onset. RESULTS: Both endotypes remained remarkably stable over time. In the DESIR cohort, patients in cluster B showed higher disease activity, worse functional outcome and higher need for anti-rheumatic drugs than patients in cluster A. CART analysis yielded three main clinical features (arthritis, enthesitis and dactylitis) that accurately determined cluster assignment. These results could be replicated in the Be-GIANT cohort. CONCLUSION: Cluster-based axSpA endotypes were reproducible in two different cohorts, stable over time and associated with different long-term outcome. The axSpA endotype with additional peripheral disease manifestations is associated with more severe disease and requires more intensive drug therapy. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, https://clinicaltrials.gov, NCT01648907.

Screening for postoperative vital signs abnormalities, and particularly hemodynamic ones, by continuous monitoring: protocol for the Biobeat-Postop cohort study.

Background: Postoperative hypotension associated with postoperative morbidity and early mortality has been studied previously. Hypertension and other hemodynamic, respiratory, and temperature abnormalities have comparatively understudied during the first postoperative days. Methods: This bi-centre observational cohort study will include 114 adult patients undergoing non-cardiac surgery hospitalized on an unmonitored general care floor and wearing a multi-signal wearable sensor, allowing remote monitoring ( Biobeat Technologies Ltd, Petah Tikva, Israel). The study will cover the first 72 hours after discharge of the patient from the post-anaesthesia care unit. Several thresholds will be used for each variable (arterial pressure, heart rate, respiratory rate, oxygen saturation, and skin temperature). Data obtained using the sensor will be compared to data obtained during the routine nurse follow-up. The primary outcome is hemodynamic abnormality. The secondary outcomes are postoperative respiratory and temperature abnormalities, artefacts and blank/null outputs from the wearable device, postoperative complications, and finally, the ease of use of the device. We hypothesize that remote monitoring will detect abnormalities in vital signs more often or more quickly than the detection by nurses' routine surveillance. Discussion: A demonstration of the ability of wireless sensors to outperform standard monitoring techniques paves the way for the creation of a loop which includes this monitoring mode, the automated creation of alerts, and the sending of these alerts to caregivers. Trial registration: ClinicalTrials.gov, NCT04585178. Registered on October 14, 2020.

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Failure of treatment is the most serious complication in community-acquired pneumonia (CAP). Objective: To assess the potential risk factors for treatment failure in clinically stable patients with CAP. Design, Setting, and Participants: This secondary analysis assesses data from a randomized clinical trial on CAP (Pneumonia Short Treatment [PTC] trial) conducted from December 19, 2013, to February 1, 2018. Data analysis was performed from July 18, 2019, to February 15, 2020. Patients hospitalized at 1 of 16 centers in France for moderately severe CAP who were clinically stable at day 3 of antibiotic treatment were included in the PTC trial and analyzed in the per-protocol trial population. Interventions: Patients were randomly assigned (1:1) on day 3 of antibiotic treatment to receive ß-lactam (amoxicillin-clavulanate [1 g/125 mg] 3 times daily) or placebo for 5 extra days. Main Outcomes and Measures: The main outcome was failure at 15 days after first antibiotic intake, defined as a temperature greater than 37.9 °C and/or absence of resolution or improvement of respiratory symptoms and/or additional antibiotic treatment for any cause. The association among demographic characteristics, baseline clinical and biological variables available (ie, at the first day of ß-lactam treatment), and treatment failure at day 15 among the per-protocol trial population was assessed by univariate and multivariable logistic regressions. Results: Overall, 310 patients were included in the study; this secondary analysis comprised 291 patients (174 [59.8%] male; mean [SD] age, 69.6 [18.5] years). The failure rate was 26.8%. Male sex (odds ratio [OR], 1.74; 95% CI, 1.01-3.07), age per year (OR, 1.03; 95% CI, 1.01-1.05), Pneumonia Severe Index score (OR, 1.01; 95% CI, 1.00-1.02), the presence of chronic lung disease (OR, 1.85; 95% CI, 1.03-3.30), and creatinine clearance (OR, 0.99; 95% CI, 0.98-1.00) were significantly associated with failure in the univariate analysis. When the Pneumonia Severe Index score was excluded to avoid collinearity with age and sex in the regression model, only male sex (OR, 1.92; 95% CI, 1.08-3.49) and age (OR, 1.02; 95% CI, 1.00-1.05) were associated with failure in the multivariable analysis. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, only male sex and age were associated with higher risk of failure, independent of antibiotic treatment duration and biomarker levels. Another randomized clinical trial is needed to evaluate the impact of treatment duration in populations at higher risk for treatment failure.

Limited impact of a top-down approach to improve enhanced recovery programme in French university hospitals: a before-after retrospective survey.

BACKGROUND: Enhanced recovery programme (ERP) after surgery needs development in Assistance Publique Hôpitaux de Paris (APHP). METHODS: A retrospective before-and-after study was performed in 2015 and 2017 on three surgical models (total knee arthroplasty (TKA), colectomy and hysterectomy) in 17 hospitals including 29 surgical departments. Data were collected in one control intervention (total hip arthroplasty (THA), gastrectomy and ovariectomy). In 2016, Massive Open Online Course on ERP and a day meeting information were developed by APHP. A national update on ERP was also organized by HAS and a regional professional partnership programme was started. Primary outcomes were length of stay (LOS) and complications after surgery. Data on ERP items were collected in the patients' chart and in anaesthetist and surgeon interview. Seventy percent application rate reflects application of ERP procedure. RESULTS: 1321 patient's files were analysed (812 in 2015 and 509 in 2017). The LOS (mean (SD)) is reduced by 1.6 day for TKA (2015, 8.7 (6.7) versus 7.1 (3.4) in 2017; p<0.001) but stable for colectomy and hysterectomy. Incidence of severe complications after surgery is unchanged in all types of surgical models. For TKA and hysterectomy respectively applied items of ERP (i.e. >70% application) increased respectively from 5 to 7 out of 17 and 16 in 2015 and 2017. For colectomy, they were stable at 6 out of 21 in 2015 and 2017. The mean application rates of ERP items stayed below 50% in all cases in 2017. The LOS was negatively correlated with ERP items' application when data collected in 2015 and 2017 were analysed together. CONCLUSION: ERP application did not significantly improved between 2015 and 2017 for three surgical models after an institutional information and diffusion of recommendations in 29 surgical departments of seventeen French University hospitals underlining the limit of a top-down approach.

Relationships between neuropsychological impairments and functional outcome eight years after severe traumatic brain injury: Results from the PariS-TBI study.

BACKGROUND/OBJECTIVES: The objective was to assess the relationships between neuropsychological impairments, functional outcome and life satisfaction in a longitudinal study of patients after a severe traumatic brain injury (TBI) (PariS-TBI study). PATIENTS: Out of 243 survivors, 86 were evaluated 8 years post-injury. They did not significantly differ from patients lost-to-follow up except for the latter being more frequently students or unemployed before the injury. METHODS: Outcome measures included the Glasgow Outcome Scale-Extended (GOS-E), a functional independence questionnaire, employment, mood, fatigue and satisfaction with life. Neuropsychological outcome was assessed by two ways: performance-based outcome measures, using neuropsychological tests and patient and relative-based measures. RESULTS: Neuropsychological measures were not significantly related to initial injury severity nor to gender, but were significantly related to age and education. After statistical correction for multiple comparisons, cognitive testing and cognitive questionnaires were significantly correlated with most outcome measures. By contrast, satisfaction with life was only related with patient-rated questionnaires. A regression analysis showed that the Trail-Making-Test-A was the best predictor of functional outcome, in addition to education duration. CONCLUSIONS: Cognitive measures, particularly slowed information processing speed, were significant indicators of functional outcome at a long-term post-injury, beyond and above demographics or injury severity measures.

Discontinuing ß-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial.

BACKGROUND: Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of ß-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. METHODS: We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with ß-lactam therapy were randomly assigned (1:1) to receive ß-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. FINDINGS: Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of ß-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or ß-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the ß-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0-84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the ß-lactam group (between-group difference of 9·42%, 95% CI -0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the ß-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI -0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the ß-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the ß-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the ß-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). INTERPRETATION: Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing ß-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. FUNDING: French Ministry of Health.