High-normal versus low-normal mean arterial pressure thresholds in critically ill patients: a systematic review and meta-analysis of randomized trials.

PURPOSE: Targeted blood pressure thresholds remain unclear in critically ill patients. Two prior systematic reviews have not shown differences in mortality with a high mean arterial pressure (MAP) threshold, but there have been new studies published since. Thus, we conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the effect of a high-normal vs low-normal MAP on mortality, favourable neurologic outcome, need for renal replacement therapy, and adverse vasopressor-induced events in critically ill patients. SOURCE: We searched six databases from inception until 1 October 2022 for RCTs of critically ill patients targeted to either a high-normal vs a low-normal MAP threshold for at least 24 hr. We assessed study quality using the revised Cochrane risk-of-bias 2 tool and the risk ratio (RR) was used as the summary measure of association. We used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence. PRINCIPAL FINDINGS: We included eight RCTs with 4,561 patients. Four trials were conducted in patients following out-of-hospital cardiac arrest, two in patients with distributive shock requiring vasopressors, one in patients with septic shock, and one in patients with hepatorenal syndrome. The pooled RRs for mortality (eight RCTs; 4,439 patients) and favourable neurologic outcome (four RCTs; 1,065 patients) were 1.06 (95% confidence interval [CI], 0.99 to 1.14; moderate certainty) and 0.99 (95% CI, 0.90 to 1.08; moderate certainty), respectively. The RR for the need for renal replacement therapy (four RCTs; 4,071 patients) was 0.97 (95% CI, 0.87 to 1.08; moderate certainty). There was no statistical between-study heterogeneity across all outcomes. CONCLUSION: This updated systematic review and meta-analysis of RCTs found no differences in mortality, favourable neurologic outcome, or the need for renal replacement therapy between critically ill patients assigned to a high-normal vs low-normal MAP target. STUDY REGISTRATION: PROSPERO (CRD42022307601); registered 28 February 2022.

RéSUMé: OBJECTIF: Les seuils de pression artérielle ciblés demeurent incertains chez les patient·es gravement malades. Deux revues systématiques antérieures n'ont pas montré de différences dans la mortalité avec un seuil élevé de pression artérielle moyenne (PAM), mais de nouvelles études ont été publiées depuis. Pour cette raison, nous avons réalisé une revue systématique mise à jour et une méta-analyse d'études randomisées contrôlées (ERC) comparant l'effet d'une PAM normale élevée vs normale faible sur la mortalité, les devenirs neurologiques favorables, la nécessité d'un traitement substitutif de l'insuffisance rénale et les événements indésirables induits par les vasopresseurs chez les patient·es gravement malades. SOURCES: Nous avons effectué des recherches dans six bases de données depuis leur création jusqu'au 1er octobre 2022 pour trouver des ERC portant sur des patient·es gravement malades chez lesquel·les un seuil de PAM normale élevée ou normale faible a été ciblé pendant au moins 24 heures. Nous avons évalué la qualité des études à l'aide de l'outil de risque de biais 2 révisé de Cochrane, et le risque relatif (RR) a été utilisé comme mesure sommaire de l'association. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Nous avons inclus huit ERC portant sur 4561 personnes traitées. Quatre études ont été menées chez des patient·es à la suite d'un arrêt cardiaque hors de l'hôpital, deux chez des patient·es présentant un choc distributif nécessitant des vasopresseurs, une chez des patient·es présentant un choc septique et une chez des patient·es atteint·es d'un syndrome hépato-rénal. Les RR combinés pour la mortalité (huit ERC; 4439 personnes) et les devenirs neurologiques favorables (quatre ERC; 1065 personnes) étaient respectivement de 1,06 (intervalle de confiance [IC] à 95 %, 0,99 à 1,14; certitude modérée) et de 0,99 (IC 95 %, 0,90 à 1,08; certitude modérée). Le RR pour le besoin de traitement substitutif de l'insuffisance rénale (quatre ERC; 4071 patient·es) était de 0,97 (IC 95 %, 0,87 à 1,08; certitude modérée). Il n'y avait pas d'hétérogénéité statistique entre les études pour tous les critères d'évaluation. CONCLUSION: Ces revue systématique et méta-analyse mises à jour des ERC n'ont révélé aucune différence dans la mortalité, les devenirs neurologiques favorables ou la nécessité d'un traitement substitutif de l'insuffisance rénale entre les patient·es gravement malades assigné·es à une cible de PAM normale élevée vs normale faible. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022307601); enregistrée le 28 février 2022.

Use of Corticosteroids in Cardiac Arrest-A Systematic Review and Meta-Analysis.

OBJECTIVES: The objective of this systematic review was to evaluate the impact of intraarrest corticosteroids on neurologic outcomes and mortality in patients with cardiac arrest. DATA SOURCES: We conducted a systematic search using the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE databases. STUDY SELECTION: We included all randomized controlled trials and comparative observational studies. We excluded single arm studies, case reports/series, narrative reviews, and studies irrelevant to the focus of this article. DATA EXTRACTION: Two reviewers independently assessed trial eligibility. Data were collected for the following outcomes: primary outcomes included good neurologic outcome, survival to hospital discharge, and survival at greater than or equal to 1 year. Secondary outcomes included incidence of return of spontaneous circulation, ICU and hospital length of stay, duration of vasopressor and inotropic treatment, and blood pressure during cardiopulmonary resuscitation and after return of spontaneous circulation. DATA SYNTHESIS: The pooled estimates from randomized controlled trials for the following subgroups were analyzed using random-effects models: 1) patients with in-hospital cardiac arrest who received vasopressin, steroids, and epinephrine; 2) patients with in-hospital cardiac arrest who used corticosteroids only (i.e., no vasopressin); and 3) patients with out-of-hospital cardiac arrest who used corticosteroids only. Results included an increase in good neurologic outcomes (relative risk, 2.84; 95% CI, 1.36-5.94) and survival to hospital discharge (relative risk, 2.58; 95% CI, 1.36-4.91) in in-hospital cardiac arrest patients receiving vasopressin, steroids, and epinephrine followed by corticosteroids for postresuscitation shock. This was further supported by an increase in return of spontaneous circulation (relative risk, 1.35; 95% CI, 1.12-1.64) and hemodynamics in this population. There was no benefit observed in in-hospital cardiac arrest or out-of-hospital cardiac arrest patients receiving corticosteroids alone. CONCLUSIONS: Our study found that there are limited high-quality data to analyze the association between corticosteroids and reducing mortality in cardiac arrest, but the available data do support future randomized controlled trials. We did find that corticosteroids given as part of a vasopressin, steroids, and epinephrine regimen in in-hospital cardiac arrest patients and for postresuscitation shock did improve neurologic outcomes, survival to hospital discharge, and surrogate outcomes that include return of spontaneous circulation and hemodynamics. We found no benefit in in-hospital cardiac arrest or out-of-hospital cardiac arrest patients receiving corticosteroids only; however, a difference cannot be ruled out due to imprecision and lack of available data.

Prone Position after Liberation from Prolonged Mechanical Ventilation in COVID-19 Respiratory Failure.

DESIGN: This is a retrospective case series describing the feasibility and tolerability of postextubation prone positioning (PEPP) and its impact on physiologic parameters in a tertiary intensive care unit during the COVID-19 pandemic. Setting and Patients. This study was conducted on patients with COVID-19 respiratory failure hospitalized in a tertiary Intensive Care Unit at Surrey Memorial Hospital during the COVID-19 pandemic. Measurements and Results. We did not find prior reports of PEPP following prolonged intubation in the literature. Four patients underwent a total of 13 PEPP sessions following liberation from prolonged mechanical ventilation. Each patient underwent a median of 3 prone sessions (IQR: 2, 4.25) lasting a median of 1.5 hours (IQR: 1.2, 2.1). PEPP sessions were associated with a reduction in median oxygen requirements, patient respiratory rate, and reintubation rate. The sessions were well tolerated by patients, nursing, and the allied health team. CONCLUSIONS: The novel practice of PEPP after liberation from prolonged mechanical ventilation in patients with COVID-19 respiratory failure is feasible and well tolerated, and may be associated with favourable clinical outcomes including improvement in oxygenation and respiratory rate and a low rate of reintubation. Larger prospective studies of PEPP are warranted.

Caractéristiques de départ et issues chez des patients atteints de COVID-19 hospitalisés dans des unités de soins intensifs à Vancouver (Canada) : série de cas.

CONTEXTE: La pandémie de maladie à coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) est associée à une mortalité élevée dans les unités de soins intensifs (USI). Nous avons voulu décrire les caractéristiques cliniques et les issues des patients gravement atteints de la maladie à coronavirus 2019 (COVID-19) en contexte canadien. MÉTHODES: Nous avons procédé à l'étude rétrospective d'une série de cas graves d'infection au SRAS-CoV-2 confirmée en laboratoire hospitalisés dans l'une des 6 USI du Vancouver métropolitain, en Colombie-Britannique (Canada), entre le 21 février et le 14 avril 2020. Les données démographiques, les renseignements sur la prise en charge et les résultats ont été recueillis à partir des dossiers médicaux, électroniques ou non, des patients. RÉSULTATS: Entre le 21 février et le 14 avril 2020, 117 patients ont été admis dans une USI avec un diagnostic confirmé de COVID-19. L'âge médian était de 69 ans (écart interquartile [EI] 60­75 ans); et 38 (32,5 %) étaient des femmes. Au moins une comorbidité était présente chez 86 patients (73,5 %). La ventilation mécanique a été nécessaire chez 74 patients (63,2 %). La durée de la ventilation mécanique a été de 13,5 jours (EI 8­22 jours) dans l'ensemble et de 11 jours (II 6­16) chez les patients qui ont reçu leur congé de l'USI. Du tocilizumab a été administré à 4 patients et de l'hydroxychloroquine à 1 patient. En date du 5 mai 2020, 18 patients (15,4 %) étaient décédés, 12 (10,3 %) étaient toujours à l'USI, 16 (13,7 %) avaient obtenu leur congé de l'USI, mais restaient hospitalisés, et 71 (60,7 %) avaient pu retourner à la maison. INTERPRÉTATION: Dans cette étude, la mortalité chez les patients gravement malades de la COVID-19 hospitalisés dans une USI a été moins élevée que chez les patients d'études précédentes. Ces résultats donnent à penser que le pronostic des cas graves de COVID-19 pourrait ne pas être aussi sombre que ce qui avait d'abord été rapporté.

The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019. DESIGN: Multicenter prospective observational study. SETTING: ICU. PATIENTS: Critically ill patients with coronavirus disease 2019 and noncoronavirus disease 2019 critically ill patients with respiratory failure (ICU control group). INTERVENTIONS: Daily measurement of serum inflammatory cytokines. MEASUREMENTS AND MAIN RESULTS: Demographics, comorbidities, clinical, physiologic, and laboratory data were collected daily. Daily serum samples were drawn for measurements of interleukin-1ß, interleukin-6, interleukin-10, and tumor necrosis factor-α. Pulmonary outcomes were the ratio of Pao2/Fio2 and static lung compliance. Twenty-six patients with coronavirus disease 2019 and 22 ICU controls were enrolled. Of the patients with coronavirus disease 2019, 58% developed acute respiratory distress syndrome, 62% required mechanical ventilation, 12% underwent extracorporeal membrane oxygenation, and 23% died. A negative correlation between interleukin-6 and Pao2/Fio2 (rho, -0.531; p = 0.0052) and static lung compliance (rho, -0.579; p = 0.033) was found selectively in the coronavirus disease 2019 group. Diagnosis of acute respiratory distress syndrome was associated with significantly elevated serum interleukin-6 and interleukin-1ß on the day of diagnosis. CONCLUSIONS: The inverse relationship between serum interleukin-6 and Pao2/Fio2 and static lung compliance is specific to severe acute respiratory syndrome coronavirus 2 infection in critically ill patients with respiratory failure. Similar observations were not found with interleukin-ß or tumor necrosis factor-α.

The association of ABO blood group with indices of disease severity and multiorgan dysfunction in COVID-19.

Studies on severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) suggest a protective effect of anti-A antibodies against viral cell entry that may hold relevance for SARS-CoV-2 infection. Therefore, we aimed to determine whether ABO blood groups are associated with different severities of COVID-19. We conducted a multicenter retrospective analysis and nested prospective observational substudy of critically ill patients with COVID-19. We collected data pertaining to age, sex, comorbidities, dates of symptom onset, hospital admission, intensive care unit (ICU) admission, mechanical ventilation, continuous renal replacement therapy (CRRT), standard laboratory parameters, and serum inflammatory cytokines. National (N = 398 671; P = .38) and provincial (n = 62 246; P = .60) ABO blood group distributions did not differ from our cohort (n = 95). A higher proportion of COVID-19 patients with blood group A or AB required mechanical ventilation (P = .02) and CRRT (P = .004) and had a longer ICU stay (P = .03) compared with patients with blood group O or B. Blood group A or AB also had an increased probability of requiring mechanical ventilation and CRRT after adjusting for age, sex, and presence of ≥1 comorbidity. Inflammatory cytokines did not differ between patients with blood group A or AB (n = 11) vs O or B (n = 14; P > .10 for all cytokines). Collectively, our data indicate that critically ill COVID-19 patients with blood group A or AB are at increased risk for requiring mechanical ventilation, CRRT, and prolonged ICU admission compared with patients with blood group O or B. Further work is needed to understand the underlying mechanisms.

How the high acuity unit changes mortality in the intensive care unit: a retrospective before-and-after study.

PURPOSE: High acuity units (HAU) are hospital units that provide patients with more acute care and closer monitoring than a general hospital ward but are not as resource intensive as an intensive care unit (ICU). Nevertheless, the impact of opening a HAU on ICU patient outcomes remains poorly defined. We investigated how the creation of a HAU impacted patient outcomes in the ICU. METHODS: This historical cohort study compared ICU patient in-hospital mortality, ICU length of stay (LOS), and hospital LOS before and after the creation of a HAU in a tertiary-care hospital with a medical/surgical ICU between 1 January 2013 and 31 December 2017. RESULTS: Data from 4,380 patients (984 in the pre-HAU group and 3,396 in the post-HAU group) were analyzed. In this cohort of ICU patients, 360 (37%) died in the pre-HAU group before the creation of a HAU, and 1,074 (32%) died in the post-HAU group after the creation of a HAU. The creation of a HAU was associated with lower relative risk of in-hospital mortality (adjusted risk ratio, 0.80; 95% confidence interval [CI], 0.72 to 0.89; P < 0.001). The creation of a HAU was also associated with reduced ICU and hospital LOS with a 12% increase in the rate of ICU discharge (adjusted sub-distribution hazard ratio [SHR], 1.12; 95% CI, 1.02 to 1.23; P = 0.02) and a 26% increase in the rate of hospital discharge (adjusted SHR, 1.26; 95% CI, 1.14 to 1.39; P < 0.001), when accounting for the competing risk of death. CONCLUSIONS: These data support the hypothesis that the creation of a HAU may be associated with reduced in-hospital mortality, ICU LOS, and hospital LOS for ICU patients.

RéSUMé: OBJECTIF: Les unités de soins intermédiaires sont des départements hospitaliers qui prodiguent des soins plus aigus et un monitorage plus serré aux patients qu'une unité générale, mais qui ne nécessitent pas autant de ressources qu'une unité de soins intensifs (USI). L'impact de l'ouverture d'une unité de soins intermédiaires sur les devenirs des patients à l'USI n'a pourtant été que peu décrit. Nous avons exploré la façon dont la création d'une unité de soins intermédiaires a eu un impact sur les devenirs des patients à l'USI. MéTHODE: Cette étude de cohorte historique a comparé la mortalité hospitalière, la durée de séjour à l'USI et la durée de séjour hospitalier des patients à l'USI avant et après la création d'une unité de soins intermédiaires dans un hôpital de soins tertiaires disposant d'une USI médicale/chirurgicale entre le 1er janvier 2013 et le 31 décembre 2017. RéSULTATS: Les données de 4380 patients (984 dans le groupe pré unité de soins intermédiaires et 3396 dans le groupe post unité de soins intermédiaires) ont été analysées. Dans cette cohorte de patients de l'USI, 360 (37 %) sont décédés avant la création de l'unité de soins intermédiaires, et 1074 (32 %) sont décédés après. La création d'une unité de soins intermédiaires a été associée à un risque relatif plus faible de mortalité hospitalière (risque relatif ajusté, 0,80; intervalle de confiance [IC] 95 %, 0,72 à 0,89; P < 0,001). La création d'une unité de soins intermédiaires a également été associée à une durée de séjour réduite à l'USI et à l'hôpital, avec une augmentation de 12 % du taux de congé de l'USI (rapport de risque ajusté [RRA], 1,12; IC 95 %, 1,02 à 1,23; P = 0,02) et une augmentation de 26 % du taux de congé de l'hôpital (RRA, 1,26; IC 95 %, 1,14 à 1,39; P < 0,001), en tenant compte du risque concurrent de décès. CONCLUSION: Ces données appuient l'hypothèse que la création d'une unité de soins intermédiaires pourrait être associée à une réduction de la mortalité hospitalière, de la durée de séjour à l'USI et de la durée de séjour à l'hôpital pour les patients de l'USI.

Association between intensive care unit occupancy at discharge, afterhours discharges, and clinical outcomes: a historical cohort study.

PURPOSE: There is a paucity of evidence evaluating whether intensive care unit (ICU) discharge occupancy is associated with clinical outcomes. It is unknown whether increased discharge occupancy leads to greater afterhours discharges and downstream consequences. We explore the association between ICU discharge occupancy and afterhours discharges, 72-hr readmission, and 30-day mortality. METHODS: This single-centre, historical cohort study included all patients discharged from the Vancouver General Hospital ICU between 5 April 2010 and 13 September 2017. Data were obtained from the British Columbia Critical Care Database. Occupancy was defined as the number of ICU bed hours utilized divided by the available bed hours for that day. Any discharge between 22:00 and 6:59 was considered afterhours. Logistic regression models adjusting for important covariates were constructed. RESULTS: We included 8,862 ICU discharges representing 7,288 individual patients. There were 1,180 (13.3%) afterhours discharges, 408 (4.6%) 72-hr readmissions, and 574 (6.5%) 30-day post-discharge deaths. Greater discharge occupancy was associated with afterhours discharges (per 10% increase: adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.03 to 1.20; P = 0.005). Discharge occupancy was not associated with 72-hr readmission (per 10% increase: aOR, 0.97; 95% CI, 0.87 to 1.09; P = 0.62) or 30-day mortality (per 10% increase: aOR, 1.05; 95% CI, 0.95 to 1.16; P = 0.32). Afterhours discharge was not associated with 72-hr readmission (aOR, 1.15; 95% CI, 0.86 to 1.54; P = 0.34) or 30-day mortality (aOR, 1.05; 95% CI, 0.82 to 1.36; P = 0.69). CONCLUSIONS: Greater ICU discharge occupancy was associated with a significant increase in afterhours discharges. Nevertheless, neither discharge occupancy nor afterhours discharge were associated with 72-hr readmission or 30-day mortality.

RéSUMé: OBJECTIF: Il n'existe que peu de données probantes évaluant si le taux d'occupation de l'unité de soins intensifs (USI) au moment du congé est associé aux devenirs cliniques. Nous ne savons pas si un taux d'occupation plus élevé au moment du congé entraîne davantage de congés pendant la nuit et si cette situation a des conséquences. Nous avons exploré l'association entre le taux d'occupation de l'USI au moment du congé et les congés donnés pendant la nuit, la réadmission dans les premières 72 h, et la mortalité à 30 jours. MéTHODE: Cette étude de cohorte historique et monocentrique a englobé tous les patients ayant reçu leur congé de l'USI de l'Hôpital général de Vancouver entre le 5 avril 2010 et le 13 septembre 2017. Les données ont été tirées de la Base de données des soins intensifs de Colombie-Britannique (British Columbia Critical Care Database). Le taux d'occupation était défini comme le nombre d'heures d'occupation de lit de l'USI utilisées divisé par le nombre d'heures d'occupation de lit disponibles pour ladite journée. Tout congé reçu entre 22 h et 6 h 59 était considéré comme survenant pendant la nuit. Des modèles de régression logistique ont été élaborés afin de tenir compte des covariables importantes. RéSULTATS: Nous avons inclus 8862 congés de l'USI, représentant 7288 patients individuels. Au total, il y a eu 1180 (13,3 %) congés donnés pendant la nuit, 408 (4,6 %) réadmissions dans les 72 h suivantes, et 574 (6,5 %) décès à 30 jours après le congé. Un taux d'occupation plus élevé au moment du congé était associé à des congés pendant la nuit (par augmentation de 10 % : rapport de cotes ajusté [RCA], 1,12; intervalle de confiance [IC] 95 %, 1,03 à 1,20; P = 0,005). Le taux d'occupation lors du congé n'a pas été associé à une réadmission dans les premières 72 h (par augmentation de 10 % : RCA, 0,97; IC 95 %, 0,87 à 1,09; P = 0,62) ou à une mortalité à 30 jours (par augmentation de 10 % : RCA, 1,05; IC 95 %, 0,95 à 1,16; P = 0,32). Les congés pendant la nuit n'ont pas été associés à une réadmission dans les 72 h suivantes (RCA, 1,15; IC 95 %, 0,86 à 1,54; P = 0,34) ou à une mortalité à 30 jours (RCA, 1,05; IC 95 %, 0,82 à 1,36; P = 0,69). CONCLUSION: Un taux d'occupation de l'USI plus élevé au moment du congé était associé à une augmentation significative des congés donnés pendant la nuit. Cependant, ni le taux d'occupation lors du congé, ni le congé donné pendant la nuit, n'étaient associés à une réadmission à 72 h ou une mortalité à 30 jours.

Baseline characteristics and outcomes of patients with COVID-19 admitted to intensive care units in Vancouver, Canada: a case series.

BACKGROUND: Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high intensive care unit (ICU) mortality. We aimed to describe the clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) in a Canadian setting. METHODS: We conducted a retrospective case series of critically ill patients with laboratory-confirmed SARS-CoV-2 infection consecutively admitted to 1 of 6 ICUs in Metro Vancouver, British Columbia, Canada, between Feb. 21 and Apr. 14, 2020. Demographic, management and outcome data were collected by review of patient charts and electronic medical records. RESULTS: Between Feb. 21 and Apr. 14, 2020, 117 patients were admitted to the ICU with a confirmed diagnosis of COVID-19. The median age was 69 (interquartile range [IQR] 60-75) years, and 38 (32.5%) were female. At least 1 comorbidity was present in 86 (73.5%) patients. Invasive mechanical ventilation was required in 74 (63.2%) patients. The duration of mechanical ventilation was 13.5 (IQR 8-22) days overall and 11 (IQR 6-16) days for patients successfully discharged from the ICU. Tocilizumab was administered to 4 patients and hydroxychloroquine to 1 patient. As of May 5, 2020, a total of 18 (15.4%) patients had died, 12 (10.3%) remained in the ICU, 16 (13.7%) were discharged from the ICU but remained in hospital, and 71 (60.7%) were discharged home. INTERPRETATION: In our setting, mortality in critically ill patients with COVID-19 admitted to the ICU was lower than in previously published studies. These data suggest that the prognosis associated with critical illness due to COVID-19 may not be as poor as previously reported.

Systematic review with meta-analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease.

BACKGROUND: Janus kinase (JAK) inhibitors represent a novel therapeutic class for treatment of inflammatory bowel disease. AIMS: To determine the efficacy and safety of JAK inhibitors compared to placebo for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: PubMed, Embase and CENTRAL were systematically searched to November 1, 2018. Randomised placebo-controlled trials (RCTs) of JAK inhibitors in adult patients with CD or UC were eligible. Open-label extension studies without a placebo comparator arm were excluded. Clinical, endoscopic, and safety outcomes were extracted and rates relative to placebo were pooled using a random-effects model. RESULTS: A total of 12 RCTs (5 CD, 7 UC) were included. Patients were randomised to placebo (n = 844), tofacitinib (n = 1882), filgotinib (n = 130), peficitinib (n = 176), upadacitinib (n = 387) or TD-1473 (n = 31). JAK inhibitor treatment was associated with induction of clinical remission in CD (RR, relative risk 1.38 [95% confidence interval CI 1.04-1.83], P = 0.025, I2  = 14%) and UC (RR 3.07 [95% CI 2.03-4.63], P < 0.001, I2  = 0%). In UC, JAK inhibitor treatment was associated with induction of endoscopic remission (endoscopic Mayo subscore MCSe = 0/1) (RR 2.43 [95% CI 1.64-3.59], P < 0.001, I2  = 27%) and mucosal healing (MCSe = 0) (RR 5.50 [95% CI 2.46-12.32], P < 0.001, I2  = 0%). JAK inhibitor treatment increased the risk of infection compared to placebo (RR 1.40 [95% CI 1.18-1.67], P < 0.001, I2  = 0%), particularly for herpes zoster. CONCLUSIONS: JAK inhibitors are effective for inducing clinical remission in CD and induction of clinical and endoscopic remission in UC, although are associated with an increased risk of infectious complications.

Line bisection in simulated homonymous hemianopia.

Hemianopic patients make a systematic error in line bisection, showing a contra-lesional bias towards their blind side, which is the opposite of that in hemineglect patients. This error has been attributed variously to the visual field defect, to long-term strategic adaptation, or to independent effects of damage to extrastriate cortex. To determine if hemianopic bisection error can occur without the latter two factors, we studied line bisection in healthy subjects with simulated homonymous hemianopia using a gaze-contingent display, with different line-lengths, and with or without markers at both ends of the lines. Simulated homonymous hemianopia did induce a contra-lesional bisection error and this was associated with increased fixations towards the blind field. This error was found with end-marked lines and was greater with very long lines. In a second experiment we showed that eccentric fixation alone produces a similar bisection error and eliminates the effect of line-end markers. We conclude that a homonymous hemianopic field defect alone is sufficient to induce both a contra-lesional line bisection error and previously described alterations in fixation distribution, and does not require long-term adaptation or extrastriate damage.