Effects of a multidisciplinary, post-discharge continuance of care intervention on quality of life, discharge satisfaction, and hospital length of stay: a randomized controlled trial.

OBJECTIVE: To determine the impact of a hospital-coordinated discharge care plan, involving a multidisciplinary team of primary health care providers, on hospital length of stay, quality of life, and both patient and general practitioner inclusion in, and satisfaction with, discharge procedures. DESIGN: This investigation comprised a prospective, randomized, controlled, clinical trial. SETTING: This multicentre and cross-jurisdictional study focused on areas of tertiary and primary health care as well as community allied health in Western Australia. PARTICIPANTS: Patients (n = 189) with chronic cardiorespiratory diagnoses were recruited from respiratory, cardiovascular, and general medical wards at two tertiary hospitals. INTERVENTION: Subjects were randomly assigned to one of two groups. Intervention group patients received a discharge care plan in accordance with that outlined in the Australian Enhanced Primary Care Package, completed before discharge and sent to the patient's general practitioner and other community service providers for review. Control patients were discharged under existing hospital processes. Outcome measures. Patients and general practitioners were surveyed pre-discharge and 7 days post-discharge for quality of life and opinion of discharge procedures. Hospital length of stay was also determined. RESULTS: Significant improvements in discharge planning involvement, health service access, confidence with discharge procedures, and opinion of discharge based on previous experience were seen for patients who received the discharge care plan. Further, improved perceptions of mental quality of life were observed within the first week post-discharge for intervention patients. Length of stay showed no difference between groups. Extent and speed of hospital-general practitioner communication were significantly improved via the intervention. CONCLUSIONS: Our results indicate that a multidisciplinary discharge care plan, initiated before separation, improves quality of life, involvement, and satisfaction with discharge care, and hospital-general practitioner integration. As such, it possesses benefits over current Western Australian hospital discharge procedures for the care of chronically ill populations.     

Is immediate chest radiograph necessary after central venous catheter placement in a surgical intensive care unit?

BACKGROUND: Current standard of care dictates that central venous catheter (CVC) insertion should be followed by an immediate chest radiograph to confirm appropriate position and rule out complications. We hypothesized that a subset of monitored intensive care unit patients exists that is at low risk for complications and might safely have radiographic evaluation of line placement deferred until the next scheduled radiograph. METHODS: Data regarding patient and procedural characteristics were obtained prospectively for 184 CVC placed between March 1, 1998, and June 30, 1999. Retrospective data regarding complications were obtained by chart review for an additional 174 CVC placed during the study period but for which data sheets were not completed. All procedures were followed by chest radiography. RESULTS: We documented a complication rate of 9% with the vast majority (25 of 31, 81%) of complications consisting of incorrect positioning. The number of needle passes was greater in the group suffering pneumothorax and arterial puncture than the uncomplicated group (5.6 versus 1.9, P = 0.008). "Straightforward" operator gestalt (P = 0.04) and number of needle passes <3 (P = 0.03) were factors correlating with the absence of complications. These factors had negative predictive values of 94% and 96%, respectively. CONCLUSION: Placement of CVC is safe in experienced hands. In monitored intensive care unit patients who undergo a "straightforward" procedure with <3 needle passes, chest radiograph can be safely deferred until the next scheduled examination.     

Tolerance to ischemia and hypoxia is reduced in aged human myocardium

BACKGROUND: Recovery of cardiac function after cardiac surgery and other interventional cardiac procedures in elderly patients is inferior to that in younger patients, suggesting that the aged myocardium is more sensitive to ischemia and other stresses. Although convincing data from animal studies of senescence now exist, there is a dearth of controlled in vitro studies that examine the specific response of aged human myocardium to the stress of hypoxia or ischemia. OBJECTIVE: We sought to determine the effect of age on the capacity of human atrial trabeculae to recover contractile function after in vitro hypoxic or ischemic stress. METHODS: Atrial pectinate trabeculae were dissected from the tip of 58 right atrial appendages harvested during an operation in patients aged between 34 and 89 years and electrically stimulated at 1 Hz in oxygenated Ringer's solution at 37 degrees C. Tissues experienced 30 minutes of either hypoxia (N(2) and perfusate) or simulated ischemia (humidified N(2) without perfusate) and were returned to normoxia for recovery of function for 30 minutes. Developed force and other contractile variables were determined during each period. RESULTS: Under normoxic conditions, no significant age difference was observed for any contractile function variable. However, after hypoxia, the old (70-89 years) and intermediate age groups (60-69 years) showed reduced recovery of developed force (48.5% +/- 22.2% [n = 11] and 44.9% +/- 19% [n = 12], respectively) compared with that found (66.4% +/- 19.7% [n = 15]) in the younger (34-59 years) group (mean +/- SD, P =.02). Similarly, after simulated ischemia, the groups of 70- to 89-year-old and 60- to 69-year-old subjects showed reduced recovery of developed force (35.7% +/- 17% [n = 5] and 51.1% +/- 11.8% [n = 9], respectively) compared with that found (68.2% +/- 10.4% [n = 6]) in the group of 34- to 59-year-old subjects (P =.01). Multivariable analysis, comparing 20 factors of surgical patient characteristics and recovery of developed force, found that only age (P =.01) and hypertension (P =.01) were predictors of reduced recovery of developed force after either hypoxia or simulated ischemia. CONCLUSIONS: In aged human atrial myocardium, the capacity to recover contractile function after in vitro hypoxia or simulated ischemia is reduced compared with the younger myocardium of mature adults. These findings suggest that enhanced myocardial protective strategies may be indicated for elderly patients undergoing cardiac surgery.     

P2 receptors in the kidney

Our understanding of the actions of extracellular ATP in controlling kidney function via stimulation of P2 receptors is still at an early stage. Recently, several groups, including our own, have begun to address this subject: in this brief review, we discuss some of these effects and speculate on likely function of extracellular nucleotides in the kidney.     

卒中医疗体系之急诊医疗服务的实施策略:美国心脏协会/美国卒中协会急诊医疗服务体系专家组和卒中委员会的政策声明

尽管卒中的预防、诊断、治疗和康复已取得一些进展,但卒中在美国仍然是第三大死亡原因和长期残疾的主要原因.每年约有70万人新发或复发卒中[1].在过去10年里,急性卒中诊治的一些进展,包括纤溶和其他短期疗法的引入,突出显示了急诊医疗服务(emergency medical services,EMS)机构和急诊医疗服务体系(emergency medical services systems,EMSS)在优化卒中医疗中的关键作用[2-7].     

QTQTN motif upstream of the furin-cleavage site plays a key role in SARS-CoV-2 infection and pathogenesis

The furin cleavage site (FCS), an unusual feature in the SARS-CoV-2 spike protein, has been spotlighted as a factor key to facilitating infection and pathogenesis by increasing spike processing. Similarly, the QTQTN motif directly upstream of the FCS is also an unusual feature for group 2B coronaviruses (CoVs). The QTQTN deletion has consistently been observed in in vitro cultured virus stocks and some clinical isolates. To determine whether the QTQTN motif is critical to SARS-CoV-2 replication and pathogenesis, we generated a mutant deleting the QTQTN motif (ΔQTQTN). Here, we report that the QTQTN deletion attenuates viral replication in respiratory cells in vitro and attenuates disease in vivo. The deletion results in a shortened, more rigid peptide loop that contains the FCS and is less accessible to host proteases, such as TMPRSS2. Thus, the deletion reduced the efficiency of spike processing and attenuates SARS-CoV-2 infection. Importantly, the QTQTN motif also contains residues that are glycosylated, and disruption of its glycosylation also attenuates virus replication in a TMPRSS2-dependent manner. Together, our results reveal that three aspects of the S1/S2 cleavage site—the FCS, loop length, and glycosylation—are required for efficient SARS-CoV-2 replication and pathogenesis.

SARS-CoV-2 emerged in late 2019 and has caused the largest pandemic since the 1918 influenza outbreak (1). An unusual feature of SARS-CoV-2 is the presence of a furin cleavage site (FCS) in its spike protein (2). The CoV spike is a trimer of spike proteins composed of the S1 and S2 subunits, responsible for receptor binding and membrane fusion, respectively (1). After receptor binding, the spike protein is proteolytically cleaved at the S1/S2 and S2′ sites to activate the fusion machinery. For SARS-CoV-2, the spike protein contains a novel cleavage motif recognized by the host cell furin protease (PRRAR) directly upstream of the S1/S2 cleavage site that facilitates cleavage prior to virion release from the producer cell. This FCS, not found in other group 2B CoVs, plays a key role in spike processing, infectivity, and pathogenesis as shown by our group and others (3, 4).Importantly, another novel amino acid motif, QTQTN, is found directly upstream of the FCS. This QTQTN motif, also absent in other group 2B CoVs, is often deleted and has been pervasive in cultured virus stocks of the alpha, beta, and delta variants (5–8). In addition, the QTQTN deletion has been observed in a small subset of patient samples as well (9–11). Because this deletion has been frequently identified, we set out to characterize it and determine whether it has consequences for viral replication and virulence. Using our infectious clone (12, 13), we demonstrated that the loss of this motif attenuates SARS-CoV-2 replication in respiratory cells in vitro and pathogenesis in hamsters. The QTQTN deletion results in reduced spike cleavage and diminished capacity to use serine proteases on the cell surface for entry. Importantly, mutations of glycosylation-enabling residues in the QTQTN motif results in similar replication attenuation despite intact spike processing. Together, our results highlight elements in the SARS-CoV-2 spike in addition to the FCS that contribute to increased replication and pathogenesis.