Screening for caregiver psychosocial risk in children with medical complexity: A cross-sectional study

Objective To quantify psychosocial risk in family caregivers of children with medical complexity using the Psychosocial Assessment Tool (PAT) and to investigate potential contributing sociodemographic factors. Design Cross-sectional study. Setting Family caregivers completed questionnaires during long-term ventilation and complex care clinic visits at The Hospital for Sick Children, Toronto, Ontario, Canada. Patients A total of 136 family caregivers of children with medical complexity completed the PAT questionnaires from 30 June 2017 through 23 August 2017. Main outcome measures Mean PAT scores in family caregivers of children with medical complexity. Caregivers were stratified as \u27Universal\u27 low risk, \u27Targeted\u27 intermediate risk or \u27Clinical\u27 high risk. The effect of sociodemographic variables on overall PAT scores was also examined using multiple linear regression analysis. Comparisons with previous paediatric studies were made using T-test statistics. Results 136 (103 females (76%)) family caregivers completed the study. Mean PAT score was 1.17 (SD=0.74), indicative of \u27Targeted\u27 intermediate risk. Sixty-one (45%) caregivers were classified as Universal risk, 60 (44%) as Targeted risk and 15 (11%) as Clinical risk. Multiple linear regression analysis revealed an overall significant model (p=0.04); however, no particular sociodemographic factor was a significant predictor of total PAT scores. Conclusion Family caregivers of children with medical complexity report PAT scores among the highest of all previously studied paediatric populations. These caregivers experience significant psychosocial risk, demonstrated by larger proportions of caregivers in the highest-risk Clinical category

Genetically defined syngeneic mouse models of ovarian cancer as tools for the discovery of combination immunotherapy

Despite advances in immuno-oncology, the relationship between tumor genotypes and response to immunotherapy remains poorly understood, particularly in high-grade serous tubo-ovarian carcinomas (HGSC). We developed a series of mouse models that carry genotypes of human HGSCs and grow in syngeneic immunocompetent hosts to address this gap. We transformed murine-fallopian tube epithelial cells to phenocopy homologous recombination-deficient tumors through a combined loss of p53, Brca1, Pten, Nf1, and overexpression of Myc and p53R172H, which was contrasted to an identical model carrying wild-type Brca1. For homologous recombination-proficient tumors, we constructed genotypes combining loss of p53, and overexpression of Ccne1, Akt2, p53R172H, and driven by KRASG12V or Brd4 or Smarca4 overexpression. These lines form tumors recapitulating human disease, including genotype-driven responses to treatment, and enabled us to identify follistatin as a driver of resistance to checkpoint inhibitors. These data provide proof of concept that our models can identify new immunotherapy targets in HGSC

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Magnetic and transport properties of single crystal LnRu 2Al 10 (Ln=Pr, Gd, Yb)

Single crystals of LnRu 2Al 10 (Ln=Pr, Gd, Yb) have been grown using the self-flux method, their structure has been determined by single crystal x-ray diffraction, and their magnetic and electronic transport properties have been studied. LnRu 2Al 10 are members of the Y bFe 2Al 10 structure type with space group Cmcm. PrRu 2Al 10 displays paramagnetic behaviour down to 13.2K, at which temperature it enters a non-magnetic singlet ground state, with a large paramagnetic Curie-Weiss temperature of 49.8(14)K. GdRu 2Al 10 orders antiferromagnetically at 15.5K. Y bRu 2Al 10 is a Pauli paramagnet indicating that the Yb is divalent. The properties of these three analogues are compared with LnM 2Al 10 (M=Fe, Ru, Os). © 2012 IOP Publishing Ltd

Peptide inhibitor of complement C1 (PIC1), a novel suppressor of classical pathway activation: mechanistic studies and clinical potential

The classical pathway of complement plays multiple physiological roles including modulating immunological effectors initiated by adaptive immune responses as well as an essential homeostatic role in the clearance of damaged self-antigens. However, dysregulated classical pathway activation is associated with antibody-initiated, inflammatory diseases processes like cold agglutinin disease (CAD), acute intravascular hemolytic transfusion reaction (AIHTR) and acute/hyperacute transplantation rejection. To date, only one putative classical pathway inhibitor, C1 esterase inhibitor (C1-INH), is currently commercially available and its only approved indication is for replacement treatment in hereditary angioedema (HAE), which is predominantly a kinin pathway disease. Given the variety of disease conditions in which the classical pathway is implicated, development of therapeutics that specifically inhibit complement initiation represents a major unmet medical need. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement. In vitro studies have demonstrated that these Peptide Inhibitors of Complement C1 (PIC1) bind to the collagen-like region of the initiator molecule of the classical pathway, C1q. PIC1 binding to C1q blocks activation of the associated serine proteases (C1s-C1r-C1r-C1s) and subsequent downstream complement activation. Rational design optimization of PIC1 has resulted in the generation of a highly potent derivative of fifteen amino acids. PIC1 inhibits classical pathway mediated complement activation in ABO incompatibility in vitro as well as inhibiting classical pathway activation in vivo in rats. This review will focus on the pre-clinical development of PIC1 and discuss its potential as a therapeutic in antibody-mediated classical pathway disease, specifically AIHTR

Crystal growth and magnetic properties of Ln-Mn-Al (Ln=Gd, Yb) compounds of the CaCr 2Al 10 and ThMn 12 structure types

We report the growth and characterization of LnMn 2xAl 10-x (Ln=Gd, Yb) crystals adopting the CaCr 2Al 10 and ThMn 12 structure types. Single crystals of LnMn 2xAl 10-x were synthesized via the self-flux method and characterized with single crystal X-ray diffraction. We compare LnMn 2xAl 10-x compounds adopting the CaCr 2Al 10 and ThMn 12 structure types, and outline synthesis methods to obtain each polymorph. Magnetic susceptibility measurements show paramagnetic behavior down to 3 K for both CaCr 2Al 10- and ThMn 12-type compounds, with observed magnetic moments of 1.3μ B for compounds adopting the CaCr 2Al 10 structure type to 4.2μ B for those adopting the ThMn 12 structure type. Compounds of both structure type exhibit metallic resistivity, with upturns at low temperature attributed to Kondo scattering. © 2012 Elsevier Inc. All rights reserved

Crystal growth, structure, and physical properties of Ln 2PdGa 12 (Ln = La, Pr, Nd, and Sm)

Single crystals of Ln 2PdGa 12 (Ln = La, Pr, Nd, Sm) were synthesized with a molten Ga flux. The intermetallic phases are isostructural to Sm 2NiGa 12 with cell dimensions of a ∼ 6.1 and c ∼ 15.5 . Pr 2PdGa 12, Nd 2PdGa 12, and Sm 2PdGa 12 order antiferromagnetically at 18, 7.5, and 7.5 K, respectively, and magnetic properties of single crystals oriented parallel and perpendicular to the magnetic field are presented. Fitting the low temperature heat capacity of Pr 2PdGa 12 gives a Sommerfeld coefficient (γ) of 250 mJ mol -1 K -2 and indicates the possibility of heavy fermion behavior. © Published by Elsevier B.V