The Epidemiology of Acute Organ System Dysfunction From Severe Sepsis Outside of the Intensive Care Unit

BACKGROUND: Severe sepsis is a common, costly, and complex problem, the epidemiology of which has only been well studied in the intensive care unit (ICU). However, nearly half of all patients with severe sepsis are cared for outside the ICU. OBJECTIVE: To determine rates of infection and organ sys- tem dysfunction in patients with severe sepsis admitted to non-ICU services. DESIGN: Retrospective cohort study. SETTING: A large, tertiary, academic medical center in the United States. PATIENTS: Adult patients initially admitted to non-ICU medical services from 2009 through 2010. MEASUREMENTS: All International Classification of Dis- eases, 9th Revision, Clinical Modification diagnosis codes were screened for severe sepsis. Three hospitalists reviewed a sample of medical records evaluating the char- acteristics of severe sepsis. The International Consensus Conference (ICC) for sepsis defines severe sepsis as an infection leading to acute organ dysfunction.1,2 Severe sepsis afflicts over 1 million patients each year in Medicare alone, and is substantially more common among older Americans than acute myocardial infarction.3–5 Recently, the Agency for Healthcare Research and Quality identified severe sepsis as the single most expensive cause of hospitalization in the United States.6 The incidence of severe sepsis continues to rise.4,5 Severe sepsis is often mischaracterized as a diagno- sis cared for primarily in the intensive care unit (ICU). Yet, studies indicate that only 32% to 50% of patients with severe sepsis require ICU care, leaving *Address for correspondence and reprint requests: Jeffrey M. Rohde, MD, Department of Internal Medicine, University of Michigan Medical School, 3119 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-5376; Telephone: 734-647-1599; Fax: 734-233-9343; E-mail: [email protected] Additional Supporting Information may be found in the online version of this article. Received: July 15, 2012; Revised: December 16, 2012; Accepted: December 26, 2012 2013SocietyofHospitalMedicine DOI10.1002/jhm.2012 Published online in Wiley Online Library (Wileyonlinelibrary.com). RESULTS: Of 23,288 hospitalizations, 14% screened posi- tive for severe sepsis. A sample of 111 cases was manually reviewed, identifying 64 cases of severe sepsis. The mean age of patients with severe sepsis was 63 years, and 39% were immunosuppressed prior to presentation. The most common site of infection was the urinary tract (41%). The most common organ system dysfunctions were cardiovas- cular (hypotension) and renal dysfunction occurring in 66% and 64% of patients, respectively. An increase in the num- ber of organ systems affected was associated with an increase in mortality and eventual ICU utilization. Severe sepsis was documented by the treating clinicians in 47% of cases. CONCLUSIONS: Severe sepsis was commonly found and poorly documented on the wards at our medical center. The epidemiology and organ dysfunctions among patients with severe sepsis appear to be different from previously described ICU severe sepsis populations.This work was supported in part by the US National Insti- tutes of Health–K08, HL091249 (TJI) and the University of Michigan Specialist–Hospitalist Allied Research Program (SHARP). This work was also supported in part by VA Ann Arbor Healthcare System, Geriatric Research Education and Clinical Center (GRECC).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102728/1/Rohde 13 JHM epi acute organ dysfxn sepsis outside ICU.pdf11

Genotype-stratified treatment for monogenic insulin resistance: a systematic review

This is the final version. Available from Nature Research via the DOI in this record. Data availability: All data used in this review is available from publicly available and herein referenced sources. A list of included studies is provided in Supplementary Data 1. All data generated or analyzed during this study are included in this published article and its supplementary information files. Source data for the figures are available as Supplementary Data 2.BACKGROUND: Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR, stratified by genetic aetiology. METHODS: Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual data were extracted and duplicates were removed. Outcomes were analysed for each gene and intervention, and in aggregate for partial, generalised and all lipodystrophy. RESULTS: 10 non-randomised experimental studies, 8 case series, and 23 case reports meet inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin use is associated with the lowering of triglycerides and haemoglobin A1c (HbA1c) in all lipodystrophy (n = 111), partial (n = 71) and generalised lipodystrophy (n = 41), and in LMNA, PPARG, AGPAT2 or BSCL2 subgroups (n = 72,13,21 and 21 respectively). Body Mass Index (BMI) is lowered in partial and generalised lipodystrophy, and in LMNA or BSCL2, but not PPARG or AGPAT2 subgroups. Thiazolidinediones are associated with improved HbA1c and triglycerides in all lipodystrophy (n = 13), improved HbA1c in PPARG (n = 5), and improved triglycerides in LMNA (n = 7). In INSR-related IR, rhIGF-1, alone or with IGFBP3, is associated with improved HbA1c (n = 17). The small size or absence of other genotype-treatment combinations preclude firm conclusions. CONCLUSIONS: The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups.Wellcome TrustWellcome Trus

Process management in hospitals: an empirically grounded maturity model

In order to improve transparency and stabilise health care costs, several countries have decided to reform their healthcare system on the basis of diagnosis-related groups (DRG). DRGs are not only used for classifying medical treatments, but also for case-based reimbursement, hence induce active competition among hospitals, forcing them to become more efficient and effective. In consequence, hospitals are investing considerably in process orientation and management. However, to date there is neither a consensus on what capabilities hospitals need to acquire for becoming process-oriented, nor a general agreement on the sequence of development stages they have to traverse. To this end, this study proposes an empirically grounded conceptualisation of process management capabilities and presents a staged capability maturity model algorithmically derived on the basis of empirical data from 129 acute somatic hospitals in Switzerland. The five capability maturity levels start with 'encouragement of process orientation' (level 1), 'case-by-case handling' (level 2), and 'defined processes' (level 3). Ultimately, hospitals can reach the levels 'occasional corrective action' (level 4) and 'closed loop improvement' (level 5). The empirically derived model reveals why existing, generic capability maturity models for process management are not applicable in the hospitals context: their comparatively high complexity on the one hand and their strong focus on topics like an adequate IT integration and process automation on the other make them inadequate for solving the problems felt in the hospital sector, which are primarily of cultural and structural nature. We deem the proposed capability maturity model capable to overcome these shortcomings

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Search for top squark production in fully hadronic final states in proton-proton collisions at root s=13 TeV

A search for production of the supersymmetric partners of the top quark, top squarks, is presented. The search is based on proton-proton collision events containing multiple jets, no leptons, and large transverse momentum imbalance. The data were collected with the CMS detector at the CERN LHC at a center-of-mass energy of 13 TeV, and correspond to an integrated luminosity of 137 fb(-1). The targeted signal production scenarios are direct and gluino-mediated top squark production, including scenarios in which the top squark and neutralino masses are nearly degenerate. The search utilizes novel algorithms based on deep neural networks that identify hadronically decaying top quarks and W bosons, which are expected in many of the targeted signal models. No statistically significant excess of events is observed relative to the expectation from the standard model, and limits on the top squark production cross section are obtained in the context of simplified supersymmetric models for various production and decay modes. Exclusion limits as high as 1310 GeVare established at the 95% confidence level on the mass of the top squark for direct top squark production models, and as high as 2260 GeV on the mass of the gluino for gluino-mediated top squark production models. These results represent a significant improvement over the results of previous searches for supersymmetry by CMS in the same final state.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

Search for long-lived particles decaying to jets with displaced vertices in proton-proton collisions at root s=13 Te V

A search is presented for long-lived particles produced in pairs in proton-proton collisions at the LHC operating at a center-of-mass energy of 13 TeV. The data were collected with the CMS detector during the period from 2015 through 2018, and correspond to a total integrated luminosity of 140 fb(-1). This search targets pairs of long-lived particles with mean proper decay lengths between 0.1 and 100 mm, each of which decays into at least two quarks that hadronize to jets, resulting in a final state with two displaced vertices. No significant excess of events with two displaced vertices is observed. In the context of R-parity violating supersymmetry models, the pair production of long-lived neutralinos, gluinos, and top squarks is excluded at 95% confidence level for cross sections larger than 0.08 fb, masses between 800 and 3000 GeV, and mean proper decay lengths between 1 and 25 mm.Peer reviewe

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe