Publications by authors named "Jackson James"

601 Publications

Delirium, depression, and long-term cognition.

Int Psychogeriatr 2021 Nov 12:1-6. Epub 2021 Nov 12.

Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Objectives: We examined whether preadmission history of depression is associated with less delirium/coma-free (DCF) days, worse 1-year depression severity and cognitive impairment.

Design And Measurements: A health proxy reported history of depression. Separate models examined the effect of preadmission history of depression on: (a) intensive care unit (ICU) course, measured as DCF days; (b) depression symptom severity at 3 and 12 months, measured by the Beck Depression Inventory-II (BDI-II); and (c) cognitive performance at 3 and 12 months, measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) global score.

Setting And Participants: Patients admitted to the medical/surgical ICU services were eligible.

Results: Of 821 subjects eligible at enrollment, 261 (33%) had preadmission history of depression. After adjusting for covariates, preadmission history of depression was not associated with less DCF days (OR 0.78, 95% CI, 0.59-1.03 p = 0.077). A prior history of depression was associated with higher BDI-II scores at 3 and 12 months (3 months OR 2.15, 95% CI, 1.42-3.24 p = <0.001; 12 months OR 1.89, 95% CI, 1.24-2.87 p = 0.003). We did not observe an association between preadmission history of depression and cognitive performance at either 3 or 12 months (3 months beta coefficient -0.04, 95% CI, -2.70-2.62 p = 0.97; 12 months 1.5, 95% CI, -1.26-4.26 p = 0.28).

Conclusion: Patients with a depression history prior to ICU stay exhibit a greater severity of depressive symptoms in the year after hospitalization.
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http://dx.doi.org/10.1017/S1041610221002556DOI Listing
November 2021

Intramolecular Relaxation Dynamics Mediated by Solvent-Solute Interactions of Substituted Fluorene Derivatives. Solute Structural Dependence.

J Phys Chem B 2021 Nov 9;125(45):12486-12499. Epub 2021 Nov 9.

Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.

Several fluorene derivatives exhibit excited-state reactivity and relaxation dynamics that remain to be understood fully. We report here the spectral relaxation dynamics of two fluorene derivatives to evaluate the role of structural modification in the intramolecular relaxation dynamics and intermolecular interactions that characterize this family of chromophores. We have examined the time-resolved spectral relaxation dynamics of two compounds, NCy- and MK-, in protic and aprotic solvents using steady-state and time-resolved emission spectroscopy and quantum chemical computations. Both compounds exhibit spectral relaxation characteristics similar to those seen in , indicating that hydrogen bonding interactions between the chromophore and solvent protons play a significant role in determining the relaxation pathways available to three excited electronic states.
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http://dx.doi.org/10.1021/acs.jpcb.1c06475DOI Listing
November 2021

Excited-State Dynamics of a Substituted Fluorene Derivative. The Central Role of Hydrogen Bonding Interactions with the Solvent.

J Phys Chem B 2021 Nov 2;125(44):12242-12253. Epub 2021 Nov 2.

Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.

Substituted fluorene structures have demonstrated unusual photochemical properties. Previous reports on the substituted fluorene Schiff base -SB demonstrated super photobase behavior with a Δp of ∼14 upon photoexcitation. In an effort to understand the basis for this unusual behavior, we have examined the electronic structure and relaxation dynamics of the structural precursor of -SB, the aldehyde , in protic and aprotic solvents using time-resolved fluorescence spectroscopy and quantum chemical calculations. The calculations show three excited singlet states in relatively close energetic proximity. The spectroscopic data are consistent with relaxation dynamics from these electronic states that depend on the presence and concentration of solvent hydroxyl functionality. These results underscore the central role of solvent hydrogen bonding to the aldehyde oxygen in mediating the relaxation dynamics within this molecule.
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http://dx.doi.org/10.1021/acs.jpcb.1c06474DOI Listing
November 2021

Burden and Quality of Life Among Female and Male Patients with Heart Failure in Europe: A Real-World Cross-Sectional Study.

Patient Prefer Adherence 2021 30;15:1693-1706. Epub 2021 Jul 30.

Novartis Pharma AG, Basel, Switzerland.

Purpose: To characterize symptoms, clinical burden, and health-related quality of life (HRQoL) among women and men with heart failure (HF) with a left ventricular ejection fraction (LVEF) of ≤60% in Europe.

Patients And Methods: A real-world cross-sectional study was conducted in France, Germany, Italy, Spain, and United Kingdom from June to November 2019. Patient record forms were completed by 257 cardiologists and 158 general practitioners for consecutive patients with HF. The same patients were invited to complete a questionnaire comprising patient-reported outcomes: the Minnesota Living with Heart Failure Questionnaire (MLHFQ), five-level five-dimension EuroQol questionnaire (EQ-5D-5L), Visual Analogue Scale (VAS), and Work Productivity and Activity Impairment questionnaire.

Results: The mean age of 804 patients (men, n=517; women, n=287) was 68.6 years (men, 67.8 years; women, 70.2 years; p=0.0022). The mean LVEF was 44.7% (men, 43.6%; women, 46.8%; p<0.0001). Patients reported dyspnoea when active (overall, 55.7%; men, 56.0%; women, 55.3%), fatigue/weakness/faintness (34.5%; men, 32.9%; women, 37.2%), and oedema (20.3%; men, 18.7%; women, 23.1%) as the most troublesome HF symptoms. Overall, 54.1% of patients reported low mood/depression (men, 50.8%; women, 60.1%). The overall MLHFQ mean score was higher (ie, poorer HRQoL) among women vs men (37.9 vs 34.6; p=0.0481). MLHFQ was consistently higher (ie, poorer HRQoL) for women vs men across the physical (18.6 vs 16.6; p=0.0041) and emotional (9.4 vs 7.9; p=0.0021) scoring domains. Mean EQ-5D utility (0.69 vs 0.75; p=0.0046) and VAS scores (55.4 vs 61.3; p<0.0001) were lower among women compared with men. Overall, 23.4% of patients were hospitalized owing to HF in the previous year (men, 22.7%; women, 24.6%). Patients reported 43.2% activity impairment due to HF (men, 41.6%; women, 46.4%; p=0.01).

Conclusion: HF causes a substantial burden on patients, with a greater burden among women vs men. This gender-related difference is consistent with other HF studies, warranting further research to understand the underlying reasons.
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http://dx.doi.org/10.2147/PPA.S312200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331086PMC
July 2021

Femtosecond dynamics and coherence of ionic retro-Diels-Alder reactions.

J Chem Phys 2021 Jul;155(4):044303

Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.

Ultrafast tunnel ionization enables femtosecond time-resolved dynamic measurements of the retro-Diels-Alder reactions of positively charged cyclohexene, norbornene, and dicyclopentadiene. Unlike the reaction times of 500-600 ps that are observed following UV excitation of neutral species, on the ionic potential energy surfaces, these reactions occur on a single picosecond timescale and, in some cases, exhibit vibrational coherence. In the case of norbornene, a 270 cm vibrational mode is found to modulate the retro-Diels-Alder reaction.
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http://dx.doi.org/10.1063/5.0048380DOI Listing
July 2021

Positive Effects of Religion and Social Ties on the Health of Former NFL Athletes.

J Relig Health 2021 Jul 27. Epub 2021 Jul 27.

Population Studies Center of the Institute for Social Research, University of Michigan, P. O. Box 1248, Ann Arbor, MI, 48106, USA.

This study explores the relationship between religious service attendance, social ties, and health among former NFL players, a population with relatively high levels of religious attendance who endure physically demanding occupations. Research shows that frequent religious service attenders tend to have better health, partly because of social connections formed through religious involvement. We analyzed a sample of 1029 former NFL players. Consistent with previous research, bivariate and multivariate OLS regression models show that frequent religious attenders have statistically significantly better self-rated health. However, this relationship is moderated by social ties. Respondents who scored lower on the social ties index exhibited a stronger significant relationship between frequent religious attendance and health; those scoring higher on the social ties index exhibited no relationship between frequent attendance and health. Future research should examine how benefits of religious attendance vary depending upon strength of social relationships.
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http://dx.doi.org/10.1007/s10943-021-01338-yDOI Listing
July 2021

Patient-Reported Outcomes for Migraine in the US and Europe: Burden Associated with Multiple Preventive Treatment Failures.

Clinicoecon Outcomes Res 2021 14;13:647-660. Epub 2021 Jul 14.

Adelphi Real World, Bollington, UK.

Purpose: To evaluate patient-reported outcomes (PROs) among patients with migraine, including those who were preventive-naïve and preventive-treated.

Methods: This was a point-in-time, real-world study of patients with migraine in the US and EU5 (France, Germany, Spain, Italy, and UK) and their physicians using data from the Adelphi Migraine Disease Specific Programme (DSP™). Physicians completed patient record forms (PRFs) for the next nine consulting patients with migraine plus a tenth patient, who did not need to be consecutive, for whom prior preventive migraine treatments had failed at least once, in order to achieve oversampling of such patients. Patients were given self-completion (PSC) forms that included the Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ), Migraine Disability Assessment Scale (MIDAS), and Work Productivity and Activity Impairment (WPAI) questionnaire. Populations of interest included preventive-naïve and preventive-treated patients defined by the number of treatment lines (1-2 or 3+ preventive regimens). Continuous variables were compared using -test or ANOVA if normally distributed and Mann-Whitney if not. Chi-squared was used for categorical variables.

Results: During August-December 2017, 615 physicians (359 PCPs, 256 neurologists) completed PRFs for 5785 patients (71% female; mean age 40 (±14) years; 65% in full- or part-time employment). Of these, 2798 completed a PSC (preventive-naïve/1-2/3+ preventive lines, n=1707/1034/57). Preventive-treated patients had a greater patient-reported burden across multiple measures versus preventive-naïve patients. Preventive-treated patients had lower MSQ scores indicating greater functional impairment, higher MIDAS scores indicating greater migraine-associated disability, and higher WPAI scores indicating greater overall work and activity impairment than preventive-naïve patients. The magnitude of difference was greatest for the 3+ preventive-treatments cohort. Patterns were similar in the US and EU5.

Conclusion: Among patients with migraine who are preventive-treated, including those with multiple lines of therapy, there remain considerable unmet needs in terms of restoring patient function.
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http://dx.doi.org/10.2147/CEOR.S304158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286727PMC
July 2021

High-Throughput Detection of Autoantigen-Specific B Cells Among Distinct Functional Subsets in Autoimmune Donors.

Front Immunol 2021 24;12:685718. Epub 2021 May 24.

Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.

Antigen-specific B cells (ASBCs) can drive autoimmune disease by presenting autoantigen to cognate T cells to drive their activation, proliferation, and effector cell differentiation and/or by differentiating into autoantibody-secreting cells. Autoantibodies are frequently used to predict risk and diagnose several autoimmune diseases. ASBCs can drive type 1 diabetes even when immune tolerance mechanisms block their differentiation into antibody-secreting cells. Furthermore, anti-histidyl tRNA synthetase syndrome patients have expanded IgM Jo-1-binding B cells, which clinically diagnostic IgG Jo-1 autoantibodies may not fully reflect. Given the potential disconnect between the pathologic function of ASBCs and autoantibody secretion, direct study of ASBCs is a necessary step towards developing better therapies for autoimmune diseases, which often have no available cure. We therefore developed a high-throughput screening pipeline to 1) phenotypically identify specific B cell subsets, 2) expand them , 3) drive them to secrete BCRs as antibody, and 4) identify wells enriched for ASBCs through ELISA detection of antibody. We tested the capacity of several B cell subset(s) to differentiate into antibody-secreting cells following this robust stimulation. IgM and/or IgD, CD27 memory, memory, switched memory, and B B cells secreted B cell receptor (BCR) as antibody following stimulation, whereas few plasmablasts responded. Bimodal responses were observed across autoimmune donors for IgM CD21 and IgM CD21 B cells, consistent with documented heterogeneity within the CD21 subset. Using this approach, we detected insulin-binding B cell bias towards CD27 memory and CD27 memory subsets in pre-symptomatic type 1 diabetes donors. We took advantage of routine detection of Jo-1-binding B cells in Jo-1+ anti-histidyl tRNA synthetase syndrome patients to show that Jo-1-binding B cells and total B cells expanded 20-30-fold using this culture system. Overall, these studies highlight technology that is amenable to small numbers of cryopreserved peripheral blood mononuclear cells that enables interrogation of phenotypic and repertoire attributes of ASBCs derived from autoimmune patients.
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http://dx.doi.org/10.3389/fimmu.2021.685718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256427PMC
October 2021

Concern about addiction is associated with lower quality of life in patients with osteoarthritis: an exploratory, real-world data analysis.

Qual Life Res 2021 Jul 5. Epub 2021 Jul 5.

Rheumatology Division of the Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Purpose: To evaluate the relationship between self-reported concerns about becoming addicted to a medication and health-related quality of life (HRQoL) in patients with osteoarthritis (OA).

Methods: This real-world study used patient-level cross-sectional survey data collected from the US Adelphi Disease Specific Programme (DSP). The DSP for OA selected 153 physicians who collected de-identified data on their next nine adult patients with OA. Each patient completed a disease-relevant survey, which included the Likert-scale question, "I am concerned about becoming addicted to my medicine," (CAA) with responses ranging from "completely disagree" [1] to "completely agree" [5]. HRQoL was measured by the EQ-5D-5L index value and the EQ Visual Analogue Scale (VAS). A set of ordinary least squares regressions using HRQoL measures as outcomes and CAA as a continuous predictor were estimated. Standardized effect size (ES) was used to gauge the magnitude of effects.

Results: A total of 866 patients with OA completed the survey (female, 61.2%; White, 77.7%; mean age, 64.2 years). Of the 775 patients who completed the CAA question, almost one-third responded that they "agree" (18%) or "completely agree" (11%), while 27% responded "completely disagree" and 20% "disagree." Regression analyses found that patients who have concerns about medication addiction have significantly different EQ-5D-5L index values and EQ VAS scores compared with patients who do not have this concern (p < 0.0001).

Conclusion: Our findings suggest that concern about medication addiction in patients with OA may have an impact on patient HRQoL, with more concerned patients reporting poorer HRQoL outcomes.
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http://dx.doi.org/10.1007/s11136-021-02907-0DOI Listing
July 2021

A chiroptical approach for the absolute stereochemical determination of -stereogenic centers.

Chem Sci 2020 Dec 7;12(5):1750-1755. Epub 2020 Dec 7.

Michigan State University, Department of Chemistry East Lansing MI 48824 USA

A simple chiroptical solution for the absolute stereochemical determination for asymmetric phosphorus V stereocenters is presented. Strong coordination of the phosphorus oxide with the Zn-metallo center of the racemic host Zn-MAPOL leads to an induced axial chirality of the host, yielding a strong ECCD signal. A mnemonic is proposed to correlate the asymmetry of the guest molecule with the observed ECCD signal.
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http://dx.doi.org/10.1039/d0sc02940hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179206PMC
December 2020

ICU Survivorship-The Relationship of Delirium, Sedation, Dementia, and Acquired Weakness.

Crit Care Med 2021 08;49(8):1227-1240

Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.

The advent of modern critical care medicine has revolutionized care of the critically ill patient in the last 50 years. The Society of Critical Care Medicine (was formed in recognition of the challenges and need for specialized treatment for these fragile patients. As the specialty has grown, it has achieved impressive scientific advances that have reduced mortality and saved lives. With those advances, however, came growing recognition that the burden of critical illness did not end at the doorstep of the hospital. Delirium, once thought to be a mere by-product of critical illness, was found to be an independent predictor of mortality, prolonged mechanical ventilation, and long-lasting cognitive impairment. Similarly, deep sedation and immobility, so often used to keep patients "comfortable" and to facilitate mechanical ventilation and recovery, worsen mortality and lead to the development of ICU-acquired weakness. The realization that these outcomes are inextricably linked to one another and how we manage our patients has helped us recognize the need for culture change. We, as a specialty, now understand that although celebrating the successes of survival, we now also have a duty to focus on those who survive their diseases. Led by initiatives such as the ICU Liberation Campaign of the Society of Critical Care Medicine, the natural progression of the field is now focused on getting patients back to their homes and lives unencumbered by disability and impairment. Much work remains to be done, but the futures of our most critically ill patients will continue to benefit if we leverage and build on the history of our first 50 years.
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http://dx.doi.org/10.1097/CCM.0000000000005125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282752PMC
August 2021

Six-month and 12-month patient outcomes based on inflammatory subphenotypes in sepsis-associated ARDS: secondary analysis of SAILS-ALTOS trial.

Thorax 2021 Jun 10. Epub 2021 Jun 10.

Outcomes After Critical Illness and Surgery (OACIS) Group, Johns Hopkins University, Baltimore, Maryland, USA

Background: Prior acute respiratory distress syndrome (ARDS) trials have identified hypoinflammatory and hyperinflammatory subphenotypes, with distinct differences in short-term outcomes. It is unknown if such differences extend beyond 90 days or are associated with physical, mental health or cognitive outcomes.

Methods: 568 patients in the multicentre Statins for Acutely Injured Lungs from Sepsis trial of rosuvastatin versus placebo were included and assigned a subphenotype. Among 6-month and 12-month survivors (N=232 and 219, respectively, representing 243 unique survivors), subphenotype status was evaluated for association with a range of patient-reported outcomes (eg, mental health symptoms, quality of life). Patient subsets also were evaluated with performance-based tests of physical function (eg, 6 min walk test) and cognition.

Findings: The hyperinflammatory versus hypoinflammatory subphenotype had lower overall 12-month cumulative survival (58% vs 72%, p<0.01); however, there was no significant difference in survival beyond 90 days (86% vs 89%, p=0.70). Most survivors had impairment across the range of outcomes, with little difference between subphenotypes at 6-month and 12-month assessments. For instance, at 6 months, in comparing the hypoinflammatory versus hyperinflammatory subphenotypes, respectively, the median (IQR) patient-reported SF-36 mental health domain score was 47 (33-56) vs 44 (35-56) (p=0.99), and the per cent predicted 6 min walk distance was 66% (48%, 80%) vs 66% (49%, 79%) (p=0.76).

Interpretation: Comparing the hyperinflammatory versus hypoinflammatory ARDS subphenotype, there was no significant difference in survival beyond 90 days and no consistent findings of important differences in 6-month or 12-month physical, cognitive and mental health outcomes. These findings, when considered with prior results, suggest that inflammatory subphenotypes largely reflect the acute phase of illness and its short-term impact.
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http://dx.doi.org/10.1136/thoraxjnl-2020-216613DOI Listing
June 2021

Randomized Trial of Radiation Therapy With Weekly Cisplatin or Cetuximab in Low-Risk HPV-Associated Oropharyngeal Cancer (TROG 12.01) - A Trans-Tasman Radiation Oncology Group Study.

Int J Radiat Oncol Biol Phys 2021 11 4;111(4):876-886. Epub 2021 Jun 4.

Genesiscare St Vincent's Hospital, Melbourne, Australia; Department of Medicine, University of Melbourne, Melbourne, Australia.

Purpose: The excellent prognosis of patients with low-risk human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiation therapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an epidermal growth factor receptor targeting antibody, when combined with radiation therapy would result in a decrease in symptom burden and toxicity with similar efficacy compared with weekly cisplatin.

Methods And Materials: TROG12.01, a randomized, multicenter trial involving 15 sites in Australia and New Zealand enrolled patients with HPV-associated oropharyngeal squamous cell carcinoma, American Joint Committee on Cancer 7th edition stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomized (1:1) to receive radiation therapy (70 Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40 mg/m, or cetuximab, loading dose of 400 mg/m followed by 7 weekly doses of 250 mg/m. The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks postcompletion of radiation therapy using the area under the curve. Trial was registered on ClinicalTrials.gov: NCT01855451.

Results: Between June 17, 2013, and June 7, 2018, 189 patients were enrolled, with 92 in cisplatin arm and 90 in cetuximab included in the main analysis. There was no difference in the primary endpoint of symptom severity; difference in area under the curve cetuximab-cisplatin was 0.05 (95% confidence interval [CI], -0.19, 0.30), P = .66. The T-score (mean number of ≥grade 3 acute adverse events) was 4.35 (standard deviation 2.48) in the cisplatin arm and 3.82 (standard deviation 1.8) in the cetuximab arm, P = .108. The 3-year failure-free survival rates were 93% (95% CI, 86%-97%) in the cisplatin arm and 80% (95% CI, 70%-87%) in the cetuximab arm (hazard ratio = 3.0 [95% CI, 1.2-7.7]); P = .015.

Conclusions: For patients with low-risk HPV-associated oropharyngeal cancer, radiation therapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared with radiation therapy and weekly cisplatin. Radiation therapy and cisplatin remain the standard of care.
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http://dx.doi.org/10.1016/j.ijrobp.2021.04.015DOI Listing
November 2021

Transitions of Care After Critical Illness-Challenges to Recovery and Adaptive Problem Solving.

Crit Care Med 2021 11;49(11):1923-1931

Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN.

Objectives: Investigate the challenges experienced by survivors of critical illness and their caregivers across the transitions of care from intensive care to community, and the potential problem-solving strategies used to navigate these challenges.

Design: Qualitative design-data generation via interviews and data analysis via the framework analysis method.

Setting: Patients and caregivers from three continents, identified through the Society of Critical Care Medicine's THRIVE international collaborative sites (follow-up clinics and peer support groups).

Subjects: Patients and caregivers following critical illness.

Interventions: Nil.

Measurements And Main Results: From 86 interviews (66 patients, 20 caregivers), we identified the following major themes: 1) Challenges for patients-interacting with the health system and gaps in care; managing others' expectations of illness and recovery. 2) Challenges for caregivers-health system shortfalls and inadequate communication; lack of support for caregivers. 3) Patient and caregiver-driven problem solving across the transitions of care-personal attributes, resources, and initiative; receiving support and helping others; and acceptance.

Conclusions: Survivors and caregivers experienced a range of challenges across the transitions of care. There were distinct and contrasting themes related to the caregiver experience. Survivors and caregivers used comparable problem-solving strategies to navigate the challenges encountered across the transitions of care.
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http://dx.doi.org/10.1097/CCM.0000000000005095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516700PMC
November 2021

Optimizing Critical Illness Recovery: Perspectives and Solutions From the Caregivers of ICU Survivors.

Crit Care Explor 2021 May 12;3(5):e0420. Epub 2021 May 12.

Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Scotland, United Kingdom.

Objectives: To understand the unmet needs of caregivers of ICU survivors, how they accessed support post ICU, and the key components of beneficial ICU recovery support systems as identified from a caregiver perspective.

Design: International, qualitative study.

Subjects: We conducted 20 semistructured interviews with a diverse group of caregivers in the United States, the United Kingdom, and Australia, 11 of whom had interacted with an ICU recovery program.

Setting: Seven hospitals in the United States, United Kingdom, and Australia.

Interventions: None.

Measurements And Main Results: Content analysis was used to explore prevalent themes related to unmet needs, as well as perceived strategies to improve ICU outcomes. Post-ICU care was perceived to be generally inadequate. Desired caregiver support fell into two main categories: practical support and emotional support. Successful care delivery initiatives included structured programs, such as post discharge telephone calls, home health programs, post-ICU clinics, and peer support groups, and standing information resources, such as written educational materials and online resources.

Conclusions: This qualitative, multicenter, international study of caregivers of critical illness survivors identified consistently unmet needs, means by which caregivers accessed support post ICU, and several care mechanisms identified by caregivers as supporting optimal ICU recovery.
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http://dx.doi.org/10.1097/CCE.0000000000000420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162533PMC
May 2021

Caregivers of Patients with Heart Failure: Burden and the Determinants of Health-Related Quality of Life.

Patient Prefer Adherence 2021 26;15:1153-1164. Epub 2021 May 26.

Real World Evidence, Cardiovascular, Renal and Metabolism Franchise, Novartis Pharma AG, Basel, Switzerland.

Purpose: To assess the burden among caregivers of patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤60%. The burden by New York Heart Association (NYHA) functional class was also characterized.

Patients And Methods: A cross-sectional study was conducted in France, Germany, Italy, Spain, and UK from June to November 2019. Patient record forms were completed by 257 cardiologists and 158 general practitioners for consecutive HF patients. Caregivers who accompanied the patient to their consultation completed a caregiver self-completion survey voluntarily, which included the Family Caregiver Quality of Life Questionnaire (FAMQOL) and 5-level 5-dimension EuroQol questionnaire (EQ-5D-5L).

Results: We analyzed 361 caregivers of patients with HF (NYHA class I, n=41; II, n=212; III IV, n=108). Mean age of caregivers was 58.8 years (NYHA I/II/III-IV: 59.1/60.8/54.6 years; p=0.0029), with majority being females (73.1%). Caregivers spent on average 19.8 hours/week caring for a HF patient, which increased with increase in NYHA class (I/II/III-IV: 11.8/18.1/25.9 hours/week; p=0.0094). Caregivers (24.1%) reported providing emotional support/encouragement to patients as the most troublesome/inconvenient caregiving activity (no significant difference across NYHA class). Nearly one-third of caregivers experienced stress (NYHA I/II/III-IV: 17.1%/28.8%/40.7%; p=0.0111) and anxiety (26.8%/24.1%/39.8%; p=0.0127) due to caregiving burden. The overall FAMQOL mean score decreased significantly (poorer QoL) with increase in NYHA class (I/II/III-IV: 58.1/56.3/52.2; p=0.0069). A trend of decreasing scores with increasing NYHA class was observed across physical, emotional, and social domains (each p≤0.012).

Conclusion: Caregivers of HF patients with LVEF ≤60% experienced a significant burden, which was higher among caregivers of patients with more severe and symptomatic disease.
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http://dx.doi.org/10.2147/PPA.S297816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165301PMC
May 2021

Health-related quality of life and lifestyle changes in patients with chronic kidney disease and hyperkalaemia: Real-world data from the US, five European countries and China.

Int J Clin Pract 2021 Aug 17;75(8):e14326. Epub 2021 May 17.

Global Payer Evidence, AstraZeneca, Cambridge, UK.

Background: Chronic kidney disease patients have impaired health-related quality of life and an increased risk of hyperkalaemia.

Aims: The objective was to evaluate the impact of hyperkalaemia on health-related quality of life, and investigate lifestyle change recommendations, in these patients.

Methods: The Adelphi Real World Chronic Kidney Disease Specific Programme™ was used. Data were collected from physicians and patients with non-dialysis dependent stage 3a, 3b and 4 chronic kidney disease from the US, France, Germany, Spain, Italy, the UK and China. Patients completed the Kidney Disease Quality of Life Instrument and EuroQol-5D-3L. Analyses compared data between hyperkalaemic (serum potassium >5.0 mmol/L) and normokalaemic (serum potassium 3.5-5.0 mmol/L) patients.

Results: Overall, 1149 patients were included (hyperkalaemic: n = 216, normokalaemic: n = 933; US: n = 376, Europe: n = 490, China: n = 283). Hyperkalaemic vs normokalaemic patients experienced more symptoms (P < .001) and had numerically lower scores, indicating poorer health-related quality of life, in all Kidney Disease Quality of Life domains, with significant differences for three/five domains. Hyperkalaemic patients reported numerically lower EuroQol-5D-3L utility index and visual analogue scores, indicating poorer health status, than normokalaemic patients. A higher proportion of hyperkalaemic than normokalaemic patients were recommended to reduce dietary potassium (P < .05). More normokalaemic than hyperkalaemic patients reported making a radical change in five/six recommended lifestyle changes, with the difference significant for four/six recommendations.

Conclusions: Hyperkalaemia is associated with an incremental impairment of the health-related quality of life in chronic kidney disease patients. A better understanding of the impact of hyperkalaemia in these patients could improve patient outcomes.
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http://dx.doi.org/10.1111/ijcp.14326DOI Listing
August 2021

Association of Delirium during Critical Illness With Mortality: Multicenter Prospective Cohort Study.

Anesth Analg 2021 11;133(5):1152-1161

Department of Anesthesiology, Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, Tennessee.

Background: The temporal association of delirium during critical illness with mortality is unclear, along with the associations of hypoactive and hyperactive motoric subtypes of delirium with mortality. We aimed to evaluate the relationship of delirium during critical illness, including hypoactive and hyperactive motoric subtypes, with mortality in the hospital and after discharge up to 1 year.

Methods: We analyzed a prospective cohort study of adults with respiratory failure and/or shock admitted to university, community, and Veterans Affairs hospitals. We assessed patients using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit (ICU) and defined the motoric subtype according to the corresponding Richmond Agitation-Sedation Scale if delirium was present. We used Cox proportional hazard models, adjusted for baseline characteristics, coma, and daily hospital events, to determine whether delirium on a given day predicted mortality the following day in patients in the hospital and also to determine whether delirium presence and duration predicted mortality after discharge up to 1 year in patients who survived to hospital discharge. We performed similar analyses for hypoactive and hyperactive subtypes of delirium.

Results: Among 1040 critically ill patients, 214 (21%) died in the hospital and 204 (20%) died out-of-hospital by 1 year. Delirium was common, occurring in 740 (71%) patients for a median (interquartile range [IQR]) of 4 (2-7) days. Hypoactive delirium occurred in 733 (70%) patients, and hyperactive occurred in 185 (18%) patients, with a median (IQR) of 3 (2-7) days and 1 (1-2) days, respectively. Delirium on a given day (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.32-6.21; P = .008), in particular the hypoactive subtype (HR, 3.35; 95% CI, 1.51-7.46; P = .003), was independently associated with an increased risk of death the following day in the hospital. Hyperactive delirium was not associated with an increased risk of death in the hospital (HR, 4.00; 95% CI, 0.49-32.51; P = .19). Among hospital survivors, neither delirium presence (HR, 1.01; 95% CI, 0.82-1.24; P = .95) nor duration (HR, 0.99; 95% CI, 0.97-1.01; P = .56), regardless of motoric subtype, was associated with mortality after hospital discharge up to 1 year.

Conclusions: Delirium during critical illness is associated with nearly a 3-fold increased risk of death the following day for patients in the hospital but is not associated with mortality after hospital discharge. This finding appears primarily driven by the hypoactive motoric subtype. The independent relationship between delirium and mortality occurs early during critical illness but does not persist after hospital discharge.
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http://dx.doi.org/10.1213/ANE.0000000000005544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542584PMC
November 2021

Trajectories of depression in sepsis survivors: an observational cohort study.

Crit Care 2021 04 29;25(1):161. Epub 2021 Apr 29.

Institute of General Practice and Family Medicine, Jena University Hospital, Bachstraße 18, 07743, Jena, Germany.

Background: Advances in critical care medicine have led to a growing number of critical illness survivors. A considerable part of them suffers from long-term sequelae, also known as post-intensive care syndrome. Among these, depressive symptoms are frequently observed. Depressive symptom trajectories and associated factors of critical illness survivors have rarely been investigated. Study objective was to explore and compare different trajectories of depressive symptoms in sepsis survivors over 1 year after discharge from ICU.

Methods: Data of a randomized controlled trial on long-term post-sepsis care were analyzed post hoc. Depressive symptoms were collected at 1, 6 and 12 months post-ICU discharge using the Major Depression Inventory (MDI), among others. Statistical analyses comprised descriptive analysis, univariate and multivariate, linear and logistic regression models and Growth Mixture Modeling.

Results: A total of 224 patients were included into this analysis. We identified three latent classes of depressive symptom trajectories: Over the course of 1 year, 152 patients recovered from mild symptoms, 27 patients showed severe persistent symptoms, and 45 patients recovered from severe symptoms. MDI sum scores significantly differed between the three classes of depressive symptom trajectories at 1 and 6 months after ICU discharge (p < 0.024 and p < 0.001, respectively). Compared with other classes, patients with the mild recovered trajectory showed lower levels of chronic pain (median sum score of 43.3 vs. 60.0/53.3 on the Graded Chronic Pain Scale, p < 0.010) and posttraumatic stress (4.6% with a sum score of ≥ 35 on the Posttraumatic Stress Scale 10 vs. 48.1%/33.3%, p < 0.003); and higher levels of health-related quality of life (HRQOL) using the Short Form-36 scale within 1 month after ICU discharge (p < 0.035).

Conclusions: In the first year after discharge from ICU, sepsis survivors showed three different trajectories of depressive symptoms. Course and severity of depressive symptoms were associated with chronic pain, posttraumatic stress and reduced HRQOL at discharge from ICU. Regular screening of sepsis survivors on symptoms of depression, chronic pain and posttraumatic stress within 1 year after ICU may be considered. Trial registration ISRCTN, ISRCTN 61744782. Registered April 19, 2011-Retrospectively registered, http://www.isrctn.com/ISRCTN61744782 .
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http://dx.doi.org/10.1186/s13054-021-03577-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082919PMC
April 2021

Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults.

Chest 2021 Sep 2;160(3):909-918. Epub 2021 Apr 2.

Department of Emergency Medicine, Vanderbilt University Medical Center, TN.

Background: Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition.

Research Question: Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function?

Study Design And Methods: This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group.

Results: Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42).

Interpretation: In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function.

Trial Registry: ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.03.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449000PMC
September 2021

Motoric Subtypes of Delirium and Long-Term Functional and Mental Health Outcomes in Adults After Critical Illness.

Crit Care Med 2021 05;49(5):e521-e532

Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center and the Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN.

Objectives: Adult ICU survivors that experience delirium are at high risk for developing new functional disabilities and mental health disorders. We sought to determine if individual motoric subtypes of delirium are associated with worse disability, depression, and/or post-traumatic stress disorder in ICU survivors.

Design: Secondary analysis of a prospective multicenter cohort study.

Setting: Academic, community, and Veteran Affairs hospitals.

Patients: Adult ICU survivors of respiratory failure and/or shock.

Interventions: We assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation and Sedation Scale daily during hospitalization. We classified delirium as hypoactive (Richmond Agitation and Sedation Scale ≤ 0) or hyperactive (Richmond Agitation and Sedation Scale > 0). At 3- and 12-month postdischarge, we assessed for dependence in activities of daily living and instrumental activities of daily living, symptoms of depression, and symptoms of post-traumatic stress disorder. Adjusting for baseline and inhospital covariates, multivariable regression examined the association of exposure to delirium motoric subtype and long-term outcomes.

Measurements And Main Results: In our cohort of 556 adults with a median age of 62 years, hypoactive delirium was more common than hyperactive (68.9% vs 16.8%). Dependence on the activities of daily living was present in 37% at 3 months and 31% at 12 months, whereas dependence on instrumental activities of daily living was present in 63% at 3 months and 56% at 12 months. At both time points, depression and post-traumatic stress disorder rates were constant at 36% and 5%, respectively. Each additional day of hypoactive delirium was associated with higher instrumental activities of daily living dependence at 3 months only (0.24 points [95% CI, 0.07-0.41; p = 0.006]). There were no associations between the motoric delirium subtype and activities of daily living dependence, depression, or post-traumatic stress disorder.

Conclusions: Longer duration of hypoactive delirium, but not hyperactive, was associated with a minimal increase in early instrumental activities of daily living dependence scores in adult survivors of critical illness. Motoric delirium subtype was neither associated with early or late activities of daily living functional dependence or mental health outcomes, nor late instrumental activities of daily living functional dependence.
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http://dx.doi.org/10.1097/CCM.0000000000004920DOI Listing
May 2021

Burden of Heart Failure on Patient Daily Life and Patient-Physician Discordance in Disease Management - Results From a Cross-Sectional Survey in Japan.

Circ Rep 2020 Nov 17;2(12):722-729. Epub 2020 Nov 17.

Medical Division, Novartis Pharma K.K. Tokyo Japan.

We investigated the impact of heart failure (HF) on daily life and satisfaction with current HF medication from the patient perspective in a real-world study in Japan. A cross-sectional survey of 154 HF patients treated by 58 cardiologists was conducted in Japan using patient self-completed questionnaires about their daily life and satisfaction with HF medication, as well as patient record forms completed by their physicians capturing corresponding data. The mean age of patients was 72.7 years. The proportion of patients within New York Heart Association Class I, II, III, and IV was 39%, 44%, 16%, and 1%, respectively. Symptoms reported by patients included dyspnea when active (46%), nocturia (43%), anxiety (18%), and depression (6%). There was a discordance between physician- and patient-reported symptoms, especially for nocturia and inability to sleep. The most frequent lifestyle recommendation from physicians was 'reduce salt/sodium intake', but only 51% of patients receiving this recommendation followed the advice. In all, 44% of patients reported dissatisfaction with their current medication; according to the patients, 27% reported no discussion with their physicians about their prescribed medication, while physicians reported the opposite. HF negatively impacts patient daily life. There is discordance between patients and physicians in symptom reporting, lifestyle modification advice and adherence, and reported medication decision making. Gaps in patient-physician communication exist.
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http://dx.doi.org/10.1253/circrep.CR-20-0073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937529PMC
November 2020

Characterizing the role of, and physical and emotional burden on caregivers of patients with heart failure: Results from a cross-sectional survey in Japan.

Geriatr Nurs 2021 Mar-Apr;42(2):379-385. Epub 2021 Feb 20.

Medical Division, Novartis Pharma K.K., Tokyo, Japan.

The aim of this cross-sectional survey was to characterize the role of and burden on caregivers of heart failure (HF) patients in Japan, since such data are limited at present. Data from 126 caregivers whose average age was 63.5 years were analyzed. Helping to prepare meals/cooking was the most frequently reported activity (47% of caregivers); 24% found this the most burdensome. The most frequently reported physical consequence of caregiving was feeling physically tired (44%); emotionally worrying about the patient (62%) was the most frequent psychological consequence. Approximately half of the caregivers reported that caring for patients impacted their lifestyle. Although 40% of caregivers asked questions to physicians regarding diet or lifestyle modifications, 19% did not ask any. Caregivers play a crucial role in the management of HF patients in Japan but experience physical and emotional burden. Solutions are required to reduce the caregiver burden associated with HF.
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http://dx.doi.org/10.1016/j.gerinurse.2021.01.010DOI Listing
September 2021

Benefits of Peer Support for Intensive Care Unit Survivors: Sharing Experiences, Care Debriefing, and Altruism.

Am J Crit Care 2021 03;30(2):145-149

Kimberley J. Haines is physiotherapy lead and senior ICU physiotherapist, Department of Physiotherapy, Western Health, Sunshine Hospital, St Albans, Australia and an associate professor, Centre for Integrated Critical Care, University of Melbourne, Australia.

Background: After critical illness, patients are often left with impairments in physical, social, emotional, and cognitive functioning. Peer support interventions have been implemented internationally to ameliorate these issues.

Objective: To explore what patients believed to be the key mechanisms of effectiveness of peer support programs implemented during critical care recovery.

Methods: In a secondary analysis of an international qualitative data set, 66 telephone interviews with patients were undertaken across 14 sites in Australia, the United Kingdom, and the United States to understand the effect of peer support during recovery from critical illness. Prevalent themes were documented with framework analysis.

Results: Most patients who had been involved in peer support programs reported benefit. Patients described 3 primary mechanisms: (1) sharing experiences, (2) care debriefing, and (3) altruism.

Conclusion: Peer support is a relatively simple intervention that could be implemented to support patients during recovery from critical illness. However, more research is required into how these programs can be implemented in a safe and sustainable way in clinical practice.
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http://dx.doi.org/10.4037/ajcc2021702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182973PMC
March 2021

Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis.

N Engl J Med 2021 04 2;384(15):1424-1436. Epub 2021 Feb 2.

From the Critical Illness, Brain Dysfunction, and Survivorship Center (C.G.H., J.C.J., A.S.H., B.T.P., O.M.O., R.R., J.L.S., A.L.K, M.B.P., N.E.B., T.D.G., R.S.D., G.R.B., E.W.E., P.P.P.), the Center for Health Services Research (C.G.H., J.C.J., R.R., M.B.P., T.D.G., R.S.D., E.W.E., P.P.P.), the Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology (C.G.H., P.P.P.), the Division of Allergy, Pulmonary, and Critical Care Medicine (J.C.J., B.T.P., G.R.B., E.W.E.), and the Division of General Internal Medicine and Public Health (R.S.D.), Department of Medicine, the Departments of Biostatistics (O.M.O., R.R.) and Pharmaceutical Services (J.L.S.), and Division of Trauma and Surgical Critical Care, Department of Surgery (M.B.P.), Vanderbilt University Medical Center, and the Anesthesia Service (C.G.H., P.P.P.), Research Service (J.C.J.), Surgical Service (M.B.P.), and Geriatric Research, Education and Clinical Center (R.S.D., E.W.E.), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System - both in Nashville; the Neuroscience Institute and Department of Critical Care Medicine, Maine Medical Center, Portland (P.T.M.); the Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston (J.W.D., M.S.D.); the Departments of Pharmacy (J.T.S., L.N.B.) and Surgery (J.T.S.) and the Center for Outcomes Research (J.T.S.), Houston Methodist, and the Pulmonary, Critical Care and Sleep Medicine Section, Ben Taub Hospital, Baylor College of Medicine (K.K.G.), Houston; the Division of Pulmonary/Critical Care Medicine, University of Texas Health, and the South Texas Veterans Health Care System, San Antonio (A.A.); and Texas Health Harris Methodist Hospital Fort Worth, Fort Worth (A.S.) - all in Texas; the University of Sydney, and the Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney, and the Department of Anesthesiology, University of Wisconsin, Madison (R.D.S.); Pulmonary and Critical Care Medicine, Baton Rouge General Medical Center and Our Lady of the Lake Regional Medical Center, Baton Rouge, LA (H.R.O.); the Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco (M.A.G.); Pulmonary and Critical Care, Mission Hospital, Asheville, NC (G.J.S.); the Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus (N.E.B.); and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh (T.D.G.).

Background: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.

Methods: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.

Results: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups.

Conclusions: Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).
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http://dx.doi.org/10.1056/NEJMoa2024922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162695PMC
April 2021

Relations between earthquake distributions, geological history, tectonics and rheology on the continents.

Philos Trans A Math Phys Eng Sci 2021 Mar 1;379(2193):20190412. Epub 2021 Feb 1.

Department of Earth Sciences, University of Cambridge, Cambridge, Cambridgeshire, UK.

This paper is concerned with the distribution of earthquakes, particularly their depths, with the temperature of the material in which they occur, and with the significance of both for the rheology and deformation of the continental lithosphere. Earthquakes on faults are generated by the sudden release of elastic energy that accumulates during slow plate motions. The nonlinear high-temperature creep that localizes such energy accumulation is, in principle, well understood and can be described by rheological models. But the same is not true of seismogenic brittle failure, the main focus of this paper, and severely limits the insights that can be obtained by simulations derived from geodynamical modelling of lithosphere deformation. Through advances in seismic tomography, we can now make increasingly detailed maps of lithosphere thickness on the continents. The lateral variations are dramatic, with some places up to 300 km thick, and clearly relate to the geological history of the continents as well as their present-day deformation. Where the lithosphere thickness is about 120 km or less, continental earthquakes are generally confined to upper crustal material that is colder than about 350°C. Within thick lithosphere, and especially on its edges, the entire crust may be seismogenic, with earthquakes sometimes extending into the uppermost mantle if the Moho is colder than 600°C, but the continental mantle is generally aseismic. Earthquakes in the continental lower crust at 400-600°C require the crust to be anhydrous and so are a useful guide or proxy to both composition and strength. These patterns and correlations have important implications for the geological evolution of the continents. They can be seen to have influenced features as diverse as the location of post-collisional rifting; cratonic basin formation; the location, origin and timing of granulite-facies metamorphism; and the formation, longevity and strength of cratons. In addition, they have important consequences for earthquake hazard assessment in the slowly deforming edges and interiors of continental shields or platforms, where the large seismogenic thickness can host very large earthquakes. This article is part of a discussion meeting issue 'Understanding earthquakes using the geological record'.
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http://dx.doi.org/10.1098/rsta.2019.0412DOI Listing
March 2021

Social and economic influences on disparities in the health of racial and ethnic group Canadian immigrants.

Can J Public Health 2021 06 8;112(3):482-492. Epub 2021 Jan 8.

Department of Psychology and Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.

Objective: To examine social, economic, and migratory influences on the health of racial and ethnic minority groups in Canada, with a special focus on Caribbean immigrants.

Methods: Combined annual cycles (2011-2016) of the Canadian Community Health Survey (CCHS) data totaling over 300,000 adult Canadian residents were aggregated. Descriptive statistics and multivariable logistic regression models were used to examine the prevalence and associated factors of (1) cardiovascular disease diagnosed by a healthcare professional, and (2) self-rated general health among racial and ethnic groups.

Results: Caribbeans in general, Black and other non-White Canadians had significantly higher odds (adjusted for age/sex) of reporting any cardiovascular disease compared with White Canadians. Only non-Caribbean Blacks had higher odds of self-rated fair or poor general health compared with White Canadians. Multivariate logistic regression models revealed that after controlling for social and demographic factors, immigration status and years since migration, Caribbean non-Blacks and Black Caribbeans were at higher odds of having a doctor-reported cardiovascular health condition compared with White Canadians. Caribbean non-Blacks also had higher odds of fair or poor self-rated health than White Canadians.

Conclusion: The results of this study highlight the need for additional investigations of other potential influences on physical health statuses, especially among migrants and those of African ancestry who might be more prone to adverse health outcomes.
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http://dx.doi.org/10.17269/s41997-020-00446-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076413PMC
June 2021

Multimodal Treatment Patterns for Osteoarthritis and Their Relationship to Patient-Reported Pain Severity: A Cross-Sectional Survey in the United States.

J Pain Res 2020 23;13:3415-3425. Epub 2020 Dec 23.

Real World Research, Adelphi Real World, Bollington, Cheshire, UK.

Purpose: The purpose of this study was to assess how patient-reported pain is related to osteoarthritis (OA) treatment patterns in routine clinical practice.

Patients And Methods: Data were collected between February and May 2017 from 153 United States (US) primary care physicians, rheumatologists, and orthopedic surgeons. Each invited up to nine consecutive patients to rate their OA pain in the last week. Physicians provided demographic, clinical, and treatment information for patients, including nonpharmacologic therapies ever recommended, currently recommended over-the-counter (OTC) medications, and currently and ever prescribed medications for the management of OA. Findings for patients with mild (0─3), moderate (4─6), and severe current pain (7─10) were compared using appropriate statistics.

Results: Among the 841 patients (61% female; mean 65 years; 57% knee OA), 45% reported mild, 36% moderate, and 19% severe current OA pain. Current treatment modalities differed by pain severity (<0.05). Most patients (70%) had been recommended nonpharmacologic therapy and 40% were currently recommended OTC medications. More patients with moderate (81%) or severe pain (78%) currently received prescription medications, with or without nonpharmacologic therapy, versus those with mild pain (67%). Overall, 47% of patients currently received just one prescription drug, while 49% had received one prescription drug ever. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common current (58%) and ever received (88%) prescriptions. Current NSAID prescriptions were not associated with pain severity. Acetaminophen recommendations, opioid prescriptions (current and ever), and multiple prescription medications tried were numerically highest in the severe pain group (all <0.05 by pain severity). In all groups, >80% of treatment switches were due to lack of efficacy.

Conclusion: Real-life treatment patterns for OA in the US are significantly associated with current patient-reported pain. Combining nonpharmacologic and pharmacologic treatments is common but higher pain ratings are associated with multiple failed prescription treatments. Current use of acetaminophen and opioids, but not NSAIDs, increases alongside pain severity.
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http://dx.doi.org/10.2147/JPR.S285124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767791PMC
December 2020

Complete resolution of acute pancreatitis-induced chylous ascites following transhepatic portal vein stenting.

BMJ Case Rep 2020 Dec 13;13(12). Epub 2020 Dec 13.

Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.

We introduce a case of a 73-year-old man who developed intractable chylous ascites due to portal vein compression as a result of peripancreatic inflammatory changes after acute biliary pancreatitis. After stenting the portal vein stenosis, the chylous ascites improved from requiring weekly paracentesis to requiring no drainage within 4 months of the procedure and at the 15-month follow-up. To our knowledge, it is the first case reported in the literature where portal vein stenting has successfully been used to treat pancreatitis-induced chylous ascites.
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http://dx.doi.org/10.1136/bcr-2020-235986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737061PMC
December 2020
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