The Metabolic Syndrome: A Modern Plague Spread by Modern Technology

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73419/1/j.1751-7176.2009.00191.x.pd

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Dialect, interaction and class positioning at school: from deficit to difference to repertoire.

Sociolinguists have been fighting dialect prejudice since the 1960s, but deficit views of non-standard English are regaining currency in educational discourse. In this paper I argue that the traditional sociolinguistic response – stressing dialect systematicity and tolerance of ‘difference’ – may no longer be effective by questioning a key assumption that both deficit and difference approaches share, namely that there exist discrete varieties of English. Based on an empirical study of the language of working-class children in north-east England, I demonstrate that non-standard dialects of English do not have a discrete system of grammar that is isolated from other varieties; rather local dialect forms interact with a range of semiotic resources (including standard forms) within speakers’ repertoires. Interactional analyses of the children’s spontaneous speech highlight this hybridity, as well as the social meanings behind the linguistic choices children make. I conclude by addressing educational responses to non-standard dialect in the classroom, suggesting that it is not the presence or absence of non-standard forms in children’s speech that raises educational issues; rather, educational responses which problematise non-standard voices risk marginalising working-class speech, and may contribute to the alienation of working-class children, or significant groups of them, within the school system

Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda

Abstract Background: The Rwanda Human Resources for Health Program (HRH Program) is a 7-year (2012-2019) health professional training initiative led by the Government of Rwanda with the goals of training a large, diverse, and competent health workforce and strengthening the capacity of academic institutions in Rwanda. Methods: The data for this organizational case study was collected through official reports from the Rwanda Ministry of Health (MoH) and 22 participating US academic institutions, databases from the MoH and the College of Medicine and Health Sciences (CMHS) in Rwanda, and surveys completed by the co-authors. Results: In the first 5 years of the HRH Program, a consortium of US academic institutions has deployed an average of 99 visiting faculty per year to support 22 training programs, which are on track to graduate almost 4600 students by 2019. The HRH Program has also built capacity within the CMHS by promoting the recruitment of Rwandan faculty and the establishment of additional partnerships and collaborations with the US academic institutions. Conclusion: The milestones achieved by the HRH Program have been substantial although some challenges persist. These challenges include adequately supporting the visiting faculty; pairing them with Rwandan faculty (twinning); ensuring strong communication and coordination among stakeholders; addressing mismatches in priorities between donors and implementers; the execution of a sustainability strategy; and the decision by one of the donors not to renew funding beyond March 2017. Over the next 2 academic years, it is critical for the sustainability of the 22 training programs supported by the HRH Program that the health-related Schools at the CMHS significantly scale up recruitment of new Rwandan faculty. The HRH Program can serve as a model for other training initiatives implemented in countries affected by a severe shortage of health professionals

The sociology of cancer: a decade of research

Biomedicine is often presented as the driving force behind improvements in cancer care, with genomics the latest innovation poised to change the meaning, diagnosis, treatment, prevention and lived experience of cancer. Reviewing sociological analyses of a diversity of patient and practitioner experiences and accounts of cancer during the last decade (2007–17), we explore the experiences of, approaches to and understandings of cancer in this period. We identify three key areas of focus: (i) cancer patient experiences and identities; (ii) cancer risk and responsibilities and (iii) bioclinical collectives. We explore these sociological studies of societal and biomedical developments and how sociologists have sought to influence developments in cancer identities, care and research. We end by suggesting that we extend our understanding of innovations in the fields of cancer research to take better account of these wider social and cultural innovations, together with patients, activists' and sociologists' contributions therein

Why Should We Preserve Fishless High Mountain Lakes?

High mountain lakes are originally fishless, although many have had introductions of non-native fish species, predominantly trout, and recently also minnows introduced by fishermen that use them as live bait. The extent of these introductions is general and substantial often involving many lakes over mountain ranges. Predation on native fauna by introduced fish involves profound ecological changes since fish occupy a higher trophic level that was previously inexistent. Fish predation produces a drastic reduction or elimination of autochthonous animal groups, such as amphibians and large macroinvertebrates in the littoral, and crustaceans in the plankton. These strong effects raise concerns for the conservation of high mountain lakes. In terms of individual species, those adapted to live in larger lakes have suffered a higher decrease in the size of their metapopulation. This ecological problem is discussed from a European perspective providing examples from two study areas: the Pyrenees and the Western Italian Alps. Species-specific studies are urgently needed to evaluate the conservation status of the more impacted species, together with conservation measures at continental and regional scales, through regulation, and at local scale, through restoration actions, aimed to stop further invasive species expansions and to restore the present situation. At different high mountain areas of the world, there have been restoration projects aiming to return lakes to their native fish-free status. In these areas autochthonous species that disappeared with the introduction of fish are progressively recovering their initial distribution when nearby fish-free lakes and ponds are available

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Effects of dexmedetomidine on oxygenation during one-lung ventilation for thoracic surgery in adults

Study Objective : To evaluate the effects of dexmedetomidine on hypoxic pulmonary vasoconstriction (HPV) and oxygenation during one-lung ventilation (OLV) in adults undergoing thoracic surgery. Design : Prospective, randomized, double-blinded trial. Setting : Tertiary care, University-based hospital. Patients : Nineteen adult patients undergoing thoracic surgery requiring OLV. Interventions : During inhalational anesthesia with desflurane, patients were randomized to receive either dexmedetomidine (bolus dose of 0.3 μg/kg followed by an infusion of 0.3 μg/kg/hr) or saline placebo. Measurements : Three arterial blood gas samples (ABG) were obtained to evaluate the effects of dexmedetomidine on oxygenation. Secondary outcomes included differences in hemodynamic parameters (heart rate and mean arterial pressure), end-tidal desflurane concentration required to maintain the bispectral index (BIS) at 40-60, supplemental fentanyl to maintain hemodynamic stability, and phenylephrine to keep the mean arterial pressure (MAP) within 10% of baseline values. Main Results : Oxygenation during OLV did not change following the administration of dexmedetomidine (PaO2/FiO2 ratio of 188 ± 115 in dexmedetomidine patients versus 135 ± 70 mmHg in placebo patients). There were no differences in hemodynamic variables or depth of anaesthesia between the two groups. With the administration of dexmedetomidine, there was a decrease in the expired concentration of desflurane required to maintain the BIS at 40-60 when compared with the control group (4.5 ± 0.8% versus 5.1 ± 0.8%). In patients receiving dexmedetomidine, fentanyl requirements were decreased when compared to placebo (2.7 μg/kg/patient versus 3.1 μg/kg/patient). However, more patients receiving dexmedetomidine required phenylephrine to maintain hemodynamic stability (6 of 9 patients versus 3 of 10 patients) and the total dose of phenylephrine was greater in patients receiving dexmedetomidine when compared with placebo 10.3 μg/kg/patient versus 1.1 μg/kg/patient). Conclusion : Dexmedetomidine does not adversely affect oxygenation during OLV in adults undergoing thoracic surgical procedures. The improvement in oxygenation in the dexmedetomidine patients may be related to a decrease in the requirements for inhalational anaesthetic agents thereby limiting its effects on HPV