Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review

Neurocritical Care - For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral...     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Preclinical Study of a Biodegradable Polymer-based Stent with Abluminal Sirolimus Release

Background

Bioabsorbable polymer stents with drug elution only on the abluminal surface may be safer than durable polymer drug-eluting stents.

Objective

To report the experimental findings with the Inspiron^TM stent - a bioabsorbable polymer-coated stent with sirolimus release from the abluminal surface only, recently approved for clinical use.

Methods

45 stents were implanted in the coronary arteries of 15 pigs. On day 28 after implantation, angiographic, intracoronary ultrasonographic and histomorphological data were collected. Five groups were analyzed: Group I (nine bare-metal stents); Group II (nine coated with bioabsorbable polymer on the luminal and abluminal surfaces); Group III (eight stents coated with bioabsorbable polymer on the abluminal surface); Group IV (nine stents with bioabsorbable polymer and sirolimus on the luminal and abluminal surfaces); and Group V (ten stents with bioabsorbable polymer and sirolimus only on the abluminal surface).

Results

The following results were observed for Groups I, II, III, IV and V, respectively: percentage stenosis of 29 ± 20; 36 ± 14; 33 ± 19; 22 ± 13 and 26 ± 15 (p = 0.443); late lumen loss (in mm) of 1.02 ± 0.60; 1.24 ± 0.48; 1.11 ± 0.54; 0.72 ± 0.44 and 0.78 ± 0.39 (p = 0.253); neointimal area (in mm²) of 2.60 ± 1.99; 2.74 ± 1.51; 2.74 ± 1.30; 1.30 ± 1.14 and 0.97 ± 0.84 (p = 0.001; Groups IV and V versus Groups I, II and III); and percentage neointimal area of 35 ± 25; 38 ± 18; 39 ± 19; 19 ± 18 and 15 ± 12 (p = 0.001; Groups IV and V versus Groups I, II and III). Injury and inflammation scores were low and with no differences between the groups.

Conclusion

The Inspiron^TM stent proved to be safe and was able to significantly inhibit the neointimal hyperplasia observed on day 28 after implantation in porcine coronary arteries.     

Impaired presynaptic function and elimination of synapses at premature stages during postnatal development of the cerebellum in the absence of CALEB (CSPG5/neuroglycan C)

Chicken acidic leucine‐rich EGF‐like domain‐containing brain protein (CALEB), also known as chondroitin sulfate proteoglycan (CSPG)5 or neuroglycan C, is a neural chondroitin sulfate‐containing and epidermal growth factor (EGF)‐domain‐containing transmembrane protein that is implicated in synaptic maturation. Here, we studied the role of CALEB within the developing cerebellum. Adult CALEB‐deficient mice displayed impaired motor coordination in Rota‐Rod experiments. Analysis of the neuronal connectivity of Purkinje cells by patch‐clamp recordings demonstrated impairments of presynaptic maturation of inhibitory synapses. GABAergic synapses on Purkinje cells revealed decreased evoked amplitudes, altered paired‐pulse facilitation and reduced depression after repetitive stimulation at early postnatal but not at mature stages. Furthermore, the elimination of supernumerary climbing fiber synapses on Purkinje cells was found to occur at earlier developmental stages in the absence of CALEB. For example, at postnatal day 8 in wild‐type mice, 54% of Purkinje cells had three or more climbing fiber synapses in contrast to mutants where this number was decreased to less than 25%. The basic properties of the climbing fiber Purkinje cell synapse remained unaffected. Using Sholl analysis of dye‐injected Purkinje cells we revealed that the branching pattern of the dendritic tree of Purkinje cells was not impaired in CALEB‐deficient mice. The alterations observed by patch‐clamp recordings correlated with a specific pattern and timing of expression of CALEB in Purkinje cells, i.e. it is dynamically regulated during development from a high chondroitin sulfate‐containing form to a non‐chondroitin sulfate‐containing form. Thus, our results demonstrated an involvement of CALEB in the presynaptic differentiation of cerebellar GABAergic synapses and revealed a new role for CALEB in synapse elimination in Purkinje cells.     

Primary health care lessons from the northeast of Brazil: the Agentes de Saúde Program.

Market-led economic reforms are usually viewed as being in conflict with government-stimulated socioeconomic development for disadvantaged groups. Nevertheless, Ceará, a poor state in the Northeast of Brazil, has since 1987 pursued both of those strategies simultaneously. One part of that approach has been a program of nurse-directed auxiliary health workers serving about 5 million people--almost all the persons outside the capital city and half of those in the capital. The system requires that the auxiliaries, called agentes de saúde, live in the local communities that they serve. The health agents visit each home once a month to carry out a small number of priority health activities. While health agent positions are in high demand, the minimum-wage salary that the agents receive makes up only a small portion of the state budget. A key aspect of the system is timely and comprehensive information, which is based on agent visits and is managed by trained nurses. Since the health agents system was launched, there has been a rapid decline in infant mortality, a rapid rise in immunization, identification of bottlenecks limiting the utilization of other medical resources, and timely interventions in times of crisis. The health agents system has combined administrative decentralization with financial centralization during a period of electoral democratization. The system has strengthened Ceará's commitment to primary care even as market-oriented changes have reduced the overall role of government. The Ceará program is being copied throughout the Northeast and other regions of Brazil. The key role that nurses play in the Ceará program in organizing and leading a system of basic primary care in poor neighborhoods and rural areas may provide useful lessons for other countries. In addition, Ceará does not have many of the favorable characteristics of other countries that have successfully invested in primary health care. Ceará thus represents a more achievable model for other countries, where, like Brazil, income, educational levels, and land tenure equity are limited.     

Metabolically healthy overweight in young adulthood: is it a matter of duration and degree of overweight?

Background and aimGiven the controversy regarding metabolically healthy obesity, we studied the association between duration and degree of body mass index (BMI) from adolescence to early adulthood and metabolic status of both overweight/obese and under/normal weight subjects.Methods and resultsParticipants of the EPITeen cohort were evaluated at 13, 17, 21 and 24 years (n = 1040). Duration and degree of BMI in the 11-year period was summarized through the area under the curve of BMI (BMI_AUC). Metabolic health at 24 y was defined as optimal levels of lipids, blood pressure and glucose. The association between BMI_AUC per year and metabolic health was estimated through binary logistic regression models, adjusted for confounders and stratified by BMI. The proportion of metabolically healthy overweight/obesity at 24 y was 13.4%. After adjustment for sociodemographic and behavioural factors, the increase of one kg/m² in BMI on average per year during the period between 13 and 24 y was associated with 14% lower odds of being metabolically healthy among under/normal weight participants (OR = 0.86, 95% CI 0.78–0.94); and 8% lower odds of metabolic health among obese/overweight participants (OR = 0.92, 95% CI 0.85–1.00). After additional adjustment for waist circumference, the association was attenuated, especially in the obese/overweight group (OR = 1.03, 95% CI 0.93–1.14). About 20% of the metabolically healthy obese/overweight at 13 y transitioned to metabolically unhealthy obesity/overweight at 24 y.ConclusionThe results support the hypothesis that the healthy obesity phenotype could be explained by a lower exposure to adiposity, either by shorter time or lower quantity, and a more favourable body fat distribution.     

Haemodynamics during liver transplantation in familial amyloidotic polyneuropathy: study of the intraoperative cardiocirculatory data of 50 patients.

BACKGROUND: Circulatory instability frequently complicates liver transplantation for familial amyloidotic polyneuropathy (FAP) and may be a source of surgical morbidity and mortality. OBJECTIVE: To evaluate FAP intraoperative haemodynamic data and their relation to the duration of surgery, and need for anaesthetic drugs. RBC and sympathomimetic amines. SETTING: Clinical study during a four year period. PATIENTS (mean +/- SD): Group I included 50 consecutive FAP ATTR Met 30 recipients of first transplantation. Age was 35.3 +/- 7.1 years, neurological score 34.3 +/- 13 in 100 and time elapsed from first symptom 5.0 +/- 2.7 years. Group II (control), not different concerning age and sex, included 51 patients transplanted during the same period with other pathologies. METHOD: Anaesthetic protocol, monitoring and surgical techniques were similar in both groups. Data of the two groups were compared either by the Student's t-test or Fisher's exact test. RESULTS: Low values of systemic vascular resistance index were observed in both groups, with no differences between them. Systemic arterial pressures were usually lower in group I, because cardiac index and heart rate were also significantly lower, although within normal values. However, in group I, isoflurane (a vasodilator anaesthetic) was used during less time (p < 0.05) and in lower concentrations (p < 0.01) and phenylephrine was necessary in 26% of patients vs 0 patients in group II (p < 0.001). CONCLUSION: FAP patients presented a different intraoperative behaviour when compared to other patients submitted to liver transplantation. From a clinical point of view, the authors stress: 1--As a result of autonomic dysfunction, the administration of anaesthetic drugs to FAP patients always presents the risk of producing significant hypotension; even the use of ketamine does not prevent hypotension; 2--Safety is ensured by beat-to-beat surveillance of arterial pressures and the capacity to act immediately to support circulation; 3--These patients seem to be very sensitive to decreases in the pre-load; 4--Hypotension is also frequent with an adequate pre-load, usually as the result of low SVR; an infusion of a vasoconstrictor drug emerges as the most frequent treatment requested and our experience supports it as an effective one.     

Determinants of violence against health workers in Portugal

The focus of this article is on the determinants of workplace violence against health workers identified in two cross-sectional analytical studies. The prevalence of victims of the several types and of any-type of workplace violence was estimated in each study, as well as the relative frequency of the associated characteristics. Each dependent variable was also analyzed, in relation to the dichotomized independent variables using a stepwise logistic regression strategy. The Ministry of Health has adopted strategies, which include guidelines on what to do to prevent and correct violence against health workers and a workplace violence observatory. Workplace violence has societal, organizational and individual determinants that can be prevented and monitored.     

Constituents of Essential Oil of Commiphora guidotti.

From the essential oil of COMMIPHORA GUIDOTTI seven sesquiterpene hydrocarbons and a furanosesquiterpenoid, furanodiene, were isolated.