Factors associated with mortality in patients with COVID-19 admitted to intensive care: a systematic review and meta-analysis.

Identification of high-risk patients admitted to intensive care with COVID-19 may inform management strategies. The objective of this meta-analysis was to determine factors associated with mortality among adults with COVID-19 admitted to intensive care by searching databases for studies published between 1 January 2020 and 6 December 2020. Observational studies of COVID-19 adults admitted to critical care were included. Studies of mixed cohorts and intensive care cohorts restricted to a specific patient sub-group were excluded. Dichotomous variables were reported with pooled OR and 95%CI, and continuous variables with pooled standardised mean difference (SMD) and 95%CI. Fifty-eight studies (44,305 patients) were included in the review. Increasing age (SMD 0.65, 95%CI 0.53-0.77); smoking (OR 1.40, 95%CI 1.03-1.90); hypertension (OR 1.54, 95%CI 1.29-1.85); diabetes (OR 1.41, 95%CI 1.22-1.63); cardiovascular disease (OR 1.91, 95%CI 1.52-2.38); respiratory disease (OR 1.75, 95%CI 1.33-2.31); renal disease (OR 2.39, 95%CI 1.68-3.40); and malignancy (OR 1.81, 95%CI 1.30-2.52) were associated with mortality. A higher sequential organ failure assessment score (SMD 0.86, 95%CI 0.63-1.10) and acute physiology and chronic health evaluation-2 score (SMD 0.89, 95%CI 0.65-1.13); a lower PaO2 :FI O2 (SMD -0.44, 95%CI -0.62 to -0.26) and the need for mechanical ventilation at admission (OR 2.53, 95%CI 1.90-3.37) were associated with mortality. Higher white cell counts (SMD 0.37, 95%CI 0.22-0.51); neutrophils (SMD 0.42, 95%CI 0.19-0.64); D-dimers (SMD 0.56, 95%CI 0.43-0.69); ferritin (SMD 0.32, 95%CI 0.19-0.45); lower platelet (SMD -0.22, 95%CI -0.35 to -0.10); and lymphocyte counts (SMD -0.37, 95%CI -0.54 to -0.19) were all associated with mortality. In conclusion, increasing age, pre-existing comorbidities, severity of illness based on validated scoring systems, and the host response to the disease were associated with mortality; while male sex and increasing BMI were not. These factors have prognostic relevance for patients admitted to intensive care with COVID-19.

Risk factors and interventions associated with mortality or survival in adult COVID-19 patients admitted to critical care: a systematic review and meta-analysis

Patients with confirmed COVID-19 admitted to intensive care units have a high mortality rate, which appears to be associated with increasing age, male sex, smoking history, hypertension and diabetes mellitus. Methods: A systematic review to determine risk factors and interventions associated with mortality/survival in adult patients admitted to an intensive care unit (ICU) with confirmed COVID-19/SARS-CoV-2 infection. The protocol was registered with PROSPERO (CRD42020181185).Results: The search identified 483 abstracts between 1 January and 7 April 2020, of which nine studies were included in the final review. Only one study was of low bias. Advanced age (odds ratio [OR] 11.99, 95% confidence interval [CI] 5.35­18.62) and a history of hypertension were associated with mortality (OR 4.17, 95% CI 2.90­5.99). Sex was not associated with mortality. There was insufficient data to assess the association between other comorbidities, laboratory results or critical care risk indices and mortality.The critical care interventions of mechanical ventilation (OR 6.25, 95% CI 0.75­51.93), prone positioning during ventilation (OR 2.06, 95% CI 0.20­21.72), and extracorporeal membrane oxygenation (ECMO) (OR 8.00, 95% CI 0.69, 92.33) were not associated with mortality. The sample size was insufficient to conclusively determine the association between these interventions and ICUmortality. The need for inotropes or vasopressors was associated with mortality (OR 6.36, 95% CI 1.89­21.36). Conclusion: The studies provided little granular data to inform risk stratification or prognostication of patients requiring intensive

Accuracy of five on-site immunoassay drugs-of-abuse testing devices.

Many current "on-site" urine drug-testing products claim performance equivalent to laboratory testing. Five commercially available products (PharmScreen, Roche TestCup, Accusign DOA 2, Status DS, and American Bio Medica-Rapid Drug Screen) were challenged with quality-control specimens of known drug metabolite concentrations, 25% above and 25% below the SAMHSA cutoffs, and with known positive and negative donor specimens previously analyzed by immunoassay and gas chromatography-mass spectrometry. The results indicate discrepancies between claims and performance for all products, particularly with amphetamines. The implications for employer-based drug testing are discussed.

Advances in the diagnosis and treatment of children with serious mental illness.

As a nation, we are becoming aware that a significant number of children develop severe neuropsychiatric disorders. Unfortunately, knowledge of DSM-IV criteria does not always help the child and family social worker identify children with these disorders. Early onset schizophrenia, bipolar disorders, and severe depression can cause child behaviors that differ markedly from symptoms manifested by adults with serious mental illness. This article provides specific information for screening and treating children who develop long-term neuropsychiatric disorders.

Development of a sensitive porcine granulosa cell bioassay for follicle-stimulating hormone (FSH).

PURPOSE: Our objective was to develop a sensitive in vitro bioassay for follicle-stimulating hormone (FSH) that does not require the housing of animals in a research facility. MATERIALS AND METHODS: Porcine granulosa cells from 1- to 3-mm follicles were cultured on laminin for 48 hr in serum-free medium in the absence or presence of FSH or with other purified pituitary hormones, supplemented with 19-OH androstenedione. Estradiol accumulation in medium per microgram of DNA of cells was determined as a reflection of FSH-induced aromatase activity. RESULTS: FSH (0.01-10 ng/ml) caused a dose-dependent increase in estradiol production per microgram of DNA, with 1, 10, and 100 ng/ml significantly higher than control. Porcine FSH was approximately two fold more biopotent than rat FSH in this system. Higher doses of FSH (100 ng/ml) caused less estradiol accumulation, presumably reflecting FSH receptor down regulation. No other pituitary hormone produced significant estradiol accumulation. Unextracted serum from a patient with premature ovarian failure (10-50 microliters) was tested in parallel to purified rat FSH (0-50 ng/ml) in this system, resulting in similar estradiol accumulation per microgram of DNA. CONCLUSIONS: We have developed a porcine granulosa cell bioassay for FSH which is sensitive, is specific for FSH, and does not require the housing of animals on site. It can be completed by a technician within 4 working days and can detect FSH in a sample of human serum.

When community resources fail. Assisting the frightened or angry parent.

The failure to receive expected community services or specialized in-home medical care can be upsetting for some parents. This article is designed to help pediatricians interpret inappropriate family behaviors and to therapeutically defuse verbal anger, unrealistic expectations, and unfounded fears.

Toward multiculturality. Implications for the pediatrician.

Pediatricians must become more aware of America's growing ethnic, racial, and immigrant populations. A pediatrician who is not a member of an ethnic group can certainly become a minority family's doctor. It is the position of this article that the pediatrician must understand the importance of cultural issues and allow the family to become his or her guide. The suggested interview is provided as an outline for readers to both use with immigrants and to discover personal areas of cultural awareness and either knowledge or sensitivity gaps. Some individuals may want to only think about the questions and mentally relate them to certain families. Considering questions of this nature can help each pediatrician to become better spontaneous interviewers and to keep cultural concepts within working memory.

Understanding and helping families with neurodevelopmental and neuropsychiatric special needs.

Children with persistent neurodevelopmental and neuropsychiatric problems have extensive treatment, care, and community service needs. The child's disabilities can create new responsibilities, emotions, roles, and goals for the family. This article provides a framework for identifying and categorizing children with special needs. In addition, methods for assessing the family's psychoeducational, social, and emotional concerns are presented.

Prenatal origin of schizophrenia in a subgroup of discordant monozygotic twins.

Neuropathological, obstetrical, and epidemiological evidence increasingly suggest that some cases of adult-onset schizophrenia have prenatal or neonatal etiological roots. We evaluated the developmental histories of 23 monozygotic twin pairs discordant for schizophrenia to determine when they markedly and permanently began diverging from each other in motor skills or unusual behavior. Seven of the twins (30%) who later developed schizophrenia had become permanently different from their cotwins by age 5 years. The early divergence group differed from the others by multivariate tests (p = 0.002) for within-twin pair effects and by univariate tests for physical anomaly scores (p = 0.01), total finger ridge counts (p = 0.001), family history of psychosis (p = 0.004), and serious perinatal complications or low birth weight (p = 0.05). It is concluded that some cases of adult-onset schizophrenia are associated with prenatal events, which may include neurodevelopmental abnormalities or specific insults such as anoxia or infectious agents.

Isopropanol ingestion: a report of six episodes with isopropanol and acetone serum concentration time data.

The disposition of isopropanol and its major metabolite acetone were observed in six isopropanol ingestion episodes among five patients. Serum admission isopropanol and peak acetone concentrations ranged from 16.5 to 220 mg/dL and 141 to 585 mg/dL respectively. Ingestions ranged from 120 to 300 mL of 70% isopropanol with concomitant ethanol ingestion in two episodes. The isopropanol and acetone apparent half-lives ranged from 2.9 to 16.2 hours (h) and 7.6 to 26.2 h respectively. Two episodes of isopropanol ingestion were observed within a 9 month period in patient one. Isopropanol terminal elimination rate constants were 0.043 and 0.085 per hour (per h) with no marked difference in acetone terminal elimination rate constants (0.025 and 0.033 per h). Discrepancy between the two isopropanol elimination rate constants reflected concomitant ethanol abuse with the first ingestion. Reductions in isopropanol and acetone half-lives were also noted among patients requiring ventilatory support.

Clinical comparison of immunoradiometric assays for intact versus beta-specific human chorionic gonadotropin.

Monoclonal immunoradiometric assays (IRMA) for human chorionic gonadotropin (hCG) are available for either intact hCG (IhCG) or beta subunit hCG (beta hCG). The authors evaluated the clinical applications of both methods. Serum samples (N = 180) were divided into the following five clinical groups: Group 1: elevated luteinizing hormone (LH), follicular stimulating hormone (FSH), and thyroid-stimulating hormone (TSH), which share alpha subunits with hCG; Group 2: pregnancy; Group 3: trophoblastic tumors; Group 4: malignancy; and Group 5: positive rheumatoid factor or anti-nuclear antibody (ANA). The values of beta hCG versus IhCG for Group 1 showed statistical significance but no clinical significance, indicating negligible cross-reactivity in the alpha subunit group. beta hCG values, although exceeding the IhCG values, correlated well (r = 0.97) in intrauterine pregnancies; however, these values were not believed to be clinically significant. There is negligible interference by alpha subunits, elevated rheumatoid factor, ANA, or malignancy in the determination of IhCG versus beta hCG. The authors conclude that either the IhCG or beta hCG assays may be used in clinical conditions in which a potential exists for interference of alpha subunits, autoantibodies, or heterophile antibodies or in malignancy.

Comparison of derivatives for determination of codeine and morphine by gas chromatography/mass spectrometry.

Pentafluoropropionic anhydride (PFPA) and heptafluorobutyric anhydride (HFBA) derivatives of morphine and codeine demonstrated poor spectra due to low abundances of secondary and tertiary ions. Trifluoroacetamide (MBTFA) has been a widely used derivative; however, the internal standard, nalorphine, displayed very poor stability and this resulted in split peaks by gas chromatography making MBTFA unsuitable for quantitative methods. Quantitation of codeine and morphine using bis-trimethylsilyltrifluoroacetamide (BSTFA/1%TMS) revealed a significant gradual decrease (p less than 0.05) of peak area ratio (PAR) of codeine and morphine compared to the internal standard using selected ion monitoring (SIM). The acetic anhydride derivative showed no significant differences in the peak area ratios for codeine/IS over a period of 24 hours, although the coefficient of variation (CV) was higher for the acetyl derivative than for the TMS derivative of codeine. There was a significant difference associated with the acetyl derivative of morphine at 4 h post derivatization compared to the initial injection (p less than 0.05); however, the acetyl derivative was stable for 24 hours and had a CV of less than 10% at a cutoff of 300 ng/mL.

Disposition of 3-hydroxyquinidine in patients receiving initial intravenous quinidine gluconate for electrophysiology testing of ventricular tachycardia.

The formation rate constant and elimination rate constant for 3-hydroxyquinidine were determined in eight patients with ventricular tachycardia. These two parameters (mean +/- SD) were found to be 0.784 +/- 0.202 and 0.042 +/- 0.058 h-1, respectively. Coefficients of determination for the computer-generated line of best fit for serum concentration-time data were 0.986 +/- 0.008. Patients received two infusions of quinidine gluconate 5 mg/kg over 30 minutes separated by a 20-30 minute electrophysiologic testing period. Unbound and total 3-hydroxyquinidine concentrations were also determined. Among the eight patients, 3-hydroxyquinidine was 61.9 percent bound. Studies in healthy volunteers had shown 50 percent binding. Linear regression of unbound and total 3-hydroxyquinidine was described by the equation Y = 0.3814X-1.448, r = 0.813. Although half-lives of 3.5-12.4 hours had been reported in healthy volunteers, prolonged half-lives were observed in all but two of our arrhythmia patients.

Social intelligence, a neurological system?

Social intelligence has been researched for almost 70 yr. without definitive findings. During this period almost no attempts have been made to consider the complexity of the brain's anatomy and functions responsible for social competence. An ecological model focusing on social abilities within a biopsychosocial context is discussed along with supporting literature and an hypothesis for research. This argument invokes social intelligence as an independent brain system. It is suggested that neurological structures and chemical activities controlling social skills are directly influenced by the environment, individual beliefs, personal goals, and physiology.

Interpretation of urine quantitative 11-nor-delta-9 tetrahydrocannabinol-9-carboxylic acid to determine abstinence from marijuana smoking.

Verification of abstinence from cannabinoid use after initial identification requires documentation of falling quantitative levels of urinary 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) over an extended time period. We present a case in which normalization of quantitative urinary THC-COOH results to urinary creatinine is required to correctly interpret a series of quantitative levels and confirm abstinence from marijuana smoking.

Comparison of disposition values obtained by two assay methods for quinidine gluconate in patients with ventricular tachycardia.

Eight patients with previously untreated ventricular tachycardia, age 48.54 +/- 28.02 years (mean +/- SD), were enrolled in a protocol evaluating the disposition of quinidine gluconate as determined by two assay methods. Patients received two infusions of 5 mg/kg over 30 minutes separated by 20-30 (24.9 +/- 4.0) minutes of electrophysiologic testing. Blood samples were obtained at 0.17 hours and just prior to the second infusion, and then at 0.17, 0.25, 0.33, 1.0, 6.0, 12.0, and 24.0 hours after the second infusion. Paired serum samples were assayed for quinidine concentrations by fluorescence polarization immunoassay and high-performance liquid chromatography. The two assays compared well, with a linear regression equation of Y = 0.927X + 0.247 with a correlation coefficient of 0.985. With the exception of the beta elimination rate constant and beta distribution volume, t test comparison of disposition values demonstrated no significant difference. Differences in the estimates of the beta elimination rate constant reflected differences in the two methods and indicated that even though both assays were comparable, subtle differences in specificity could be reflected in significant differences in this variable.