Obstetric anesthesia services in Israel snapshot (OASIS) study: A 72 hour cross-sectional observational study of workforce supply and demand

BACKGROUND: We planned an observational study to assess obstetric anesthesia services nationwide. We aimed to assess the effect of the anesthesia workload/workforce ratio on quality and safety outcomes of obstetric anesthesia care. METHODS: Observers prospectively collected data from labor units over 72 h (Wednesday, Thursday and Friday). Independent variables were workload (WL) and workforce (WF). WL was assessed by the Obstetric Anesthesia Activity Index (OAAI), which is the estimated time in a 24-h period spent on epidurals and all cesarean deliveries. Workforce (WF) was assessed by the number of anesthesiologists dedicated to the labor ward per week. Dependent variables were the time until anesthesiologist arrival for epidural (quality measure) and the occurrence of general anesthesia for urgent Cesarean section, CS, (safety measure). This census included vaginal deliveries and unscheduled (but not elective) CS. RESULTS: Data on 575 deliveries are from 12 maternity units only, primarily because a major hospital chain chose not to participate; eight other hospitals lacked institutional review board approval. The epidural response rate was 94.4%; 321 of 340 parturients who requested epidural analgesia (EA) received it. Of the 19 women who requested EA but gave birth without it, 14 (77%) were due to late arrival of the anesthesiologist. Median waiting times for anesthesiologist arrival ranged from 5 to 28 min. The OAAI varied from 4.6 to 25.1 and WF ranged from 0 to 2 per shift. Request rates for EA in hospitals serving predominantly orthodox Jewish communities and in peripheral hospitals were similar to those of the entire sample. More than a fifth (13/62; 21%) of the unscheduled CS received general anesthesia, and of these almost a quarter (3/13; 23%) were attributed to delayed anesthesiologist arrival. CONCLUSIONS: Inadequate WF allocations may impair quality and safety outcomes in obstetric anesthesia services. OAAI is a better predictor of WL than delivery numbers alone, especially concerning WF shortage. To assess the quality and safety of anesthetic services to labor units nationally, observational data on workforce, workload, and clinical outcomes should be collected prospectively in all labor units in Israel

Ashkenazi Jewish Centenarians Do Not Demonstrate Enrichment in Mitochondrial Haplogroup J

BACKGROUND: Association of mitochondrial haplogroup J with longevity has been reported in several population subgroups. While studies from northern Italy and Finland, have described a higher frequency of haplogroup J among centenarians in comparison to non-centenarian, several other studies could not replicate these results and suggested various explanations for the discrepancy. METHODOLOGY/PRINCIPAL FINDINGS: We have evaluated haplogroup frequencies among Ashkenazi Jewish centenarians using two different sets of matched controls. No difference was observed in the haplogroup J frequencies between the centenarians or either matched control group, despite adequate statistical power to detect such a difference. Furthermore, the lack of association was robust to population substructure in the Ashkenazi Jewish population. Given this discrepancy with the previous reported associations in the northern Italian and the Finnish populations, we conducted re-analysis of these previously published data, which supported one of several possible explanations: i) inadequate matching of cases and controls; ii) inadequate adjustment for multiple comparison testing; iii) cryptic population stratification. CONCLUSIONS/SIGNIFICANCE: There does not exist a universal association of mitochondrial haplogroup J with longevity across all population groups. Reported associations in specialized populations may reflect genetic or other interactions specific to those populations or else cryptic confounding influences, such as inadequate matching attributable to population substructure, which are of general relevance to all studies of the possible association of mitochondrial DNA haplogroups with common complex phenotypes

An Enantiomer of an Oral Small Molecule TSH Receptor Agonist Exhibits Improved Pharmacologic Properties

We are developing an orally available small molecule, allosteric TSH receptor (TSHR) agonist for follow up diagnostics of patients with thyroid cancer. The agonist C2 (NCGC00161870) that we have studied so far is a racemic mixture containing equal amounts of two enantiomers, E1 and E2. As enantiomers of many drugs exhibit different pharmacologic properties, we assessed the properties of E1 and E2. We separated the two enantiomers by chiral chromatography and determined E2 as the (S)-(+) isomer via crystal structure analysis. E1 and E2 were shown to bind differently to a homology model of the transmembrane domain of TSHR in which E2 was calculated to exhibit lower binding energy than E1 and was therefore predicted to be more potent than E1. In HEK293 cells expressing human TSHRs, C2, E1, and E2 were equally efficacious in stimulating cAMP production, but their potencies were different. E2 was more potent (EC50 = 18 nM) than C2 (EC50 = 46 nM) which was more potent than E1 (EC50 = 217 nM). In primary cultures of human thyrocytes, C2, E1, and E2 stimulated increases in thyroperoxidase mRNA of 92-, 55-, and 137-fold and in sodium-iodide symporter mRNA of 20-fold, 4-fold and 121-fold above basal levels, respectively. In mice, C2 stimulated an increase in radioactive iodine uptake of 1.5-fold and E2 of 2.8-fold above basal level, whereas E1 did not have an effect. C2 stimulated an increase in serum T4 of 2.4-fold, E1 of 1.9-fold, and E2 of 5.6-fold above basal levels, and a 5 day oral dosing regimen of E2 increased serum T4 levels comparable to recombinant human TSH (rhTSH, Thyrogen®). Thus, E2 is more effective than either C2 or E1 in stimulating thyroid function and as efficacious as rhTSH in vivo. E2 represents the next step toward developing an oral drug for patients with thyroid cancer