Enhanced recovery after surgery protocol and postoperative opioid prescribing for cesarean delivery: an interrupted time series analysis.

INTRODUCTION: Enhanced recovery after surgery (ERAS) pathways have emerged as a promising strategy to reduce postoperative opioid use and decrease the risk of developing new persistent opioid use in surgical patients. However, the association between ERAS implementation and discharge opioid prescribing practices is unclear. STUDY DESIGN: We conducted a retrospective observational quasi-experimental study of opioid-naïve patients aged 18+ undergoing cesarean delivery between February 2015 and December 2019 at a large academic center. An interrupted time series analysis (ITSA) was used to model the changes in pain medication prescribing associated with the implementation of ERAS to account for pre-existing temporal trends. RESULTS: Among the 1473 patients (out of 2249 total) who underwent cesarean delivery after ERAS implementation, 80.72% received a discharge opioid prescription vs. 95.36% at baseline. Pre-ERAS daily oral morphine equivalents (OME) on the discharge prescription decreased by 0.48 OME each month (p<0.01). There was a level shift of 35 more OME prescribed (p<0.01), followed by a monthly decrease of 1.4 OMEs per month after ERAS implementation (p<0.01). Among those who received a prescription, 61.35% received a total daily dose greater than 90 OME compared to 11.35% pre-implementation (p<0.01), while prescriptions with a total daily dose less than 50 OME decreased from 79.86 to 25.85% after ERAS implementation(p<0.01). CONCLUSION: Although ERAS implementation reduced the overall proportion of patients receiving a discharge opioid prescription after cesarean delivery, for the subset of patients receiving an opioid prescription, ERAS implementation may have inadvertently increased the prescribing of daily doses greater than 90 OME. This finding highlights the importance of early and continued evaluation after new policies are implemented.

Thyroglobulin-induced T-cell in vitro proliferation in Hashimoto's thyroiditis: identification of the responsive subset and effect of monoclonal antibodies directed to Ia antigens.

Recently it was reported that the peripheral blood and thyroid gland of patients with Hashimoto's thyroiditis contain activated (Ia+ and/or MLR4+) T cells and high levels of 5/9+ ("helper") T lymphocytes. In normal individuals the 5/9 monoclonal antibody recognizes a T-cell fraction that includes all T lymphocytes with inducer activities. Here, circulating 5/9+ and 5/9- T lymphocytes were isolated from patients with Hashimoto's disease, and the proliferative response induced by human thyroglobulin was investigated. The results show that the total thyroglobulin-induced lymphocyte DNA synthesis is confined to the 5/9+ T-cell fraction. Further subfractionation of 5/9+ into MLR4+ and MLR4- cells clearly indicates that no substantial differences exist in their proliferative capacities. Whether 5/9, MLR4, and Ia antigens, all expressed on the thyroglobulin-responsive T-cell subset, are involved in thyroglobulin-induced cell proliferation, was also analyzed. Although both 5/9 and MLR4 monoclonal antibodies had no effect, complete inhibition of antigen-induced blastogenesis was observed upon addition of monoclonal antibodies (D1/12 and BT2/9) directed to common determinants of Ia antigens. This inhibitory effect was also observed when T or non-T fractions were separately incubated with the monoclonal antibodies before culture. These results indicate that in humans, as in animals, the major histocompatibility complex may play a role in autoimmune thyroiditis. The data show that (a) the thyroglobulin-induced proliferative response is confined to a subset (5/9+) of T lymphocytes and (b) Ia antigens are involved in thyroglobulin-induced lymphocyte DNA synthesis in Hashimoto's disease.

Deficiency of the autologous mixed lymphocyte reaction in patients with autoimmune thyroid disease.

The proliferative response of T lymphocytes when cocultured with autologous non-T cells in the absence of any other stimulating substance has been termed the autologous mixed lymphocyte reaction (AMLR). The AMLR has been shown to be impaired in several autoimmune disorders, such as systemic lupus erythematosus, Sjögren's syndrome, and primary biliary cirrhosis. In this study we report marked deficiency in the AMLR in two autoimmune disorders: Hashimoto's and Graves' diseases. This impaired AMLR, probably related to previously described T cell subset imbalances, provides further evidence of altered interactions between the immunocompetent cellular subsets in patients with these pathological conditions. Additional preliminary observations suggest defective allogeneic mixed lymphocyte reactions as well.

[Methodological problems concerning the assay of sex hormone binding globulin with DEAE-cellulose]. / Problemi metodologici inerenti al radiodosaggio della sex hormone binding globulin con DEAE cellulosa.

Since 1966 a carrier protein for the sex hormones, testosterone and estradiol, has been identified. Mickelson and Petra measured SHBG concentration by adsorption method in 1974. The SHBG contained in serum is incubated with DHT-3H and adsorbed to a cellulose filter. In this study we have reviewed this method. The method showed good reproducibility with a coefficient of variation of 8,1% for low concentration of SHBG and 11,6% for high concentration. No effects of serum dilution was observed. Normal values, expressed as micrograms DHT bound in 100 ml serum, resulted: females, 0,88 +/- 0,08 (ES); males, 0,58 +/- 0,04; pregnancy, 2,94 +/- 0,4. The mean value for males was significantly lower than the mean value for normal females (P < 0,005); pregnancy had a mean value statistically different from the normal females (P < 0,001).