Electroencephalography for predicting antidepressant treatment success: A systematic review and meta-analysis.

BACKGROUND: Patients suffering from major depressive disorder (MDD) regularly experience non-response to treatment for their depressive episode. Personalized clinical decision making could shorten depressive episodes and reduce patient suffering. Although no clinical tools are currently available, machine learning analysis of electroencephalography (EEG) shows promise in treatment response prediction. METHODS: With a systematic review and meta-analysis, we evaluated the accuracy of EEG for individual patient response prediction. Importantly, we included only prediction studies that used cross-validation. We used a bivariate model to calculate prediction success, as expressed by area-under the curve, sensitivity and specificity. Furthermore, we analyzed prediction success for separate antidepressant interventions. RESULTS: 15 studies with 12 individual patient samples and a total of 479 patients were included. Research methods varied considerably between studies. Meta-analysis of results from this heterogeneous set of studies resulted in an area under the curve of 0.91, a sensitivity of 83 % (95 % CI 74-89 %), and a specificity of 86 % (95 % CI 81-90 %). Classification performance did not significantly differ between treatments. Although studies were all internally validated, no externally validated studies have been reported. We found substantial risk of bias caused by methodological shortcomings such as non-independent feature selection, though performance of non-biased studies was comparable. LIMITATIONS: Sample sizes were relatively small and no study used external validation, increasing the risk of overestimation of accuracy. CONCLUSIONS: Electroencephalography can predict the response to antidepressant treatment with high accuracy. However, future studies with more rigorous validation are needed to produce a clinical tool to guide interventions in MDD. PROSPERO REGISTRATION NUMBER: CRD42021268169.

Response times for emergency cesarean delivery: use of simulation drills to assess and improve obstetric team performance.

OBJECTIVE: We documented time to key milestones and determined reasons for transport-related delays during simulated emergency cesarean. STUDY DESIGN: Prospective, observational investigation of delivery of care processes by multidisciplinary teams of obstetric providers on the labor and delivery unit at Lucile Packard Children's Hospital, Stanford, CA, USA, during 14 simulated uterine rupture scenarios. The primary outcome measure was the total time from recognition of the emergency (time zero) to that of surgical incision. RESULT: The median (interquartile range) from time zero until incision was 9 min 27 s (8:55 to 10:27 min:s). CONCLUSION: In this series of emergency cesarean drills, our teams required approximately nine and a half minutes to move from the labor room to the nearby operating room (OR) and make the surgical incision. Multiple barriers to efficient transport were identified. This study demonstrates the utility of simulation to identify and correct institution-specific barriers that delay transport to the OR and initiation of emergency cesarean delivery.

Intrathecal fentanyl added to bupivacaine and morphine for cesarean delivery may induce a subtle acute opioid tolerance.

BACKGROUND: Previous studies have demonstrated that the addition of intrathecal fentanyl to a spinal anesthetic for cesarean delivery improves intraoperative analgesia. However, intrathecal fentanyl may induce acute tolerance to opioids. The objective of this study was to investigate whether the addition of intrathecal fentanyl to spinal anesthesia with intrathecal morphine increases postoperative analgesic requirements and pain scores. METHODS: In this randomized, double-blinded study, 40 women having elective cesarean delivery were enrolled. Patients received spinal anesthesia with hyperbaric bupivacaine 12 mg, morphine 200 µg, and fentanyl 0, 5, 10 or 25 µg. Each patient received intravenous patient-controlled analgesia morphine for 24h postoperatively. Outcome measures included postoperative morphine usage and pain scores, as well as intraoperative pain, nausea, hypotension and vasopressor use. RESULTS: Total morphine use over the 24-h post-spinal study period was similar among the study groups (P=0.129). Postoperative pain scores were higher in patients receiving fentanyl 5, 10 and 25 µg compared to fentanyl 0 µg control group (P=0.003). CONCLUSIONS: The study results suggest that intrathecal fentanyl may induce acute tolerance to intrathecal morphine. However, because there was no difference in postoperative analgesia requirement and the difference in pain scores was small, the clinical significance of this finding is uncertain.

Minimum effective bolus dose of oxytocin during elective Caesarean delivery.

BACKGROUND: The aim of this study was to determine the lowest effective bolus dose of oxytocin to produce adequate uterine tone (UT) during elective Caesarean delivery (CD). METHODS: Seventy-five pregnant patients undergoing elective CD under spinal anaesthesia were randomized to receive oxytocin (0.5, 1, 3, 5 units) or placebo. UT was assessed by a blinded obstetrician as either adequate or inadequate, and using a verbal numerical scale score (0-10; 0, no UT; 10, optimal UT) at 2, 3, 6, and 9 min after oxytocin administration. Minimum effective doses of oxytocin were analysed (ED(50) and ED(95)) using logistic regression. Oxytocin-related side-effects (including hypotension) were recorded. RESULTS: There were no significant differences in the prevalence of adequate UT among the study groups at 2 min (73%, 100%, 93%, 100%, and 93% for 0, 0.5, 1, 3, and 5 units oxytocin, respectively). The high prevalence of adequate UT after placebo and low-dose oxytocin precluded determination of the ED(50) and ED(95). UT scores were significantly lower in patients receiving 0 unit oxytocin at 2 and 3 min compared with 3 and 5 units oxytocin (P<0.05, respectively). The prevalence of hypotension was significantly higher after 5 units oxytocin vs 0 unit at 1 min (47% vs 7%; P=0.04). CONCLUSIONS: The routine use of 5 units oxytocin during elective CD can no longer be recommended, as adequate UT can occur with lower doses of oxytocin (0.5-3 units).

Hetastarch co-loading is as effective as pre-loading for the prevention of hypotension following spinal anesthesia for cesarean delivery.

BACKGROUND: Pre-loading with hetastarch decreases the incidence and severity of hypotension after spinal anesthesia for cesarean delivery. However, pharmacokinetic studies with crystalloid predict that fluid loading should be more efficacious if rapidly administered immediately after induction of spinal anesthesia. The aim of this study was to compare pre- and co-loading of hetastarch for the prevention of hypotension following spinal anesthesia for cesarean delivery. METHODS: Forty-six healthy term parturients scheduled for cesarean delivery were randomized to receive 500 mL of 6% hetastarch intravenously, either slowly before spinal anesthesia (pre-loading) or as quickly as possible immediately after spinal anesthesia (co-loading). Systolic blood pressure was maintained at or above 90% of baseline with intravenous vasopressor boluses (ephedrine 5mg/mL+phenylephrine 25 microg/mL). The primary outcome was the volume of vasopressor mix required. Secondary outcomes included blood pressure and heart rate changes, time to first vasopressor use, nausea or vomiting, and neonatal outcomes (umbilical artery and vein pH, Apgar scores). RESULTS: The pre-loading group used 3.5+/-2 mL (mean+/-SD) of vasopressor mixture compared with 3.2+/-3 mL in the co-loading group (P=0.6). There were no differences in any important maternal hemodynamic or neonatal outcome values between the two study groups. CONCLUSION: Hetastarch co-loading is as effective as pre-loading for the prevention of hypotension after spinal anesthesia for cesarean delivery. Surgery need not be delayed to allow a predetermined pre-load to be administered before induction of spinal anesthesia.

Assessment of knowledge regarding cardiopulmonary resuscitation of pregnant women.

INTRODUCTION: The 2000-2002 triennial UK Report on Confidential Enquiries into Maternal Deaths concluded that over 50% of maternal deaths involved substandard care and that many could have been prevented. Catastrophic events leading to cardio-respiratory arrest may necessitate the resuscitation of pregnant women in various hospital locations. This study was designed to evaluate knowledge about resuscitation of parturients among anesthesiologists, obstetricians and emergency physicians. METHODS: A 12-question survey was distributed anonymously to residents and faculty in the anesthesia (ANES), obstetrics (OB), and emergency medicine (EM) departments at Stanford University Medical Center/Lucile Packard Children's Hospital, Stanford, California. Questions were designed to elicit knowledge deficiencies in four critical areas: need for left uterine displacement (LUD), advanced cardiac life support algorithms (ACLS), physiologic changes of pregnancy (PHYS), and the recommendation to perform cesarean delivery in parturients (>20 weeks gestation) after 4-5 min of unsuccessful resuscitation for cardiac arrest (5CD). RESULTS: In total, 74/75 physicians (43% ANES, 37% OB, and 20% EM) completed the test. ANES scored highest in overall test scores, and in knowledge of PHYS (P<0.05). Scores for LUD and 5CD were similar among groups, but 25-40% of these questions were answered incorrectly. In the ACLS category, the EM group scored highest (93%). CONCLUSION: We conclude that knowledge of important basic concepts, including the need for LUD and the potential benefit of early cesarean delivery during cardiac arrest, is inadequate among all three specialties. All three departments should provide ACLS physician training with emphasis on the special considerations for parturients.

Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study.

AIM: The aim of this study was to compare the efficacy and tolerability of vildagliptin vs. pioglitazone as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy. METHODS: This 24-week, multicentre, double-blind, randomized, active-controlled study compared vildagliptin (100 mg daily, given as equally divided doses, n = 295) and pioglitazone (30 mg daily, given as a single q.d. dose, n = 281) in patients with inadequate glycaemic control (A1C 7.5-11%) while receiving a stable metformin dose (> or =1500 mg daily). The adjusted mean changes from baseline to study endpoint (AMDelta) in A1C, fasting plasma glucose (FPG), fasting lipids and body weight were compared by analysis of covariance. RESULTS: When added to a stable dose of metformin (mean dose at baseline >2000 mg/day), both vildagliptin and pioglitazone decreased A1C (AMDelta = -0.9 +/- 0.1% and -1.0 +/- 0.1%, respectively) from identical baseline values (8.4 +/- 0.1%). The between-group difference in AMDelta A1C was 0.1 +/- 0.1%, and non-inferiority of vildagliptin to pioglitazone was established at both 0.4 and 0.3% margins for upper limit of the 95% confidence intervals. Pioglitazone decreased FPG (AMDelta = -2.1 +/- 0.1 mmol/l) to a greater extent than vildagliptin (AMDelta = -1.4 +/- 0.1 mmol/l), but only pioglitazone increased body weight (AMDelta = +1.9 +/- 0.2 kg: between-group difference = -1.6 +/- 0.3 kg, p < 0.001). Adverse events (AEs) were reported by 60% of vildagliptin-treated patients and by 56.4% of pioglitazone-treated patients; serious AEs were reported by 2.0 and 4.6% of patients receiving vildagliptin and pioglitazone respectively. Mild hypoglycaemia was reported by one patient (0.3%) in the vildagliptin group and by no patients receiving pioglitazone. CONCLUSIONS: When added to metformin, the efficacy of vildagliptin is non-inferior to that of pioglitazone. The treatments were similarly well tolerated, but only pioglitazone increased body weight.

Local infiltration of epinephrine-containing lidocaine with bicarbonate reduces superficial bleeding and pain during labor epidural catheter insertion: a randomized trial.

BACKGROUND: Superficial bleeding after labor epidural catheter placement is a common phenomenon. In addition to delaying securing the epidural catheter, it may loosen the adhesive catheter dressing. The primary aim of this study was to determine whether skin infiltration with epinephrine-containing rather than plain lidocaine reduces superficial bleeding after catheter placement. Secondary objectives were to determine whether adding epinephrine and/or sodium bicarbonate affected infiltration pain. METHODS: After institutional review board approval and informed consent, 80 healthy women receiving epidural analgesia during labor were randomly assigned in a double-blind manner to four local anesthetic mixtures (n=20 in each group): group L: lidocaine 1.5%, group LB: lidocaine 1.5% with 8.4% sodium bicarbonate, group LE: lidocaine 1.5% with epinephrine 1:200000, and group LEB: lidocaine 1.5% with epinephrine 1:200000 and 8.4% sodium bicarbonate. Clinical endpoints included the amount of superficial bleeding at the catheter site, pain during local anesthetic infiltration and epidural catheter movement during labor. RESULTS: Demographic data were similar among the groups. The addition of epinephrine to lidocaine significantly reduced superficial bleeding. Solutions containing epinephrine were well tolerated and caused no cardiovascular disturbances. The addition of epinephrine did not increase pain, while bicarbonate reduced it [verbal score (scale 0-10) 3.6+/-2.2 vs. 2.6+/-1.8; P=0.04]. There were no differences in epidural catheter movement among the groups; no catheters became displaced during labor. CONCLUSION: Local infiltration of epinephrine-containing lidocaine before epidural catheter insertion reduces superficial bleeding and the addition of bicarbonate decreases pain during skin infiltration.

A survey of labor patient-controlled epidural anesthesia practice in California hospitals.

BACKGROUND: Patient-controlled epidural analgesia (PCEA) offers many advantages over continuous epidural infusions for labor analgesia including fewer physician interventions, improved analgesia and satisfaction, and reduced local anesthetic doses. However, anesthesiologists have been slow to adopt this technique, first described in 1988. No previous studies have evaluated specific labor patient-controlled epidural analgesia practices in the United States. The aim of this study was to determine labor epidural and patient-controlled epidural analgesia practices among California hospitals. METHODS: Following institutional review board exemption approval, an online survey was created using freeonlinesurveys.com. An anonymous survey was sent via e-mail to 230 California Society of Anesthesiologists' members chosen at random to represent their hospitals' labor analgesia practices. RESULTS: We received 133 replies from the 230 survey requests sent, a 58% response rate. The median labor epidural rate among the hospitals involved was 65% (range 0-95%). Overall, only 25% of California hospitals use patient-controlled epidural analgesia for analgesia in labor, with greater use among hospitals with dedicated obstetric anesthesia coverage and larger numbers of deliveries. Reasons given for not using patient-controlled epidural analgesia include cost, clinician preference, safety concerns and the inconvenience of change. CONCLUSIONS: Despite the potential advantages of patient-controlled epidural analgesia over continuous epidural infusions for labor analgesia, patient-controlled epidural analgesia has not been widely adopted in California hospitals. Education regarding this technique is needed to encourage its increased use.

"Ultra-light" patient-controlled epidural analgesia during labor: effects of varying regimens on analgesia and physician workload.

BACKGROUND: Patient-controlled epidural analgesia (PCEA) offers many advantages over continuous epidural infusions for maintenance of labor analgesia. Some of these benefits may depend on the PCEA settings. This study evaluated several regimens for "ultra-light" (0.125%) PCEA with basal continuous infusion (CI) in labor with goals of minimizing physician interventions while providing good analgesia. METHODS: Two hundred and twenty ASA I-II women receiving epidural analgesia during active labor (cervical dilation <5 cm) were randomly assigned in a double-blind manner to four treatment groups (n=30 in each). Analgesia was maintained with a PCEA/CI pump using bupivacaine 0.0625% + sufentanil 0.35 microg/mL. PCEA settings were: group A: CI 10 mL/h, PCEA bolus 6 mL, 8-min lockout; group B: CI 10 mL/h, PCEA bolus 12 mL, 16-min lockout; group C: CI 15 mL/h, PCEA bolus 6 mL, 8-min lockout; group D: CI 15 mL/h, PCEA bolus 12 mL, 16-min lockout. RESULTS: In groups A, B, C and D, 76, 77, 75 and 85% of parturients respectively, required no physician rescue boluses. Pain scores were low and maternal satisfaction was high in all groups, with minimal differences among them. Spontaneous vaginal delivery occurred in 78% of patients overall, instrumental (forceps or vacuum) delivery in 10% and cesarean section in 12%. CONCLUSIONS: These ultra-light PCEA regimens provided excellent analgesia with minimal physician workload and a high spontaneous delivery rate. Use of moderate to high-volume, ultra-light PCEA/CI techniques should facilitate provision of labor analgesia in busy obstetric units.

Correction of intraoperative coagulopathy in a patient with neurofibromatosis type I with intravenous desmopressin (DDAVP).

A patient with the genetic condition neurofibromatosis type I and no known coagulopathy undergoing cesarean delivery, had diffuse uterine and surgical site bleeding that was not correctable by oxytocin, methylergonovine and PGF2 alpha. Despite good uterine tone, hemorrhage continued from the uterus and the surrounding tissues, persisting even after surgical ligation of the uterine arteries. With no change in her condition, which was behaving clinically as a coagulopathy, an infusion of desmopressin acetate (DDAVP) was begun. The patient's bleeding promptly resolved shortly after infusion of this agent. A review of relevant literature suggests that platelet reactivity of patients with neurofibromatosis type 1 is attenuated in some in vitro conditions. Thus, there may be some theoretical basis for using DDAVP in patients with neurofibromatosis type 1 who have bleeding problems with no other known source, such as in the case presented here.

Effects of insulin-sensitising agents in mice with hepatic insulin resistance.

AIMS/HYPOTHESIS: The metabolic abnormalities of insulin resistance are ameliorated by insulin sensitisers via different mechanisms. Metformin decreases hepatic glucose output, whereas rosiglitazone (RSG) is an agonist for peroxisome proliferator activated receptor (PPAR)gamma, highly expressed in fat. To gain insight into the mechanisms of action of these drugs, we compared their actions in two models of insulin resistance: the obese, hyperglycaemic ob/ob mouse and the liver specific insulin receptor knockout (LIRKO) mouse. METHODS: Control, ob/ob, and LIRKO mice were divided into three groups that received metformin (300 mg/kg body weight/day), RSG (3 mg/kg body weight/day), or placebo for 3 weeks. RESULTS: In the presence of the severe hepatic insulin resistance of the LIRKO mouse, neither metformin nor RSG had any significant effect on glucose or insulin tolerance tests. On the other hand, RSG decreased serum concentrations of total cholesterol, LDL, and HDL in LIRKO mice. Adipocyte PPARgamma gene and protein expression, and adipocyte size were all increased in LIRKO mice treated with RSG, whereas fat-cell size in control animals was decreased by RSG. CONCLUSION/INTERPRETATION: TZDs probably improve some lipid parameters of the dysmetabolic syndrome associated with diabetes mellitus even in the presence of absolute hepatic insulin resistance, but both metformin and TZDs require an operating insulin signalling system in the liver for their effects in glucose homeostasis.

Phenylephrine added to prophylactic ephedrine infusion during spinal anesthesia for elective cesarean section.

BACKGROUND: Because ephedrine infusion (2 mg/min) does not adequately prevent spinal hypotension during cesarean delivery, the authors investigated whether adding phenylephrine would improve its efficacy. METHODS: Thirty-nine parturients with American Society of Anesthesiologists physical status I-II who were scheduled for cesarean delivery received a crystalloid preload of 15 ml/kg. Spinal anesthesia was performed using 11 mg hyperbaric bupivacaine, 2.5 microg sufentanil, and 0.1 mg morphine. Maternal heart rate and systolic blood pressure were measured at frequent intervals. A vasopressor infusion was started immediately after spinal injection of either 2 mg/min ephedrine plus 10 microg/min phenylephrine or 2 mg/min ephedrine alone. Treatments were assigned randomly in a double-blind fashion. The infusion rate was adjusted according to systolic blood pressure using a predefined algorithm. Hypotension, defined as systolic blood pressure less than 100 mmHg and less than 80% of baseline, was treated with 6 mg ephedrine bolus doses. RESULTS: Hypotension occurred less frequently in the ephedrine-phenylephrine group than in the ephedrine-alone group: 37% versus 75% (P = 0.02). Ephedrine (36+/-16 mg, mean +/- SD) plus 178+/-81 microg phenylephrine was infused in former group, whereas 54+/-18 mg ephedrine was infused in the latter. Median supplemental ephedrine requirements and nausea scores (0-3) were less in the ephedrine-phenylephrine group (0 vs. 12 mg, P = 0.02; and 0 vs. 1.5, P = 0.01, respectively). Umbilical artery pH values were significantly higher in the ephedrine-phenylephrine group than in the group that received ephedrine alone (7.24 vs. 7.19). Apgar scores were similarly good in both groups. CONCLUSION: Phenylephrine added to an infusion of ephedrine halved the incidence of hypotension and increased umbilical cord pH.

Walking with labor epidural analgesia: the impact of bupivacaine concentration and a lidocaine-epinephrine test dose.

BACKGROUND: Regional analgesia techniques for labor that permit ambulation are popular among parturients. This study evaluated the influence of bupivacaine bolus concentration and a 3-ml 1.5% lidocaine-epinephrine test dose, on analgesic effectiveness and the ability to walk after block placement. METHODS: Using a randomized double-blind study design, epidural analgesia was initiated in 60 parturients undergoing labor as follows: Group TD/B.0625 received a 3-ml lidocaine-epinephrine test dose + 12 ml bupivacaine, 0.0625%; group TD/B.125 received a 3-ml test dose + 12 ml bupivacaine, 0.125%; group B.0625 received 15 ml bupivacaine, 0.0625% (no test dose); and group B.125 received 15 ml bupivacaine, 0.125% (no test dose). Initial boluses in all groups contained 10 microg sufentanil. Bupivacaine, 0.0625%, with 0.33 microg/ml sufentanil was infused throughout labor at 13.5-15 ml/h. Analgesia balance, proprioception, motor block, and patient ability to stand and walk were evaluated at various intervals. RESULTS: A bolus of 0.125% bupivacaine containing sufentanil, without a previous test dose, proved to be optimal with respect to analgesia and early ambulation. When a test dose was given before bupivacaine, 0.125%, fewer women walked within 1 h of block placement. Bupivacaine, 0.0625%, with sufentanil, with or without a test dose, provided inadequate analgesia, necessitating additional bupivacaine, which impaired the ability to walk. A high percentage of women in all groups (73-93%) walked at some stage during labor. CONCLUSIONS: Omitting a lidocaine-epinephrine test dose and using 0.125% bupivacaine for the initial bolus should permit ambulation in the early postblock period for most parturients who elect this option.

Progression of microalbuminuria to proteinuria in type 1 diabetes: nonlinear relationship with hyperglycemia.

While small clinical trials have shown that improved glycemic control reduces the risk of progression of microalbuminuria to proteinuria, two recent clinical trials did not confirm this finding. We sought to reconcile the contradictory evidence by examining the dose-response relationship between hyperglycemia and progression of microalbuminuria to proteinuria in individuals with type 1 diabetes and microalbuminuria (n = 312) who were followed for 4 years with repeated assessments of urinary albumin excretion. Since 33 patients did not participate in follow-up (10.6%), data for 279 patients were analyzed. Urinary albumin excretion level worsened to proteinuria in 40 (4.1 per 100 person-years). To examine the dose-response relationship, baseline HbA1c was divided into four roughly equal groups using the cut points 8, 9, and 10%. The incidence rate varied significantly among the four groups (P = 0.008). Among those with HbA1c <8.0%, the incidence rate of progression was only 1.3 per 100 person-years, while it was 5.1, 4.2, and 6.7 per 100 person-years in the three other groups. We used generalized additive models to examine the dose-response curve using HbA1c as a continuous variable and found that the risk of progression rises steeply between an HbA1c of 7.5-8.5% and then remains approximately constant across higher levels. In conclusion, the results of this study suggest that, in patients with microalbuminuria, the risk of progression to overt proteinuria can be reduced by improved glycemic control only if the HbA1c is maintained below 8.5%. Moreover, below that value, the risk declines as the level of HbA1c decreases.

Maternal sensitivity during infancy and subsequent life events relate to attachment representation at early adulthood.

A prospective longitudinal research study of 86 prematurely born children from birth to age 18 years provided empirical evidence for continuity from infancy experience to representations of attachment at age 18 years. Young adults whose representation of attachment was dismissing had been objectively observed during infancy, 16-17 years earlier, to receive less sensitive maternal care than those infants who were later judged at early adulthood to have secure or preoccupied representations. Infancy experience alone did not differentiate young adults with secure representations from those with preoccupied representations. Rather, adverse life events through age 12, particularly parental divorce, reduced the likelihood of secure representations and increased the likelihood of preoccupied representations. The absence of adverse life events did not increase the likelihood of security for those who had not experienced early sensitive caregiving.