Maternal cytomegalovirus-specific immune responses and symptomatic postnatal cytomegalovirus transmission in very low-birth-weight preterm infants.

INTRODUCTION: Transmission of cytomegalovirus (CMV) via breast milk can lead to severe acute illness in very low-birth-weight (VLBW) preterm infants. Although the majority of CMV-seropositive women shed CMV in milk, symptomatic postnatal infection of VLBW infants occurs infrequently, suggesting that virologic or immunologic factors in milk may be associated with the risk and severity of postnatal CMV infection. METHODS: We investigated the magnitude of CMV-specific cellular and humoral immune responses in milk of 30 seropositive mothers of VLWB preterm infants and assessed their relationship to milk CMV load and symptomatic CMV transmission. RESULTS: Milk immunoglobulin G (IgG) avidity was inversely correlated to milk CMV load (r = -0.47; P = .009). However, milk CMV load and CMV-specific cellular and humoral immune responses were similar in mothers of VLBW infants with and those without symptomatic postnatal CMV infection. CONCLUSIONS: Similar immunologic parameters in milk of CMV-seropositive mothers of VLBW infants with and without symptomatic postnatal CMV infection indicate that screening milk by these parameters may not predict disease risk. However, the inverse correlation between milk CMV IgG avidity and CMV load may suggest that enhancement of maternal CMV-specific IgG responses could aid in reduction of CMV shedding into breast milk.

Olanzapine Plus Samidorphan in Subjects with Schizophrenia and Comorbid Alcohol Use Disorder: Rationale and Design for a Phase II, Double-blind, Randomized Study.

Background: Alcohol use disorder (AUD) is a common comorbidity in patients with schizophrenia. Although pharmacological options for the management of each disease exist separately, there is no agent approved for both. Moreover, studies conducted in this patient population, who face practical and social challenges as a consequence of being diagnosed with schizophrenia and comorbid AUD, are limited. Methods: We describe the design of a Phase II, double-blind, randomized trial to evaluate adult outpatients with schizophrenia and comorbid AUD receiving a combination of olanzapine plus samidorphan (OLZ+SAM; ALKS 3831), a novel entity currently under development for the treatment of schizophrenia. The combination drug formulation of OLZ+SAM is intended to provide the antipsychotic efficacy of OLZ while mitigating the weight gain and concomitant metabolic abnormalities commonly associated with OLZ alone. In considering this patient population, the novel primary efficacy endpoint is the time from randomization to the first event of exacerbation of disease symptoms (EEDS) based on the occurrence of any of eight prespecified events related to worsening of disease symptoms and/or AUD, as confirmed by a blinded independent adjudication committee. The rate and number of EEDS, improvement in drinking level, and the safety and tolerability of OLZ in combination with SAM will also be assessed. Discussion: A limited number of studies have been conducted in patients with schizophrenia and AUD, and the need for further research in this difficult-to-study population is well documented. This study is, to our knowledge, the largest and longest trial with a randomized, double-blind, active-controlled design. In addition to providing evidence for the development of OLZ+SAM (ALKS 3831) as a therapeutic option, the study aims to provide insights into the clinical management of subjects with schizophrenia and comorbid AUD. Trial registration: Clinical trials NCT02161718, registered May 2014; EudraCT Number: 2014-001211-39.

Adverse events of conscious sedation in ambulatory spine procedures.

BACKGROUND CONTEXT: Interventional spine procedures are commonly performed in the ambulatory surgical setting, often using conscious sedation. The rate of adverse events with conscious sedation has not been previously assessed in the interventional spine procedure setting. PURPOSE: The goal of this study was to determine the rate of adverse events when using conscious sedation in the ambulatory interventional spine setting. STUDY DESIGN: A retrospective cohort chart review analysis was performed on all interventional spine procedures performed during one calendar year at a university-affiliated ambulatory surgery center by six nonanesthesia-trained spine interventionalists. PATIENT SAMPLE: Of the 3,342 procedures performed that year, 2,494 charts (74.6%) were available for review. OUTCOME MEASURES: Adverse events were documented immediately after the procedure and at a maximum 3-day follow-up phone call. METHODS: The rate and type of adverse events were analyzed and compared between those who received conscious sedation with local anesthesia and those who received local anesthesia alone. RESULTS: Of the 2,494 cases reviewed, 1,228 spine procedures were performed with local anesthesia and conscious sedation, and 1,266 procedures were performed with local anesthesia alone. Of these cases, 66 immediate adverse events (5.12%) were documented in the conscious sedation group, and 61 immediate adverse events (4.82%) were documented in the local anesthesia alone group. At maximum 3-day follow-up, 670 patients of the conscious sedation group were available for contact, and 699 patients were available from the local anesthesia group. Thirty-two adverse events (4.77%) were noted in the conscious sedation group, and 28 adverse events (4.00%) were noted in the local anesthesia group. Comparison of these rates found no significant statistical difference. However, patients in the local anesthesia group had a significantly higher rate of postoperative hypertension. Adverse events reported both immediately and at follow-up were determined to be mild, with no serious adverse events reported. CONCLUSION: The findings of this study suggest that mild to moderate conscious sedation in interventional spine procedures is associated with low rates of adverse events when established protocols are followed.