Inflammation of the Embryonic Choroid Plexus Barrier following Maternal Immune Activation.

The choroid plexus (ChP) regulates brain development by secreting instructive cues and providing a protective brain barrier. Here, we show that polyI:C-mediated maternal immune activation leads to an inflammatory response in the developing embryonic mouse brain that manifests as pro-inflammatory cerebrospinal fluid (CSF) and accumulation of ChP macrophages. Elevation of CSF-CCL2 was sufficient to drive ChP immune cell recruitment, activation, and proliferation. In addition, ChP macrophages abandoned their regular tiling pattern and relocated to the ChP-free margin where they breached the weakened epithelial barrier. We further found that these immune cells entered from the ChP into the brain via anatomically specialized "hotspots" at the distal tips of ChP villi. In vivo two-photon imaging demonstrated that surveillance behaviors in ChP macrophages had already emerged at this early stage of embryogenesis. Thus, the embryonic ChP forms a functional brain barrier that can mount an inflammatory response to external insults.

Use of the 5 As for Teen Alcohol Use.

Clinical guidelines recommend addressing adolescent alcohol use in primary care; the 5 As (Ask, Advise, Assess, Assist, Arrange) may be a useful model for intervention. We audio-recorded 540 visits with 49 physicians and adolescents, compared alcohol disclosure rates in the encounter with those in a survey, and analyzed conversations for use of the 5 As and their relation to adolescent reports of drinking 3 months after the encounter. When physicians asked clear, nonleading questions, drinkers were more likely to disclose alcohol use ( P = .004). In 64% of visits in which alcohol was discussed, physicians used one or more of the 5 As, most frequently "Ask." No physician used all 5 As. Among drinkers, there was no association between physicians' partial use of the 5 As and adolescent alcohol consumption at 3 months. Physicians can learn more effective ways to "Ask" about alcohol use to increase disclosure of drinking and to be more comprehensive in their counseling.

The effects of fasting in Muslim patients taking warfarin.

BACKGROUND: Anticoagulation with warfarin is influenced by dietary changes but the effect of fasting on warfarin therapy is unknown. OBJECTIVES: To study changes in international normalized ratio (INR) and the percentage of time within therapeutic range (%TTR) before, during and after the Muslim fasting month (Ramadan) in stable warfarinised Muslim patients. METHODS/PATIENTS: In this prospective study, weekly INR readings were taken at home visits from participating patients during three study periods: before, during and after Ramadan. Readings were blinded to patients and their primary physicians except for when pre-set study endpoints were reached. RESULTS: Among 32 participating patients, mean INR increased by 0.23 (P = 0.006) during Ramadan from the pre-Ramadan month and decreased by 0.28 (P < 0.001) after Ramadan. There was no significant difference (P = 1.000) in mean INR between the non-Ramadan months. %TTR declined from 80.99% before Ramadan to 69.56% during Ramadan (P = 0.453). The first out-of-range INR was seen around 12.1 days (95% CI, 9.0-15.1) after the start of fasting and returned to range at about 10.8 days (95% CI, 7.9-13.7) after Ramadan. Time above range increased from 10.80% pre-Ramadan to 29.87% during Ramadan (P = 0.027), while time below range increased from 0.57% during Ramadan to 15.49% post-Ramadan (P = 0.006). No bleeding or thrombotic events were recorded. CONCLUSIONS: Fasting significantly increases the mean INR of medically stable patients taking warfarin and the likelihood of having an INR above therapeutic targets. For patients maintained at the higher end of INR target ranges or at increased risk of bleeding, closer monitoring or dosage adjustment may be necessary during fasting.

Risk of hepatitis B reactivation and the role of novel agents and stem-cell transplantation in multiple myeloma patients with hepatitis B virus (HBV) infection.

BACKGROUND: The purpose of the study is to analyse the prevalence of hepatitis B virus (HBV) infection and its incidence of reactivation among multiple myeloma (MM) patients treated in the era of novel therapy in an endemic Asian setting. PATIENTS AND METHODS: From 2000 to 2008, 273 patients with newly diagnosed MM were screened for the presence of hepatitis B virus surface antigen and HBV core antibody. HBV-infected patients were prospectively followed for reactivation with serial monitoring of serum alanine transferase and HBV DNA load. The patterns of HBV reactivation in relation to treatment received, exposure to high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) and novel agents were studied. RESULTS: The prevalence of HBV infection was 5.5%. Three cases of HBV reactivation despite lamivudine prophylaxis were reported. Two patients reactivated 3-5 months after HDT/ASCT while receiving thalidomide maintenance and one reactivated 3 years after HDT/ASCT and shortly after bortezomib salvage therapy. Emergence of a mutant HBV strain was documented in one patient. CONCLUSIONS: Use of prophylaxis may reduce but will not preclude HBV reactivation. Highest risk occurs during immune reconstitution phase of HDT/ASCT. The role of immunomodulatory agents in HBV reactivation needs to be further elucidated. Separate HBV prophylaxis and surveillance guidelines ought to be developed for patients with MM.

Resuscitation of likely nonviable infants: a cost-utility analysis after the Born-Alive Infant Protection Act.

OBJECTIVE: The purpose of this study was to compare the effects of universal vs selective resuscitation on maternal utilities, perinatal costs, and outcomes of preterm delivery and termination of pregnancy at 20-23 weeks 6 days' gestation. STUDY DESIGN: We used studies on medical practices, prematurity outcomes, costs, and maternal utilities to construct decision-analytic models for a cohort of annual US deliveries after preterm delivery or induced termination. Outcome measures were (1) the numbers of infants who survived intact or with mild, moderate, or severe sequelae; (2) maternal quality-adjusted life years (QALYs); and (3) incremental cost-effectiveness ratios. RESULTS: Universal resuscitation of spontaneously delivered infants between 20-23 weeks 6 days' gestation increases costs by $313.1 million and decreases QALYs by 329.3 QALYs; after a termination, universal resuscitation increases costs by $15.6 million and decreases QALYs by 19.2 QALYs. With universal resuscitation, 153 more infants survive: 44 infants are intact or mildly affected; 36 infants are moderately impaired, and 73 infants are severely disabled. CONCLUSION: Selective intervention constitutes the highest utility and least costly treatment for infants at the margin of viability.

Resuscitation of likely nonviable newborns: would neonatology practices in California change if the Born-Alive Infants Protection Act were enforced?

BACKGROUND: The effects of the Born-Alive Infants Protection Act of 2002, which defines the legal status of live-born infants have not been evaluated. OBJECTIVE: To study neonatologists' perceptions and the potential effects of the Born-Alive Infants Protection Act and subsequent Department of Health and Human Services enforcement guidelines on resuscitation and comfort care for infants born at 20 to 24 weeks' gestation. METHODS: From August 2005 to November 2005, we mailed surveys to all 354 neonatologists practicing in California. Surveys asked physicians to characterize their knowledge of and attitudes toward this legislation and enforcement guidelines, current resuscitation and comfort-care practices for extreme prematurity, anticipated changes in practice were the enforced, and demographic information. We hypothesized that enforcement would alter thresholds for resuscitation and care. RESULTS: We obtained 156 completed surveys (response rate: 44%); 140 fulfilled criteria for analysis. More than half of the neonatologists had not heard of this Act or the enforcement guidelines. Screening examinations at birth were infrequent (<20%) at gestational ages of <23 weeks. Although 63% of neonatologists felt that the Act clarified the definition of born-alive infants, nearly all (>90%) criticized the legislation; only 6% felt that it should be enforced. If it were enforced, physicians predicted that they would lower birth weight and gestational age thresholds for resuscitation and comfort care. CONCLUSIONS: The Born-Alive Infants Protection Act clarified the legal status of "born-alive" infants, but enforcement guidelines fail to clarify what measures are appropriate when survival is unlikely. The Act may constrain resuscitation options offered to parents, because neonatologists anticipate medicolegal threats if they pursue nonintervention. If this legislation were enforced, respondents predicted more aggressive resuscitation potentially increasing risks of disability or delayed death. Until outcomes for infants of <24 weeks' gestation improve, legislation that changes resuscitation practices for extreme prematurity seems an unjustifiable restriction of physician practice and parental rights.