Management of maternal ventriculo-atrial shunt malfunction during pregnancy

AbstractHydrocephalic females reaching childbearing age is increasing due to treatment advances. It has been suggested that ventriculo-atrial (VA) shunts be preferred over ventriculo-peritoneal (VP) shunts during pregnancy. We present a case with multiple VA shunt malfunctions during two separate pregnancies. We treated the patient with a valveless VA shunt during both and were able to achieve near-term deliveries. During the second pregnancy the patient had an emergent caesarian section due to severe hydrocephalus and stunted fetal growth. Delivering the child also relieved her hydrocephalus. Of unclear reasons the right atrium failed as a distal absorption site during both pregnancies, and we must conclude that VA shunts do not necessarily alleviate problems regarding pressure at the distal end of the shunt system but never the less should be considered a treatment option on a case-by-case basis. Furthermore we conclude that a valveless shunt should be considered in select cases of maternal shunt malfunction where valves exert to high pressure resistance

Music Therapy vs. Music Listening for Negative Symptoms in Schizophrenia:Randomized, Controlled, Assessor- and Patient-Blinded Trial

Objective: To investigate the efficacy of music therapy for negative symptoms in patients with schizophrenia. Methods: Randomized, participant- and assessor-blinded, multicenter, controlled trial including patients diagnosed with schizophrenia according to ICD-10 with predominantly negative symptoms, between 18 and 65 years. Participants were randomized to 25 successive weekly individual sessions (excluding holidays, including cancellation by the participant) of either music therapy conducted by trained music therapists, or music listening together with a social care worker. The primary outcome was reduction in negative symptoms as measured by The Positive and negative Syndrome Scale (PANSS) negative subscale total score, assessed by a blinded rater, utilizing mixed-effects model analysis. Results: In total, 57 participants were randomized; 39 completed the study's initial 15 weeks, and 30 completed follow-up at 25 weeks. On the primary outcome of PANSS negative subscale, no significant difference was observed between groups with a coefficient of −0.24 (95% CI −1.76 to 1.27, P = 0.754) in the intention to treat analysis, and −0.98 (95% CI −5.06 to 3.09, P = 0.625) when only analyzing completers. Both interventions showed significant reduction from baseline to 25 weeks on PANSS negative subscale. On secondary outcomes, no between group differences were observed in The Brief Negative Symptom Scale, WHOQOL-Bref (Quality of Life), The Helping Alliance Questionnaire and The Global Assessment of Functioning in the intention to treat or completers populations utilizing Mixed Effects Models. Conclusion: No difference between groups randomized to music therapy vs. musical listening was observed resulting in no clear recommendation for which intervention to use as the first choice for treatment of patients diagnosed with schizophrenia and predominantly having negative symptoms. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02942459

Serum levels of perfluorinated compounds and sperm Y:X chromosome ratio in two European populations and in Inuit from Greenland.

This study investigated whether perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS), which exhibit reproductive toxicity in experimental animals, affect sperm sex chromosome ratio. The Y:X ratio was determined by fluorescence in situ hybridization. Serum concentrations of PFOA and PFOS were measured in 607 men from Greenland, Poland and Ukraine using liquid chromatography-tandem mass spectrometry. Data was analyzed by linear and nonlinear regression. We observed no associations between PFOA and Y:X ratio (p=0.845 in a linear model, p=0.296 in a nonlinear model). A positive nonlinear association between PFOS and Y:X ratio was observed (p=0.016), with no association in a linear model (p=0.118). Analyzing the populations separately, a negative trend between categorized PFOS exposure and Y:X ratio was observed for the Inuit (B=-0.002, p=0.044). In conclusion, there was a negative trend between Y:X ratio and PFOS in the Inuit, while there was no association between PFOA and the Y:X ratio in adult men

Intraoperative low field MRI in transsphenoidal pituitary surgery

Background: Intraoperative low field MRI (iMRI, 0.15 T) during transsphenoidal surgery on pituitary adenomas (PAs) may significantly improve tumor removal. However, extensive surgery can lead to pituitary hormone deficiency. Furthermore, introduction of iMRI will prolong duration of surgery, which may elevate risk of postoperative infections. Methods: Overall, 180 transsphenoidal surgeries for PAs from 2007 to 2015 were included. IMRI was available from 2011 to 2015, during this period 67/78 (86%) surgeries were with iMRI (iMRI, n = 67). A total of 113 surgeries were performed without iMRI (controls). All surgical procedures were performed by microscopic technique. Tumor size, hormonal status and vision were assessed before surgery and 3–5 months postoperatively. Results: Gross total resection (GTR), mean tumor remnant volume and Δ-volumes were comparable between iMRI and controls: 15% (10/66) vs 23% (26/109) (P = 0.17), 2.97 cm3 (0.9–5) vs 2.1 cm3 (1.6–2.6) (P = 0.3) and 4.5 cm3 (3.6–5.5) vs 5.1 cm3 (4.2–6) (P = 0.4), respectively. Duration of surgery was significantly longer during iMRI vs controls: 126 min (117–135) vs 98 min (92–103) (P 0.1). Conclusion: Tumor remnant after pituitary surgery was not significantly reduced using intraoperative low field MRI. Duration of surgery was increased in iMRI, but was not associated with increased infection rate. Pituitary hormonal function and vision were comparable between iMRI and controls

Perfluorooctane sulfonate concentrations in amniotic fluid, biomarkers of fetal Leydig cell function, and cryptorchidism and hypospadias in Danish boys (1980–1996)

Background: Exposure to perfluorooctane sulfonate (PFOS) may potentially disturb fetal Leydig cell hormone production and male genital development. Objectives: We aimed to study the associations between levels of amniotic fluid PFOS, fetal steroid hormone, and insulin-like factor 3 (INSL3) and the prevalence of cryptorchidism and hypospadias. Methods: Using the Danish National Patient Registry, we selected 270 cryptorchidism cases,75 hypospadias cases, and 300 controls with stored maternal amniotic fluid samples available in a Danish pregnancy-screening biobank (1980–1996). We used mass spectrometry to measure PFOS in amniotic fluid from 645 persons and steroid hormones in samples from 545 persons. INSL3 was measured by immunoassay from 475 persons. Associations between PFOS concentration in amniotic fluid, hormone levels, and genital malformations were assessed by confounder-adjusted linear and logistic regression. Results: The highest tertile of PFOS exposure (> 1.4 ng/mL) in amniotic fluid was associated with a 40% (95% CI: –69, –11%) lower INSL3 level and an 18% (95% CI: 7, 29%) higher testosterone level compared with the lowest tertile (< 0.8 ng/mL). Amniotic fluid PFOS concentration was not associated with cryptorchidism or hypospadias. Conclusions: Environmental PFOS exposure was associated with steroid hormone and INSL3 concentrations in amniotic fluid, but was not associated with cryptorchidism or hypospadias in our study population. Additional studies are needed to determine whether associations with fetal hormone levels may have long-term implications for reproductive health

Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation:nationwide cohort study

Study question What are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding associated with restarting antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation? Methods This Danish cohort study (1996-2012) included all patients with atrial fibrillation discharged from hospital after gastrointestinal bleeding while receiving antithrombotic treatment. Restarted treatment regimens were single or combined antithrombotic drugs with oral anticoagulation and antiplatelets. Follow-up started 90 days after discharge to avoid confounding from use of previously prescribed drugs on discharge. Risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding were estimated with competing risks models and time dependent multiple Cox regression models. Study answer and limitations 4602 patients (mean age 78 years) were included. Within two years, 39.9% (95% confidence interval 38.4% to 41.3%, n=1745) of the patients had died, 12.0% (11.0% to 13.0%, n=526) had experienced thromboembolism, 17.7% (16.5% to 18.8%, n=788) major bleeding, and 12.1% (11.1% to 13.1%, n=546) recurrent gastrointestinal bleeding. 27.1% (n=924) of patients did not resume antithrombotic treatment. Compared with non-resumption of treatment, a reduced risk of all cause mortality was found in association with restart of oral anticoagulation (hazard ratio 0.39, 95% confidence interval 0.34 to 0.46), an antiplatelet agent (0.76, 0.68 to 0.86), and oral anticoagulation plus an antiplatelet agent (0.41, 0.32 to 0.52), and a reduced risk of thromboembolism was found in association with restart of oral anticoagulation (0.41, 0.31 to 0.54), an antiplatelet agent (0.76, 0.61 to 0.95), and oral anticoagulation plus an antiplatelet agent (0.54, 0.36 to 0.82). Restarting oral anticoagulation alone was the only regimen with an increased risk of major bleeding (1.37, 1.06 to 1.77) compared with non-resumption of treatment; however, the difference in risk of recurrent gastrointestinal bleeding was not significant between patients who restarted an antithrombotic treatment regimen and those who did not resume treatment. What this study adds Among patients with atrial fibrillation who experience gastrointestinal bleeding while receiving antithrombotic treatment; subsequent restart of oral anticoagulation alone was associated with better outcomes for all cause mortality and thromboembolism compared with patients who did not resume treatment. This was despite an increased longitudinal associated risk of bleeding. Funding, competing interests, data sharing This study was supported by a grant from Boehringer-Ingelheim. Competing interests are available in the full paper on bmj.com. The authors have no additional data to share

Dioxin-like activities in serum across European and Inuit populations

BACKGROUND: Persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay. RESULTS: The European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group. CONCLUSION: No consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors

Pregnancy serum concentrations of perfluorinated alkyl substances and offspring behaviour and motor development at age 5-9 years--a prospective study

Background: In animal studies, perfluorinated alkyl substances affect growth and neuro-behavioural outcomes. Human epidemiological studies are sparse. The aim was to investigate the association between pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and offspring behaviour and motor development at 5-9 years of age. Methods: Maternal sera from the INUENDO cohort (2002-2004) comprising 1,106 mother-child pairs from Greenland, Kharkiv (Ukraine) and Warsaw (Poland) were analysed for PFOS and PFOA, using liquid-chromatography-tandem-mass-spectrometry. Exposures were grouped into country specific as well as pooled tertiles as well as being used as continuous variables for statistical analyses. Child motor development and behaviour at follow-up (2010-2012) were measured by the Developmental Coordination Disorder Questionnaire 2007 (DCDQ) and Strength and Difficulties Questionnaire (SDQ), respectively. Exposure-outcome associations were analysed by multiple logistic and linear regression analyses. Results: In the pooled analysis, odds ratio (OR) (95% confidence interval (CI)) for hyperactivity was 3.1 (1.3, 7.2) comparing children prenatally exposed to the highest PFOA tertile with those exposed to the lowest PFOA tertile. Comparing children in the highest PFOS tertile with those in the lowest PFOS tertile showed elevated but statistically non-significant OR of hyperactivity (OR (95% CI) 1.7 (0.9, 3.2)). In Greenland, elevated PFOS was associated with higher SDQ-total scores indicating more behavioural problems (beta (95% CI) = 1.0 (0.1, 2.0)) and elevated PFOA was associated with higher hyperactivity sub-scale scores indicating more hyperactive behaviour (beta (95% CI) = 0.5 (0.1, 0.9)). Prenatal PFOS and PFOA exposures were not associated with motor difficulties. Conclusions: Prenatal exposure to PFOS and PFOA may have a small to moderate effect on children's neuro-behavioural development, specifically in terms of hyperactive behaviour. The associations were strongest in Greenland where exposure contrast is largest