Search

We read with interest the recently published manuscript by Bell I et al i . entitled I Systematic review and meta-analysis: Safety of vedolizumab during pregnancy in patients with inflammatory bowel disease i . 11 Bröms G, Granath F, Linder M, Stephansson O, Elmberg M, Kieler H. Birth outcomes in women with inflammatory bowel disease: effects of disease activity and drug exposure. This significantly exceeded rates of active disease in the infliximab and adalimumab exposed cohorts of 9% and 0%, respectively ( I P i = 0.012).5 Two of the three adverse pregnancy outcomes described in the vedolizumab exposed cohort (the preterm deliveries) occurred in women with significant IBD activity. [Extracted from the article]

Background Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under-recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility ( AGID). Methods Twenty-three subjects evaluated at the Mayo Clinic for suspected AGID ( August 2006- February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy-manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6-12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). Key Results Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra-intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re-evaluated had scintigraphic evidence of improvement. The majority of responders who were re-evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). Conclusions & Inferences This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy. [ABSTRACT FROM AUTHOR]

(i) To determine whether neurology is the medical specialty with which Irish students and doctors have most difficulty, (ii) appraise attitudes towards how neurology is taught, and (iii) suggest ways teaching might be improved. A questionnaire on medical teaching was given to 457 medical students and junior doctors in Ireland. Perceived difficulties with neurology compared with seven other medical specialties were analysed. Other aspects of teaching were assessed including why neurology is perceived as difficult and ways teaching could be improved. Neurology was perceived as the most difficult of the eight medical specialties assessed. Participants felt they learned most at bedside tutorials with surprisingly few learning online. Neurology was perceived as difficult because of insufficient exposure to the subject, lack of teaching, and perceived complexity. Neurology teaching could be improved by increasing the number of bedside tutorials and by greater exposure to neurological patients for the students in clinical training. Medical students and doctors find neurology difficult. The teaching of neurology is reported as moderate to poor. The reasons for this are wide ranging but an emphasis on increased numbers of tutorials and greater integration of pre-clinical neurology to clinical years would improve teaching. [ABSTRACT FROM AUTHOR]

The author discusses the autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. He relates the study "Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a retrospective study," by Y. Long and colleagues which shows the incidence of autoimmune GFAP astrocytopathy in China, its neuropathology, and diagnosis.

The article describes the case of a 37 year old Asian woman presented for assessment of abnormal liver function after a neddle-stick injury. It refers to the case as an unusual case of hepatitise B virus HBV diagnostic escape variant where the standard HBsAG immunoassay was negative and suggests that routine testing for HBV infection should always include serology for HBsAg and anti-HBs and HBc and cites the importance of keeping an index of suspicion in high-risk individuals.

A letter to the editor on amiodarone-associated neuromyopathy is presented.

Background: Ustekinumab is increasingly used in pregnant women with inflammatory bowel disease (IBD). Existing safety data are reassuring, but the stability of ustekinumab levels in pregnancy, degree of transfer to the infant and time to infant clearance are unknown., Methods: In this prospective observational study, ustekinumab-exposed women with IBD had trough levels measured in each trimester of pregnancy and at delivery. Infant ustekinumab levels were measured at delivery and ongoing until clearance was achieved. Trough ustekinumab level stability in individuals across pregnancy was compared by Skillings-Mack test. Spearman coefficients were used to correlate maternal and infant delivery levels, and median time to infant ustekinumab clearance was defined., Results: 19 pregnant women receiving ustekinumab were included. There was no difference in ustekinumab levels across pregnancy in those with two or more representative trough levels (P = 0.83, n = 11). Infant delivery ustekinumab levels were higher than maternal levels, with a median infant:maternal ratio of 1.79 (IQR 1.26-3.1). There was a positive correlation between maternal and infant delivery ustekinumab levels (r = 0.75, P = 0.001) and an inverse correlation between the number of days from final antenatal dose and delivery infant ustekinumab level (r = -0.65, P = 0.006). Median time of infant ustekinumab clearance was 9 (range 6-19) weeks (n = 9)., Conclusion: Ustekinumab drug levels appear stable in pregnancy, with a delivery infant:maternal ratio similar to that of anti-TNFs. Infant ustekinumab clearance was complete by 20 weeks post-partum, however, infants exposed in utero should avoid live vaccination before 12 months of age until further clearance data are obtained., (© 2021 John Wiley & Sons Ltd.)

Background: Azathioprine and mercaptopurine are considered safe during pregnancy. However, the pharmacokinetic effects of pregnancy on thiopurine metabolism are undefined., Aims: To characterise thiopurine metabolism in pregnancy and measure infant metabolite levels and outcomes., Methods: Women with IBD who were taking a thiopurine and pregnant or trying to conceive were recruited. Maternal thiopurine metabolites were measured pre-conception, in each trimester, at delivery and post-partum. Infant metabolite levels, full blood examination and liver function testing were performed at birth, and repeated until levels undetectable and haematological and biochemical abnormalities resolved., Results: Forty patients were included with measurements on at least two occasions, and two with only mother-baby levels at delivery. The median maternal 6-TGN level dropped in the second trimester compared with post-partum (179.0 vs 323.5 pmol/8 × 10 8 RBCs, P < 0.001) and the median 6-MMP level increased in the second trimester compared with post-partum (1103.0 vs 329.5 pmol/8 × 10 8 RBCs, P < 0.01). At delivery, the median 6-TGN level was lower in infants (n = 20) than mothers (78.5 vs 217 pmol/8 × 10 8 RBCs) (P < 0.001). Metabolites were not detected at 6 weeks in any infants. Anaemia was not seen, but thrombocytosis and abnormal liver biochemistry were detected in 80% of infants from 6 weeks, which gradually improved., Conclusions: 6-TGN levels decrease and 6-MMP levels increase in the second trimester of pregnancy. Infants are exposed to thiopurine metabolites at low levels with clearance by 6 weeks and no anaemia. The cause of infant thrombocytosis and abnormal liver biochemistry in the absence of metabolites is unclear., (© 2021 John Wiley & Sons Ltd.)

Background: The impact of pregnancy on levels of biologic agents in patients with IBD is undefined and time to elimination in vedolizumab-exposed infants is unknown., Aims: To determine the effect of pregnancy on infliximab, adalimumab and vedolizumab levels and to study infant vedolizumab clearance METHODS: In a prospective observational study, maternal drug levels were measured pre-conception, in each trimester, at delivery and postpartum. The association between drug levels and gestation in weeks was assessed using generalised estimating equation modelling. Infant vedolizumab levels were performed at birth (cord blood), 6 weeks and 3 months or until undetectable., Results: We included 50 IBD patients (23 on infliximab, 15 on adalimumab and 12 on vedolizumab) with at least two intrapartum observations, plus 5 patients on vedolizumab with only mother and baby samples at delivery. Modelling showed no change in adalimumab levels, an increase in infliximab levels of 0.16 (95% CI 0.08-0.24) µg/L/week (P < 0.001) and a decrease of 0.18 (95% CI: -0.33 to -0.02) µg/L/week (P = 0.03) for vedolizumab. In 17 mother-baby pairs, median infant vedolizumab levels at birth were lower than maternal levels (P < 0.05) with an infant:maternal ratio of 0.7 (IQR 0.5-0.9). Vedolizumab was undetectable between 15 and 16 weeks of age in all 12 infants completing follow-up testing., Conclusions: During pregnancy, adalimumab levels remain stable, while infliximab levels increase and vedolizumab levels decrease. However, the increments were small suggesting that intrapartum therapeutic drug monitoring and dose adjustment are not indicated. Unlike infliximab and adalimumab, infant vedolizumab levels are lower in cord blood than in mothers and appear to clear rapidly., (© 2020 John Wiley & Sons Ltd.)

A couple and their five-year-old daughter are in a car accident. The parents are not expected to survive. The child is transported to a children's hospital, and urgent treatment decisions must be made. Whom should the attending physician approach to make decisions for the child? When such cases arise in, for example, the hospitals where we work, the social worker or chaplain is instructed to use the Illinois Health Care Surrogacy Act as a guidepost to identify a decision-maker. But in our state and the country overall, the limitations of such statutes leave hospital workers to make a judgment call among friends, family, and clergy who may come forward. While surrogate decision-making statutes comprehensively address surrogate decision-makers for adults, a patchwork of laws-permanency statutes, kinship provider statutes, standby guardianship statutes, and, in some cases, surrogate decision-making statutes-provide variable decision-making pathways for children., (© 2020 The Hastings Center.)

Objective: Difficulties with sex often develop following sexual trauma, yet are rarely targeted within treatment of post-traumatic stress disorder (PTSD). Where outcomes of sexual function are included, they are secondary to other measures. This review aimed to assess whether psychological treatment for PTSD (from sexual trauma) has an effect on sexual functioning., Methods: Systematic searches of MEDLINE, PsycINFO, EMBASE, and trial registers were performed. Five studies met inclusion criteria. Pre-post treatment effect sizes were also calculated., Results: Data from four good-quality RCTs were included in the meta-analyses. These examined females (n = 799) who had experienced adult sexual trauma or child sexual abuse. Studies compared psychological treatment to control conditions, but no effect on outcomes of sexual concerns, standardized mean difference (SMD) = 0.03 and dysfunctional sexual behaviour, SMD = 0.02, was found. Pre-post treatment effect sizes were small to medium (SMD = 0.36 and 0.47, respectively)., Conclusions: While firm conclusions cannot be drawn, the available evidence suggests that psychological treatment for PTSD has no effect on sexual problems. Pre-post effects indicate some improvement over the course of treatment, which may be strengthened if treatment actively targeted sexual problems. The paucity of evidence in this area suggests that there is substantial need for further research in order to establish a set of evidence-based guidelines for practitioners implementing treatment in this area., Practitioner Points: The measurement of sexual problems is overlooked in psychological treatment RCTs for sexual trauma. Current treatments for post-traumatic stress disorder (PTSD) from sexual trauma do not appear to be addressing sexual problems. Integrated treatments for comorbid sexual problems and PTSD treatment may be warranted. It is imperative that in future, RCTs that examine people with PTSD from sexual trauma use outcomes of sexual problems., (© 2015 The British Psychological Society.)

Background/aims: Endoscopic screening for high-risk gastro-oesophageal varices (GOV) is recommended for compensated cirrhotic patients with transient elastography identifying increasing numbers of patients with cirrhosis without portal hypertension. Using liver stiffness measurement (LSM) ± platelet count, the aim was to develop a simple clinical rule to exclude the presence of high-risk GOV in patients with Child-Pugh A cirrhosis., Methods: A retrospective analysis of 71 patients with Child-Pugh A cirrhosis diagnosed by transient elastography (LSM >13.6 kPa) who underwent screening gastroscopy was conducted. A predictive model using LSM ± platelet count was assessed to exclude the presence of high-risk GOV (diameter >5 mm and/or the presence of high-risk stigmata) and validated using a second cohort of 200 patients from two independent centres., Results: High-risk GOV were present in 10 (15%) and 16 (8%) of the training and validation cohorts, respectively, which was associated with LSM and Pl count (P < 0.05). A combined model based on LSM and Pl count was more accurate for excluding the presence of high-risk GOV than either alone (training cohort AUROC: 0.87 [0.77-0.96] vs. 0.78 [0.65-0.92] for LSM and 0.71 [0.52-0.90] for platelets) with the combination of LSM ≤25 kPa and Pl ≥100 having a NPV of 100% in both the training and validation cohorts. A total of 107 (39%) patients meet this criterion., Conclusion: The combination of LSM ≤25 kPa and Pl ≥100 can be used in clinical practice to exclude the presence of high-risk GOV in patients with Child-Pugh A cirrhosis., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)