Paroxetine use in pregnancy and cardiovascular defects

Background: Paroxetine (Paxil,) is an SSRI, used for thetreatment of depression, obsessive compulsive disorder,anxiety disorders and premenstrual dysphoria. Untilrecently, no studies had associated SSRIs as a group withan increased risk for major malformations above the 1%-3% baseline rate. However, in the past year, several studiesnoted specifically, an increase risk of cardiovascular defectsassociated with paroxetine, compared to other antidepressantswithin its class.Objectives: To determine whether paroxetine increases therisk of cardiovascular defects in infants of women exposedduring the first trimester of pregnancy.Methods: We collected prospectively ascertained cases ofinfants from Teratogen Information Services throughout theworld, exposed to paroxetine in the first trimester of pregnancyand compared them to a non-exposed Motheriskcohort.We also contacted the authors of data base studies thathad been published on antidepressants as a class, to determinehow many of these women had been exposed to paroxetineand the rates of cardiovascular defects in their infants.Results: We were able to ascertain the outcomes of 1177infants from 9 services. The rate of heart defects in the paroxetineparoxetinegroup was 0.8% versus 0.7% non-exposed group.The combined rate in the data base studies was 1.5%.Conclusions: Paroxetine does not appear to be associated withan increase risk for cardiovascular defects following use inpregnancy, as the incidence in more than 3000 infants was wellwithin the population incidence of approximately 1%.

Incidence of Infectious Complications in Kidney Transplant Recipients Receiving Induction with Basiliximab, Thymoglobulin or Both

Background: The possible additional risk of infection in patients receiving induction with both basiliximab (Ba) and thymoglobulin (Th) is unclear. We assessed the 1-year incidence of infectious complications in 3 groups of kidney transplant recipients according to the type of induction therapy received.Methods: We compared the incidence of infection at 1 year in 3 groups of patients at our institution: fi rst transplant recipients received Ba 20mg at days 0 and 4 (Group Ba); in case of retransplantation or if PRA was >20% patients received Th 1 mg/kg for 3-5 days (Group Th); in case of delayed graft function (DGF), Ba was discontinued and Th was initiated (Group Ba+Th) or prolonged in Group Th. Kaplan-Meier curves were used to calculate the incidence of infection. A Cox analysis was used to identify risk factors for the development of infection.Results: Over 5 years, 170 consecutive kidney transplant recipients were performed:n=113 in Group Ba, n=39 in Group Th and n=18 in Group Ba+Th. As expected, more patients in Group Th received a second transplant (p<0.001). No differences in CMV serostatus were observed between groups (p=0.9). Incidences of CMV infection, CMV disease, BK viremia, BK nephropathy and urinary tract infection (UTI) is shown in Table 1. Table 1 Group Ba (n=113) Group Th (n=38) Group Ba+Th (n=18) CMV infection 31 (27%) 20 (51%) 8 (44%) CMV disease 7 (6%) 4 (10%) 0 BK viremia 11 (8%) 5 (13%) 4 (22%) BK nephropathy 5 (4%) 1 (2%) 2 (11%) UTI 43 (38%) 23 (59%) 6 (33%) Incidences of infection according to type of induction In a multivariate model taking into account CMV serostatus, age, pretransplant dialysis, type of organ transplanted, number of transplants and type of induction, Group Ba carried a lower risk of CMV infection (OR 0.45, p=0.006), and UTI (OR=0.6, p=0.05), but there were no differences in CMV disease (p=0.38). There was a trend towards higher incidence of BK viremia, but not nephropathy in Group Ba+Th (OR 2.2, p=0.23). There were no signifi cant differences in kidney function or graft loss at 1 year between groups.Conclusion: By multivariate analysis, we observed a lower risk of CMV infection andUTI in patients receiving Ba. The group Ba+Th had a similar risk for infection than the group receiving Th alone. Larger studies are needed to clarify whether combining Ba+Th in the setting of DGF may increase the risk of infectious complications, in particular BK infection.

Patients at risk of complications of Staphylococcus aureus bloodstream infection.

Staphylococcus aureus is one of the most common causative pathogens of bloodstream infections (BSIs). In approximately one-half of patients with S. aureus BSI, no portal of entry can be documented. This group of patients has a high risk of developing septic metastases. Similarly, patient populations at high risk of S. aureus BSI and BSI-associated complications include patients receiving hemodialysis, injection drug users, patients with diabetes, and patients with preexisting cardiac conditions or other comorbidities. One of the most severe complications of S. aureus BSI is infective endocarditis, and S. aureus is now the most common cause of infective endocarditis in the developed world. Patients with methicillin-resistant S. aureus BSI or infective endocarditis have higher rates of mortality, compared with patients with methicillin-susceptible S. aureus infection. Nasal carriage is the most important source of S. aureus BSI. Better eradication and control strategies, including nasal decolonization and more-active antibiotics, are needed to combat S. aureus BSIs.

Termination of pregnancy among teenagers - why more surgical terminations?

Introduction: In 2012, a study by K. Chatziioannidou and S-C. Renteria showed that teenagers chose to undergo a surgical termination of pregnancy (TOP) more often than a medical TOP (mifepristone followed by misoprostol) when they decided to terminate a pregnancy. It also showed that the teenagers' choice for a medical versus surgical method is inversely proportional to the adults' choice although the efficiency of the medical method showed even better results for teenagers than for adults. According to the hypothesis made, the reasons for this choice might be influenced by the following facts: (i) the belated call to make an appointment, the medical procedure not being available after 9 weeks of gestation; (ii) the imperative request for confidentiality; (iii) the beliefs and subjective appreciation of the medical staff. Objectives: The aim of this retrospective and qualitative study is to analyse the reasons why, in case of a TOP, teenagers chose the surgical method more often than their adult counterparts. Material: (i) All teenagers who were admitted for an abortive procedure during 2011 in the in- or outpatient ward. (ii) The professional team (midwives and sexual and reproductive counsellors) in charge in the case of a TOP request. Methods: The information about the patient's history and the biopsycho- social data was retrieved from the patient files filled out by midwives and sexual and reproductive health counsellors during the first appointment for a TOP request or during its process. The professionals' appreciation was evaluated by means of a semi-structured questionnaire. Results: Concerning the choice of the method for a pregnancy termination, the results of our research show that: (i) Out of 47 teenagers, 27 chose the surgical method and 17 the medical method. (ii) Three had a second trimester abortion (which includes use of the medical method). (iii) Fifteen teenagers out of the 27 who chose a surgical method consulted between the 9th and 14th weeks of amenorrhoea and therefore did not have any other choice. The reasons for their 'late arrival' will be explained in detail. The 12 teenagers who arrived before the 8th week of amenorrhoea and chose to undertake abortion by suction & curettage under general anaesthesia did it for the following reasons: (i) Four were afraid of bleeding and pain. (ii) Five thought that the organisation of the surgical procedure was easier. (iii) Two did not trust the abortion pill. (iv) One was taken to her mother's gynaecologist where she had a D&C. Confidentiality was requested nine times out of 27 when choosing the surgical method, and six times out of 17 when choosing the medical method. Therefore, although confidentiality concerns a third of the teenagers' pregnancy termination requests, it does not seem to be a significant element for the choice of the method. As for the subjective appreciation of the professionals, the first results of the discussions seem to show that teenagers were reluctant or resistant towards the medical method. Conclusion: This study shows that the reasons why teenagers still prefer the use of the surgical over the medical method compared to adults, seem to include the late request for an appointment, fear of pain and bleeding and organisational issues. Confidentiality does not seem to greatly influence the teenagers' choice. Nonetheless, medical professionals seem to favour the suction curettage procedure performed under anesthesia because they associate young age with vulnerability and psychological frailty and consequently diminished ability to cope with pain and emotional distress during the medical procedures.

Medication exposure during pregnancy: a pilot pharmacovigilance system using health and demographic surveillance platform.

BACKGROUND: There is limited safety information on most drugs used during pregnancy. This is especially true for medication against tropical diseases because pharmacovigilance systems are not much developed in these settings. The aim of the present study was to demonstrate feasibility of using Health and Demographic Surveillance System (HDSS) as a platform to monitor drug safety in pregnancy. METHODS: Pregnant women with gestational age below 20 weeks were recruited from Reproductive and Child Health (RCH) clinics or from monthly house visits carried out for the HDSS. A structured questionnaire was used to interview pregnant women. Participants were followed on monthly basis to record any new drug used as well as pregnancy outcome. RESULTS: 1089 pregnant women were recruited; 994 (91.3%) completed the follow-up until delivery. 98% women reported to have taken at least one medication during pregnancy, mainly those used in antenatal programmes. Other most reported drugs were analgesics (24%), antibiotics (17%), and antimalarial (15%), excluding IPTp. Artemether-lumefantrine (AL) was the most used antimalarial for treating illness by nearly 3/4 compared to other groups of malaria drugs. Overall, antimalarial and antibiotic exposures in pregnancy were not significantly associated with adverse pregnancy outcome. Iron and folic acid supplementation were associated with decreased risk of miscarriage/stillbirth (OR 0.1; 0.08 - 0.3). CONCLUSION: Almost all women were exposed to medication during pregnancy. Exposure to iron and folic acid had a beneficial effect on pregnancy outcome. HDSS proved to be a useful platform to establish a reliable pharmacovigilance system in resource-limited countries. Widening drug safety information is essential to facilitate evidence based risk-benefit decision for treatment during pregnancy, a major challenge with newly marketed medicines.

Complications biliaires après tranplantation hépatique

RESUME Après transplantation hépatique (TH), il persiste une morbidité et une mortalité liées aux complications immunologiques, infectieuses, rénales, vasculaires et, en particulier, aux complications biliaires - le "talon d'Achille" de la TH. Dans ce travail de thèse, nous avons analysé la fréquence et les caractéristiques des complications biliaires après TH dans l'expérience du CHUV à Lausanne entre 1988 et 2003. Au total 185 transplantations orthotopiques ont été réalisées chez 168 patients de décembre 1988 à mars 2003 (103 patients transplantés étaient de sexe masculin et 65 de sexe féminin). L'âge moyen pour les hommes était de 51 ans, celui de femmes étant de 49. Pendant la TH, une anastomose cholédoco-cholédocienne a été réalisée à 168 reprises et une anastomose cholédoco-jejunale à 17 reprises. Trente cas de complications biliaires ont été recensés, soit 16% des cas, avec un taux de mortalité de 0% durant le traitement de ces complications. Il s'agissait d'obstructions biliaires, fuites biliaires, lithiase biliaire isolée et sténoses biliaires. Les complications biliaires après TH restent donc relativement fréquentes et sont parfois graves. Elles nécessitent un diagnostic précoce et doivent être suspectées lors de fièvre, d'ictère, de douleurs abdominales ou de cholestase. En conclusion, l'incidence et le type de complications retrouvés dans la série lausannoise sont représentatifs des résultats observés dans d'autres centres de TH. Le traitement adéquat de ces complications, souvent graves, est de la plus haute importance et aura un impact important sur le pronostic.

Patterns and factors associated with low adherence to psychotropic medications during pregnancy-a cross-sectional, multinational web-based study.

BACKGROUND: No previous studies have explored how closely women follow their psychotropic drug regimens during pregnancy. This study aimed to explore patterns of and factors associated with low adherence to psychotropic medication during pregnancy. METHODS: Multinational web-based study was performed in 18 countries in Europe, North America, and Australia. Uniform data collection was ensured via an electronic questionnaire. Pregnant women were eligible to participate. Adherence was measured via the 8-item Morisky Medication Adherence Scale (MMAS-8). The Beliefs about Prescribed Medicines Questionnaire (BMQ-specific), the Edinburgh Postnatal Depression Scale (EPDS), and a numeric rating scale were utilized to measure women's beliefs, depressive symptoms, and antidepressant risk perception, respectively. Participants reporting use of psychotropic medication during pregnancy (n = 160) were included in the analysis. RESULTS: On the basis of the MMAS-8, 78 of 160 women (48.8%, 95% CI: 41.1-56.4%) demonstrated low adherence during pregnancy. The rates of low adherence were 51.3% for medication for anxiety, 47.2% for depression, and 42.9% for other psychiatric disorders. Smoking during pregnancy, elevated antidepressant risk perception (risk≥6), and depressive symptoms were associated with a significant 3.9-, 2.3-, and 2.5-fold increased likelihood of low medication adherence, respectively. Women on psychotropic polytherapy were less likely to demonstrate low adherence. The belief that the benefit of pharmacotherapy outweighed the risks positively correlated (r = .282) with higher medication adherence. CONCLUSIONS: Approximately one of two pregnant women using psychotropic medication demonstrated low adherence in pregnancy. Life-style factors, risk perception, depressive symptoms, and individual beliefs are important factors related to adherence to psychotropic medication in pregnancy.

Complications of systemic juvenile idiopathic arthritis: risk factors and management recommendations.

Systemic juvenile idiopathic arthritis (SJIA) is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. Systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that SJIA is an autoinflammatory disorder. IL-1 and IL-6 play a major role in the pathogenesis of SJIA, and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. However, complications of SJIA, including macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation, continue to be a major issue in SJIA patients' care. Translational research leading to a profound understanding of the cytokine crosstalk in SJIA and the identification of risk factors for SJIA complications will help to improve long-term outcome.

The border of reproductive control: undocumented immigration as a risk factor for unintended pregnancy in Switzerland.

Unintended pregnancies reflect an unmet need for family planning, and are part of health disparities. Using the only database to inquire about pregnancy intention among women in Switzerland, this study examined the relationship between immigrant documentation and unintended pregnancy (UP). Among pregnant women presenting to a Swiss hospital, we compared pregnancy intention between documented and undocumented women. We used logistic regression to examine whether undocumented status was associated with UP after adjusting for other significant predictors. Undocumented women had more unintended pregnancies (75.2 vs. 20.6 %, p = 0.00). Undocumented status was associated with UP after adjustment (OR 6.23, 95 % CI 1.83-21.2), as was a history of psychological problems (OR 4.09, 95 % CI 1.32-12.7). Contraception non-use was notably associated with lower odds of UP (OR 0.01, 95 % CI 0.004-0.04). Undocumented status was significantly associated with UP, even after adjusting for well-recognized risk factors. This highlights the tremendous risk of undocumented status on UP among women in Switzerland.

Pregnancy outcome following maternal exposure to mirtazapine: a multicenter, prospective study.

This multicenter, observational prospective cohort study addresses the risk associated with exposure to mirtazapine during pregnancy. Pregnancy outcomes after exposure to mirtazapine were compared with 2 matched control groups: (1) exposure to any selective serotonin reuptake inhibitor (SSRI, control subjects with a psychiatric condition) and (2) no exposure to medication known to be teratogenic or any antidepressant (general control subjects). Data were collected by members of the European Network of Teratology Information Services between 1995 and 2011. Observations from 357 exposed pregnancies were compared with 357 pregnancies from each control group. The rate of major birth defects between the mirtazapine and the SSRI group did not differ significantly (4.5% vs 4.2%; odds ratio [OR], 1.1; 95% confidence interval [95% CI], 0.5-2.3; P = 0.9). A trend toward a higher rate of birth defects in the mirtazapine group compared with general control subjects (4.5% vs 1.9%; OR, 2.4; 95% CI, 0.9-6.3; P = 0.08) reached statistical significance after exclusion of chromosomal or genetic anomalies (4.1% vs 1.3%; OR, 3.3; 95% CI, 1.04-10.3; P = 0.03), but this difference became again nonsignificant if cases of exposure not comprising the first trimester were excluded from the analysis (3.4% vs 1.9%; OR, 1.8; 95% CI, 0.6-5.0; P = 0.26). The crude miscarriage rate did not differ significantly between the mirtazapine, the SSRI, and the general control groups (12.1% vs 12.0% vs 9.3%; P = 0.44). However, a higher rate of elective pregnancy termination was observed in the mirtazapine group compared with SSRI and general control subjects (7.8% vs 3.4% vs 5.6%; P = 0.03). This study did not observe a statistically significant difference in the rate of major birth defects after first-trimester exposure between mirtazapine, SSRI-exposed, and nonexposed pregnancies. A marginally higher rate of birth defects was, however, observed in the mirtazapine and SSRI groups compared with the low rate of birth defects in our general control subjects. Overall pregnancy outcome after mirtazapine exposure was similar to that of the SSRI-exposed control group.