Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study.

孕早期口服氟康唑使用与先天性畸形风险: 基于人群的队列研究。

  • 影响因子:0
  • DOI:10.1136/bmj.m1494
  • 作者列表:"Zhu Y","Bateman BT","Gray KJ","Hernandez-Diaz S","Mogun H","Straub L","Huybrechts KF
  • 发表时间:2020-05-20

OBJECTIVE:To examine the risk of congenital malformations associated with exposure to oral fluconazole at commonly used doses in the first trimester of pregnancy for the treatment of vulvovaginal candidiasis. DESIGN:Population based cohort study. SETTING:A cohort of pregnancies publicly insured in the United States, with data from the nationwide Medicaid Analytic eXtract 2000-14. PARTICIPANTS:Pregnancies of women enrolled in Medicaid from three or more months before the last menstrual period to one month after delivery, and infants enrolled for three or more months after birth. INTERVENTIONS:Use of fluconazole and topical azoles was established by requiring one or more prescriptions during the first trimester of pregnancy. MAIN OUTCOME MEASURES:Risk of musculoskeletal malformations, conotruncal malformations, and oral clefts (primary outcomes), associated with exposure to oral fluconazole, diagnosed during the first 90 days after delivery, were examined. RESULTS:The study cohort of 1 969 954 pregnancies included 37 650 (1.9%) pregnancies exposed to oral fluconazole and 82 090 (4.2%) pregnancies exposed to topical azoles during the first trimester. The risk of musculoskeletal malformations was 52.1 (95% confidence interval 44.8 to 59.3) per 10 000 pregnancies exposed to fluconazole versus 37.3 (33.1 to 41.4) per 10 000 pregnancies exposed to topical azoles. The risks of conotruncal malformations were 9.6 (6.4 to 12.7) versus 8.3 (6.3 to 10.3) per 10 000 pregnancies exposed to fluconazole and topical azoles, respectively; risks of oral clefts were 9.3 (6.2 to 12.4) versus 10.6 (8.4 to 12.8) per 10 000 pregnancies, respectively. The adjusted relative risk after fine stratification of the propensity score was 1.30 (1.09 to 1.56) for musculoskeletal malformations, 1.04 (0.70 to 1.55) for conotruncal malformations, and 0.91 (0.61 to 1.35) for oral clefts overall. Based on cumulative doses of fluconazole, the adjusted relative risks for musculoskeletal malformations, conotruncal malformations, and oral clefts overall were 1.29 (1.05 to 1.58), 1.12 (0.71 to 1.77), and 0.88 (0.55 to 1.40) for 150 mg of fluconazole; 1.24 (0.93 to 1.66), 0.61 (0.26 to 1.39), and 1.08 (0.58 to 2.04) for more than 150 mg up to 450 mg of fluconazole; and 1.98 (1.23 to 3.17), 2.30 (0.93 to 5.65), and 0.94 (0.23 to 3.82) for more than 450 mg of fluconazole, respectively. CONCLUSIONS:Oral fluconazole use in the first trimester was not associated with oral clefts or conotruncal malformations, but an association with musculoskeletal malformations was found, corresponding to a small adjusted risk difference of about 12 incidents per 10 000 exposed pregnancies overall.


目的: 研究妊娠早期口服氟康唑治疗外阴阴道念珠菌病相关先天畸形的风险。 设计: 基于人群的队列研究。 设置: 美国公开保险的妊娠队列,数据来自全国医疗补助分析提取物 2000-14。 参与者: 从最后一次月经前三个月或更长时间到分娩后一个月,以及出生后三个月或更长时间的婴儿参加医疗补助的妇女的怀孕。 干预措施: 通过在妊娠早期需要一个或多个处方来确定氟康唑和局部唑类药物的使用。 主要结局指标: 检查了分娩后前 90 天诊断的与口服氟康唑暴露相关的肌肉骨骼畸形、圆锥干畸形和口腔裂隙的风险 (主要结局)。 结果: 研究队列 1 969 954 例妊娠包括 37 650 例 (1。9%) 暴露于口服氟康唑的妊娠和 82 090 (4.2%) 妊娠暴露于孕早期局部唑类。暴露于氟康唑的每 10 000 例妊娠中肌肉骨骼畸形的风险为 52.1 (95% 置信区间 44.8 至 59.3),而暴露于局部唑类的每 10 000 例妊娠中,肌肉骨骼畸形的风险为 37.3 (33.1 至 41.4)。每 10 000 名孕妇暴露于氟康唑和局部唑类药物后,圆锥干畸形的风险分别为 9.6 (6.4-12.7) 和 8.3 (6.3-10.3); 每 10 000 例妊娠中口腔裂隙的风险分别为 9.3 (6.2-12.4) 和 10.6 (8.4-12.8)。倾向评分精细分层后的校正相对风险为: 肌肉骨骼畸形 1.30 (1.09 ~ 1.56),圆锥干畸形 1.04 (0.70 ~ 1.55),0.91 (0.61 ~ 1.35) 对于整体口腔裂缝。基于氟康唑的累积剂量,肌肉骨骼畸形、圆锥干畸形和口腔裂缝的调整相对风险总体为 1.29 (1.05 至 1.58) 、 1.12 (0.71 至 1.77),和 0.88 (0.55 至 1.40) 用于 150 mg氟康唑; 1.24 (0.93 至 1.66),0.61 (0.26 至 1.39),1.08 (0.58 至 2.04) 超过 150 mg至 450 mg氟康唑; 1.98 (1.23 至 3.17),2.30 (0.93 至 5.65),0.94 mg以上的氟康唑分别为 0.23 (3.82 ~ 450)。 结论: 孕早期口服氟康唑与口腔裂隙或圆锥干畸形无关,但与肌肉骨骼畸形有关。对应于总体每 10 000 次暴露妊娠约 12 次事件的小调整风险差异。



作者列表:["Peyroux E","Babinet MN","Cannarsa C","Madelaine C","Favre E","Demily C","Michael GA"]

METHODS::Impairments in social cognition have been frequently described in 22q11.2 deletion syndrome (22q11.2DS) and are thought to be a hallmark of difficulties in social interactions. The present study addresses aspects that are critical for everyday social cognitive functioning but have received little attention so far. Sixteen children with 22q11.2DS and 22 controls completed 1 task of facial expression recognition, 1 task of attribution of facial expressions to faceless characters involved in visually presented social interactions, and 1 task of attribution of facial expressions to characters involved in aurally presented dialogues. All three tasks have in common to involve processing of emotions. All participants also completed two tasks of attention and two tasks of visual spatial perception, and their parents completed some scales regarding behavioural problems of their children. Patients performed worse than controls in all three tasks of emotion processing, and even worse in the second and third tasks. However, they performed above chance level in all three tasks, and the results were independent of IQ, age and gender. The analysis of error patterns suggests that patients tend to coarsely categorize situations as either attractive or repulsive and also that they have difficulties in differentiating emotions that are associated with threats. An isolated association between the tasks of emotion and behaviour was found, showing that the more frequently patients with 22q11.2DS perceive happiness where there is not, the less they exhibit aggressive behaviour.

作者列表:["Sheridan GA","Nagle M","Howells C","Gallagher O","Kiely PJ","O'Toole P","Kelly PM","Moore DP"]

METHODS:BACKGROUND:We describe the first radiographic clinic in the literature for DDH and how this novel clinic can significantly improve the efficiency and cost-effectiveness of service in a tertiary referral centre. AIMS:A radiographic clinic for the management of developmental dysplasia of the hip was introduced in 2017 in our institution. We performed a detailed cost analysis to assess the economic savings made with the introduction of this new clinic. We assessed the efficiency of the service by identifying how many unnecessary outpatient visits were prevented. We also assessed the difference in times from referral to review between the two clinics. METHODS:Analysis of the clinic activity in 2017 was possible as all data was collected prospectively by the DDH CNS and stored in our database. Cost analysis was performed, and the savings made per patient along with the financial benefit to our institution was recorded. RESULTS:The new radiographic clinic reduced the cost of reviewing one patient by €162.51 per patient. There was a 73% discharge rate from the clinic which prevented 251 unnecessary patient visits to the outpatient department over the course of the year. There was a significant 11-day reduction in waiting times between referral and review when comparing the radiographic to the conventional clinic (p < 0.05). CONCLUSIONS:A radiographic clinic for the management of developmental dysplasia of the hip has a significant effect on the efficiency and overall cost-effectiveness of service provision in a tertiary referral centre.

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作者列表:["Grigoryan G","Korcek L","Eidelman M","Paley D","Nelson S"]

METHODS:INTRODUCTION:Triple pelvic osteotomy (TPO) involves periacetabular osteotomies of the ilium, ischium, and pubis to reorient the acetabulum. This operation is indicated in certain situations for the treatment of developmental dysplasia of the hip, dysplastic neuromuscular hips, and for containment of the femoral head in cases of Legg-Calvé-Perthes disease. METHODS:This retrospective cohort study compares radiographic outcomes of patients who underwent TPO using two different techniques and describes a novel single-incision direct lateral approach. TPO was performed on 22 patients by the senior author. The first 10 patients underwent TPO through a single-incision anterolateral approach. The last 12 patients underwent TPO using the direct lateral approach. Preoperative and postoperative pelvic radiographs were reviewed for each patient, and the migration index and center-edge angle were recorded. RESULTS:The migration index and center-edge angle were evaluated and were not found to be significantly different between the anterolateral and direct lateral groups. The direct lateral approach is described. CONCLUSION:The direct lateral approach for TPO is equivalent to the anterolateral approach on radiographic evaluation. Advantages of the direct lateral approach include direct visualization of the ischial osteotomy, effective mobilization of the acetabulum, and safety of the sciatic nerve.

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