Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum.

Nausea and vomiting of pregnancy (NVP) affects 80% of pregnancies. Its severe form, hyperemesis gravidarum (HG), results in dehydration, electrolyte imbalance, the need for hospitalisation and can, rarely, be fatal. This was a prospective, open-labelled, controlled, interventional study to evaluate the effectiveness of pre-emptive treatment of NVP symptoms in women who experienced severe NVP or HG in their previous pregnancy. Twenty-five women who reported severe symptoms of NVP with or without HG in their previous pregnancy were recruited and counselled to commence the use of antiemetics as soon as they became aware of the present pregnancy, and no later than the beginning of symptoms. They were followed-up prospectively through the index pregnancy for symptoms of NVP, and were counselled continuously as to how to modify antiemetic doses based on symptoms. A comparison group consisted of randomly selected women also counselled by us for NVP, who had also had severe NVP in the previous pregnancy, but who did not call before a planned pregnancy and thus could not be offered pre-emptive therapy. The recruited women commenced pre-emptive drug therapy for NVP before conception or up to 7 weeks' gestation, before the appearance of NVP symptoms in all cases. In comparison to the previous pregnancy, only eight of these 18 women experienced a HG again in the index pregnancy (P = 0.01). The majority of study the women had an improvement in severity of NVP symptoms compared to the previous pregnancy. In the comparison group (n = 35), symptoms in the index pregnancy remained severe in 28 cases (80%), decreased to moderate in six (16.6%) and decreased to mild in five cases (13.9%). There were five cases of HG in the previous pregnancy and three in the index pregnancy. The pre-emptive group was improved significantly compared to the control group (P = 0.01). Pre-emptive symptom management appears to be effective in preventing severe NVP in general, and HG in particular. Women who have experienced severe NVP in a previous pregnancy may benefit from taking antiemetics before, or immediately at the start of symptoms in a subsequent pregnancy.     

Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists.

PURPOSE: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. PATIENTS AND METHODS: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. RESULTS: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. CONCLUSION: These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.     

Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications.

PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer.     

Using fMRI to quantify the time dependence of remifentanil analgesia in the human brain.

To understand and exploit centrally acting drugs requires reliable measures of their time course of action in the human brain. Functional magnetic resonance imaging (fMRI) is able to measure noninvasively, drug-induced changes in task-related brain activity. Here, we have characterized, in a specific region of the brain, the time of onset of action and the half-life of action of a clinically relevant dose of a potent opioid analgesic agent, remifentanil. These times were established from the temporal variation of the amplitude of the blood oxygen level-dependent response in the insular cortex contralateral to a painfully hot thermal stimulus, in volunteers receiving a remifentanil infusion. The insular cortex has repeatedly been reported as activated by noxious thermal stimulation. The times of onset and offset of drug action were each characterized by a half-life for changes in fMRI signal from within the insula. These characteristic times agreed with the observed drug-induced analgesia and previous pharmacokinetic-pharmacodynamic measurements for remifentanil. We have successfully measured, for the first time using fMRI, temporal pharmacological parameters for a CNS-active drug based on its effect on task-related activity in a specific brain region. Comparison of the time course of regional brain activity with pain perception could reveal those regions engaged in drug-induced analgesia.     

Hypercalcemic crisis in third trimenon: evaluating the optimal treatment strategy

Hypercalcemia due to primary hyperparathyroidism during pregnancy is a rare condition and associated with increased morbidity and mortality for the mother and the unborn child. Whereas parathyroidectomy is favored during the second trimester, no clear recommendations exist for its management during the third trimenon. We here report the case of a 26-year-old woman in the 29th week of her first pregnancy, who was admitted to our clinic with hypertension, intra-uterine growth retardation and polyhydramnios. Severe hypercalcemia due to primary hyperparathyroidism was diagnosed (total calcium 3.34?mmol/l; PTH 216?pg/ml), but no enlarged parathyroid gland could be localized by ultrasound. Treatment with calcitonin and cinacalcet could not control hypercalcemia. Therefore explorative surgery was performed and a single parathyroid adenoma was resected, resulting in normalization of serum calcium levels. The surgical procedure was tolerated well by the mother and fetus. Hypercalcemia-induced hypertension and polyhydramnios ameliorated before C-section was performed two weeks later and unrelated to the intervention. This case report underlines the importance of early diagnosis and treatment of primary hyperparathyroidism during pregnancy. If diagnosed in the third trimenon, an interdisciplinary approach is crucial. If medical treatment fails to sufficiently control hypercalcemia, surgical parathyroid exploration should be considered even in cases of unsuccessful localization of adenomatous parathyroid glands.     

Design and Testing of BACRA,a Web-Based Tool for Middle Managers at Health Care Facilities to Lead the Search for Solutions to Patient Safety Incidents

BackgroundLack of time, lack of familiarity with root cause analysis, or suspicion that the reporting may result in negative consequences hinder involvement in the analysis of safety incidents and the search for preventive actions that can improve patient safety.ObjectiveThe aim was develop a tool that enables hospitals and primary care professionals to immediately analyze the causes of incidents and to propose and implement measures intended to prevent their recurrence.MethodsThe design of the Web-based tool (BACRA) considered research on the barriers for reporting, review of incident analysis tools, and the experience of eight managers from the field of patient safety. BACRA’s design was improved in successive versions (BACRA v1.1 and BACRA v1.2) based on feedback from 86 middle managers. BACRA v1.1 was used by 13 frontline professionals to analyze incidents of safety; 59 professionals used BACRA v1.2 and assessed the respective usefulness and ease of use of both versions.ResultsBACRA contains seven tabs that guide the user through the process of analyzing a safety incident and proposing preventive actions for similar future incidents. BACRA does not identify the person completing each analysis since the password introduced to hide said analysis only is linked to the information concerning the incident and not to any personal data. The tool was used by 72 professionals from hospitals and primary care centers. BACRA v1.2 was assessed more favorably than BACRA v1.1, both in terms of its usefulness (z=2.2, P=.03) and its ease of use (z=3.0, P=.003).ConclusionsBACRA helps to analyze incidents of safety and to propose preventive actions. BACRA guarantees anonymity of the analysis and reduces the reluctance of professionals to carry out this task. BACRA is useful and easy to use.     

Emotion,cognitive load and learning outcomes during simulation training

Medical Education 2012: 46 : 1055–1062 CONTEXT Simulation training has emerged as an effective way to complement clinical training of medical students. Yet outcomes from simulation training must be considered suboptimal when 25–30% of students fail to recognise a cardiac murmur on which they were trained 1 hour previously. There are several possible explanations for failure to improve following simulation training, which include the impact of heightened emotions on learning and cognitive overload caused by interactivity with high‐fidelity simulators. This study was conducted to assess emotion during simulation training and to explore the relationships between emotion and cognitive load, and diagnostic performance. METHODS We trained 84 Year 1 medical students on a scenario of chest pain caused by symptomatic aortic stenosis. After training, students were asked to rate their emotional state and cognitive load. We then provided training on a dyspnoea scenario before asking participants to diagnose the murmur in which they had been trained (aortic stenosis) and a novel murmur (mitral regurgitation). We used factor analysis to identify the principal components of emotion, and then studied the associations between these components of emotion and cognitive load and diagnostic performance. RESULTS We identified two principal components of emotion, which we felt represented invigoration and tranquillity. Both of these were associated with cognitive load with adjusted regression coefficients of 0.63 (95% confidence interval [CI] 0.28–0.99; p = 0.001) and ? 0.44 (95% CI ? 0.77 to ? 0.10; p = 0.009), respectively. We found a significant negative association between cognitive load and the odds of subsequently identifying the trained murmur (odds ratio 0.27, 95% CI 0.11–0.67; p = 0.004). CONCLUSIONS We found that increased invigoration and reduced tranquillity during simulation training were associated with increased cognitive load, and that the likelihood of correctly identifying a trained murmur declined with increasing cognitive load. Further studies are needed to evaluate the impact on performance of strategies to alter emotion and cognitive load during simulation training.     

Health Canada advisory on domperidone: Should I avoid prescribing domperidone to women to increase milk production?

Question I often prescribe domperidone to women as a galactagogue starting at a dose of 30 mg and increasing the dose as needed. In March of this year, Health Canada released an advisory warning of domperidone use and abnormal heart rhythms and sudden cardiac death. Should I cap doses at 30 mg or stop prescribing domperidone all together to these women?Answer The Health Canada warning is based on 2 studies. The results of the studies are not directly applicable to breastfeeding and should not change the way you normally manage otherwise healthy breastfeeding women.