Lower accuracy in prediction of delivery date in Stockholm County following introduction of new guidelines.

INTRODUCTION: In Stockholm County, new guidelines for predicting the day of delivery were introduced in 2010. Recent clinical use has indicated that the predictive quality might be suboptimal. This study compares the accuracy of three equations applied during the first (crown-rump length or bi-parietal diameter) and second trimesters (bi-parietal diameter or bi-parietal diameter combined with femur length). MATERIAL AND METHODS: The accuracy of estimated delivery date was compared in 14 239 ultrasound exams using median deviations from actual birth date, proportion of postterms, births within ±seven days of estimated delivery date, accuracy variations depending on fetal size, alternative fetal measurements obtained on the same occasion, and menstrual age. RESULTS: The bi-parietal diameter and crown-rump length formulae overestimated pregnancy length by two and three days respectively, causing 7-8% of pregnancies to be labelled postterm. A combined bi-parietal diameter+femur length formula overestimated by one day, with 5.1% postterms. No significant difference was found in the proportion of births within ±seven days. Second trimester estimated delivery date assessment had larger median variations than did first trimester assessment and suffered from shifting deviations across fetal size. The comparison of different biometry formulae in the same individual demonstrated one day extra deviation for bi-parietal diameter and three days extra deviation for crown-rump length compared with the combined bi-parietal diameter+femur length formula. CONCLUSIONS: The algorithms and dating occasions tested seem inappropriate for the present 280-day term definition. Alternative formulae ought to be sought, and the assumed duration of pregnancy reconsidered; 283 days corresponds to the observed pregnancy length calculated from last menstrual period, and would better fit the observed results for first trimester ultrasound scans.

Maternal emotional wellbeing over time and attachment to the fetus when a malformation is detected.

OBJECTIVES: To explore women's emotional wellbeing and attachment to the fetus when informed during pregnancy of a fetal malformation. METHODS: In a longitudinal community-based study, 56 pregnant women with a detected fetal malformation and continued pregnancy were invited to complete questionnaires in mid-pregnancy, two months postpartum and one year postpartum. The questionnaire included the Edinburgh Postnatal Depression Scale, the Cambridge Worry Scale, the State-Trait Anxiety Inventory, and the Maternal-Fetal Attachment Scale. Socio-demographics and obstetric background data were also collected. Descriptive statistical analyses were performed. RESULTS: Approximately 84% returned the questionnaires and 37% of women in mid-pregnancy, 26.5% two months postpartum and 22% one year postpartum were found to have depressive symptoms. In mid-pregnancy 8.9% had thoughts of harming themselves, and almost all reported at least one major worry. Worry about the relationship with their husband or partner increased two months postpartum and one year postpartum. The means of both state and trait anxiety levels were high on all three measuring occasions and the mean score for maternal-fetal attachment was 3.7 (SD 0.67), indicating a high level of attachment. CONCLUSION: The results highlight the importance of adequate support when fetal malformations are detected on ultrasound examination.

Novel topical formulation of lidocaine provides significant pain relief for intrauterine device insertion: pharmacokinetic evaluation and randomized placebo-controlled trial.

OBJECTIVE: To investigate the pharmacokinetics, safety, and analgesic efficacy of a novel topical formulation of lidocaine at insertion of an intrauterine device (IUD). DESIGN: Randomized controlled trial; phase-I and phase-II studies. SETTING: University and public hospitals. PATIENT(S): Women aged ≥18 years who wanted to receive an IUD. Four women were parous in phase I; all in phase II were nulliparous. INTERVENTION(S): A single, 8.5-mL dose of lidocaine formulation (SHACT) was administered (to the portio, cervix, and uterus) with a specially designed applicator. MAIN OUTCOME MEASURE(S): The phase-I study (single-arm) was designed for pharmacokinetic assessment; the phase-II study (randomized) was intended for investigation of efficacy and safety. RESULT(S): From the phase-I study (15 participants), mean pharmacokinetic values were: maximum plasma concentration: 351 ± 205 ng/mL; time taken to reach maximum concentration: 68 ± 41 minutes; and area under the concentration-time curve from 0 to 180 minutes: 717 ± 421 ng*h/mL. Pain relief was observed with lidocaine vs. placebo in the phase-II study (218 women, randomized). Mean visual analog scale score for maximum pain during the first 10 minutes after IUD insertion was 36% lower with lidocaine than with placebo (28.3 ± 24.6 vs. 44.2 ± 26.0). Pain intensity was also significantly lower in the lidocaine group at 30 minutes. On average, 3 of 4 patients will have less pain with lidocaine than with placebo. Adverse events were similar in the placebo and lidocaine groups. No serious adverse events were reported. CONCLUSION(S): Lidocaine provides pain relief lasting for 30-60 minutes for women undergoing IUD insertion, without any safety concerns. Further studies of this lidocaine formulation, for IUD insertion and other clinical applications, are planned. CLINICAL TRIAL REGISTRATION NUMBER: 2011-005660-18 and 2011-006220-20 (EudraCT).

Pregnancy termination due to fetal anomaly: women's reactions, satisfaction and experiences of care.

OBJECTIVE: to explore what women who have had a pregnancy terminated due to a detected fetal malformation perceived as having been important in their encounters with caregivers for promoting their healthy adjustment and well-being. METHOD: an exploratory descriptive design was used. Semi-structured interviews were audiotaped, and the information pathway described. The text was processed through qualitative content analysis in six steps. SETTING: four fetal care referral centres in Stockholm, Sweden. PARTICIPANTS: 11 women opting for pregnancy termination due to fetal malformation. FINDINGS: in-depth understanding and compassion are important factors in providing the feeling of support people need so they are able to adapt to crisis. The women emphasised that the caregivers have to communicate a sense of responsibility, hope and respect and provide on-going care for them to feel assured of receiving good medical care and treatment. Aside from existing psychological conditions, the women identified as having emotional distress directly after termination and for at least the following three months. Most women experienced a range of negative emotions after pregnancy termination, including sadness, meaninglessness, loneliness, tiredness, grief, anger and frustration. Still some of this group had positive reactions because they experienced empathy and well-organised care. CONCLUSION AND IMPLICATIONS FOR PRACTICE: The most important factors associated with satisfaction regarding pregnancy termination due to a fetal malformation are the human aspects of care, namely state-dependent communication and in-depth understanding and compassion. The changes in care most often asked for were improvements in the level of standards and provision of adequate support through state-dependent communication, in-depth understanding and compassion, and complete follow-up routines and increased resources. Targeted education for the caregivers may be suited to ensuring that they properly meet needs of their patients.

Pregnant women's perspectives on decision-making when a fetal malformation is detected by ultrasound examination.

OBJECTIVES: The aims of the study were to explore factors influencing the decision to continue or terminate pregnancy due to detection of fetal malformation following ultrasound examination, to elucidate the need for more information or other routines to facilitate the decision-making process and to assess satisfaction with the decision made. DESIGN: Descriptive study. SETTING: Four fetal care referral centres in Stockholm, Sweden. POPULATION: Pregnant women with a detected fetal malformation. METHODS: Data was collected by questionnaires. 134 women participated, 99 completing the questionnaire. Descriptive statistical analysis was performed. RESULTS: Both women who continued and those who terminated pregnancy based their decision on the severity of the malformation. Other reasons for terminating the pregnancy were aspects including socioeconomic considerations. None stated religious factors. The doctor at the fetal care unit also had an influence on the decision-making. The timeframe receiving information was regarded as long enough in duration but not the number of occasions. In both groups the women made the decision by themselves or together with their partners. The majority experienced that they had made the right decision. Women who terminated their pregnancy had a significant higher rate (51.2%) (p < or = 0.004) of previous abortions than those in the continuing group (23.2%). CONCLUSION: The decision to continue or terminate the pregnancy was to a great extent based on the severity of the malformation. Religious aspects did not seem to influence the decision. Many women expressed a need for additional occasion of information. The vast majority of women were satisfied with their decision.

Poor quality of antenatal care services--is lack of competence and support the reason? An observational and interview study in rural areas of Lao PDR.

OBJECTIVE: to explore the health-care providers' performance and their own perceptions of the ANC services they provide. DESIGN, SETTING AND PARTICIPANTS: this cross-sectional exploratory survey was carried out in 2009 at four district hospitals and 18 health centres in Khammouane and Champasack provinces in rural areas of Laos. MEASUREMENTS AND FINDINGS: combinations of quantitative and qualitative methods were used: (i) 59 observations of ANC sessions (components performed and equipment used); (ii) 26 semi-structured interviews with health-care providers engaged in ANC services, interpreted through content analysis. The findings indicated an overall poor quality and performance of ANC services in rural health facilities with lack of routines, scarce or insufficient equipment and limited skills among providers. The health-care providers gave an often pessimistic picture of their competence and motivation to work with ANC. Some articulated a resignation due to lack of feedback from the patients and they expressed a need for support from health-care superiors. Compared to the district hospitals, the health centres were less well-equipped and supplied, and the providers had a heavier workload, because all activities including ANC were carried out by the same provider. The average consultation time for each woman was 5mins. CONCLUSIONS: the quality of ANC services in rural health facilities in Laos was poor due to lack of resources, the providers' limited skills concurrent with inadequate routines and insufficient backup from superiors. IMPLICATIONS FOR PRACTICE: to comply with national and international recommendations for ANC services, our suggestion is to improve the quality of the rural health facilities in Laos by providing basic equipment, support from experienced superiors and in-service training.

Pregnant women's experiences, needs, and preferences regarding information about malformations detected by ultrasound scan.

OBJECTIVES: The aim of the study was to explore pregnant women's experiences of received information in relation to fetal malformation detected on ultrasound. METHOD: An exploratory descriptive design was used. Semi-structured interviews with women who continued their pregnancy and women who chose to terminate were audiotaped, the information pathway described, and the text subjected to qualitative content analysis. RESULTS: Most of the women who expected a baby with an abnormality experienced the information given as insufficient, often misleading, conflicting, or incoherent, and sometimes negative. Important factors for interaction between women and caregivers were timing, duration, and manner of the initial dialog and ongoing support. Positive interactions improved the women's ability to understand the information, fostered feelings of trust and safety which reduced their anxiety. CONCLUSION: Women expressed dissatisfaction both regarding the care-givers' methods of giving information and apply for information from different specialists and continuity. The study highlights important factors which may be helpful to the professionals for improving the information to this vulnerable group of women.

Orally active aminopyridines as inhibitors of tetrameric fructose-1,6-bisphosphatase.

A novel sulfonylureido pyridine series exemplified by compound 19 yielded potent inhibitors of FBPase showing significant glucose reduction and modest glycogen lowering in the acute db/db mouse model for Type-2 diabetes. Our inhibitors occupy the allosteric binding site and also extend into the dyad interface region of tetrameric FBPase.

Aryl- and heteroaryl-substituted aminobenzo[a]quinolizines as dipeptidyl peptidase IV inhibitors.

Synthesis and SAR are described for a structurally distinct class of DPP-IV inhibitors based on aminobenzo[a]quinolizines bearing (hetero-)aromatic substituents in the S1 specificity pocket. The m-(fluoromethyl)-phenyl derivative (S,S,S)-2g possesses the best fit in the S1 pocket. However, (S,S,S)-2i, bearing a more hydrophilic 5-methyl-pyridin-2-yl residue as substituent for the S1 pocket, displays excellent in vivo activity and superior drug-like properties.

Sulfonylureido thiazoles as fructose-1,6-bisphosphatase inhibitors for the treatment of type-2 diabetes.

Sulfonylureido thiazoles were identified from a HTS campaign and optimized through a combination of structure-activity studies, X-ray crystallography and molecular modeling to yield potent inhibitors of fructose-1,6-bisphosphatase. Compound 12 showed favorable ADME properties, for example, F=70%, and a robust 32% glucose reduction in the acute db/db mouse model for Type-2 diabetes.

Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): efficient formation of products derived from aryl radicals.

Tetrakis(dimethylamino)ethylene (TDAE 1), has been exploited for the first time as a mild reagent for the reduction of arenediazonium salts to aryl radical intermediates through a single electron transfer (SET) pathway. Cyclization of the aryl radicals produced in this way led, in appropriate substrates, to syntheses of indolines and indoles. Cascade radical cyclizations of aryl radicals derived from arenediazonium salts are also reported. The relative ease of removal of the oxidized by-products of TDAE from the reaction mixture makes the methodology synthetically attractive.

1,3-disubstituted 4-aminopiperidines as useful tools in the optimization of the 2-aminobenzo[a]quinolizine dipeptidyl peptidase IV inhibitors.

In a search for novel DPP-IV inhibitors, 2-aminobenzo[a]quinolizines were identified as submicromolar HTS hits. Due to the difficult synthetic access to this compound class, 1,3-disubstituted 4-aminopiperidines were used as model compounds for optimization. The developed synthetic methodology and the SAR could be transferred to the 2-aminobenzo[a]quinolizine series, leading to highly active DPP-IV inhibitors.

Selective and orally bioavailable phenylglycine tissue factor/factor VIIa inhibitors.

We describe the structure-based design and synthesis of highly potent, orally bioavailable tissue factor/factor VIIa inhibitors which interfere with the coagulation cascade by selective inhibition of the extrinsic pathway.

Novel deoxygenation reaction of epoxides by indium.

[reaction: see text] A novel, mild, ecofriendly protocol for the deoxygenation of epoxides to alkenes using indium metal and indium(I) chloride or ammonium chloride in alcohol has been developed. It was necessary for the presence of good radical-stabilizing groups adjacent to the oxirane ring for the deoxygenation reaction to occur. It is proposed that this reaction occurs through an SET process with indium as an electron donor.

Asymmetric [2,3]-rearrangement of glycine-derived allyl ammonium ylids.

The first examples of highly enantioselective [2,3]-sigmatropic rearrangements of acyclic allylic ammonium ylids are reported. Thus, a range of N-{2'-[(N'-allyl-N',N'-dialkyl)ammonium]}acetyl camphor sultams undergo rearrangement at 0 degrees C in DME solution with high diastereofacial control (up to 99:1 dr) to give allylglycines in generally high yield. The power of the method has been demonstrated in a rapid and efficient synthesis of (R)-allyl glycine.

Health-seeking patterns among fatally ill Capeverdian women.

The circumstances of 94 deaths among females aged 15-49 years in Cape Verde were investigated to assess their access to effective care. Persons associated with the deceased women were interviewed (verbal autopsy) to explore contributing causes of death, perceived illnesses and treatment efforts. The certainty of diagnosis and avoidability of the fatal outcome were assessed by a panel ofexperts. A model of health care accessibility is elaborated to identity restricting (delay) factors. Deliberate avoidance of modern medical care and reliance on traditional medicine were major delay factors, while unawareness of the severity of symptoms and affordability limits were minor delay factors in this population. A detailed sorting of cases by health care level is used to identify the effectiveness of diagnosing, referral and care provided. Since a high proportion of avoidable deaths occurred in hospital, the quality of care may have been sub-optimal.

Copper(II)-catalyzed [2,3]-sigmatropic rearrangement of N-methyltetrahydropyridinium ylids.

A ring-contractive and highly diastereoselective [2,3]-sigmatropic rearrangement occurs when N-methyl-1,2,3,6-tetrahydropyridine is treated with sub-stoichiometric amounts of copper or rhodium salts, in the presence of ethyl diazoacetate, giving ethyl cis-N-methyl-3-ethenyl proline (4).