Opening the door: midwives' perceptions of two models of psychosocial assessment in pregnancy- a mixed methods study.

BACKGROUND: One in five women experience psychological distress in the perinatal period. To support women appropriately, Australian guidelines recommend routine depression screening and psychosocial risk assessment by midwives in pregnancy. However, there is some evidence that current screening processes results in higher rates of false positives. The Perinatal Integrated Psychosocial Assessment (PIPA) Project compared two models of psychosocial assessment and referral - Usual Care and the PIPA model - with a view to improving referral decisions. This paper describes midwives' perspectives on psychosocial assessment, depression screening and referral at the antenatal booking appointment and compares midwives' experiences with, and perspectives on, the two models of care under investigation. METHODS: A two-phase, convergent mixed methods design was used. Midwives providing antenatal care completed a self-report survey in phase one prior to implementation of the new model of psychosocial assessment (n = 26) and again in phase two, following implementation (n = 27). Sixteen midwives also participated in two focus groups in phase two. Quantitative and qualitative data were compared and integrated in the presentation of results and interpretation of findings. RESULTS: Midwives supported psychosocial assessment believing it was a catalyst for 'Opening the door" to conversations with women. Midwives were comfortable asking the questions and tailored their approach to build rapport and trust. Overall. midwives expressed favourable views towards the PIPA model. A greater proportion of midwives relied mostly or entirely on the suggested wording for the psychosocial questions in the PIPA model compared to Usual Care (44.4% vs 12.0%, χ2=5.17, p=.023, φ =-.36). All midwives reported finding the referral or action message displayed at the end of the PIPA psychosocial assessment to be 'somewhat' or 'very' helpful, compared to 42.3% in Usual Care (χ2 = 18.36, p < .001, φ = -.64). Midwives were also more likely to act on or implement the message often or all of the time) in the PIPA model (PIPA = 69.2% vs Usual Care = 32.0%, (χ2 = 5.66, p < .017, φ = -.37). CONCLUSION: The study identified benefits of the new model and can inform improvements in psychosocial screening, referral and related care processes within maternity settings. The study demonstrates that psychosocial assessment can, over time, become normalised and embedded in practice.

History of mood or anxiety disorders and risk of gestational diabetes mellitus in a population-based cohort.

AIM: To examine the association between mood and anxiety disorders and the development of gestational diabetes mellitus in a retrospective population-based cohort study. METHODS: Clinical data from a provincial perinatal health registry were linked to physician claims, hospitalization records and emergency visits to identify any diagnoses of mood or anxiety disorders in the 2 years prior to pregnancy and a subsequent diagnosis of gestational diabetes during pregnancy. The study population included all singleton pregnancies in the Canadian province of Alberta from 1 April 2000 to 31 March 2010. Generalized estimating equations were used to determine the adjusted odds ratio of gestational diabetes, comparing women with and without a history of mood or anxiety disorders. RESULTS: Among 373 674 pregnancies from 253 911 women, 25.7% had a history of mood or anxiety disorders, and 3.8% developed gestational diabetes. The multivariate-adjusted odds of developing gestational diabetes were higher among women with a history of mood or anxiety disorders (odds ratio 1.10, 95% CI 1.06-1.14). CONCLUSIONS: Women with a history of mood or anxiety disorders had a moderately increased risk of developing gestational diabetes.

Does non-pharmacological therapy for antenatal depression reduce risks for the infant?

Depression during pregnancy has been associated with an increased risk of adverse outcomes for the infant such as preterm birth. These risks are not reduced with pharmacological treatment, but the effect of non-pharmacological therapies is unknown. We performed a systematic review to assess the risk of adverse perinatal outcomes in non-pharmacologically treated depressed women compared to non-depressed women. We found no studies that met our inclusion criteria, highlighting a critical need for research on this topic.

Clinical and economic impact of a switch from high- to low-volume renal replacement therapy in patients with acute kidney injury.

High-intensity renal replacement therapy protocols in intensive care patients with acute kidney injury have failed to translate to improved patient outcomes when compared with lower-intensity protocols. This retrospective study explored the clinical and economic impacts of switching from a 30-35 ml.kg(-1) .h(-1) (high-volume) to a 20 ml.kg(-1) .h(-1) (low-volume) protocol. Patients (n = 366) admitted 12 months before (n = 187) and after (n = 179) the switch were included in the study. There was no difference in in-hospital mortality (77/187 (41%) vs 75/179 (42%), respectively, p = 0.92), intensive care unit mortality (55/187 (29%) vs 61/179 (34%), respectively, p = 0.40), duration of organ support or extent of renal recovery between the high- and low-volume cohorts. A 25% reduction in daily replacement fluid usage was observed, equating to a cost saving of over £27 000 per annum. In conclusion, a switch from high- to low-volume continuous haemodiafiltration had minimal effects on clinical outcomes and resulted in marked cost savings.

Migrant women's utilization of prenatal care: a systematic review.

Our objectives were to determine whether migrant women in Western industrialized countries have higher odds of inadequate prenatal care (PNC) compared to receiving-country women and to summarize factors that are associated with inadequate PNC among migrant women in these countries. We conducted searches of electronic databases (MEDLINE, EMBASE, and PsycINFO), reference lists, known experts, and an existing database of the Reproductive Outcomes And Migration international research collaboration for articles published between January, 1995 and April, 2010. Title and abstract review and quality appraisal were conducted independently by 2 reviewers using established criteria, with consensus achieved through discussion. In this systematic review of 29 studies, the majority of studies demonstrated that migrant women were more likely to receive inadequate PNC than receiving-country women, with most reporting moderate to large effect sizes. Rates of inadequate PNC among migrant women varied widely by country of birth. Only three studies explored predictors of inadequate PNC among migrant women. These studies found that inadequate PNC among migrant women was associated with being less than 20 years of age, multiparous, single, having poor or fair language proficiency, education less than 5 years, an unplanned pregnancy, and not having health insurance. We concluded that migrant women as a whole were more likely to have inadequate PNC and the magnitude of this risk differed by country of origin. Few studies addressed predictors of PNC utilization in migrant women and this limits our ability to provide effective PNC in this population.

Genotoxicity and carcinogenicity in rats and mice of 2-amino-3,6-dihydro-3-methyl-7H-imidazolo[4,5-f]quinolin-7- one: an intestinal bacterial metabolite of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline.

BACKGROUND: Compounds formed on the surface of fried or grilled meat and fish may be associated with increased risk of colon cancer. Normal intestinal bacteria can convert one of these compounds, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), to the 7-hydroxy metabolite, 2-amino-3,6-dihydro-3-methyl-7H-imidazolo[4,5-f]quinolin-7-o ne (7-OHIQ), a direct-acting mutagen. PURPOSE: We studied the genotoxicity and carcinogenicity of 7-OHIQ to determine if it is responsible for the colon-specific activity of IQ. METHODS: The effects of pure, synthetic 7-OHIQ on DNA were evaluated in the Ames Salmonella typhimurium TA98 test, with and without an induced rat liver S9 fraction, and in the Williams DNA repair test using freshly explanted rat hepatocytes. 7-OHIQ was also subjected to an in vivo bioassay for 21 months by long-term intrarectal infusion in male F344 rats, using IQ and N-nitrosomethylurea (NMU) given intrarectally as positive tumor-producing controls. The standard NIH-07 rodent diet was supplemented with 15% corn oil to maximize any effect of the infused materials on the colon. A parallel bioassay involved intraperitoneal injection of 7-OHIQ in newborn mice, followed by dietary administration from week 11 to week 67. Again, IQ and NMU were used as positive controls. RESULTS: We confirmed that 7-OHIQ is a direct-acting mutagen in the Ames test, with added S9 liver fraction giving higher mutagenicity. 7-OHIQ was negative in the Williams test, whereas IQ was positive. 7-OHIQ did not induce colon cancer in rats, and in the newborn mouse test it produced only a low incidence of liver neoplasms. CONCLUSIONS: 7-OHIQ is not genotoxic, for to be so classified it must be definitely positive in both the Ames and Williams tests; moreover, it is not carcinogenic, in marked contrast to IQ and NMU.

Raf-1/bcl-2 phosphorylation: a step from microtubule damage to cell death.

Recent studies have shown that paclitaxel leads to activation of Raf-1 kinase and have suggested that this activation is essential for bcl-2 phosphorylation and apoptosis. In the present study, we demonstrate that, in addition to paclitaxel, other agents that interact with tubulin and microtubules also induce Raf-1/bcl-2 phosphorylation, whereas DNA-damaging drugs, antimetabolites, and alkylating agents do not. Activation of Raf-1 kinase by paclitaxel is linked to tubulin polymerization; the effect is blunted in paclitaxel-resistant cells, the tubulin of which does not polymerize following the addition of paclitaxel. In contrast, vincristine and vinblastine, drugs to which the paclitaxel-resistant cells retain sensitivity were able to bring about Raf-1 phosphorylation. The requirement for disruption of microtubules in this signaling cascade was strengthened further using paclitaxel analogues by demonstrating a correlation between tubulin polymerization, Raf-1/bcl-2 phosphorylation, and cytotoxicity. Inhibition of RNA or protein synthesis prevents Raf-1 activation and bcl-2 phosphorylation, suggesting that an intermediate protein(s) acts upstream of Raf-1 in this microtubule damage-activating pathway. A model is proposed that envisions a pathway of Raf-1 activation and bcl-2 phosphorylation following disruption of microtubular architecture, serving a role similar to p53 induction following DNA damage.

Evaluation of a two rubber band technique for finger ring removal.

INTRODUCTION: Rings are required to be removed from a finger in many clinical situations. Rings that are difficult to remove is a problem encountered frequently. Many techniques have been reported for this problem. This study looks at the effectiveness of a single technique for removing difficult rings from fingers. METHODS: A two rubber band technique was used in this study of 69 difficult to remove rings. Success of the technique and time to removal were recorded. RESULTS: Difficult rings were removed in 92.5% of cases, in a mean time of 10.7 seconds. No fingers or rings suffered damage during the study. CONCLUSIONS: This two rubber band technique is a rapid, safe and effective method for removing rings that cannot be removed easily.

A prospective review of appetite loss and recovery time in primary joint replacement patients.

INTRODUCTION: Appetite loss is commonly reported by patients following major surgery, including total joint arthroplasty (TJA). A number of studies have examined related problems, particularly in relation to physiological responses to surgery. However, no published paper has looked specifically at the duration of appetite loss in total knee arthroplasty (TKA) and total hip arthroplasty (THA) patients. METHODS: A simple, established appetite screening tool was administered preoperatively and at 2-week intervals postoperatively in 50 TJA patients until appetite levels returned to preoperative levels. The results were examined for various descriptive parameters and compared using the chi-squared test. RESULTS: Thirty-three patients underwent TKA and 17 THA. There were 27 female and 23 male patients. No patients were lost to follow-up. The median time for return of appetite in both male and female patients was 4 weeks (interquartile range [IQR]: male, 2-4; female, 4-6). The median time for return of appetite was 4 weeks both in TKA patients (IQR 4-6) and in those undergoing THA (IQR 4-4). The time to return of appetite was not significantly associated with either the gender of the patients (p=0.13) or the type of joint replacement (p=0.49). CONCLUSIONS: The study provides a clear time frame for return of appetite in uncomplicated primary joint replacements. This is a commonly noted patient problem that has not previously been specifically reviewed.

Taxol: the chemistry and structure-activity relationships of a novel anticancer agent.

Taxol is an exciting new anticancer drug, showing clinical activity against ovarian and breast cancer. Its development as a clinically useful drug has involved major efforts to overcome the supply problem; this has now been done, and the focus of interest has moved to the development of improved analogs of the drug. Recent notable achievements include the first total synthesis of taxol, and the first indications of its binding site on tubulin.

Molecular mobility of nitroxyl-labelled taxol during tubulin assembly.

Taxol is an important natural anticancer agent that binds to beta-tubulin and suppresses microtubule depolymerization. We have used electron paramagnetic resonance (EPR) spectroscopy to analyze the molecular motion of three novel nitroxyl free radical taxol analogues. Taxol was chemically modified at C2 or C7 carbon of the taxane ring with the TEMPO free radical to yield two spin-labelled taxols and concurrently at C2' and 3'N of the side chain to yield a spin-labelled taxol biradical. Nitroxyl moieties attached to the taxane ring are significantly restricted in their molecular motion during microtubule assembly, and they show no molecular restriction upon binding to tubulin. We conclude that taxol binds to tubulin in a way such that the taxane ring is not constrained by the dimer structure. However, the taxane ring is strongly immobilized after polymerization of tubulin, i.e. it is incorporated into the structure of microtubule. In contrast, the nitroxy moieties of the taxol biradical show strong immobilization upon attachment to tubulin. The nitroxyl energy exchange is restricted prior to the assembly of microtubules, and no differences associated with the process of polymerization were detected. The taxol side chain resides in a region that is not significantly constrained during polymerization.

Characterization of a mutagenic bacterial product in human feces.

Mutagens detectable with the Ames assay have been found in the feces of apparently healthy individuals and the incidence of this mutagenic activity was found to be greater in a population at high risk for colon cancer than in a population at low risk. A compound accounting for the mutagenic activity has been isolated by high performance liquid chromatography. Two closely related forms which behave identically chemically could be resolved. The compound was active on Salmonella typhimurium TA98 and TA100, had a characteristic ultraviolet absorption spectrum with maxima at about 320, 340, and 365 nm, fluoresced green in long wavelength ultraviolet light, and had the same mobility on the thin-layer chromatography as the mutagenic activity in a direct ether extract of feces. The compound was unstable in air but could be stabilized in the presence of butylated hydroxytoluene. Upon oxidation the compound lost its mutagenicity and its ultraviolet absorption spectrum underwent a blue shift so that the absorption maxima were at 295, 310, and 325 nm. Determination of the structure of the mutagen has been difficult since the compound was not volatile and production of a volatile derivative has not been successful. On thin-layer chromatography plates the compound reacted with reagents that detect chlorinated compounds. By thermal energy analysis it did not appear to contain a nitroso group. The compound increased in concentration upon anaerobic incubation of feces at 37 C and this increase was prevented by cold, air, and antimicrobial agents. This suggests to us that the fecal flora produces the compound.

The use of the peroxidase reaction to obliterate staining of eosinophils by fluorescein-labelled conjugates.

The staining of eosinophils by fluorescein conjugates can be obliterated by utilising the peroxidase activity of the eosinophil. The brown reaction product of 3,4,3',4'-tetraaminobiphenyl hydrochloride (DAB) with hydrogen peroxide was more effective than Lendrum's stain. A satisfactory alternative to the possibly carcinogenic DAB was 2,7-fluorenediamine.

Synthesis and biological evaluation of 2-acyl analogues of paclitaxel (Taxol).

The anticancer drug paclitaxel (Taxol) has been converted to a large number of 2-debenzoyl-2-aroyl derivatives by three different methods. The bioactivities of the resulting analogues were determined in both tubulin polymerization and cytotoxicity assays, and several analogues with enhanced activity as compared with paclitaxel were discovered. Correlation of cytotoxicity in three cell lines with tubulin polymerization activity showed reasonable agreement. Among the cell lines examined, the closest correlation with antitubulin activity was observed with a human ovarian carcinoma cell line.

Carcinogenicity tests of fecapentaene-12 in mice and rats.

Fecapentaenes, a class of direct-acting bacterial mutagens, have been isolated from the feces and intestinal tract of humans on a Western meat-containing diet. Two bioassays to test pure fecapentaene-12 (FP-12) for carcinogenicity were performed. FP-12 in dimethylsulfoxide (DMSO) solution was injected i.p. into newborn ICR/MA mice on days 1, 3, 7, 10, 14 and 21. The mice killed after 21 months had neoplasms in liver, lung, glandular stomach and subcutaneous fibrosarcoma. Intrarectal (i.r.) infusion of FP-12 in an aqueous vehicle into male F344 rats for 71 weeks, and killing the rats after 21 weeks more, displayed no evidence of neoplasia associated with FP-12 exposure. The positive control, N-nitrosomethylurea (NMU), given i.r. as 4 2-mg doses in 2 weeks, as expected, yielded multiple colonic neoplasms in less than 11 months. Fecapentaene may exert its effect in bacteria and in newborn mice through the generation of hydroxy radicals. However, adult rodent and human colon may have adequate biochemical defense mechanisms against low level, even continuous exposures to chemicals like FP-12, and thus be at low risk of neoplasia, as was found.

The first naturally occurring Tie2 kinase inhibitor.

[structure: see text] Bioassay-guided fractionation of the plant Acacia aulacocarpa, guided by a bioassay for Tie2 tyrosine kinase activity, yielded the novel triterpene 3,21-dioxo-olean-18-en-oic acid (1) as the first naturally occurring non-protein inhibitor of Tie2 kinase. The structure of 1 was assigned by analysis of spectral data. In addition to its activity as an inhibitor of Tie2 kinase, compound 1 also shows modest activity against a variety of cultured mammalian cells.

Synthesis and biological evaluation of novel macrocyclic paclitaxel analogues.

[reaction: see text] This work describes the synthesis of two novel macrocyclic taxoid constructs by ring-closing olefin metathesis (RCM) and their biological evaluation. Computational studies examine conformational profiles of 1 and 2 for their fit to the beta-tubulin binding site determined by electron crystallography. The results support the hypothesis that paclitaxel binds to microtubules in a "T" conformation.

Plasma cell counts on human jejunal biopsy specimens examined by immunofluorescence and immunoperoxidase techniques: a comparative study.

Ten human jejunal biopsy specimens were examined by both immunofluorescence (IF) and immunoperoxidase (IP) methods to compare both plasma cell counts and the distribution of extracellular immunoglobulins. Each specimen was cut into at least two portions, one fixed in 5% formaldehyde in phosphate-buffered saline before being snap-frozen and sectioned on a cryostat for IF, the other being fixed in half-strength Zenker and embedded in paraffin wax by standard methods for IP. Plasma cell counts were comparable in the eight biopsy specimens for which they could be estimated, geometric mean values being IgA 22.9 (IF), 19.3 (IP) and IgM 9.5 (IF), 10.6 (IP). Two specimens showing subtotal villous atrophy had too much extracellular IgA for plasma cell counts to be feasible. For these the IF methods had the advantage that the extracellular immunoglobulin was more readily distinguishable from background staining.

Jejunal mucosal morphometry in children with and without gut symptoms and in normal adults.

Nineteen diagnostic peroral biopsy specimens from 18 children without diarrhoea, vomiting, or abdominal pain ('control' children) were compared with those taken from 23 children with diarrhoea of varying aetiology to establish the morphometric characteristics of jejunal mucosa in childhood. Comparison was also made with normal jejunal mucosa from adults. Statistical analysis of each characteristic individually showed no significant difference between the 'control' children and those with diarrhoea, but there were significant differences between the mucosae of 'control' children and those of adults; the villi tended to be shorter and the crypts longer in children. Thirty-seven per cent of specimens from the 'control' children showed a partial villous atrophy, that is, they were abnormal by adult criteria. Discriminant analysis of the features measured showed effective separation of the following groups: normal histology from partial villous atrophy in children, healthy adults from 'control' children, and normal histology in adults from normal histology in children.

A convenient tubulin-based quantitative assay for paclitaxel (Taxol) derivatives more effective in inducing assembly than the parent compound.

A room temperature biochemical assay, based on centrifugal removal of tubulin polymer, was developed to permit ready detection of paclitaxel analogs more active than the parent compound and to permit reliable quantification of differences in activity relative to paclitaxel in terms of drug concentration. The assay was validated by comparing paclitaxel to two compounds (docetaxel and 2-debenzoyl-2-meta-azidobenzoylpaclitaxel) known to be more active under multiple reaction conditions. The assay was designed to yield a relatively high EC50 (23 microM) for paclitaxel. This was possible because paclitaxel only weakly induced tubulin assembly at room temperature in 0.4 M glutamate without exogenous GTP. Under these same reaction conditions 50% assembly occurred with 4.7 microM 2-debenzoyl-2-meta-azidobenzoylpaclitaxel and 11 microM docetaxel. These biochemical EC50 values were in agreement with the relative cytotoxicity of the three compounds for human Burkitt lymphoma CA46 cells (IC50 values for paclitaxel, docetaxel, and 2-debenzoyl-2-meta-azidobenzoylpaclitaxel were 40, 10, and 3 nM, respectively).