Predicting risk of postpartum haemorrhage: a systematic review.

BACKGROUND: Postpartum haemorrhage (PPH) causes substantial morbidity and mortality worldwide. A reliable prognostic tool for PPH has potential to aid prevention efforts. OBJECTIVE: Systematically to identify and appraise prognostic modelling studies for prediction of PPH. SEARCH STRATEGY: MEDLINE, Embase, CINAHL and the Cochrane Library were searched using a combination of terms and synonyms including 'prediction tool', 'risk score' and 'postpartum haemorrhage'. SELECTION CRITERIA: Any observational or experimental study developing a prognostic model for women's risk of PPH. English language publications. DATA COLLECTION AND ANALYSIS: Predesigned data extraction form to record: data source; participant criteria; outcome; candidate predictors; actual predictors; sample size; missing data; model development; model performance; model evaluation; interpretation. MAIN RESULTS: Of 2146 citations screened, 14 studies were eligible for inclusion. Studies addressed populations of women who experienced placenta praevia, placenta accreta spectrum, vaginal birth, caesarean birth (CS) and the general obstetric population. All studies were at high risk of bias due to low sample size, no internal validation, suboptimal or no external validation or no reporting or handling of missing data. Five studies raised applicability concerns. Three externally validated and three internally validated studies show potential for robust external validation. CONCLUSION: Of 14 prognostic models for PPH risk, three have some potential for clinical use: in CS, in placenta accreta spectrum disorders with MRI placental Evaluation and in placenta praevia. Future research requires robust internal and external validation of existing tools and development of a model for use in the general obstetric population. TWEETABLE ABSTRACT: Current PPH prediction tools need external validation: one for CS, one for placenta praevia and one for placenta accreta. Tools are needed for labouring women.

Breast infections - Microbiology and treatment in an era of antibiotic resistance.

INTRODUCTION: Primary breast abscesses occur in <1% of non-lactating women, rising to 11% in women with lactational mastitis. In patients undergoing breast cancer surgery, the inflammatory response to post-operative surgical site infection (SSI) has been implicated in recurrence. Anti-microbial resistance increasingly hampers treatment in each group. AIMS: Describe the demographic and predisposing characteristics of patients with primary breast abscesses and secondary infections, identify the microbial and antimicrobial patterns and formulate an evidence-based protocol for treating breast infections. METHODS: Retrospective cohort study of all breast infections (primary and post-operative) treated at UHL from 2014 to 2017. Data collected from microbiology databases and patient records was analysed using Minitab V18. RESULTS: 537 cultures from 108 patients were analysed. 47 (43.5%) had primary abscesses, 12 (11.1%) were lactational and 49 (45.4%) were post-operative SSI. For primary infections, the mean age was 41.9 (±12.2) and reinfection rate 33%. For SSIs the mean age was 51.8 (±14.52) and reinfection rate 11.8%. Overall, 29.3% were smokers, 6.4% diabetic and 2.9% pregnant. 60 (43%) patients required radiological drainage and 2 (1%) surgical drainage. 57.5% had mixed growth. The most common isolate was Staphylococcus aureus; cultured in 16.7% of primary abscesses and 24% of SSIs. 13 empiric antibiotic regimes were prescribed before 26.4% of patients changed to 12 different targeted regimes. CONCLUSION: Breast infections are frequently polymicrobial with a wide variety of organisms isolated, suggesting the need for broad spectrum coverage until culture results become available. Based on our local culture results, the addition of clindamycin to flucloxacillin would provide excellent empiric coverage for all categories of breast infection. An evidence-based treatment guideline is required and should be formulated in close collaboration with microbiology specialists.

Nuclear translocation of the catalytic subunit of protein kinase A induced by an antisense oligonucleotide directed against the RIalpha regulatory subunit.

The regulatory (R) subunits of cAMP-dependent protein kinase (PKA) are implicated in the regulation of cell proliferation and differentiation. There are two isoforms of PKA that are distinguished by two types of R subunit, RI and RII. Evidence suggests that RI is associated with proliferation and RII is associated with cell differentiation. Previous work in this laboratory has demonstrated that depletion of the RIalpha subunit by treatment with an antisense oligonucleotide (ODN) induces differentiation in leukemia cells and growth arrest and apoptosis in epithelial cancer cells. Using the prostate cancer cell line PC3M as a model system, we have developed a cell line that overexpresses a retroviral vector construct containing the RIalpha antisense gene. This cell line has been characterized and the effectiveness of the construct determined. In the work presented here, we demonstrate by immunocytochemistry that treatment with RIalpha antisense ODN induces translocation of the Calpha subunit of PKA to the nucleus of PC3M prostate cancer cells. The translocation of Calpha triggered by exogenous antisense ODN treatment mirrors that observed in cells endogenously overexpressing the antisense gene. Triggering the nuclear translocation of the Calpha subunit of PKA in the cell may be an important mechanism of action of RIalpha antisense that regulates cell growth independent of adenylate cyclase and cellular cAMP levels. The nuclear localization of the Calpha subunit of PKA may be an essential step in revealing the mechanism whereby this critical kinase regulates cell growth.

Antisense DNAs as multisite genomic modulators identified by DNA microarray.

Antisense oligodeoxynucleotides can selectively block disease-causing genes, and cancer genes have been chosen as potential targets for antisense drugs to treat cancer. However, nonspecific side effects have clouded the true antisense mechanism of action and hampered clinical development of antisense therapeutics. Using DNA microarrays, we have conducted a systematic characterization of gene expression in cells exposed to antisense, either exogenously or endogenously. Here, we show that in a sequence-specific manner, antisense targeted to protein kinase A RIalpha alters expression of the clusters of coordinately expressed genes at a specific stage of cell growth, differentiation, and activation. The genes that define the proliferation-transformation signature are down-regulated, whereas those that define the differentiation-reverse transformation signature are up-regulated in antisense-treated cancer cells and tumors, but not in host livers. In this differentiation signature, the genes showing the highest induction include genes for the G proteins Rap1 and Cdc42. The expression signature induced by the exogenously supplied antisense oligodeoxynucleotide overlaps strikingly with that induced by endogenous antisense gene overexpression. Defining antisense DNAs on the basis of their effects on global gene expression can lead to identification of clinically relevant antisense therapeutics and can identify which molecular and cellular events might be important in complex biological processes, such as cell growth and differentiation.

Helmet slippage during visual tracking: the effect of voluntary head movements.

The influence of visual tracking on head movement and on the head/helmet system was investigated for two different helmets (a motorcycle helmet and a flying helmet) under static laboratory conditions. Subjects visually refixated between pairs of illuminated targets located at various horizontal (up to 160 degrees) and vertical (up to 90 degrees) distances apart while head position and helmet slippage were measured in azimuth, pitch, roll, X, Y, and Z using a double magnetic coil system. Results showed that for both helmets, root mean square (RMS) head movement increased with refixation distance, especially in the main axis of refixation, and that RMS helmet slippage can be a function of RMS head motion. Further, large individual differences in the degree of head motion were found. These findings may have implications for designers and investigators of helmet-mounted avionics.

Some visual, optometric and perceptual effects of coloured glasses.

We examined 20 individuals who had worn coloured glasses (Irlen filters) for a period of at least 3 months and who claimed to find them beneficial. Sixteen had a history of reading difficulties. The performance of a variety of visual tasks was compared: (1) using the coloured lenses; (2) using neutral density filters of similar photopic transmittance; and (3) using trial lenses to correct any residual refractive error. The coloured lenses appeared to reduce discomfort and susceptibility to anomalous perceptual effects upon viewing grating patterns. They also improved the speed of visual search by a small amount. The lenses had idiosyncratic effects on ocular muscle balance and acuity. They did not affect contrast sensitivity at a spatial frequency of 4 c/deg.

The effect of high frequency flicker on accommodation.

Monocular accommodation was measured by a laser optometer while two subjects viewed a letter matrix target illuminated by steady or intermittent (300, 100, 50 and 25 Hz) light and presented at a number of optical distances (0.5, 1.5, 2.5, 3.5 and 4.5 D). At certain rates of intermittent illumination, both above (50 Hz) and below (25 Hz) flicker fusion, an increased accommodation response was found. This increase occurred at all optical distances, except for the distance closest to each subject's dark focus, and resulted in a more accurate accommodation response for one subject, and a less accurate one for the other. Furthermore, for both subjects, evidence of an increase in the amplitude of the fluctuations in accommodation at 50 and 25 Hz was found for the higher stimulus levels. The implications of these findings for the control of accommodation and for practical problems of visual performance in the environment, such as visual discomfort associated with fluorescent lighting and intermittently illuminated visual display units, are discussed.

Effects of phosphor persistence on perception and the control of eye movements.

When a rapid eye movement (saccade) is made across material displayed on cathode ray tube monitors with short-persistence phosphors, various perceptual phenomena occur. The phenomena do not occur when the monitor has a long-persistence phosphor. These phenomena were observed for certain spatial arrays, their possible physiological basis noted, and their effect on the control of eye movements examined. When the display consisted simply of two dots, and a saccade was made from one to the other, a transient ghost image was seen just beyond the destination target. When the display consisted of vertical lines, tilting and displacement of the lines occurred. The phenomena were more intrusive for the latter display and there was a significant increase in the number of corrective saccades. These results are interpreted in terms of the effects of fluctuating illumination (and hence phosphor persistence) on saccadic suppression.

Renal biopsy and antineutrophil antibodies in the diagnosis and assessment of Wegener's granuloma.

Seventeen patients with Wegener's granuloma (WG), all of whom had renal biopsies taken at presentation, are reviewed. In conjunction with nasal or transbronchial biopsies renal biopsies aided diagnosis and also yielded prognostic information. The detection of antineutrophil cytoplasm antibodies in the serum of patients with WG is a useful supplementary diagnostic tool.

Distribution of IgE-bearing cells in renal biopsies in Wegener's granuloma.

A comparison was made between the renal biopsy appearances of Wegener's granuloma, microscopic polyarteritis and diffuse endocapillary proliferative glomerulonephritis, including the distribution of surface IgE-bearing mast cells. In microscopic polyarteritis and in other inflammatory conditions mast cells were usually associated with areas of interstitial inflammatory infiltrate, whereas in Wegener's granuloma mast cells were usually separate from areas of inflammation, suggesting a role for mast cells in the development of the renal lesion of Wegener's granulomatosis.

Use of eye movement auditory biofeedback in the control of nystagmus.

Eye movement auditory biofeedback was used in weekly training sessions to control nystagmus in five adult patients. Within the 1st hr of training, all patients were able to reduce nystagmus. Average maximum group reduction of nystagmus amplitude, peak slow-phase velocity, and frequency achieved during training with auditory biofeedback was 82, 86, and 34%, respectively. At periodic intervals during training, audio information was withheld and patients were able to maintain reduced nystagmus for several minutes. In addition, patients were able to reduce nystagmus upon command without audio cues but with conscious effort while engaging in conversation and other tasks with the experimenters. Visual acuity improvement with conscious patient effort to control nystagmus but without auditory biofeedback averaged 10% Snell-Sterling. One of two patients who returned for post-training reevaluation was able to reduce his nystagmus quickly without auditory biofeedback to 50% of the pretraining level, and both patients were able with the aid of auditory cues to reduce their nystagmus rapidly to the level achieved during training. In addition to the improvement in vision, cosmetic and psychological benefits accrued. Eye movement auditory biofeedback should be considered in the treatment of nystagmus, either alone or in conjunction with orthoptic and/or surgical procedures.