Combined infant and young child feeding with small-quantity lipid-based nutrient supplementation is associated with a reduction in anemia but no changes in anthropometric status of young children from Katanga Province of the Democratic Republic of Congo: a quasi-experimental effectiveness study.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNS) are efficacious in controlled settings; data are scarce on the effectiveness utilizing health care delivery platforms. OBJECTIVE: We evaluated the impact of an infant young child feeding (IYCF)-SQ-LNS intervention on anemia and growth in children aged 6-18 mo in the Democratic Republic of Congo following a quasi-experimental effectiveness design. METHODS: An intervention health zone (HZ) received enhanced IYCF including improved counseling on IYCF during pregnancy until 12 mo after birth and daily use of SQ-LNS for infants 6-12 mo; the control HZ received the standard IYCF package. We analyzed data from 2995 children, collected in repeated cross-sectional surveys. We used adjusted difference-in-difference analyses to calculate changes in anemia, iron and vitamin A deficiencies, stunting, wasting, and underweight. RESULTS: Of mothers, 70.5% received SQ-LNS at least once in the intervention HZ, with 99.6% of their children consuming SQ-LNS at least once. The mean number of batches of SQ-LNS (28 sachets per batch, 6 batches total) received was 2.3 ± 0.8 (i.e., 64.4 ± 22.4 d of SQ-LNS). The enhanced program was associated with an 11.0% point (95% CI: -18.1, -3.8; P < 0.01) adjusted relative reduction in anemia prevalence and a mean +0.26-g/dL (95% CI: 0.04, 0.48; P = 0.02) increase in hemoglobin but no effect on anthropometry or iron or vitamin A deficiencies. At endline in the intervention HZ, children aged 8-13 mo who received ≥3 monthly SQ-LNS batch distributions had higher anthropometry z scores [length-for-age z score (LAZ): +0.40, P = 0.04; weight-for-age z score (WAZ): +0.37, P = 0.04] and hemoglobin (+0.65 g/dL, P = 0.007) and a lower adjusted prevalence difference of stunting (-16.7%, P = 0.03) compared with those who received none. CONCLUSIONS: The enhanced IYCF-SQ-LNS intervention using the existing health care delivery platform was associated with a reduction in prevalence of anemia and improvement in mean hemoglobin. At endline among the subpopulation receiving ≥3 mo of SQ-LNS, their LAZ, WAZ, and hemoglobin improved. Future research could explore contextual tools to maximize coverage and intake adherence in programs using SQ-LNS.

Dynamic optical coherence tomography of skin blood vessels - proposed terminology and practical guidelines.

BACKGROUND: Dynamic optical coherence tomography (D-OCT) has recently been introduced in dermatology. In contrast to 'Standard' OCT imaging, which exclusively relies on the morphological analysis of the tissue, D-OCT allows the in vivo visualization of blood flow. Preliminary D-OCT data showed differences in the vascularization of nevus to melanoma transition, suggesting that this technology may help to differentiate between benign and malignant lesions. OBJECTIVE: Several factors may influence the quality of D-OCT imaging. Therefore, standard operating procedures as well as a common terminology are required for better validation and comparison of the images. METHODS: Here, we present practical guidelines for optimal image acquisition and a proposed terminology on vascular patterns observed by D-OCT. RESULTS: Dynamic OCT allows the morphologic distinction of different vascular shapes (e.g. dots, blobs, curves, lines), their distribution and organization within skin lesions. CONCLUSION: D-OCT adds functional information on skin microvasculature and the vascular networks within lesions.

Enteral feeding reduces metabolic activity of the intestinal microbiome in Crohn's disease: an observational study.

BACKGROUND/OBJECTIVES: Enteral feeding will induce remission in as many as 80-90% of compliant patients with active Crohn's disease (CD), but its method of action remains uncertain. This study was designed to examine its effects on the colonic microbiome. METHODS/SUBJECTS: Healthy volunteers and patients with CD followed a regimen confined to enteral feeds alone for 1 or 2 weeks, respectively. Chemicals excreted on breath or in faeces were characterised at the start and at the end of the feeding period by gas chromatography/mass spectrometry. RESULTS: One week of feeding in healthy volunteers caused significant changes in stool colour and deterioration in breath odour, together with increased excretion of phenol and indoles on the breath. Feeding for 2 weeks in patients with CD produced significant improvements in symptoms and a decrease in the concentration of C-reactive protein. The faecal concentrations of microbial products, including short-chain fatty acids (SCFAs), and potentially toxic substances, including 1-propanol, 1-butanol and the methyl and ethyl esters of SCFAs, showed significant falls. CONCLUSIONS: A significant change occurs in the production of microbial metabolites after enteral feeding in both healthy volunteers and patients with CD. Many of those detected in CD are toxic and may feasibly lead to the immunological attack on the gut microbiota, which is characteristic of inflammatory bowel disease. The reduction in the production of such metabolites after enteral feeding may be the reason for its effectiveness in CD.

Validation of Dynamic optical coherence tomography for non-invasive, in vivo microcirculation imaging of the skin.

OBJECTIVES: Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D-OCT technique for imaging of the vascular networks in skin as well as to validate the method by comparing the results against already accepted blood flow measuring tools. METHODS: 35 healthy subjects were recruited for the multicentre study, consisting of three experiments set up to examine the vascular blood perfusion during different induced physiologic changes in the blood flow. In order to validate the D-OCT images against existing techniques for blood flow measuring we performed consecutive D-OCT, chromametry and laser speckle contrast imager (LSCI) measurements on identical skin sites in all of the experiments. Blinded observer evaluations were performed in order to evaluate the vascular morphology in the D-OCT images. RESULTS: The results showed a statistically significant positive correlation between the D-OCT measurements and the LCSI flux measurements (rs=0.494; 95% CI [0.357, 0.615]; p<0.001), and also the redness a* measurements were positively correlated with the D-OCT measurements (r=0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow. CONCLUSION: This study has initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo microcirculation imaging of the skin.

Lineage-specific RUNX3 hypomethylation marks the preneoplastic immune component of gastric cancer.

Runt domain transcription factor 3 (RUNX3) is widely regarded as a tumour-suppressor gene inactivated by DNA hypermethylation of its canonical CpG (cytidine-phosphate-guanidine) island (CGI) promoter in gastric cancer (GC). Absence of RUNX3 expression from normal gastric epithelial cells (GECs), the progenitors to GC, coupled with frequent RUNX3 overexpression in GC progression, challenge this longstanding paradigm. However, epigenetic models to better describe RUNX3 deregulation in GC have not emerged. Here, we identify lineage-specific DNA methylation at an alternate, non-CGI promoter (P1) as a new mechanism of RUNX3 epigenetic control. In normal GECs, P1 was hypermethylated and repressed, whereas in immune lineages P1 was hypomethylated and widely expressed. In human GC development, we detected aberrant P1 hypomethylation signatures associated with the early inflammatory, preneoplastic and tumour stages. Aberrant P1 hypomethylation was fully recapitulated in mouse models of gastric inflammation and tumorigenesis. Cell sorting showed that P1 hypomethylation reflects altered cell-type composition of the gastric epithelium/tumour microenvironment caused by immune cell recruitment, not methylation loss. Finally, via long-term culture of gastric tumour epithelium, we revealed that de novo methylation of the RUNX3 canonical CGI promoter is a bystander effect of oncogenic immortalization and not likely causal in GC pathogenesis as previously argued. We propose a new model of RUNX3 epigenetic control in cancer, based on immune-specific, non-CGI promoter hypomethylation. This novel epigenetic signature may have utility in early detection of GC and possibly other epithelial cancers with premalignant immune involvement.

An outbreak of Burkholderia multivorans beyond cystic fibrosis patients.

Strains of the Burkholderia cepacia complex (Bcc) are opportunistic pathogens capable of causing serious infection in cystic fibrosis patients. Recently we identified a suspected outbreak of infection with Bcc strains at the University Hospital Olomouc. Seventy-four Bcc strains were isolated from 52 patients, most of whom (N = 48) did not suffer from cystic fibrosis. Most frequently (N = 46) Burkholderia multivorans was isolated and 24 (52.2%) of these strains were clonal. Fifteen of these strains were isolated from intensive care patients, five of whom died from hospital-acquired pneumonia. B. multivorans can cause serious outbreaks of infection beyond cystic fibrosis sufferers.

GABA(B) receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline.

Peripherally restricted analgesics are desirable to avoid central nervous system (CNS) side effects of opioids. Nonsteroidal anti-inflammatory drugs produce peripheral analgesia but have significant toxicity. GABA(B) receptors represent peripheral targets for analgesia but selective GABA(B) agonists like baclofen cross the blood-brain barrier. Recently, we found that the CNS-impermeant amino acid, isovaline, produces analgesia without apparent CNS effects. On observing that isovaline has GABA(B) activity in brain slices, we examined the hypothesis that isovaline produces peripheral analgesia mediated by GABA(B) receptors. We compared the peripheral analgesic and CNS effect profiles of isovaline, baclofen, and GABA (a CNS-impermeant, unselective GABA(B) agonist). All three amino acids attenuated allodynia induced by prostaglandin E2 injection into the mouse hindpaw and tested with von Frey filaments. The antiallodynic actions of isovaline, baclofen, and GABA were blocked by the GABA(B) antagonist, CGP52432, and potentiated by the GABA(B) modulator, CGP7930. We measured Behavioural Hyperactivity Scores and temperature change as indicators of GABAergic action in the CNS. ED(95) doses of isovaline and GABA produced no CNS effects while baclofen produced substantial sedation and hypothermia. In a mouse model of osteoarthritis, isovaline restored performance during forced exercise to baseline values. Immunohistochemical staining of cutaneous layers of the analgesic test site demonstrated co-localization of GABA(B1) and GABA(B2) receptor subunits on fine nerve endings and keratinocytes. Isovaline represents a new class of peripherally restricted analgesics without CNS effects, mediated by cutaneous GABA(B) receptors.

[Detection of Burkholderia cepacia complex strains in the University Hospital Olomouc]. / Záchyt kmenu Burkholderia cepacia komplex ve Fakultní nemocnici Olomouc.

BACKGROUND: The aim was to assess the epidemiology of Burkholderia cepacia complex strains isolated at the Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, determine the most frequent strains and confirm or rule out potential clonal spread of the strains. MATERIAL AND METHODS: Over a period of eight months, all strains classified as Burkholderia cepacia complex were collected. Susceptibility to selected antimicrobial agents was determined and adequate molecular genetic methods were used to assess their genetic relationship. RESULTS: A total of 52 isolates were tested, with the most frequent (88.5 %) being genomovar II (Burkholderia multivorans). More than 46 % of them were genetically related; 58.3 % of them were detected in intensive care units. All isolates were highly resistant to antimicrobial agents. In four cases, deaths associated with Burkholderia multivorans infection were reported. CONCLUSION: It may be assumed that genetically related strains of Burkholderia multivorans spread from the hospital setting. As yet, the source of infection has not been determined and further investigations are needed.

Magnetic phase transition in a nanonetwork of solid 3He in aerogel.

When immersed in liquid 3He, the nanometer strands of aerogel are coated with a thin layer of solid 3He, forming a network of irregular nanotubes. Owing to its high purity and weak interactions, this system is ideal for studying fundamental processes. We report the first experiments on solid 3He in aerogel at ultralow temperatures, cooled by direct adiabatic demagnetization. Simultaneous nuclear magnetic susceptibility and heat capacity measurements indicate a magnetic phase transition.

WITHDRAWN: Anticoagulant and aspirin prophylaxis for preventing thromboembolism after major gynaecological surgery.

BACKGROUND: The reported overall risk of deep venous thrombosis in gynaecological surgery ranges from 7 to 45%. Fatal pulmonary embolism is estimated to occur in nearly 1% of these women. Pharmaceutical interventions are one possible prophylactic measure for preventing emboli in women undergoing major gynaecological surgery. Agents include unfractionated heparin (low -dose and adjusted-dose), low-molecular-weight heparins, heparinoids and warfarin. OBJECTIVES: The objective of this review was to evaluate the effectiveness of warfarin, heparin and aspirin in preventing thromboembolism after major gynaecological surgery. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 15 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library issue 2, 2003), MEDLINE (1966 to April 2003), EMBASE (1985 to April 2003), and CINAHL (1982 to April 2003). References from relevant articles were searched and authors contacted where necessary. In addition we contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomised controlled trials of heparins, warfarin or aspirin to prevent thromboembolism after major gynaecological surgery were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Thirty-three trials were identified in the initial search. On careful inspection only eight of these met the inclusion criteria. Trials were data extracted and assessed for quality by at least two reviewers. Data were combined for meta-analysis using odds ratios for dichotomous data or weighted mean difference for continuous data. A random effects statistical model was used. MAIN RESULTS: The meta-analysis of heparin versus placebo found a statistically significant decrease in the number of DVTs in both the all women group (including those with and without malignancy) (OR 0.30, 95% CI 0.12 to 0.76) and the subgroup of only women with malignancy (OR 0.30, 95% CI 0.10 to 0.89). There was no significant difference in the incidence of PE. Oral warfarin reduced DVT when compared to placebo in all women (OR 0.22, 95% CI 0.06 to 0.86) and in women with malignancy (OR 0.18, 95% CI 0.04 to 0.87). Meta-analyses of UH and LMWH showed no statistical difference in any comparison. No studies compared aspirin alone to placebo, heparin or warfarin. There was a statistically significant increase in injection site haematomas associated with heparin compared to placebo (OR 0.30, 95% CI 0.10 to 0.89). AUTHORS' CONCLUSIONS: Women, undergoing major gynaecological surgery and without contraindications to anticoagulants should be offered thromboprophylaxis. Evidence suggests that UH and LMWH are equally as effective in preventing DVT and the one trial available suggests that warfarin is as effective as UH. There is no evidence as yet to suggest that warfarin, heparin or aspirin reduce incidence of PE.

Oncogenic K-RAS subverts the antiapoptotic role of N-RAS and alters modulation of the N-RAS:gelsolin complex.

Activating mutations in members of the RAS family of genes are among the most common genetic events in human tumorigenesis. Once thought to be functionally interchangeable, it is increasingly recognized that the classical members of this protein family (H-RAS, N-RAS and K-RAS4B) exhibit unique and shared functions that are highly context-dependent. Herein, we demonstrate that the presence of an oncogenic KRAS allele results in elevated levels of GTP-bound N-RAS (N-RAS.GTP) in two human colorectal cancer cell lines, HCT 116 and DLD-1, compared to their isogenic counterparts in which the mutant KRAS allele has been disrupted by homologous recombination. N-RAS subserves an antiapoptotic role in cells expressing wild-type K-RAS; this function is compromised, however, by the presence of mutant K-RAS, and these cells display increased sensitivity to apoptotic stimuli. We additionally identify a physical interaction between N-RAS and gelsolin, a factor that has been shown to promote survival and show that the N-RAS:gelsolin complex is modulated differently in wild-type and mutant K-RAS environments following apoptotic challenge. These findings represent the first biochemical evidence of a functional relationship between endogenous RAS proteins and identify a dynamic physical interaction between endogenous N-RAS and gelsolin that correlates with survival.

Different responses to nitrate and nitrite by the model organism Escherichia coli and the human pathogen Neisseria gonorrhoeae.

The ability of Escherichia coli to use both nitrate and nitrite as terminal electron acceptors during anaerobic growth is mediated by the dual-acting two-component regulatory systems NarX-NarL and NarQ-NarP. In contrast, Neisseria gonorrhoeae responds only to nitrite: it expresses only NarQ-NarP. We have shown that although N. gonorrhoeae NarQ can phosphorylate E. coli NarL and NarP, the N. gonorrhoeae NarP is unable to regulate gene expression in E. coli. Mutagenesis experiments have revealed residues in E. coli NarQ that are essential for nitrate and nitrite sensing. Chimaeric proteins revealed domains of NarQ that are important for ligand sensing.

Fluid therapy for acute bacterial meningitis.

BACKGROUND: Acute bacterial meningitis remains a disease with high mortality and morbidity rates. However, with prompt and adequate antimicrobial and supportive treatment, the chances for survival have improved, especially in infants and children. Careful management of fluid and electrolyte balance is an important supportive therapy. Both over and under hydration are associated with adverse outcomes. OBJECTIVES: The objective of this review was to evaluate differing volumes of fluid given in the initial management of bacterial meningitis. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infection Group's trials register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to March 2005), EMBASE (1980 to December 2004), and CINAHL (1982 to February 2005). References from relevant articles were searched and authors contacted where necessary. In addition, we contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomised controlled trials of differing volumes of fluid given in the initial management of bacterial meningitis were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Six trials were identified in the initial search. On careful inspection three of these met the inclusion criteria. Data were extracted and trials were assessed for quality by all four reviewers. Data were combined for meta-analysis using relative risks for dichotomous data or weighted mean difference for continuous data. A fixed-effect statistical model was used. MAIN RESULTS: The largest of the three trials was conducted in settings with high mortality rates. The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% CI 0.53 to 1.27); acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08); or in mild to moderate sequelae (RR 1.24, 95% CI 0.58 to 2.65). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group in regard to spasticity (RR 0.50, 95% CI 0.27 to 0.93), seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83) and 14 days (RR 0.19, 95% CI 0.04 to 0.88), and chronic severe neurological sequelae at three-months follow up (RR 0.42, 95% CI 0.20 to 0.89). AUTHORS' CONCLUSIONS: There is some evidence to support the use of intravenous maintenance fluids in preference to restricted fluid intake in the first 48 hours in settings with high mortality rates and where patients present late. However, where children present early and mortality rates are lower there is insufficient evidence to guide practice.

Oxidation of Fe(II) in rainwater.

Photochemically produced Fe(II) is oxidized within hours under environmentally realistic conditions in rainwater. The diurnal variation between photochemical production and reoxidation of Fe(II) observed in our laboratory accurately mimics the behavior of ferrous iron observed in field studies where the highest concentrations of dissolved Fe(ll) occur in afternoon rain during the period of maximum sunlight intensity followed by gradually decreasing concentrations eventually returning to early morning pre-light values. The experimental work presented here, along with the results of kinetics studies done by others, suggests thatthe primary process responsible for the decline in photochemically produced Fe(II) concentrations is oxidation by hydrogen peroxide. This reaction is first order with respect to both the concentrations of Fe(II) and H2O2. The second-order rate constant determined for six different authentic rain samples varied over an order of magnitude and was always less than or equal to the rate constant determined for this reaction in simple acidic solutions. Oxidation of photochemically produced ferrous iron by other oxidants including molecular oxygen, ozone, hydroxyl radical, hydroperoxyl/superoxide radical, and hexavalent chromium were found to be insignificant under the conditions present in rainwater. This study shows that Fe(II) occurs as at least two different chemical species in rain; photochemically produced Fe(II) that is oxidized over time periods of hours, and a background Fe(II) that is protected against oxidation, perhaps by organic complexation, and is stable against oxidation for days. Because the rate of oxidation of photochemically produced Fe(II) does not increase with increasing rainwater pH, the speciation of this more labile form of Fe(II) is also not controlled by simple hydrolysis reactions.

Quantum turbulence in superfluid 3He illuminated by a beam of quasiparticle excitations.

We have measured directly the Andreev scattering of a controllable beam of quasiparticle excitations by a localized tangle of quantum vortices in superfluid 3He-B at low temperatures. We present a microscopic description of the Andreev scattering from a vortex line allowing us to estimate the vortex separation scale in a dilute tangle of vortices, providing a better comparison of the observed decay time of the turbulence with recent numerical simulations. The experiments also suggest that below 200 microK we reach the low temperature limit for turbulent dynamics.

Ghanaian infant growth study.

The future revised WHO growth references for infancy and early childhood will have an international basis rather than just an American one, as is the case with the current NCHS/WHO ones. The anthropometric data for analysis will be collected from babies breastfed in accordance with WHO guidelines. An important stipulation, however, is that their growth must have been unrestricted by environmental factors. A paper from Ghana describes a quantitative provisional study that has revealed how such a condition can be satisfied within a developing country. Family income and especially the higher education of the father up to university level can still be important variables in the achievement of optimal growth of babies, even those brought up in situations of relative affluence.

Photochemical production of Fe(II) in rainwater.

Significant concentrations of Fe(II) were produced upon irradiation of authentic rainwater with simulated sunlight. The magnitude of photoproduction was dependent on initial Fe(II), Fe(III), and hydrogen ion concentrations, with more Fe(II) photoproduction when initial Fe(III) and H+ concentrations were high and initial Fe(II) concentrations were low. An equation was developed that accurately predicts photoproduction of Fe(II) in rainwater based on initial Fe speciation values and pH. The quantum yield of Fe(II) photochemical production in rain decreased dramatically with increasing wavelength and decreasing energy of incoming radiation with the average quantum yield at 265 nm approximately an order of magnitude greater than at 546 nm. Probable photochemical precursors of Fe(II) in authentic rain include iron(III) oxalate, iron(III) hydroxide, and an undefined Fe(III) complex. The wavelength-dependent Fe(II) production was modeled using the average Fe(II) efficiency spectrum, an average rainwater absorption spectrum, and the modeled actinic flux for temperate latitudes in both summer and winter. The response spectrum has the highest photoproduction of Fe(II) in summer and winter at 325 and 330 nm, respectively, with greater production in summer rain due to increased actinic flux and longer hours of irradiation.

Progestogen for preventing miscarriage.

BACKGROUND: Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progestogens. Therefore, progestational agents have been used, beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage. OBJECTIVES: To determine the efficacy and safety of progestogens as a preventative therapy against miscarriage. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (April 2003), CENTRAL, MEDLINE (1966 to April 2003), EMBASE (1980 to April 2003), CINAHL (1982 to April 2003), NHMRC Clinical Trials Register (April 2003) and Meta-Register (April 2003). We searched references from relevant articles, attempting to contact authors where necessary, and contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage. DATA COLLECTION AND ANALYSIS: Thirty trials were identified in the initial search. At least, two reviewers assessed trial quality and extracted data. Data for all outcomes were in dichotomous form and the Peto odds ratio was used in the meta-analysis for all comparisons. MAIN RESULTS: Fourteen trials (1988 women) met the inclusion criteria. The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen and placebo or no treatment groups (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.83 to 1.34) and no statistically significant difference in the incidence of adverse effect in either mother or baby. In a subgroup analysis of three trials involving women who had recurrent miscarriages (three or more consecutive miscarriages), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (OR 0.39, 95% CI 0.17 to 0.91). No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment. REVIEWER'S CONCLUSIONS: There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid pregnancy. However, further trials in women with a history of recurrent miscarriage may be warranted, given the trend for improved live birth rates in these women and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence.

Anticoagulant and aspirin prophylaxis for preventing thromboembolism after major gynaecological surgery.

BACKGROUND: The reported overall risk of deep venous thrombosis in gynaecological surgery ranges from 7 to 45%. Fatal pulmonary embolism is estimated to occur in nearly 1% of these women. Pharmaceutical interventions are one possible prophylactic measure for preventing emboli in women undergoing major gynaecological surgery. Agents include unfractionated heparin (low -dose and adjusted-dose), low-molecular-weight heparins, heparinoids and warfarin. OBJECTIVES: The objective of this review was to evaluate the effectiveness of warfarin, heparin and aspirin in preventing thromboembolism after major gynaecological surgery. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 15 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library issue 2, 2003), MEDLINE (1966 to April 2003), EMBASE (1985 to April 2003), and CINAHL (1982 to April 2003). References from relevant articles were searched and authors contacted where necessary. In addition we contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomised controlled trials of heparins, warfarin or aspirin to prevent thromboembolism after major gynaecological surgery were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Thirty-three trials were identified in the initial search. On careful inspection only eight of these met the inclusion criteria. Trials were data extracted and assessed for quality by at least two reviewers. Data were combined for meta-analysis using odds ratios for dichotomous data or weighted mean difference for continuous data. A random effects statistical model was used. MAIN RESULTS: The meta-analysis of heparin versus placebo found a statistically significant decrease in the number of DVTs in both the all women group (including those with and without malignancy) (OR 0.30, 95% CI 0.12 to 0.76) and the subgroup of only women with malignancy (OR 0.30, 95% CI 0.10 to 0.89). There was no significant difference in the incidence of PE. Oral warfarin reduced DVT when compared to placebo in all women (OR 0.22, 95% CI 0.06 to 0.86) and in women with malignancy (OR 0.18, 95% CI 0.04 to 0.87). Meta-analyses of UH and LMWH showed no statistical difference in any comparison. No studies compared aspirin alone to placebo, heparin or warfarin. There was a statistically significant increase in injection site haematomas associated with heparin compared to placebo (OR 0.30, 95% CI 0.10 to 0.89). REVIEWER'S CONCLUSIONS: Women, undergoing major gynaecological surgery and without contraindications to anticoagulants should be offered thromboprophylaxis. Evidence suggests that UH and LMWH are equally as effective in preventing DVT and the one trial available suggests that warfarin is as effective as UH. There is no evidence as yet to suggest that warfarin, heparin or aspirin reduce incidence of PE.