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  • Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer--a systematic review and meta-analysis.

    25 December 2017

    BACKGROUND: In response to the ongoing debate on the long-term effects of assisted reproduction technologies, such as IVF, we systematically reviewed and meta-analyzed available evidence on the association between controlled ovarian hyperstimulation for IVF and risk of ovarian, endometrial and cervical cancer. METHODS: Eligible studies were identified and pooled effect estimates for relative risk (RR) were calculated by cancer type among two reference groups (general population or infertile women), through fixed- or random-effects models as appropriate. RESULTS: Nine cohort studies were synthesized, corresponding to a total size of 109 969 women exposed to IVF, among whom 76 incident cases of ovarian, 18 of endometrial and 207 cases of cervical cancer were studied. The synthesis of studies with general population as the reference group pointed to a statistically significant positive association between IVF and increased risk for ovarian (RR = 1.50, 95% confidence interval (CI): 1.17-1.92) and endometrial (RR = 2.04, 95% CI: 1.22-3.43), but not cervical (RR = 0.86, 95% CI: 0.49-1.49) cancers. On the contrary, when infertile women were used as the reference group, no significant associations with ovarian, endometrial or cervical cancer types were noted (RR = 1.26, 95% CI: 0.62-2.55 RR = 0.45, 95% CI: 0.18-1.14 and RR = 5.70, 95% CI: 0.28-117.20, respectively). CONCLUSIONS: IVF does not seem to be associated with elevated cervical cancer risk, nor with ovarian or endometrial cancer when the confounding effect of infertility was neutralized in studies allowing such comparisons. Of note, only one study provided follow-up longer than 10 years for the group exposed to IVF. Future cohort studies should preferably use infertile women as the reference group, rely on IVF-registered valid exposure data, adjust for a variety of meaningful confounders and adopt relatively longer follow-up periods before sound conclusions are drawn.

  • Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma.

    27 December 2017

    The few studies published on angiogenesis in lymphoma have raised the question of whether or not microvessel density (MVD) is associated with more aggressive disease and have reported the observation that in follicular lymphomas, vessels are mature rather than immature. We investigated MVD and the vascular phenotype within follicular or diffuse large B-cell lymphomas, reactive nodes and tonsils. Vascular phenotype was defined by the expression or loss of reactivity to the antibody LH39 (detecting the LH39 laminin epitope of the basement membrane in mature vessels) and by detection of alpha V beta 3 (expressed on immature vessels). In reactive nodes and in follicular lymphomas, MVD was higher in the paracortex than in germinal centres or in neoplastic follicles. However, in neoplastic follicles an increase in alpha V beta 3-positive endothelium suggested the activation of an angiogenic pathway different from that present in the reactive follicles. In large B-cell lymphomas, MVD was higher than in reactive and neoplastic follicles but lower than in the reactive paracortex. The number of immature vessels (LH39 negative) and of alpha V beta 3-positive vessels was higher than in reactive lymph nodes and follicular lymphoma suggesting that a switch to a different angiogenic pathway has occurred. Finally, we have demonstrated that within reactive and neoplastic follicles vascular regression is occurring, perhaps constraining the growth of reactive follicles alongside other phenomena such as apoptosis. Vascular regression was previously believed to occur in adults only in ovarian and endometrial tissue. We conclude that different types of angiogenesis are present in follicular lymphomas and large B-cell lymphomas. This has implications for possible future therapies.

  • Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas.

    9 January 2018

    We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing alphaVbeta3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and alphaVbeta3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0--60%) expressed LH39, while alphaVbeta3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5--90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed.

  • Demand for and supply of out of hours care from general practitioners in England and Scotland: observational study based on routinely collected data.

    8 December 2017

    OBJECTIVES: To determine the level of demand and supply of out of hours care from a nationally representative sample of general practice cooperatives. DESIGN: Observational study based on routinely collected data on telephone calls, patient population data from general practices, and information about cooperatives from interviews with managers. SETTING: 20 cooperatives in England and Scotland selected after stratification by region and by size. SUBJECTS: 899 657 out of hours telephone calls over 12 months. MAIN OUTCOME MEASURES: Numbers and age and sex specific rates of calls; variation in demand and activity in relation to characteristics of the population; timing of calls; proportion of patients consulting at home, at a primary care centre, or on the telephone; response times; hospital admission rates. RESULTS: The out of hours call rate (excluding bank holidays) was 159 calls per 1000 patients/year, with rates in children aged under 5 years four times higher than for adults. Little variation occurred by day of the week or seasonally. Cooperatives in Scotland experienced higher demand than those in England. Patients living in deprived areas made 70% more calls than those in non-deprived areas, but this had little effect on the overall variation in demand. 45.4% (408 407) of calls were handled by telephone advice, 23.6% (212 550) by a home visit, and 29.8% (267 663) at a centre. Cooperatives responded to 60% of calls within 30 minutes and to 83% within one hour. Hospital admission followed 5.5% (30 743/554 179) of out of hours calls (8 admissions per 1000 patients/year). CONCLUSIONS: This project provides national baseline data for the planning of services and the analysis of future changes.

  • A Double-Blind Randomized Placebo-Controlled Withdrawal Trial Comparing Memantine and Antipsychotics for the Long-Term Treatment of Function and Neuropsychiatric Symptoms in People With Alzheimer's Disease (MAIN-AD)

    10 January 2018

    © 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Background: Neuropsychiatric symptoms in Alzheimer disease (AD) cause significant distress and present a complex clinical challenge for treatment. Pharmacological treatment options are limited to antipsychotics, which carry extensive safety issues. There is emerging evidence to support the potential benefits of memantine, currently licensed for moderate to severe AD, in the prophylaxis of neuropsychiatric symptoms. Methods: The MAIN-AD study is a double-blind randomized placebo-controlled withdrawal trial comparing memantine with antipsychotics for the treatment of neuropsychiatric symptoms over 24weeks. A total of 199 people with probable AD living in care homes already receiving an antipsychotic were randomized to receive either memantine or to continue an antipsychotic. The primary outcomes were function (Bristol Activities of Daily Living Scale [BADLS]) and agitation (Cohen-Mansfield Agitation Inventory [CMAI] ). Secondary outcomes were Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and mortality. Results: There was no significant difference between groups on the BADLS or CMAI. At 24weeks, there was a nonsignificant adjusted difference in favor of memantine on the BADLS of 0.23 (95% CI -1.80-2.27; P=.82) and in favor of antipsychotic on the CMAI of 0.09 (95% CI -0.35-8.53; P=.07). Although there were no significant differences in total NPI, there were 5.01 (95% CI -1.68-11.70; P=.05) and 3.63 (95% CI -1.40-8.67; P=.16) point advantages favoring antipsychotics at weeks 12 and 24, respectively. In addition, in an exploratory analysis, individuals allocated to antipsychotics were significantly less likely to experience relapse of neuropsychiatric symptoms at all time points. The group receiving memantine had a nonsignificant 1.3-point advantage on the MMSE at 24weeks. Discussion: This study indicates no benefits for memantine in the long-term treatment and prophylaxis of clinically significant neuropsychiatric symptoms. The results did indicate some benefits for antipsychotic medications in reducing the relapse of neuropsychiatric symptoms, but this must be balanced against increased mortality risk.

  • Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia.

    29 November 2017

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of different platelet transfusion thresholds prior to the insertion of a lumbar puncture or epidural anaesthesia in people with thrombocytopenia (low platelet count).

  • Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia.

    10 January 2018

    BACKGROUND: Patients with a low platelet count (thrombocytopenia) often require the insertion of central lines (central venous catheters (CVCs)). CVCs have a number of uses; these include: administration of chemotherapy; intensive monitoring and treatment of critically-ill patients; administration of total parenteral nutrition; and long-term intermittent intravenous access for patients requiring repeated treatments. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to CVC insertion, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to CVC insertion varies significantly from country to country. This indicates significant uncertainty among clinicians of the correct management of these patients. The risk of bleeding after a central line insertion appears to be low if an ultrasound-guided technique is used. Patients may therefore be exposed to the risks of a platelet transfusion without any obvious clinical benefit. OBJECTIVES: To assess the effects of different platelet transfusion thresholds prior to the insertion of a central line in patients with thrombocytopenia (low platelet count). SEARCH METHODS: We searched for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2015, Issue 2), MEDLINE (from 1946), EMBASE (from 1974), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 23 February 2015. SELECTION CRITERIA: We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in patients of any age with thrombocytopenia requiring insertion of a CVC. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: One RCT was identified that compared different platelet transfusion thresholds prior to insertion of a CVC in people with chronic liver disease. This study is still recruiting participants (expected recruitment: up to 165 participants) and is due to be completed in December 2017. There were no completed studies. There were no studies that compared no platelet transfusions to a platelet transfusion threshold. AUTHORS' CONCLUSIONS: There is no evidence from RCTs to determine whether platelet transfusions are required prior to central line insertion in patients with thrombocytopenia, and, if a platelet transfusion is required, what is the correct platelet transfusion threshold. Further randomised trials with robust methodology are required to develop the optimal transfusion strategy for such patients. The one ongoing RCT involving people with cirrhosis will not be able to answer this review's questions, because it is a small study that assesses one patient group and does not address all of the comparisons included in this review. To detect an increase in the proportion of participants who had major bleeding from 1 in 100 to 2 in 100 would require a study containing at least 4634 participants (80% power, 5% significance).