Improved effectiveness of partner notification for patients with sexually transmitted infections: systematic review

Objective: To examine the effectiveness of methods to improve partner notification by patient referral (index patient has responsibility for informing sex partners of their exposure to a sexually transmitted infection). Design: Systematic review of randomised trials of any intervention to supplement simple patient referral. Data sources: Seven electronic databases searched (January 1990 to December 2005) without language restriction, and reference lists of retrieved articles. Review methods: Selection of trials, data extraction, and quality assessment were done by two independent reviewers. The primary outcome was a reduction of incidence or prevalence of sexually transmitted infections in index patients. If this was not reported data were extracted according to a hierarchy of secondary outcomes: number of partners treated; number of partners tested or testing positive; and number of partners notified, located, or elicited. Random effects meta-analysis was carried out when appropriate. Results: 14 trials were included with 12 389 women and men diagnosed as having gonorrhoea, chlamydia, non-gonococcal urethritis, trichomoniasis, or a sexually transmitted infection syndrome. All studies had methodological weaknesses that could have biased their results. Three strategies were used. Six trials examined patient delivered partner therapy. Meta-analysis of five of these showed a reduced risk of persistent or recurrent infection in patients with chlamydia or gonorrhoea (summary risk ratio 0.73, 95% confidence interval 0.57 to 0.93). Supplementing patient referral with information for partners was as effective as patient delivered partner therapy. Neither strategy was effective in women with trichomoniasis. Two trials found that providing index patients with chlamydia with sampling kits for their partners increased the number of partners who got treated. Conclusions: Involving index patients in shared responsibility for the management of sexual partners improves outcomes. Health professionals should consider the following strategies for the management of individual patients: patient delivered partner therapy, home sampling for partners, and providing additional information for partners

Superefficiency in Nonparametric Function Estimation

Fixed parameter asymptotic statements are often used in the context of nonparametric curve estimation problems (e.g., nonparametric density or regression estimation). In this context several forms of superefficiency can occur. In contrast to what can happen in regular parametric problems, here every parameter point (e.g., unknown density or regression function) can be a point of superefficiency. We begin with an example which shows how fixed parameter asymptotic statements have often appeared in the study of adaptive kernel estimators, and how superefficiency can occur in this context. We then carry out a more systematic study of such fixed parameter statements. It is shown in four general settings how the degree of superefficiency attainable depends on the structural assumptions in each case

The SNARE Protein Syntaxin 3 Confers Specificity for Polarized Axonal Trafficking in Neurons.

Cell polarity and precise subcellular protein localization are pivotal to neuronal function. The SNARE machinery underlies intracellular membrane fusion events, but its role in neuronal polarity and selective protein targeting remain unclear. Here we report that syntaxin 3 is involved in orchestrating polarized trafficking in cultured rat hippocampal neurons. We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips, whereas syntaxin 4 localizes to the somatodendritic plasma membrane. Disruption of a conserved N-terminal targeting motif, which causes mislocalization of syntaxin 3, results in coincident mistargeting of the axonal cargos neuron-glia cell adhesion molecule (NgCAM) and neurexin, but not transferrin receptor, a somatodendritic cargo. Similarly, RNAi-mediated knockdown of endogenous syntaxin 3 leads to partial mistargeting of NgCAM, demonstrating that syntaxin 3 plays an important role in its targeting. Additionally, overexpression of syntaxin 3 results in increased axonal growth. Our findings suggest an important role for syntaxin 3 in maintaining neuronal polarity and in the critical task of selective trafficking of membrane protein to axons

Effectiveness of chlamydia screening: systematic review

Background Screening programmes are promoted to control transmission of and prevent female reproductive tract morbidity caused by genital chlamydia. The objective of this study was to examine the effectiveness of register-based and opportunistic chlamydia screening interventions. Methods We searched seven electronic databases (Cinahl, Cochrane Controlled Trials Register, DARE, Embase, Medline, PsycINFO and SIGLE) without language restrictions from January 1990 to October 2007 and reference lists of retrieved articles to identify studies published before 1990. We included studies examining primary outcomes (pelvic inflammatory disease, ectopic pregnancy, infertility, adverse pregnancy outcomes, neonatal infection, chlamydia prevalence) and harms of chlamydia screening in men and non-pregnant and pregnant women. We extracted data in duplicate and synthesized the data narratively or used random effects meta-analysis, where appropriate. Results We included six systematic reviews, five randomized trials, one non-randomized comparative study and one time trend study. Five reviews recommended screening of women at high risk of chlamydia. Two randomized trials found that register-based screening of women at high risk of chlamydia and of female and male high school students reduced the incidence of pelvic inflammatory disease in women at 1 year. Methodological inadequacies could have overestimated the observed benefits. One randomized trial showed that opportunistic screening in women undergoing surgical termination of pregnancy reduced post-abortal rates of pelvic inflammatory disease compared with no screening. We found no randomized trials showing a benefit of opportunistic screening in other populations, no trial examining the effects of more than one screening round and no trials examining the harms of chlamydia screening. Conclusion There is an absence of evidence supporting opportunistic chlamydia screening in the general population younger than 25 years, the most commonly recommended approach. Equipoise remains, so high-quality randomized trials of multiple rounds of screening with biological outcome measures are still needed to determine the balance of benefits and harms of chlamydia screenin

Psychosocial impact of alternative management policies for low-grade cervical abnormalities : results from the TOMBOLA randomised controlled trial

Background: Large numbers of women who participate in cervical screening require follow-up for minor cytological abnormalities. Little is known about the psychological consequences of alternative management policies for these women. We compared, over 30-months, psychosocial outcomes of two policies: cytological surveillance (repeat cervical cytology tests in primary care) and a hospital-based colposcopy examination. Methods: Women attending for a routine cytology test within the UK NHS Cervical Screening Programmes were eligible to participate. 3399 women, aged 20–59 years, with low-grade abnormal cytology, were randomised to cytological surveillance (six-monthly tests; n = 1703) or initial colposcopy with biopsies and/or subsequent treatment based on colposcopic and histological findings (n = 1696). At 12, 18, 24 and 30-months post-recruitment, women completed the Hospital Anxiety and Depression Scale (HADS). A subgroup (n = 2354) completed the Impact of Event Scale (IES) six weeks after the colposcopy episode or first surveillance cytology test. Primary outcomes were percentages over the entire follow-up period of significant depression (≥8) and significant anxiety (≥11; “30-month percentages”). Secondary outcomes were point prevalences of significant depression, significant anxiety and procedure-related distress (≥9). Outcomes were compared between arms by calculating fully-adjusted odds ratios (ORs) for initial colposcopy versus cytological surveillance. Results: There was no significant difference in 30-month percentages of significant depression (OR = 0.99, 95% CI 0.80–1.21) or anxiety (OR = 0.97, 95% CI 0.81–1.16) between arms. At the six-week assessment, anxiety and distress, but not depression, were significantly less common in the initial colposcopy arm (anxiety: 7.9% vs 13.4%; OR = 0.55, 95% CI 0.38–0.81; distress: 30.6% vs 39.3%, OR = 0.67 95% CI 0.54–0.84). Neither anxiety nor depression differed between arms at subsequent time-points. Conclusions: There was no difference in the longer-term psychosocial impact of management policies based on cytological surveillance or initial colposcopy. Policy-makers, clinicians, and women themselves can be reassured that neither management policy has a significantly greater psychosocial cost

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy : multicentre randomised controlled trial

Peer reviewedPublisher PD

Accounting for Outward Direct Investment from Hong Kong and Singapore: Who Controls What?

After a brief introduction and examination of the economic rationale for accounting for foreign direct investment (FDI), we survey information on outward investors from Hong Kong and Singapore with the aim of illuminating the implications of accounting for such FDI by geographical source or by country of ultimate beneficial owner. By any measure it is clear that a large part of FDI from these economies comes from foreign-controlled firms and hence that ownership-based estimates of FDI from these two economies would be much smaller than the standard, geography-based estimates. However, because outward investment by foreign firms in Hong Kong and Singapore often involves sub- stantial contributions from local staff and partners, an attempt is made to examine the extent of control over investment decisions exercised by these local staff and partners. Case studies from Hong Kong indicate a tendency for for local control over investment decisions to be relatively strong in 4 types of foreign-controlled Hong Kong firms, recently acquired firms, firms with strong local entrepreneurial involvement, customer-oriented firms, and relocated holding companies. On the other hand, evidence froma sample of Thai affiliates of foreign-controlled Hong Kong or Singapore investors suggested that many of the investors were acting as part of an integrated network of foreign investors. Thus, although it is clear local staff and partners have a large influence over the investment decisions of foreign-controlled outward investors in Hong Kong and Singapore, it does not appear that such firms are a majority among foreign-controlled investors in these economies.

Effectiveness of chlamydia screening: systematic review

BACKGROUND: Screening programmes are promoted to control transmission of and prevent female reproductive tract morbidity caused by genital chlamydia. The objective of this study was to examine the effectiveness of register-based and opportunistic chlamydia screening interventions. METHODS: We searched seven electronic databases (Cinahl, Cochrane Controlled Trials Register, DARE, Embase, Medline, PsycINFO and SIGLE) without language restrictions from January 1990 to October 2007 and reference lists of retrieved articles to identify studies published before 1990. We included studies examining primary outcomes (pelvic inflammatory disease, ectopic pregnancy, infertility, adverse pregnancy outcomes, neonatal infection, chlamydia prevalence) and harms of chlamydia screening in men and non-pregnant and pregnant women. We extracted data in duplicate and synthesized the data narratively or used random effects meta-analysis, where appropriate. RESULTS: We included six systematic reviews, five randomized trials, one non-randomized comparative study and one time trend study. Five reviews recommended screening of women at high risk of chlamydia. Two randomized trials found that register-based screening of women at high risk of chlamydia and of female and male high school students reduced the incidence of pelvic inflammatory disease in women at 1 year. Methodological inadequacies could have overestimated the observed benefits. One randomized trial showed that opportunistic screening in women undergoing surgical termination of pregnancy reduced post-abortal rates of pelvic inflammatory disease compared with no screening. We found no randomized trials showing a benefit of opportunistic screening in other populations, no trial examining the effects of more than one screening round and no trials examining the harms of chlamydia screening. CONCLUSION: There is an absence of evidence supporting opportunistic chlamydia screening in the general population younger than 25 years, the most commonly recommended approach. Equipoise remains, so high-quality randomized trials of multiple rounds of screening with biological outcome measures are still needed to determine the balance of benefits and harms of chlamydia screening

Assessment of folate receptor-β expression in human neoplastic tissues

Over-expression of folate receptor alpha on cancer cells has been frequently exploited for delivery of folate-targeted imaging and therapeutic agents to tumors. Because limited information exists on expression of the beta isoform of the folate receptor in human cancers (FR-β), we have evaluated the immunohistochemical staining pattern of FR-β in 992 tumor sections from 20 different human cancer types using a new anti-human FR-β monoclonal antibody. FR-β expression was shown to be more pronounced in cells within the stroma, primarily macrophages and macrophage-like cells than cancer cells in every cancer type studied. Moreover, FR-β expression in both cancer and stromal cells was found to be statistically more prominent in females than males. A significant positive correlation was also observed between FR-β expression on stromal cells and both the stage of the cancer and the presence of lymph node metastases. Based on these data we conclude FR-β may constitute a good target for specific delivery of therapeutic agents to activated macrophages and that accumulation of FR-β positive macrophages in the stroma could serve as a useful indicator of a tumor's metastatic potential