Testing for sexually transmitted infections in general practice: cross-sectional study

Background: Primary care is an important provider of sexual health care in England. We sought to explore the extent of testing for chlamydia and HIV in general practice and its relation to associated measures of sexual health in two contrasting geographical settings.Methods: We analysed chlamydia and HIV testing data from 64 general practices and one genitourinary medicine (GUM) clinic in Brent (from mid-2003 to mid-2006) and 143 general practices and two GUM clinics in Avon (2004). We examined associations between practice testing status, practice characteristics and hypothesised markers of population need (area level teenage conception rates and Index of Multiple Deprivation, IMD scores).Results: No HIV or chlamydia testing was done in 19% (12/64) of general practices in Brent, compared to 2.1% (3/143) in Avon. In Brent, the mean age of general practitioners (GPs) in Brent practices that tested for chlamydia or HIV was lower than in those that had not conducted testing. Practices where no HIV testing was done had slightly higher local teenage conception rates (median 23.5 vs. 17.4/1000 women aged 15-44, p = 0.07) and served more deprived areas (median IMD score 27.1 vs. 21.8, p = 0.05). Mean yearly chlamydia and HIV testing rates, in practices that did test were 33.2 and 0.6 (per 1000 patients aged 15-44 years) in Brent, and 34.1 and 10.3 in Avon, respectively. In Brent practices only 20% of chlamydia tests were conducted in patients aged under 25 years, compared with 39% in Avon.Conclusions: There are substantial geographical differences in the intensity of chlamydia and HIV testing in general practice. Interventions to facilitate sexually transmitted infection and HIV testing in general practice are needed to improve access to effective sexual health care. The use of routinely-collected laboratory, practice-level and demographic data for monitoring sexual health service provision and informing service planning should be more widely evaluated

Phase i trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours

BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective secondgeneration inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS: In all, 49 patients received axitinib 5mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5mg b.i.d. with paclitaxel/carboplatin. RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia (n¼1) in the paclitaxel/carboplatin cohort and fatigue (n¼1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No gradeX3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n¼27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n¼21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. CONCLUSION: Axitinib 5mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug–drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.This study was sponsored by Pfizer Inc. Support was provided in part by National Institutes of Health grant P30 CA006927 to the Fox Chase Cancer Center. We thank the patients who participated in this study and the physicians who referred them, as well as the study coordinators and data managers, Shelley Mayfield and Carol Martins at Pfizer Inc. for support of the study conduct, and Gamal ElSawah, Pfizer Medical Affairs, for his review of the manuscript. Medical writing support was provided by Joanna Bloom, of UBC Scientific Solutions (Southport, CT, USA) and Christine Arris at ACUMED (Tytherington, UK) and was funded by Pfizer In

Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study

In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06–1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women

Elimination Therapy for the Endemic Malarias

Most malaria diagnosed outside endemic zones occurs in patients experiencing the consequences of what was likely a single infectious bite by an anopheline mosquito. A single species of parasite is nearly always involved and expert opinion on malaria chemotherapy uniformly prescribes species- and stage-specific treatments. However the vast majority of people experiencing malaria, those resident in endemic zones, do so repeatedly and very often with the involvement of two or more species and stages of parasite. Silent forms of these infections—asymptomatic and beyond the reach of diagnostics—may accumulate to form substantial and unchallenged reservoirs of infection. In such settings treating only the species and stage of malaria revealed by diagnosis and not others may not be sensible or appropriate. Developing therapeutic strategies that address all species and stages independently of diagnostic evidence may substantially improve the effectiveness of the control and elimination of endemic malaria