IntroductionIn the Greater Mekong Subregion, adults are at highest risk for malaria. The most relevant disease vectors bite during daytime and outdoors which makes forest work a high-risk activity ...for malaria. The absence of effective vector control strategies and limited periods of exposure during forest visits suggest that chemoprophylaxis could be an appropriate strategy to protect forest goers against malaria.Methods and analysisThe protocol describes an open-label randomised controlled trial of artemether-lumefantrine (AL) versus multivitamin as prophylaxis against malaria among forest goers aged 16–65 years in rural northeast Cambodia. The primary objective is to compare the efficacy of the artemisinin combination therapy AL versus a multivitamin preparation as defined by the 28-day PCR parasite positivity rate and incidence of confirmed clinical malaria of any species. The sample size is 2200 patient-episodes of duration 1 month in each arm. The duration of follow-up and prophylaxis for each participant is 1, 2 or 3 consecutive 28-day periods, followed by a further 28 days of post-exposure prophylaxis, depending on whether they continue to visit the forest. Analysis will be done both by intention to treat and per protocol.Ethics and disseminationAll participants will provide written, informed consent. Ethical approval was obtained from the Oxford Tropical Research Ethics Committee and the Cambodia National Ethics Committee for Health Research. Results will be disseminated by peer-reviewed open access publication together with open data.Trial registration numberNCT04041973; Pre-result.
The effectiveness of extrapleural pneumonectomy (EPP) to extend quality-adjusted survival in malignant pleural mesothelioma within multimodality treatment should be proven in a randomized controlled ...trial if this radical surgery is to be regarded as the standard of care. The question was whether randomization to surgery versus no surgery would be possible.
The Mesothelioma and Radical Surgery trial was planned to randomize 50 patients to test feasibility. There was a two-stage consent process. At first consent, the patients who were possible candidates for radical surgery were registered into the trial for completion of assessment and staging. All received platinum-based chemotherapy. If still eligible, they completed a second consent to be randomized to have either EPP followed by radical hemithorax radiotherapy or to have continued best care.
Patients were recruited through 11 collaborating centers in the United Kingdom. One hundred twelve potentially eligible patients gave informed consent to enter the registration phase and undergo chemotherapy. One died, 27 progressed, five were inoperable, four were treated off trial, and 18 withdrew either during or after chemotherapy but before final review. Additionally six were deemed inoperable at review after completing chemotherapy and one more patient withdrew. The remaining 50 were randomized; 24 to EPP and 26 to continued best care.
In this study, 50/112 (45%) of patients entering the evaluation and induction phase of the trial went on to be randomized. We have shown that this randomization between surgery and no surgery is feasible. This was the primary aim of the Mesothelioma and Radical Surgery trial.
IntroductionIn low-income and middle-income countries in Southeast Asia, the burden of diseases among rural population remains poorly understood, posing a challenge for effective healthcare ...prioritisation and resource allocation. Addressing this knowledge gap, the South and Southeast Asia Community-based Trials Network (SEACTN) will undertake a survey that aims to determine the prevalence of a wide range of non-communicable and communicable diseases, as one of the key initiatives of its first project—the Rural Febrile Illness project (RFI). This survey, alongside other RFI studies that explore fever aetiology, leading causes of mortality, and establishing village and health facility maps and profiles, will provide an updated epidemiological background of the rural areas where the network is operational.Methods and analysisDuring 2022–2023, a cross-sectional household survey will be conducted across three SEACTN sites in Bangladesh, Cambodia and Thailand. Using a two-stage cluster-sampling approach, we will employ a probability-proportional-to-size sample method for village, and a simple random sample for household, selection, enrolling all members from the selected households. Approximately 1500 participants will be enrolled per country. Participants will undergo questionnaire interview, physical examination and haemoglobin point-of-care testing. Blood samples will be collected and sent to central laboratories to test for chronic and acute infections, and biomarkers associated with cardiovascular disease, and diabetes. Prevalences will be presented as an overall estimate by country, and stratified and compared across sites and participants’ sociodemographic characteristics. Associations between disease status, risk factors and other characteristics will be explored.Ethics and disseminationThis study protocol has been approved by the Oxford Tropical Research Ethics Committee, National Research Ethics Committee of Bangladesh Medical Research Council, the Cambodian National Ethics Committee for Health Research, the Chiang Rai Provincial Public Health Research Ethical Committee. The results will be disseminated via the local health authorities and partners, peer-reviewed journals and conference presentations.Trial registration numberNCT05389540.
Recent whole genome association studies of prostate, breast, and colorectal cancer have identified susceptibility loci on
8q24. We genotyped three variants associated with prostate cancer ...(rs10090154, rs13254738, and rs7000448), one associated
with both prostate and colorectal cancer (rs6983267), and one associated with breast cancer (rs13281615) in a series of 1,499
breast cancer cases and 1,390 controls. 1,267 (85%) of the cases had two primary breast cancers. Our analysis provides further
evidence of the relationship between rs13281615 and risk of breast cancer, with heterozygote odds ratio (OR) 1.30 95% confidence
interval (CI) 1.09-1.54 and homozygote OR 1.52 (95% CI, 1.22-1.89; P trend = 0.00003), and confirms the prediction that the risk is substantially higher in this genetically enriched series (OR per
allele, 1.24; 95% CI, 1.12-1.38) than in a large series of mainly unselected cases (reported OR per allele, 1.08; 95% CI,
1.05-1.11). We observed a protective effect of rs13254738 for breast cancer (allelic OR, 0.88; 95% CI, 0.78-0.98; P = 0.02), which is supported by the Cancer Genetic Markers of Susceptibility data (pooled allelic OR, 0.88; 95% CI, 0.81-0.96;
P = 0.003). None of the other three single nucleotide polymorphisms, two associated with prostate (rs10090154 and rs7000448)
and one with both prostate and colorectal cancers (rs6583267), was associated with breast cancer risk in our study. This evidence
of a protective effect for breast cancer of one variant (rs13254738) that has been associated previously with a 1.25-fold
increased risk of prostate cancer, with no effect for the two other variants, indicates that the effects of the risk alleles
clustered at 8q24 are cancer site specific. (Cancer Epidemiol Biomarkers Prev 2008;17(3):702–5)
If breast cancers arise independently in each breast the odds ratio (OR) for bilateral breast cancer for carriers of CHEK2*1100delC should be ∼5.5, the square of the reported OR for a first primary ...(OR, 2.34). In the subset of bilateral cases with one or
more affected relatives, the predicted carrier OR should be ∼9. We have tested these predictions in a pooled set of 1,828
cases with 2 primaries and 7,030 controls from 8 studies. The second primary OR for CHEK2*1100delC carriers was 6.43 (95% confidence interval, 4.33-9.56; P < 0.0001), significantly greater than the published estimate for a first primary ( P < 0.001) but consistent with its square. The predicted increase in carrier OR with increasing numbers of affected relatives
was seen using bilateral cases from the UK ( P trend = 0.0003) and Finland ( P trend = 0.37), although not using those from the Netherlands and Russia ( P = 0.001 for heterogeneity between countries). Based on a standard genetic model, we predict lifetime risks for CHEK2*1100delC carrier and noncarrier daughters of bilateral breast cancer cases of 37% and 18%, respectively. Our results imply that clinical
management of the daughter of a woman with bilateral breast cancer should depend on her CHEK2*1100delC carrier status. This
and other moderate penetrance breast cancer susceptibility alleles, together with family history data, will thus identify
increasing numbers of women at potentially very high risk. Before such predictions are accepted by clinical geneticists, however,
further population-based evidence is needed on the effect of CHEK2*1100delC and other moderate penetrance alleles in women with a family history of breast cancer. (Cancer Epidemiol Biomarkers Prev
2009;18(1):230–4)
High levels of circulating insulin-like growth factor-I (IGF-I) and its major binding protein (IGFBP-3) at premenopausal ages
have been associated with an increased breast cancer risk. We conducted a ...cross-sectional study (215 premenopausal women and
241 after natural menopause) nested within the Guernsey prospective studies to examine the relationship between the IGF system
and mammographic features of the breast. The mammographically dense area in the breast increased with increasing serum levels
of IGF-I ( P for linear trend, P t = 0.05), IGF-II ( P t = 0.08), and IGFBP-3 ( P t = 0.01) only in premenopausal women. IGF-II and IGFBP-3 serum levels were associated with increases in the mammographically
lucent area in both premenopausal ( P t = 0.01 and 0.04, respectively) and postmenopausal women ( P t < 0.001 for both), but these associations were no longer statistically significant after adjustment for body mass index and
waist circumference. Neither the IGF-I/IGFBP-3 nor the IGF-II/IGFBP-3 molar ratio was associated with any of these mammographic
features. The number of A alleles at a polymorphic locus in the promoter region of the IGFBP-3 gene was associated with increasing mean IGFBP-3 levels in both premenopausal ( P t = 0.01) and postmenopausal ( P t <0.001) women but not with mammographically dense area. These results support the hypothesis that the IGF system may affect
the amount of mammographically dense tissue in premenopausal women, possibly by promoting cell proliferation and inhibiting
apoptosis in the fibroglandular tissue. The findings also show strong relations between IGF-II and IGFBP-3 levels and the
amount of mammographically lucent tissue, reflecting the associations between body adiposity and amount of fat tissue in the
breast and between body adiposity and circulating levels of these growth factors. (Cancer Epidemiol Biomarkers Prev 2006;15(3):449–55)
Highlights ► In triage of LSIL, methods more specific than general hrHPV DNA tests may be preferred. ► To predict failure of treatment of high-grade cervical precancer, HPV tests are more sensitive ...than and as specific as cytology. ► In screening, a negative hrHPV DNA test is associated with a low future risk of precancer and cancer. ► HPV-screening followed by cytology triage of HPV+ women (30 years or older) is more effective than cytology-based screening.
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