Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: a pooled analysis of 26 epidemiological studies

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The Lancet Oncology, Early Online Publication, 13 September 2011

doi:10.1016/S1470-2045(11)70223-6

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Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: a pooled analysis of 26 epidemiological studies

Dr Xavier Castellsagué MD a d

, Mireia Díaz MSc a, Salvatore Vaccarella PhD b, Silvia de Sanjosé MD a d, Nubia Muñoz MDa, Rolando Herrero MD b, Silvia Franceschi MD b, Prof Chris J L M Meijer MD c, F Xavier Bosch MD a e

Summary

Background

Intrauterine device (IUD) use has been shown to reduce the risk of endometrial cancer, but little is known about its association with cervical cancer risk. We assessed whether IUD use affects cervical human papillomavirus (HPV) infection and the risk of developing cervical cancer.

Methods

We did a pooled analysis of individual data from two large studies by the International Agency for Research on Cancer and Institut Català d’Oncologia research programme on HPV and cervical cancer; one study included data from ten case—control studies of cervical cancer done in eight countries, and the other included data from 16 HPV prevalence surveys of women from the general population in 14 countries. 2205 women with cervical cancer and 2214 matched control women without cervical cancer were included from the case—control studies, and 15 272 healthy women from the HPV surveys. Information on IUD use was obtained by personal interview. HPV DNA was tested by PCR-based assays. Odds ratios and 95% CIs were estimated using multivariate unconditional logistic regression for the associations between IUD use, cervical HPV DNA, and cervical cancer.

Findings

After adjusting for relevant covariates, including cervical HPV DNA and number of previous Papanicolaou smears, a strong inverse association was found between ever use of IUDs and cervical cancer (odds ratio 0·55, 95% CI 0·42—0·70; p<0·0001). A protective association was noted for squamous-cell carcinoma (0·56, 0·43—0·72; p<0·0001), adenocarcinoma and adenosquamous carcinoma (0·46, 0·22—0·97; p=0·035), but not among HPV-positive women (0·68, 0·44—1·06; p=0·11). No association was found between IUD use and detection of cervical HPV DNA among women without cervical cancer.

Interpretation

Our data suggest that IUD use might act as a protective cofactor in cervical carcinogenesis. Cellular immunity triggered by the device might be one of several mechanisms that could explain our findings.

Funding

Instituto de Salud Carlos III; Agència de Gestió d’Ajuts Universitaris i Recerca; Marató TV3 Foundation; Bill & Melinda Gates Foundation; International Agency for Research on Cancer; European Community; Fondo de Investigaciones Sanitarias, Spain; Preventiefonds, Netherlands; Programa Interministerial de Investigación y Desarrollo, Spain; Conselho Nacional de Desenvolvimiento Cientifico e Tecnologico, Brazil; and Department of Reproductive Health & Research, WHO.

Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial

Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial
Ms Heather Powell MMedSc,Vanessa E Murphy PhD,Prof D Robin Taylor MD,Prof Michael J Hensley PhD,Kirsten McCaffery PhD,Warwick Giles PhD,Vicki L Clifton PhD,Prof Peter G Gibson MBBS
The Lancet – 10 September 2011 ( Vol. 378, Issue 9795, Pages 983-990 )
DOI: 10.1016/S0140-6736(11)60971-9

Background

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Asthma exacerbations during pregnancy are common and can be associated with substantial maternal and fetal morbidity. Treatment decisions based on sputum eosinophil counts reduce exacerbations in non-pregnant women with asthma, but results with the fraction of exhaled nitric oxide (FENO) to guide management are equivocal. We tested the hypothesis that a management algorithm for asthma in pregnancy based on FENO and symptoms would reduce asthma exacerbations.

Methods

We undertook a double-blind, parallel-group, controlled trial in two antenatal clinics in Australia. 220 pregnant, non-smoking women with asthma were randomly assigned, by a computer-generated random number list, before 22 weeks’ gestation to treatment adjustment at monthly visits by an algorithm using clinical symptoms (control group) or FENO concentrations (active intervention group) used to uptitrate (FENO >29 ppb) or downtitrate (FENO <16 ppb) inhaled corticosteroid dose. Participants, caregivers, and outcome assessors were masked to group assignment. Longacting β2 agonist and minimum dose inhaled corticosteroid were used to treat symptoms when FENO was not increased. The primary outcome was total asthma exacerbations (moderate and severe). Analysis was by intention to treat. This study is registered with the Australian and New Zealand Clinical Trials Registry, number 12607000561482.

Findings

111 women were randomly assigned to the FENO group (100 completed) and 109 to the control group (103 completed). The exacerbation rate was lower in the FENO group than in the control group (0·288 vs 0·615 exacerbations per pregnancy; incidence rate ratio 0·496, 95% CI 0·325—0·755; p=0·001). The number needed to treat was 6. In the FENO group, quality of life was improved (score on short form 12 mental summary was 56·9 [95% CI 50·2—59·3] in FENO group vs 54·2 [46·1—57·6] in control group; p=0·037) and neonatal hospitalisations were reduced (eight [8%] vs 18 [17%]; p=0·046).

Interpretation

Asthma exacerbations during pregnancy can be significantly reduced with a validated FENO-based treatment algorithm.

Funding

National Health and Medical Research Council of Australia.

Vaccine production, distribution, access, and uptake

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The Lancet, Volume 378, Issue 9789, Pages 428 – 438, 30 July 2011

Published Online: 09 June 2011

doi:10.1016/S0140-6736(11)60478-9

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Vaccine production, distribution, access, and uptake

Jon Smith PhD a, Prof Marc Lipsitch DPhil b, Prof Jeffrey W Almond PhD a

Summary

For human vaccines to be available on a global scale, complex production methods, meticulous quality control, and reliable distribution channels are needed to ensure that the products are potent and effective at the point of use. The technologies used to manufacture different types of vaccines can strongly affect vaccine cost, ease of industrial scale-up, stability, and, ultimately, worldwide availability. The complexity of manufacturing is compounded by the need for different formulations in different countries and age-groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, to ensure optimum access and uptake, strong partnerships are needed between private manufacturers, regulatory authorities, and national and international public health services. For vaccines whose supply is insufficient to meet demand, prioritisation of target groups can increase the effect of these vaccines. In this report, we draw from our experience of vaccine development and focus on influenza vaccines as an example to consider production, distribution, access, and other factors that affect vaccine uptake and population-level effectiveness.

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Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial

Image via WikipediaGriffin SJ, Borch-Johnsen K, Davies MJ, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet. 2011 Jun 24. (Original) PMID: 21705063

BACKGROUND: Intensive treatment of multiple cardiovascular risk factors can halve mortality among people with established type 2 diabetes. We investigated the effect of early multifactorial treatment after diagnosis by screening.
METHODS: In a pragmatic, cluster-randomised, parallel-group trial done in Denmark, the Netherlands, and the UK, 343 general practices were randomly assigned screening of registered patients aged 40-69 years without known diabetes followed by routine care of diabetes or screening followed by intensive treatment of multiple risk factors. The primary endpoint was first cardiovascular event, including cardiovascular mortality and morbidity, revascularisation, and non-traumatic amputation within 5 years. Patients and staff assessing outcomes were unaware of the practice`s study group assignment. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00237549.
FINDINGS: Primary endpoint data were available for 3055 (99.9%) of 3057 screen-detected patients. The mean age was 60.3 (SD 6.9) years and the mean duration of follow-up was 5.3 (SD 1.6) years. Improvements in cardiovascular risk factors (HbA(1c) and cholesterol concentrations and blood pressure) were slightly but significantly better in the intensive treatment group. The incidence of first cardiovascular event was 7.2% (13.5 per 1000 person-years) in the intensive treatment group and 8.5% (15.9 per 1000 person-years) in the routine care group (hazard ratio 0.83, 95% CI 0.65-1.05), and of all-cause mortality 6.2% (11.6 per 1000 person-years) and 6.7% (12.5 per 1000 person-years; 0.91, 0.69-1.21), respectively.
INTERPRETATION: An intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death.
FUNDING: National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Wellcome Trust, UK Medical Research Council, UK NIHR Health Technology Assessment Programme, UK National Health Service R&D, UK National Institute for Health Research, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Novo Nordisk, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Merck.

Prevencion

Dos excelentes articulos de Juan Gervas y Barbara Starfield sobre prevencion. Sin duda y como es de esperar, polemicos como siempre. Espero los disfruten:

Two amazing papers by Juan Gervas (Spain) and Barbara Starfield (USA) about prevention. Without doubt, as we ever expect from them, a good issue to argue the pro and cons. I hope you enjoy them as I did. Thanks Juan, Thanks Barbara.

prevention_concept_JECH_2008.pdf

prevention_Lancet_2008_publ.pdf

prevention J.Gerva…

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prevencion-Gervas …

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Prevencion

Dos excelentes articulos de Juan Gervas y Barbara Starfield sobre prevencion. Sin duda y como es de esperar, polemicos como siempre. Espero los disfruten:

prevention_concept_JECH_2008.pdf

prevention_Lancet_2008_publ.pdf

prevention J.Gerva…

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prevencion-Gervas …

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Telmisartan: estudio Trascend

Publicado en Lancet: Estudio Trascend

– 5926 pacientes, 2954 recibieron 80 mgr de Telmisartan, 2972 placebo. Estudio aleatorizado, controlado.

– Analisis por intencion de tratar. Seguimiento entre 51 a 64 meses.

– Disminucion de la TA media: HR 0,92 (IC 95% 0.81-1.05). No significativo.

– Resultados de muerte cardiovascular, IAM, ACV: 0,87 (IC 95% 0.76-1.00). Significativo a p 0,05 pero no a 0,01.

– Hospitalizacion por eventos cardiovasculares: RR 0,92 (CI 95% 0.85-0.99). No significativo a p 0.01.

– Telmisartan fue bien tolerado en pacientes que no toleran IECAs. Aunque el medicamento no mostro diferencias significativas en los resultados primariso, los cuales incluyeron fallta cardica, y una modesta reduccion del riesgo de padecer una serie de eventos cardiovascularses mayores compuestos (muerte cardiovascular, IAM, ACV).

– Financiamiento: Boheringer Ingelheim.

Conclusion: para que sirve el telmisartan????

Telmisartan: estudio Trascend

Publicado en Lancet: Estudio Trascend

– 5926 pacientes, 2954 recibieron 80 mgr de Telmisartan, 2972 placebo. Estudio aleatorizado, controlado.

– Analisis por intencion de tratar. Seguimiento entre 51 a 64 meses.

– Disminucion de la TA media: HR 0,92 (IC 95% 0.81-1.05). No significativo.

– Resultados de muerte cardiovascular, IAM, ACV: 0,87 (IC 95% 0.76-1.00). Significativo a p 0,05 pero no a 0,01.

– Hospitalizacion por eventos cardiovasculares: RR 0,92 (CI 95% 0.85-0.99). No significativo a p 0.01.

– Financiamiento: Boheringer Ingelheim.

Conclusion: para que sirve el telmisartan????

Fiebre, paracetamol y riesgo de asma, rinoconjuntivitis y eczema

Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6–7 years: analysis from Phase Three of the ISAAC programme

Prof Richard Beasley DSc a , Tadd Clayton MSc b, Prof Julian CraneMBBS c, Prof Erika von Mutius MD d, Prof Christopher KW Lai DM e, ProfStephen Montefort PhD f and Alistair Stewart BSc g, for the ISAAC Phase Three Study Group
‡Members listed at end of paper

Summary

Background

Exposure to paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma. We studied 6–7-year-old children from Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) programme to investigate the association between paracetamol consumption and asthma.

Methods

As part of Phase Three of ISAAC, parents or guardians of children aged 6–7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis, and eczema, and several risk factors, including the use of paracetamol for fever in the child’s first year of life and the frequency of paracetamol use in the past 12 months. The primary outcome variable was the odds ratio (OR) of asthma symptoms in these children associated with the use of paracetamol for fever in the first year of life, as calculated by logistic regression.

Findings

205 487 children aged 6–7 years from 73 centres in 31 countries were included in the analysis. In the multivariate analyses, use of paracetamol for fever in the first year of life was associated with an increased risk of asthma symptoms when aged 6–7 years (OR 1·46 [95% CI 1·36–1·56]). Current use of paracetamol was associated with a dose-dependent increased risk of asthma symptoms (1·61 [1·46–1·77] and 3·23 [2·91–3·60] for medium and high use vs no use, respectively). Use of paracetamol was similarly associated with the risk of severe asthma symptoms, with population-attributable risks between 22% and 38%. Paracetamol use, both in the first year of life and in children aged 6–7 years, was also associated with an increased risk of symptoms of rhinoconjunctivitis and eczema.

Interpretation

Use of paracetamol in the first year of life and in later childhood, is associated with risk of asthma, rhinoconjunctivitis, and eczema at age 6 to 7 years. We suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood.

Funding

The BUPA Foundation, the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Hawke’s Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the New Zealand Lottery Board, Astra Zeneca New Zealand, and Glaxo Wellcome International Medical Affairs.

Affiliations

a. Medical Research Institute of New Zealand, Wellington, New Zealand
b. Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
c. Department of Medicine, Otago University Wellington, Wellington, New Zealand
d. Dr von Haunersches University Children’s Hospital, Ludwig-Maximilians University Munich, Germany
e. Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, SAR China
f. Department of Medicine, University of Malta, Malta
g. School of Population Health, University of Auckland, Auckland, New Zealand

Correspondence to: Prof Richard Beasley, Medical Research Institute of New Zealand, PO Box 10055, Wellington 6143, New Zealand

Fiebre, paracetamol y riesgo de asma, rinoconjuntivitis y eczema

Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6–7 years: analysis from Phase Three of the ISAAC programme

Summary

Background

Methods

Findings

Interpretation

Funding

Affiliations

Correspondence to: Prof Richard Beasley, Medical Research Institute of New Zealand, PO Box 10055, Wellington 6143, New Zealand

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Safety of drug-eluting stents: demystifying network meta-analysis

Given concerns about the safety of drug-eluting stents, Christoph Stettler and colleagues (Sept 15, p 937) provide the most extensive meta-analysis to date comparing sirolimus-eluting stents, paclitaxel-eluting stents, and bare-metal stents: 38 trials in 18 023 patients.

Asthma guidelines on house dust mites are not evidence-basedIn your Sept 8 Editorial (p 802), you describe the new US guidelines for asthma control as being rigorous and evidence-based. This is not correct for the recommendations on house dust mites.

Lamotrigine and the risk of fulminant hepatic failureI refer to a letter by Debbie Shawcross and colleagues (July 28, p 314), written in response to the SANAD study, in which a case of fatal hepatic failure is attributed to lamotrigine. As the consultant neurologist involved in the care of this patient, I would like to add some relevant information that seems to have been either omitted or neglected: continuous exposure to valproate before the liver failed, and a concomitant acute cytomegalovirus infection.

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Clinical update: treating osteoarthritis

Osteoarthritis is the most common joint disease, and a leading cause of pain and physical disability in older people. It is also associated with a major disease burden in middle-aged people, and represents 4–5% of disability-adjusted life-years in those aged 30–60 years. The burden of disease caused by osteoarthritis is greater for women than for men, and is projected to increase as the population ages. Joint damage in osteoarthritis is caused by several predisposing systemic factors (including genetics), and local mechanical factors (including joint injury and load) that determine its distribution and severity. The knee, hand, and hip are most often affected. Joint damage might be associated with use-related joint pain and restricted movement. Diagnostic criteria are ambiguous and disease assessment is difficult: for example, pain and radiographical severity of joint damage are only weakly associated. Socioeconomic and psychosocial factors have an important role in establishing disease burden for the individual with osteoarthritis, as in many other musculoskeletal diseases.

The Lancet. Vol. 370. Núm. 76329

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Korenkov M; Sauerland S. Clinical update: bariatric surgery. Págs. 1988-1990 TC (s) PDF (s)

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Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: a pooled analysis of 26 epidemiological studies

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Vaccine production, distribution, access, and uptake

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