12,063,407 research outputs found

    Contraceptive confidence and timing of first birth in Moldova: an event history analysis of retrospective data

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    Objectives: To test the contraceptive confidence hypothesis in a modern context. The hypothesis is that women using effective or modern contraceptive methods have increased contraceptive confidence and hence a shorter interval between marriage and first birth than users of ineffective or traditional methods. We extend the hypothesis to incorporate the role of abortion, arguing that it acts as a substitute for contraception in the study context.Setting: Moldova, a country in South-East Europe. Moldova exhibits high use of traditional contraceptive methods and abortion compared with other European countries.Participants: Data are from a secondary analysis of the 2005 Moldovan Demographic and Health Survey, a nationally representative sample survey. 5377 unmarried women were selected.Primary and secondary outcome measures: The outcome measure was the interval between marriage and first birth. This was modelled using a piecewise-constant hazard regression, with abortion and contraceptive method types as primary variables along with relevant sociodemographic controls.Results: Women with high contraceptive confidence (modern method users) have a higher cumulative hazard of first birth 36?months following marriage (0.88 (0.87 to 0.89)) compared with women with low contraceptive confidence (traditional method users, cumulative hazard: 0.85 (0.84 to 0.85)). This is consistent with the contraceptive confidence hypothesis. There is a higher cumulative hazard of first birth among women with low (0.80 (0.79 to 0.80)) and moderate abortion propensities (0.76 (0.75 to 0.77)) than women with no abortion propensity (0.73 (0.72 to 0.74)) 24?months after marriage.Conclusions: Effective contraceptive use tends to increase contraceptive confidence and is associated with a shorter interval between marriage and first birth. Increased use of abortion also tends to increase contraceptive confidence and shorten birth duration, although this effect is non-linear—women with a very high use of abortion tend to have lengthy intervals between marriage and first birth

    Identifying acne treatment uncertainties via a James Lind Alliance Priority Setting Partnership

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    Objectives: The Acne Priority Setting Partnership (PSP) was set up to identify and rank treatment uncertainties by bringing together people with acne, and professionals providing care within and beyond the National Health Service (NHS). Setting: The UK with international participation. Participants: Teenagers and adults with acne, parents, partners, nurses, clinicians, pharmacists, private practitioners. Methods: Treatment uncertainties were collected via separate online harvesting surveys, embedded within the PSP website, for patients and professionals. A wide variety of approaches were used to promote the surveys to stakeholder groups with a particular emphasis on teenagers and young adults. Survey submissions were collated using keywords and verified as uncertainties by appraising existing evidence. The 30 most popular themes were ranked via weighted scores from an online vote. At a priority setting workshop, patients and professionals discussed the 18 highest-scoring questions from the vote, and reached consensus on the top 10. Results: In the harvesting survey, 2310 people, including 652 professionals and 1456 patients (58% aged 24 y or younger), made submissions containing at least one research question. After checking for relevance and rephrasing, a total of 6255 questions were collated into themes. Valid votes ranking the 30 most common themes were obtained from 2807 participants. The top 10 uncertainties prioritised at the workshop were largely focused on management strategies, optimum use of common prescription medications and the role of nondrug based interventions. More female than male patients took part in the harvesting surveys and vote. A wider range of uncertainties were provided by patients compared to professionals. Conclusions: Engaging teenagers and young adults in priority setting is achievable using a variety of promotional methods. The top 10 uncertainties reveal an extensive knowledge gap about widely used interventions and the relative merits of drug versus non-drug based treatments in acne management

    Caspase-8 controls the gut response to microbial challenges by Tnf-alpha-dependent and independent pathways

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    Objectives: Intestinal epithelial cells (IEC) express toll-like receptors (TLR) that facilitate microbial recognition. Stimulation of TLR ligands induces a transient increase in epithelial cell shedding, a mechanism that serves the antibacterial and antiviral host defence of the epithelium and promotes elimination of intracellular pathogens. Although activation of the extrinsic apoptosis pathway has been described during inflammatory shedding, its functional involvement is currently unclear. Design: We investigated the functional involvement of caspase-8 signalling in microbial-induced intestinal cell shedding by injecting Lipopolysaccharide (LPS) to mimic bacterial pathogens and poly(I:C) as a probe for RNA viruses in vivo. Results: TLR stimulation of IEC was associated with a rapid activation of caspase-8 and increased epithelial cell shedding. In mice with an epithelial cell-specific deletion of caspase-8 TLR stimulation caused Rip3-dependent epithelial necroptosis instead of apoptosis. Mortality and tissue damage were more severe in mice in which IECs died by necroptosis than apoptosis. Inhibition of receptor-interacting protein (Rip) kinases rescued the epithelium from TLR-induced gut damage. TLR3-induced necroptosis was directly mediated via TRIF-dependent pathways, independent of Tnf-α and type III interferons, whereas TLR4-induced tissue damage was critically dependent on Tnf-α. Conclusions: Together, our data demonstrate an essential role for caspase-8 in maintaining the gut barrier in response to mucosal pathogens by permitting inflammatory shedding and preventing necroptosis of infected cells. These data suggest that therapeutic strategies targeting the cell death machinery represent a promising new option for the treatment of inflammatory and infective enteropathies

    A systematic review of ICD complications in randomised controlled trials versus registries: is our 'real-world' data an underestimation?

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    Implantable cardioverter defibrillator (ICD) implantation carries a significant risk of complications, however published estimates appear inconsistent. We aimed to present a contemporary systematic review using meta-analysis methods of ICD complications in randomised controlled trials (RCTs) and compare it to recent data from the largest international ICD registry, the US National Cardiovascular Data Registry (NCDR). PubMed was searched for any RCTs involving ICD implantation published 1999-2013; 18 were identified for analysis including 6433 patients, mean follow-up 3 months-5.6 years. Exclusion criteria were studies of children, hypertrophic cardiomyopathy, congenital heart disease, resynchronisation therapy and generator changes. Total pooled complication rate from the RCTs (excluding inappropriate shocks) was 9.1%, including displacement 3.1%, pneumothorax 1.1% and haematoma 1.2%. Infection rate was 1.5%.There were no predictors of complications but longer follow-up showed a trend to higher complication rates (p=0.07). In contrast, data from the NCDR ICD, reporting on 356 515 implants (2006-2010) showed a statistically significant threefold lower total major complication rate of 3.08% with lead displacement 1.02%, haematoma 0.86% and pneumothorax 0.44%. The overall ICD complication rate in our meta-analysis is 9.1% over 16 months. The ICD complication reported in the NCDR ICD registry is significantly lower despite a similar population. This may reflect under-reporting of complications in registries. Reporting of ICD complications in RCTs and registries is very variable and there is a need to standardise classification of complications internationally

    Emergency supply of prescription-only medicines to patients by community pharmacists: a mixed methods evaluation incorporating patient, pharmacist and GP perspectives

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    Objective To evaluate and inform emergency supply of prescription-only medicines by community pharmacists (CPs), including how the service could form an integral component of established healthcare provision to maximise adherence. Design Mixed methods. 4 phases: prospective audit of emergency supply requests for prescribed medicines (October–November 2012 and April 2013); interviews with CPs (February–April 2013); follow-up interviews with patients (April–May 2013); interactive feedback sessions with general practice teams (October–November 2013). Setting 22 community pharmacies and 6 general practices in Northwest England. Participants 27 CPs with experience of dealing with requests for emergency supplies; 25 patients who received an emergency supply of a prescribed medicine; 58 staff at 6 general practices. Results Clinical audit in 22 pharmacies over two 4-week periods reported that 526 medicines were requested by 450 patients. Requests peaked over a bank holiday and around weekends. A significant number of supplies were made during practice opening hours. Most requests were for older patients and for medicines used in long-term conditions. Difficulty in renewing repeat medication (forgetting to order, or prescription delays) was the major reason for requests. The majority of medicines were ‘loaned’ in advance of a National Health Service (NHS) prescription. Interviews with CPs and patients indicated that continuous supply had a positive impact on medicines adherence, removing the need to access urgent care. General practice staff were surprised and concerned by the extent of emergency supply episodes. Conclusions CPs regularly provide emergency supplies to patients who run out of their repeat medication, including during practice opening hours. This may aid adherence. There is currently no feedback loop, however, to general practice. Patient care and interprofessional communication may be better served by the introduction of a formally structured and funded NHS emergency supply service from community pharmacies, with ongoing optimisation of repeat prescribing

    PPAR gamma/mTOR signalling: striking the right balance in cartilage homeostasis

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    This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0http://dx.doi.org/10.1136/annrheumdis-2014-20574

    Common visual problems in children with disability

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    Children with disability are at a substantially higher risk of visual impairment (VI) (10.5% compared with 0.16%) but also of ocular disorders of all types, including refractive errors and strabismus. The aetiology of VI in children with disability reflects that of the general population and includes cerebral VI, optic atrophy, as well as primary visual disorders such as retinal dystrophies and structural eye anomalies. VI and other potentially correctable ocular disorders may not be recognised without careful assessment and are frequently unidentified in children with complex needs. Although assessment may be more challenging than in other children, identifying these potential additional barriers to learning and development may be critical. There is a need to develop clearer guidelines, referral pathways and closer working between all professionals involved in the care of children with disability and visual disorders to improve our focus on the assessment of vision and outcomes for children with disability

    Longitudinal impact of demographic and clinical variables on Health-Related Quality of Life in Cystic Fibrosis

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    Objectives: The insights that people with cystic fibrosis have concerning their health are important given that aspects of health-related quality of life (HRQoL) are independent predictors of survival and a decrease in lung function is associated with a decrease in HRQoL over time. Cross-sectional data suggest that key variables, other than lung function, are also associated with HRQoL - although study results are equivocal. This work evaluates the relationship between these key demographic and clinical variables and HRQoL longitudinally. Design: Longitudinal observational study. Observations were obtained at seven time points: approximately every two years over a twelve year period. Setting: Large Adult Cystic Fibrosis Centre in the UK. Participants: 234 participants aged 14-48 years at recruitment. Outcome measure: Nine domains of HRQoL (Cystic Fibrosis Quality of Life Questionnaire) in relation to demographic (age, gender) and clinical measures (FEV1% predicted, BMI, cystic fibrosis related diabetes, B. cepacia complex, totally implantable vascular access device, nutritional and transplant status). Results: A total of 770 patient assessments were obtained for 234 patients. The results of random coefficients modelling indicated that demographic and clinical variables were identified as being significant for HRQoL over time. In addition to lung function, transplant status, age, having a totally implantable vascular access device, cystic fibrosis related diabetes, BMI and B. cepacia complex impacted on many HRQoL domains longitudinally. Gender was important for the domain of Body image. Conclusion: Demographic and changes in clinical variables were independently associated with a change in health-related quality of life over time. Compared with these longitudinal data, cross-sectional data are inadequate when evaluating the relationships between HRQoL domains and key demographic and clinical variables, as they fail to recognise the full impact of the CF disease trajectory and its treatments on quality of life

    Monetary costs of agitation in older adults with Alzheimer's disease in the UK: prospective cohort study

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    While nearly half of all people with Alzheimer's disease (AD) have agitation symptoms every month, little is known about the costs of agitation in AD. We calculated the monetary costs associated with agitation in older adults with AD in the UK from a National Health Service and personal social services perspective
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