Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase II clinical trials.

Rifapentine is a highly active antituberculosis antibiotic with treatment-shortening potential; however, exposure-response relations and the dose needed for maximal bactericidal activity have not been established. We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine (n = 405) with rifampin (n = 252) as part of intensive-phase therapy. Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed-effects modeling. Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy. Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus, black, male, or fasting when taking drug. Rifapentine exposure, large lung cavity size, and geographic region were independently associated with time to culture conversion in liquid media. Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily. Patients with large lung cavities appear less responsive to treatment, even at high rifapentine doses

Bias of Selection on Human Copy-Number Variants

Although large-scale copy-number variation is an important contributor to conspecific genomic diversity, whether these variants frequently contribute to human phenotype differences remains unknown. If they have few functional consequences, then copy-number variants (CNVs) might be expected both to be distributed uniformly throughout the human genome and to encode genes that are characteristic of the genome as a whole. We find that human CNVs are significantly overrepresented close to telomeres and centromeres and in simple tandem repeat sequences. Additionally, human CNVs were observed to be unusually enriched in those protein-coding genes that have experienced significantly elevated synonymous and nonsynonymous nucleotide substitution rates, estimated between single human and mouse orthologues. CNV genes encode disproportionately large numbers of secreted, olfactory, and immunity proteins, although they contain fewer than expected genes associated with Mendelian disease. Despite mouse CNVs also exhibiting a significant elevation in synonymous substitution rates, in most other respects they do not differ significantly from the genomic background. Nevertheless, they encode proteins that are depleted in olfactory function, and they exhibit significantly decreased amino acid sequence divergence. Natural selection appears to have acted discriminately among human CNV genes. The significant overabundance, within human CNVs, of genes associated with olfaction, immunity, protein secretion, and elevated coding sequence divergence, indicates that a subset may have been retained in the human population due to the adaptive benefit of increased gene dosage. By contrast, the functional characteristics of mouse CNVs either suggest that advantageous gene copies have been depleted during recent selective breeding of laboratory mouse strains or suggest that they were preferentially fixed as a consequence of the larger effective population size of wild mice. It thus appears that CNV differences among mouse strains do not provide an appropriate model for large-scale sequence variations in the human population

Effectiveness of structured patient-clinician communication with a solution focused approach (DIALOG+) in community treatment of patients with psychosis - a cluster randomised controlled trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Oral health indices predict individualised recall interval

Objectives: The individualised recall interval (IRI) is part of the oral health examination. This observational, register-based study aimed to explore how oral health indices DMFT (decayed, missing, filled teeth), DT (decayed teeth), CPI (Community Periodontal Index, maximum value of individual was used) and number of teeth are associated with IRI for adults. Methods: Oral health examination includes an assessment of all oral tissues, diagnosis, a treatment plan and assessment and a determination of the interval before the next assessment. It is called the IRI. This cross-sectional study population included 42,533 adults (age range 18-89 years), who had visited for an oral health examination during 2009, provided by the Helsinki City Social Services and Health Care. The recall interval was categorised into an ordinal scale (0-12, 13-24, 25-36 and 37-60 months) and was modelled using a proportional odds model. ORs less than one indicated a shorter recall interval. Results: Recall interval categories in the study population were 0-12 months (n = 4,569; 11%), 13-24 months (n = 23,732; 56%), 25-36 months (n = 12,049; 28%), and 37-60 months (n = 2,183; 5%). The results of statistical models clearly showed an association between the length of recall intervals and oral health indices. In all models, higher values of DMFT, DT and CPI indicated a shorter recall interval. The number of teeth were not so relevant. The association was not influenced when different combinations of other predictors (age, gender, socioeconomic status, chronic diseases) were included in the model. The severity of periodontitis predicted a short recall interval, for example, in the Model 1, CPI maximum value 4 was OR = 0.35 (95% confidence interval 0.31-0.40). Conclusions: The oral health indices showed a clear association with the length of the IRI. Poor oral health reduced IRI. The indices provide information about the amount of oral health prevention required and are useful to health organisations.Peer reviewe

Healthy families: the present and future role of the supermarket

In this report, we contend that the grocery industry must be accountable for their role in an obesogenic environment. The social context most likely to support making healthy behaviour changes is the family. For families, supermarkets represent more than merely places in which to spend their money. They establish the values that underpin the ways in which people conduct their lives

Diffusion of e-health innovations in 'post-conflict' settings: a qualitative study on the personal experiences of health workers.

BACKGROUND: Technological innovations have the potential to strengthen human resources for health and improve access and quality of care in challenging 'post-conflict' contexts. However, analyses on the adoption of technology for health (that is, 'e-health') and whether and how e-health can strengthen a health workforce in these settings have been limited so far. This study explores the personal experiences of health workers using e-health innovations in selected post-conflict situations. METHODS: This study had a cross-sectional qualitative design. Telephone interviews were conducted with 12 health workers, from a variety of cadres and stages in their careers, from four post-conflict settings (Liberia, West Bank and Gaza, Sierra Leone and Somaliland) in 2012. Everett Roger's diffusion of innovation-decision model (that is, knowledge, persuasion, decision, implementation, contemplation) guided the thematic analysis. RESULTS: All health workers interviewed held positive perceptions of e-health, related to their beliefs that e-health can help them to access information and communicate with other health workers. However, understanding of the scope of e-health was generally limited, and often based on innovations that health workers have been introduced through by their international partners. Health workers reported a range of engagement with e-health innovations, mostly for communication (for example, email) and educational purposes (for example, online learning platforms). Poor, unreliable and unaffordable Internet was a commonly mentioned barrier to e-health use. Scaling-up existing e-health partnerships and innovations were suggested starting points to increase e-health innovation dissemination. CONCLUSIONS: Results from this study showed ICT based e-health innovations can relieve information and communication needs of health workers in post-conflict settings. However, more efforts and investments, preferably driven by healthcare workers within the post-conflict context, are needed to make e-health more widespread and sustainable. Increased awareness is necessary among health professionals, even among current e-health users, and physical and financial access barriers need to be addressed. Future e-health initiatives are likely to increase their impact if based on perceived health information needs of intended users

A critical review of the formation of mono- and dicarboxylated metabolic intermediates of alkylphenol polyethoxylates during wastewater treatment and their environmental significance

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.Alkylphenoxyacetic acids, the metabolic biodegradation products of alkylphenol ethoxylates, are commonly found in wastewaters and sewage effluents. These persistent hydrophilic derivatives possess intrinsic estrogenic activity, which can mimic natural hormones. Their concentrations increase through the sewage treatment works as a result of biodegradation and biotransformation, and when discharged can disrupt endocrine function in fish. These acidic metabolites represent the dominant alkylphenolic compounds found in wastewater effluent and their presence is cause for concern as, potentially, through further biotransformation and biodegradation, they can act as sources of nonylphenol, which is toxic and estrogenic. The authors aim to assess the mechanisms of formation as well as elimination of alkylphenoxyacetic acids within conventional sewage treatment works with the emphasis on the activated sludge process. In addition, they evaluate the various factors influencing their degradation and formation in laboratory scale and full-scale systems. The environmental implications of these compounds are considered, as is the need for tertiary treatment processes for their removal

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation

Insulin detemir in a twice daily insulin regimen versus a three times daily insulin regimen in the treatment of type 1 diabetes in children: A pilot randomized controlled trial

Article deposited according to agreement with BMC, December 6, 2010.YesFunding provided by the Open Access Authors Fund

Informing the design of a national screening and treatment programme for chronic viral hepatitis in primary care: qualitative study of at-risk immigrant communities and healthcare professionals

n Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThis paper presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-1209-10038).