Promoting chlamydia screening with posters and leaflets in general practice - a qualitative study

<p>Abstract</p> <p>Background</p> <p>General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP), have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening.</p> <p>Methods</p> <p>Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach.</p> <p>Results</p> <p>Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets.</p> <p>Conclusion</p> <p>The NCSP should consider developing a range of more discrete but eye catching posters and small leaflets specifically to promote chlamydia screening in different scenarios within general practice; coordinators should audit their use. Practice staff need to discuss, with their screening co-ordinator, how different practice staff can promote chlamydia screening most effectively using the NCSP promotional materials, and change them regularly so that they do not loose their impact. Education to change all practice staff's attitudes towards sexual health is needed to reduce their worries about displaying the chlamydia materials, and how they may follow up the advertising up with a verbal offer of screening opportunistically to 15-24 year olds whenever they visit the practice.</p

Recovery of forearm and fine digit function after chronic spinal cord injury by simultaneous blockade of inhibitory matrix CSPG production and the receptor PTPσ

Spinal cord injuries (SCI), for which there are limited effective treatments, result in enduring paralysis and hypoesthesia, in part because of the inhibitory microenvironment that develops and limits regeneration/sprouting, especially during chronic stages. Recently, we discovered that targeted enzymatic removal of the inhibitory chondroitin sulfate proteoglycan (CSPG) component of the extracellular and perineuronal net (PNN) matrix via Chondroitinase ABC (ChABC) rapidly restored robust respiratory function to the previously paralyzed hemi-diaphragm after remarkably long times post-injury (up to 1.5 years) following a cervical level 2 lateral hemi-transection. Importantly, ChABC treatment at cervical level 4 in this chronic model also elicited improvements in gross upper arm function. In the present study, we focused on arm and hand function, seeking to highlight and optimize crude as well as fine motor control of the forearm and digits at lengthy chronic stages post-injury. However, instead of using ChABC, we utilized a novel and more clinically relevant systemic combinatorial treatment strategy designed to simultaneously reduce and overcome inhibitory CSPGs. Following a 3-month upper cervical spinal hemi-lesion using adult female Sprague Dawley rats, we show that the combined treatment had a profound effect on functional recovery of the chronically paralyzed forelimb and paw, as well as on precision movements of the digits. The regenerative and immune system related events that we describe deepen our basic understanding of the crucial role of CSPG-mediated inhibition via the PTPσ receptor in constraining functional synaptic plasticity at lengthy time points following SCI, hopefully leading to clinically relevant translational benefits

Same-Day Tools, Including Xpert Ultra and IRISA-TB, for Rapid Diagnosis of Pleural Tuberculosis: a Prospective Observational Study.

The diagnosis of pleural tuberculosis (TB) is problematic. The comparative performance of newer same-day tools for pleural TB, including Xpert MTB/RIF Ultra (ULTRA), has hitherto not been comprehensively studied. Adenosine deaminase (ADA), IRISA-TB (interferon gamma ultrasensitive rapid immunosuspension assay), Xpert MTB/RIF, and ULTRA performance outcomes were evaluated in pleural fluid samples from 149 patients with suspected pleural TB. The reference standard was culture positivity (fluid, biopsy specimen, or sputum) and/or pleural biopsy histopathology (termed definite TB). Those designated as having non-TB were negative by microbiological testing and were not initiated on anti-TB treatment. To determine the effect of sample concentration, 65 samples underwent pelleting by centrifugation, followed by conventional Xpert MTB/RIF and ULTRA. Of the 149 patients, 49 had definite TB, 16 had probable TB (not definite but treated for TB), and 84 had non-TB. ULTRA sensitivity and specificity (95% confidence intervals [CI]) were similar to those of Xpert MTB/RIF [sensitivity, 37.5% (25.3 to 51.2) versus 28.6% (15.9 to 41.2), respectively; specificity, 98.8% (96.5 to 100) versus 98.8% (96.5 to 100), respectively]. Centrifugation did not significantly improve ULTRA sensitivity (29.5% versus 31.3%, respectively). Adenosine deaminase and IRISA-TB sensitivity were 84.4% (73.9 to 95.0) and 89.8% (81.3 to 98.3), respectively. However, IRISA-TB demonstrated significantly better specificity (96.4% versus 87.5% [P = 0.034]), positive predictive value (93.6% versus 80.9 [P = 0.028]), and positive likelihood ratio (25.1 versus 6.8 [P = 0.032]) than ADA. In summary, Xpert ULTRA has poor sensitivity for the diagnosis of pleural TB. Alternative assays (ADA and IRISA-TB) are significantly more sensitive, with IRISA-TB demonstrating a higher specificity and rule-in value than ADA in this high-TB-burden setting where HIV is endemic

TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis

BACKGROUND: Tuberculosis (TB) affects one third of the global population, and TB of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumour necrosis factor (TNF) plays a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) which involves the activation of innate immune cells and structure maintenance of granulomas. However, the contribution of TNF, in particular neuron-derived TNF, in the control of cerebral M. tuberculosis infection and its protective immune responses in the CNS were not clear. METHODS: We generated neuron-specific TNF-deficient (NsTNF / ) mice and compared outcomes of disease against TNF f/f control and global TNF / mice. Mycobacterial burden in brains, lungs and spleens were compared, and cerebral pathology and cellular contributions analysed by microscopy and flow cytometry after M. tuberculosis infection. Activation of innate immune cells was measured by flow cytometry and cell function assessed by cytokine and chemokine quantification using enzyme-linked immunosorbent assay (ELISA). RESULTS: Intracerebral M. tuberculosis infection of TNF / mice rendered animals highly susceptible, accompanied by uncontrolled bacilli replication and eventual mortality. In contrast, NsTNF / mice were resistant to infection and presented with a phenotype similar to that in TNF f/f control mice. Impaired immunity in TNF / mice was associated with altered cytokine and chemokine synthesis in the brain and characterised by a reduced number of activated innate immune cells. Brain pathology reflected enhanced inflammation dominated by neutrophil influx. CONCLUSION: Our data show that neuron-derived TNF has a limited role in immune responses, but overall TNF production is necessary for protective immunity against CNS-TB

Reactivation of M. tuberculosis Infection in Trans-Membrane Tumour Necrosis Factor Mice

Of those individuals who are infected with M. tuberculosis, 90% do not develop active disease and represents a large reservoir of M. tuberculosis with the potential for reactivation of infection. Sustained TNF expression is required for containment of persistent infection and TNF neutralization leads to tuberculosis reactivation. In this study, we investigated the contribution of soluble TNF (solTNF) and transmembrane TNF (Tm-TNF) in immune responses generated against reactivating tuberculosis. In a chemotherapy induced tuberculosis reactivation model, mice were challenged by aerosol inhalation infection with low dose M. tuberculosis for three weeks to establish infection followed chemotherapeutic treatment for six weeks, after which therapy was terminated and tuberculosis reactivation investigated. We demonstrate that complete absence of TNF results in host susceptibility to M. tuberculosis reactivation in the presence of established mycobacteria-specific adaptive immunity with mice displaying unrestricted bacilli growth and diffused granuloma structures compared to WT control mice. Interestingly, bacterial re-emergence is contained in Tm-TNF mice during the initial phases of tuberculosis reactivation, indicating that Tm-TNF sustains immune pressure as in WT mice. However, Tm-TNF mice show susceptibility to long term M. tuberculosis reactivation associated with uncontrolled influx of leukocytes in the lungs and reduced IL-12p70, IFNγ and IL-10, enlarged granuloma structures, and failure to contain mycobacterial replication relative to WT mice. In conclusion, we demonstrate that both solTNF and Tm-TNF are required for maintaining immune pressure to contain reactivating M. tuberculosis bacilli even after mycobacteria-specific immunity has been established

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells.

Breast cancer remains one of the leading causes of cancer-associated death worldwide. Conventional treatment is associated with substantial toxicity and suboptimal efficacy. We, therefore, developed and evaluated the in vitro efficacy of an autologous dendritic cell (DC) vaccine to treat breast cancer. We recruited 12 female patients with stage 1, 2, or 3 breast cancer and matured their DCs with autologous tumour-specific lysate, a toll-like receptor (TLR)-3 and 7/8 agonist, and an interferon-containing cocktail. The efficacy of the vaccine was evaluated by its ability to elicit a cytotoxic T-lymphocyte response to autologous breast cancer cells in vitro. Matured DCs (≥ 60% upregulation of CD80, CD86, CD83, and CCR7) produced high levels of the Th1 effector cytokine, IL12-p70 (1.2 ng/ml; p < 0.0001), compared to DCs pulsed with tumour lysate, or matured with an interferon-containing cocktail alone. We further showed that matured DCs enhance antigen-specific CD8 + T-cell responses to HER-2 (4.5%; p < 0.005) and MUC-1 (19%; p < 0.05) tetramers. The mature DCs could elicit a robust and dose-dependent antigen-specific cytotoxic T-lymphocyte response (65%) which was tumoricidal to autologous breast cancer cells in vitro compared to T-lymphocytes that were primed with autologous lysate loaded-DCs (p < 0.005). Lastly, we showed that the mature DCs post-cryopreservation maintained high viability, maintained their mature phenotype, and remained free of endotoxins or mycoplasma. We have developed a DC vaccine that is cytotoxic to autologous breast cancer cells in vitro. The tools and technology generated here will now be applied to a phase I/IIa clinical trial

Community prevalence of SARS-CoV-2 in England from April to November, 2020: results from the ONS Coronavirus Infection Survey

Background: Decisions about the continued need for control measures to contain the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rely on accurate and up-to-date information about the number of people testing positive for SARS-CoV-2 and risk factors for testing positive. Existing surveillance systems are generally not based on population samples and are not longitudinal in design. Methods: Samples were collected from individuals aged 2 years and older living in private households in England that were randomly selected from address lists and previous Office for National Statistics surveys in repeated crosssectional household surveys with additional serial sampling and longitudinal follow-up. Participants completed a questionnaire and did nose and throat self-swabs. The percentage of individuals testing positive for SARS-CoV-2 RNA was estimated over time by use of dynamic multilevel regression and poststratification, to account for potential residual non-representativeness. Potential changes in risk factors for testing positive over time were also assessed. The study is registered with the ISRCTN Registry, ISRCTN21086382. Findings: Between April 26 and Nov 1, 2020, results were available from 1 191 170 samples from 280327 individuals; 5231 samples were positive overall, from 3923 individuals. The percentage of people testing positive for SARS-CoV-2 changed substantially over time, with an initial decrease between April 26 and June 28, 2020, from 0·40% (95% credible interval 0·29–0·54) to 0·06% (0·04–0·07), followed by low levels during July and August, 2020, before substantial increases at the end of August, 2020, with percentages testing positive above 1% from the end of October, 2020. Having a patient facing role and working outside your home were important risk factors for testing positive for SARS-CoV-2 at the end of the first wave (April 26 to June 28, 2020), but not in the second wave (from the end of August to Nov 1, 2020). Age (young adults, particularly those aged 17–24 years) was an important initial driver of increased positivity rates in the second wave. For example, the estimated percentage of individuals testing positive was more than six times higher in those aged 17–24 years than in those aged 70 years or older at the end of September, 2020. A substantial proportion of infections were in individuals not reporting symptoms around their positive test (45–68%, dependent on calendar time. Interpretation: Important risk factors for testing positive for SARS-CoV-2 varied substantially between the part of the first wave that was captured by the study (April to June, 2020) and the first part of the second wave of increased positivity rates (end of August to Nov 1, 2020), and a substantial proportion of infections were in individuals not reporting symptoms, indicating that continued monitoring for SARS-CoV-2 in the community will be important for managing the COVID-19 pandemic moving forwards