scholarly journals An inducible transposon mutagenesis approach for the intracellular human pathogen Chlamydia trachomatis

2021 ◽  
Vol 6 ◽  
pp. 312
Author(s):  
Colette E. O'Neill ◽  
Rachel J. Skilton ◽  
Jade Forster ◽  
David W. Cleary ◽  
Sarah A. Pearson ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Gene Function ◽  
Transposon Mutagenesis ◽  
Saturation Mutagenesis ◽  
Significant Advance ◽  
Human Pathogen ◽  
Long Term Conditions ◽  
Transposase Gene ◽  
Inducible Transposon

Background: Chlamydia trachomatis is a prolific human pathogen that can cause serious long-term conditions if left untreated. Recent developments in Chlamydia genetics have opened the door to conducting targeted and random mutagenesis experiments to identify gene function. In the present study, an inducible transposon mutagenesis approach was developed for C. trachomatis using a self-replicating vector to deliver the transposon-transposase cassette - a significant step towards our ultimate aim of achieving saturation mutagenesis of the Chlamydia genome. Methods: The low transformation efficiency of C. trachomatis necessitated the design of a self-replicating vector carrying the transposon mutagenesis cassette (i.e. the Himar-1 transposon containing the beta lactamase gene as well as a hyperactive transposase gene under inducible control of the tet promoter system with the addition of a riboswitch). Chlamydia transformed with this vector (pSW2-RiboA-C9Q) were induced at 24 hours post-infection. Through dual control of transcription and translation, basal expression of transposase was tightly regulated to stabilise the plasmid prior to transposition. Results: Here we present the preliminary sequencing results of transposon mutant pools of both C. trachomatis biovars, using two plasmid-free representatives: urogenital strain  C. trachomatis SWFP- and the lymphogranuloma venereum isolate L2(25667R). DNA sequencing libraries were generated and analysed using Oxford Nanopore Technologies’ MinION technology. This enabled ‘proof of concept’ for the methods as an initial low-throughput screen of mutant libraries; the next step is to employ high throughput sequencing to assess saturation mutagenesis. Conclusions: This significant advance provides an efficient method for assaying C. trachomatis gene function and will enable the identification of the essential gene set of C. trachomatis. In the long-term, the methods described herein will add to the growing knowledge of chlamydial infection biology leading to the discovery of novel drug or vaccine targets.

The use of a bespoke website developed for people with dementia and carers: Users’ experiences, perceptions and support needs

Dementia ◽  
2021 ◽  
pp. 147130122110284
Author(s):  
Emma Wolverson ◽  
Caroline White ◽  
Rosie Dunn ◽  
Katie Cunnah ◽  
David Howe ◽  
...  
Keyword(s):  
Personal Information ◽  
Information Source ◽  
Website Design ◽  
Long Term Conditions ◽  
People With Dementia ◽  
Barriers To Use ◽  
Credible Information ◽  
Training And Support ◽  
Design And Methods

Background: Current policy emphasises the role of digital technologies in facilitating the management of long-term conditions. While digital resources have been developed for carers, there has been little attention to their development for people with dementia. The Caregiverspro-MMD website was developed as a joint resource for people with dementia and carers, delivering access to information, informal content, games and peer support. Research Design and Methods: This study explored the experiences of dyads consisting of people with dementia and carers of using the website. Interviews and focus groups were conducted with 43 participants. Findings: Thematic analysis identified 10 subthemes grouped under three superordinate themes which highlight participants’ experiences of and responses to the website functions; important aspects of the website design and delivery; and barriers to use. Discussion: Findings highlight the value of a credible information source which negated the need for arduous online searches, the pleasure associated with playing games and interacting with others online. However, participants were reluctant to share personal information online, preferring to create ‘informal content’ which celebrated everyday life, and were reluctant to ‘friend’ people online who they had not met in person. The importance of training and support to use the website was highlighted. Health problems, lack of interest or difficulties using technology, and time were all identified as barriers to use.

scholarly journals Are the needs of people with multiple long-term conditions being met? Evidence from the 2018 General Practice Patient Survey

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e041569
Author(s):  
Lucina Rolewicz ◽  
Eilís Keeble ◽  
Charlotte Paddison ◽  
Sarah Scobie
Keyword(s):  
General Practice ◽  
Unmet Need ◽  
Patient Survey ◽  
Secondary Outcome ◽  
Community Based ◽  
Long Term Conditions ◽  
Local Services ◽  
Community Based Services ◽  
Practice Patient

ObjectivesTo investigate individual, practice and area level variation in patient-reported unmet need among those with long-term conditions, in the context of general practice (GP) appointments and support from community-based services in England.DesignCross-sectional study using data from 199 150 survey responses.SettingPrimary care and community-based services.ParticipantsRespondents to the 2018 English General Practice Patient Survey with at least one long-term condition.Primary and secondary outcome measuresThe primary outcomes were the levels of unmet need in GP and local services among patients with multiple long-term conditions. Secondary outcomes were the proportion of variation explained by practice and area-level factors.ResultsThere was no relationship between needs being fully met in patients’ last practice appointment and number of long-term conditions once sociodemographic characteristics and health status were taken into account (5+conditions−OR=1.04, 95% CI 0.99 to 1.09), but there was a relationship for having enough support from local services to manage conditions (5+conditions−OR=0.84, 95% CI 0.80 to 0.88). Patients with multimorbidity that were younger, non-white or frail were less likely to have their needs fully met, both in GP and from local services. Differences between practices and local authorities explained minimal variation in unmet need.ConclusionsLevels of unmet need are high, particularly for support from community services to manage multiple conditions. Patients who could be targeted for support include people who feel socially isolated, and those who have difficulties with their day-to-day living. Younger patients and certain ethnic groups with multimorbidity are also more likely to have unmet needs. Increased personalisation and coordination of care among these groups may help in addressing their needs.

scholarly journals Long-term condition management for prisoners: improving the processes between community and prison

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
NMJ Wright ◽  
F Hankins ◽  
P Hearty
Keyword(s):  
Qualitative Interviews ◽  
Electronic Record ◽  
Medicines Management ◽  
Long Term Conditions ◽  
Police Custody ◽  
Barriers To Screening ◽  
High Prevalence ◽  
Facilitators And Barriers ◽  
Ongoing Monitoring

Abstract Background Prisoner populations have a disproportionately high prevalence of risk factors for long-term conditions (LTCs), and movement between community and prisons is a period of potential disruption in the ongoing monitoring and management of LTCs. Method Nineteen qualitative interviews with staff, recruited by purposive sampling for professional background, were conducted to explore facilitators and barriers to screening, monitoring and medicines management for LTCs. Results There is variability in prisoner behaviours regarding bringing community GP-prescribed medication to prison following arrest and detention in police custody, which affects service ability regarding seamless continuation of community prescribing actions. Systems for actively inputting clinical data into existing, nationally agreed, electronic record templates for QOF monitoring are under-developed in prisons and such activity is dependent upon individual “enthusiast(s)”. Conclusion There is a pressing need to embed standardised QOF monitoring systems within an integrated community/prison commissioning framework, supported by connectivity between prison and community primary care records, including all activity related to QOF compliance.

scholarly journals M.I.C.E—Mental Health Intervention for Children with Epilepsy: a randomised controlled, multi-centre clinical trial evaluating the clinical and cost-effectiveness of MATCH-ADTC in addition to usual care compared to usual care alone for children and young people with common mental health disorders and epilepsy—study protocol

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sophie D. Bennett ◽  
◽  
J. Helen Cross ◽  
Anna E. Coughtrey ◽  
Isobel Heyman ◽  
...  
Keyword(s):  
Mental Health ◽  
Young People ◽  
Usual Care ◽  
Psychological Intervention ◽  
Mental Health Disorders ◽  
Long Term Conditions ◽  
Children And Young People ◽  
Health Disorders ◽  
Randomised Controlled

Abstract Background Mental health disorders in the context of long-term conditions in children and young people are currently overlooked and undertreated. Evidence-based psychological treatments for common childhood mental health disorders (anxiety, depression and disruptive behaviour disorders) have not been systematically evaluated in young people with epilepsy despite their high prevalence in this population. The aim of this multi-site randomised controlled trial is to determine the clinical and cost-effectiveness of adding a modular psychological intervention to usual care for the mental health disorders in comparison to assessment-enhanced usual care alone. Methods In total, 334 participants aged 3–18 years attending epilepsy services will be screened for mental health disorders with the Strengths and Difficulties Questionnaire (SDQ) and the diagnostic Development and Wellbeing Assessment (DAWBA). Those identified as having a mental health disorder and consenting to the trial will be randomised to either receive up to 22 sessions of the modular psychological intervention (MATCH-ADTC) delivered over the telephone over 6 months by non-mental health professionals in addition to usual care or to assessment-enhanced usual care alone. Outcomes will be measured at baseline, 6 months and 12 months post-randomisation. It is hypothesised that MATCH-ADTC plus usual care will be superior to assessment-enhanced usual care in improving emotional and behavioural symptoms. The primary outcome is the SDQ reported by parents at 6 months. Secondary outcomes include parent-reported mental health measures such as the Revised Children’s Anxiety and Depression Scale, quality of life measures such as the Paediatric Quality of Life Inventory and physical health measures such as the Hague Seizure Severity Scale. Outcome assessors will be blinded to group assignment. Qualitative process evaluations and a health economic evaluation will also be completed. Discussion This trial aims to determine whether a systematic and integrated approach to the identification and treatment of mental health disorders in children and young people with epilepsy is clinically and cost-effective. The findings will contribute to policies and practice with regard to addressing mental health needs in children and young people with other long-term conditions. Trial registration ISRCTN ISRCTN57823197. Registered on 25 February 2019.

scholarly journals Adapting the definition of multimorbidity – development of a locality-based consensus for selecting included Long Term Conditions

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nasrin Hafezparast ◽  
Ellie Bragan Turner ◽  
Rupert Dunbar-Rees ◽  
Alice Vodden ◽  
Hiten Dodhia ◽  
...  
Keyword(s):  
Literature Review ◽  
Selection Process ◽  
Final Decision ◽  
Local Health ◽  
Urban Context ◽  
Long Term Conditions ◽  
Large Cities ◽  
Second Stage ◽  
Local Health Service

Abstract Background Defining multimorbidity has proved elusive in spite of attempts to standardise definitions. For national studies, a broad definition is required to capture national diversity. For locally based studies, the definition may need to reflect demographic and morbidity patterns. We aimed to define multimorbidity for an inner city, multi-ethnic, deprived, young age community typical of many large cities. Methods We used a scoping literature review to identify the international literature, standards and guidelines on Long Term Condition (LTC) definitions for inclusion in our multimorbidity definition. Consensus was categorised into high, medium or low consensus, depending on the number of literature sources citing each LTC. Findings were presented to a workshop consisting of local health service stakeholders who were asked to select LTCs for inclusion in a second stage review. In the second stage, each LTC was tested against seven evaluation domains: prevalence, impact, preventability, treatment burden, progression to multiple LTCs, impact on younger people, data quality. These domains were used to create 12 target criteria. LTC rankings according to consensus group and target criteria scores were presented to a second workshop for a final decision about LTC inclusion. Results The literature review identified 18 literature sources citing 86 LTCs: 11 were excluded because they were LTC clusters. The remainder were allocated into consensus groupings: 13 LTCs were ‘high consensus’ (cited by ≥ 11 sources); 15 were ‘medium consensus’ (cited by 5–10 sources); 47 were ‘low consensus’ (cited by < 5 sources). The first workshop excluded 31 LTCs. The remaining 44 LTCs consisted of: 13 high consensus LTCs, all with high target score (score 6–12); 15 medium consensus LTCs, 11 with high target scores; 16 low consensus LTCs, 6 with high target scores. The final workshop selected the 12 high consensus conditions, 12 medium consensus LTCs (10 with high target scores) and 8 low consensus LTCs (3 with high target scores), producing a final selection of 32 LTCs. Conclusions Redefining multimorbidity for an urban context ensures local relevance but may diminish national generalisability. We describe a detailed LTC selection process which should be generalisable to other contexts, both local and national.

The burden of multimorbidity

2021 ◽  
Vol 2021 (4) ◽  
pp. 12-13
Author(s):  
Mark Greener
Keyword(s):  
Long Term Conditions

Mark Greener summarises the latest research on how long-term conditions cluster together

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