bluuebunny/crossref_metadata_2025 huggingface dataset:
47 Respite Care for People with Dementia and their Carers: A Qualitative Study with Multiple Stakeholders
Authors: O'Shea Emma , O'Shea Eamon , Timmons Suzanne , Irving Kate
Published: September 2019

Background

Traditional models of respite, particularly those based within residential care settings, may not always be effective, and there is evidence of low acceptability for some people with dementia and carers. The aim of this study was to synthesise multiple stakeholders’ experiences of respite services for dementia and their perspectives on respite service development.

Methods

Purposive sampling was employed. Semi-structured interviews were conducted with 35 key stakeholders, including people with dementia (n=6), carers (n=9), front-line staff (n=7), managers (n=8), policy-makers/academics (n=5). Data were interpreted inductively using thematic analysis, with a focus on latent patterns of meaning.

Results

Three salient themes were identified (‘Phases of Transition’, ‘Person-centred Respite Care’; and ‘Recalibrating Respite’). Three distinct phases of respite transitions for people with dementia and carers are discussed. Respite services that actively support transitions through empathic communication regarding clients’ concerns, support needs and preferences are highly valued. Clients described care resembling a ‘person-centred’ approach as their ideal, without using that term, but people with dementia do not always experience this type of care. The majority of providers indicated that they provide ‘person-centred care’, but many demonstrated a poor understanding of the concept; many of these providers have a biomedical view of dementia and the personhood status of people with dementia. Regarding service development, clients would prefer more choice, flexibility and responsiveness, including a shift away from residential provision towards an integrated continuum of personalised, strengths-focused community-based and in-home supports.

Conclusion

Any recalibration of respite towards a home/community focus will require a transformation in how dementia is constructed by society, as well as a significant financial investment. Other implementation considerations include: staffing and staff competency; and the co-ordination, integration and regulation of personalised, home-based care models. Finally, it may be necessary to replace the outdated term ‘respite’ with an alternative nomenclature that is not discordant with person-centred care principles.
52 Involvement of People with Dementia and Caregivers in Irish Dementia Research: Experiences, Challenges and Opportunities
Authors: Philbin Laura O , Quaid Kevin
Published: September 2019

Background

People with dementia and caregivers of people with dementia have the right to inclusion and involvement in research that pertains to them. They can bring unique insights that add significant value to research. Person/Patient Public Involvement (PPI) occurs when the public/patients work in partnership with researchers in setting priorities, planning and managing research studies, as well as in disseminating findings and putting results into practice. In line with Alzheimer Europe’s position, a dementia charity is working hard to support and build capacity for PPI in Irish dementia research.

Methods

The Dementia Research Advisory Team was established in April 2019 and is supported by the charity. It is a group of Experts by Experience (5 caregivers and 5 people living with dementia) who influence, advise and work with researchers across Ireland in a PPI capacity. Team members collectively developed terms of reference detailing their expectations of researchers, the charity, and their role in all PPI activities. Team members will focus on becoming active stakeholders in Irish dementia research, and the charity will support them to build their capacity to be involved through capacity-building workshops and continuous evaluation.

Results

This joint presentation will discuss the development, capacity building, and experiences of the Dementia Research Advisory Team. A person with dementia, will discuss the progress of the team and report on members’ experiences of being involved in Irish dementia research. They will also discuss the impact of involvement on team members, and on the research they have been involved in. Practical ‘lessons learned’ on what did and did not work well will be presented, in addition to how the Dementia Research Advisory Team has navigated challenges and opportunities for involvement of people living with dementia and caregivers in research.

Conclusion

Members of the Dementia Research Advisory Team represent key stakeholders in Irish dementia research.
85 Linking Diabetes and Dementia Risk: A Role for Aβ-42 Induced Activation of the NLRP3 Inflammasome? Results from the ENBIND Study
Authors: Dyer Adam , Batten Isabella , Killane Isabelle , Woods Conor , Gibney James , O'Neill Desmond , Reilly Richard , Bourke Nollaig , Kennelly Sean
Published: September 2019

Background

Midlife Type 2 Diabetes Mellitus (T2DM) is associated with a greater risk of dementia in later life. The innate immune NLRP3 inflammasome, an innate immune receptor, has been implicated in both T2DM and Alzheimer’s Dementia (AD) and can become activated by Amyloid-β 42 (Aβ-42). We analysed inflammasome-dependent cytokine responses in midlife T2DM and correlated these with cognitive and gait performance

Methods

Peripheral Blood Mononuclear Cells (PBMCs) of otherwise healthy patients with T2DM (n=30; 52 ± 8 yrs) and matched controls (n=15; 52.5 ± 7.86 yrs) were incubated for 18h with the following NLRP3 ligands: (i) Lipopolysaccharide (LPS), (ii) Aβ42 or (ii) LPS & Aβ42. Cell supernatants were analysed for production of the inflammasome-dependent cytokine IL-1β. Cognitive function was assessed using the MoCA and gait speed assessed under self-selected, maximal and cognitive dual-task conditions. Mann-Whitney, Wilcoxon tests and linear regression of log-transformed data were used to analyse results

Results

Incubation of PBMCs from all participants with NLRP3 agonists was associated with significant production of IL-1β (all p<0.001). There were no statistically significant between-group differences in IL-1β production. MoCA score did not predict IL-1β production by PBMCs. However, poorer performance on the cognitive dual-task gait paradigm was associated with significantly greater IL-1β production in response to LPS & Aβ42 in those with T2DM (p=0.015), which persisted after robust control for demographic, cognitive and cardiovascular covariates (p=0.003). The same association was not seen for healthy controls (p=0.58).

Conclusion

Both LPS & Aβ42 induce significant IL-1β production in PBMCs which did not differ between those with midlife T2DM and healthy controls. Poorer performance on the cognitive dual task gait paradigm was associated with significantly greater IL-1β production in response to LPS & Aβ42. Given the value of dual task gait in predicting cognitive decline, longitudinal follow up of this cohort may provide insight into the underlying pathophysiological mechanisms and potential biomarkers of dementia risk in T2DM.
92 Medication Related Quality of Life (MRQoL) in Ambulatory Older Adults with Polypharmacy and Multi-morbidity – a Measurable Outcome?
Authors: Jennings Emma , Jorgensen Katrine , Lewis Natasha , Byrne Stephen , Gallagher Paul , O’Mahony Denis
Published: September 2019

Background

With increasing numbers of older multi-morbid people being exposed to polypharmacy, research needs to focus on medication-related outcomes affecting quality-of-life (QoL). This study examines older-patients’ medication-related QoL (MRQoL), its relationship to medication burden/complexity, frailty, health-related QoL (HRQoL) and potentially inappropriate medications (PIMs.

Methods

A cross-sectional-study was conducted in older-patients attending out-patients and day-hospital services of a tertiary-teaching-hospital. Participants were aged ≥65 years, first-time attendees, taking ≥5 chronic-medications for ≥3 chronic-conditions and mini-mental state examination score ≥26/30. Demographic, medication, comorbidity, frailty status, PIMs(STOPP/STARTv.2 criteria), MRQoL (MRQoL-LS v1.0) HRQoL (Short-form-12; SF-12) and medication burden (Living with Medicines Questionnaire v.2; LMQv2) data were collected. Drg compliance was measured using the Medication Adherence Rating Scale (MARS). Lower MRQoL-LS v1.0 scores indicate better MRQoL (range 0-84). Higher LMQv2 scores indicate higher medication burden (range from 60-300). A negative age-specific mean-difference score in SF-12 physical and mental health composite scale scores (SF12-PCS, SF12-MCS) indicates poorer health.

Results

Over 12 months, 234 patients (attending 78 clinics) were screened, 59 met inclusion criteria and 30 were recruited; 3 patients were subsequently identified as ineligible. Eighteen patients were female (66%), mean age was 79.4 years (SD±6.2), median number of daily medications was 10 (IQR 8-13), median number of comorbidities was 11 (IQR 9-14).

Participants were generally drug-compliant, median MARS score of 9 (IQR 6.5-10). Patients’ median MRQoL score was 14 (IQR 14-22.5); mean LMQ v2 score was 115.64 (SD± 25.18). Mean age specific mean-difference SF12-PCS and SF12-MCS scores were -22.61 (SD±11.7) and -22.1 (SD±17.5) respectively. There was no significant correlation between MRQoL and number of daily medications, number of comorbidities, LMQ, HRQoL, or PIMs(Pearson’s 2-tailed test).

Conclusion

This study demonstrates that MRQoL-LS v.1 is not applicable to most patients attending geriatric ambulatory services. Furthermore, polypharmacy, multimorbidity, presence of PIMs poorer HRQoL do not correlate significantly with MRQoL.
98 Use of Drgs with Anticholinergic Properties in People Living with Alzheimer’s Disease: Data from NILVAD
Authors: Kennelly Sean P , Dyer Adam H , Murphy Claire , Lawlor Brian
Published: September 2019

Background

Prolonged exposure to anticholinergic medication, particularly in midlife, is associated with increased risk of cognitive impairment/dementia. Less well explored is the ongoing use of drugs with anticholinergic properties in patients with Alzheimer’s Disease (AD), where the potential to accelerate cognitive decline may be greatest.

Methods

We analysed medication data from the NILVAD trial, a clinical trial examining the efficacy of Nilvadapine in mild-moderate Alzheimer’s Disease (AD). Drgs were coded based on their Anatomical Therapeutic Chemical (ATC) classification and Anticholinergic Burden Scale (ABS) applied to each participant’s medication list. Logistic and linear regression were used to model predictors of potential anticholinergic medication use/total ABS score.

Results

Of 510 participants with AD (mean age 72.8 +/-8.3 years; 62% female), just over one-quarter (N = 134, 26.27%) were prescribed a drug with potential/definite anticholinergic properties. Half of these had an anticholinergic burden score of 3 or greater (N = 67, 13.4%). The most frequent definite anticholinergics prescribed included quetiapine (N=27) oxybutynin (N = 22), paroxetine (N=14) and amitriptyline (N=8). Usage did not significantly differ by country or study arm. Overall, 88.43% of patients were prescribed a cholinesterase inhibitor. On multivariate analysis of potential/definite anticholinergic usage, age (p=0.044; OR 1.03, 1.01-1.06), total number of medications (p=0.001, OR 1.3, 1.18-1.41) as well as a greater dementia severity rated using the Alzheimer’s Disease Assessment Scale (ADAS-Cog) (p=0.008; 1.04 1.01-1.07) were associated with likelihood of anticholinergic use.

Conclusion

Over one-quarter of community-dwelling older patients with AD are prescribed a drug with potential or definite anticholinergic properties. Use of drugs with potential/definite anticholinergic properties were associated with total medication burden in addition to greater dementia severity at baseline. This is particularly pertinent given the deleterious cognitive effects of anticholinergic medication. Further attention to reducing total anticholinergic burden in patients with dementia is warranted.
109 Impact of Transport Mode on Psychosocial Wellbeing in Community-dwelling Adults Aged ≥50 years: Results from TILDA
Authors: Donoghue Orna , McGarrigle Christine , Anne Kenny Rose
Published: September 2019

Background

Older adults with access to a car report increased social participation, better quality of life and better mental health. Existing research often compares the car to public transport, however we hypothesise that individuals who drive themselves or are driven by spouses have better outcomes compared to those driven by family or friends or taking public transport. This study examined how differences in transport mode affect psychosocial wellbeing in community-dwelling adults aged ≥50 years in Ireland.

Methods

Data were collected from 8092 adults during wave 1 of The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort study. Participants indicated their most frequent mode of transport: car, car (driven by partner/spouse), car (driven by family/friends/taxi), public transport. Regression analysis was used to examine associations between transport mode with depressive symptoms, quality of life and loneliness.

Results

89.8% of adults travel most frequently by car with 72.2% driving themselves. Driving was independently associated with lower depressive symptoms (beta=-1.9, 95% CI: -2.59, -1.30, p<0.001) and loneliness (beta =-0.45, 95% CI: -0.70, -0.21, p<0.001) and better quality of life OR=4.11, 95% CI: 3.13, 5.08, p<0.001) compared to relying on lifts from family/friends/taxi. Being driven by a spouse/partner or taking public transport were also associated with more positive effects although to a lesser extent. Interaction analysis showed that men who regularly travelled by public transport had higher loneliness scores than women (beta=0.67, 95% CI: 0.16, 1.18, p<0.05).

Conclusion

Most adults aged ≥50 years in Ireland rely on the car for transport. Driving, being driven by a spouse/partner or taking public transport are associated with better psychosocial wellbeing compared to being driven by others, highlighting the importance or independent travel, whether by car or public transport. Opportunities to support this should be considered when planning the future transport needs of ageing populations.
124 Creating Greater Public Understanding of Dementia: Findings on the Impact of a Coalition-led National Awareness Programme
Authors: Foley Fiona , Guiry Roisin
Published: September 2019

Background

Dementia Understand Together is a public support, awareness and stigma reduction campaign aimed at inspiring people from all sections of society to stand together with the 55,000 Irish people living with dementia. Led by the HSE working with The Alzheimer Society of Ireland and Genio it is supported by over 40 partner organisations and 230+ community champions, who are creating communities that actively embrace and include those living with dementia and their families.

Methods

The campaign uses personal testimonial TV commercials, radio advertising, social media and national and local news stories to build understanding among the general public about dementia. At a local level the campaign is growing a movement of people who are taking action to creative inclusive communities across Ireland.

Extensive research using national biennial public surveys (2016 and 2018) (N=1003) and campaign evaluation tools has and continues to inform the development and progression of the campaign.

Results

33% of respondents described themselves as knowing a lot about dementia, up from 24% in January 2016. There was a significant difference in attitudes between those who were aware of the campaign and those who were not.

Dementia risk reduction is a key message of the national campaign and 52% of respondents were aware that there are things they can do to potentially reduce their risk – up from 46% in 2016.

59% who saw the TV campaign said they were impacted in some way as a result of the personal stories featured and stated that they took some action, such as calling into a friend.

Conclusion

The development and implementation of the campaign is a partnership approach between the leading organisations working in the area of dementia. Findings show that the campaign is creating better understanding of dementia among the general public, increasing awareness of the condition and risk reduction, and is inspiring people to take actions.
125 A Quality Improvement Initiative of the Day Hospital Service
Authors: Lambe Avril , Vandenberg Niamh , O'Dwyer Clodagh , Ball Ciara , Cronin Annemarie , Byrne Marina , Jones Joyce , Falvey Diane , Mallin Mary , Fitzgerald Deirdre , Harpur Ann
Published: September 2019

Background

The Day Hospital had the potential to assist the hospital in achieving its target of reducing length of stay and early supported discharge. However the service was not providing a timely, quality service. The Day Hospital was reviewed as part of a week-long Rapid Improvement Event (RIE) to optimise the service.

Methods

Lean methodologies were utilised, including process mapping, gap analysis and A3 thinking. Data collection and analysis was gathered on the initial state prior to the RIE. Patient interviews were conducted and visual management systems were used to clarify the therapy schedules and rapid experiments of clinic flow boards. The key areas for service development were identified and changes were implemented and audited at 90 days and one year.

Results

Results at one year review showed that wait time for patients to attend an appointment was reduced by 75% (average of 270 days to 70 days) from 2017 to 2018. There was a 184% increase in new patient referrals from 2017 to 2018 and 98% of feedback from the patient surveys was positive. Five new clinic pathways were developed and added to the three existing clinics. Slots were also made available at clinics for early supported discharge from the hospital. Communication between staff was greatly improved through monthly meetings and utilizing a visual management system. Patient feedback surveys were checked monthly and streamlining the administration process improved the capacity of the service.

Conclusion

The RIE produced positive outcomes for the hospital, patients and staff. It achieved the key targets of providing a quality and timely service. The data at key time points indicate positive sustainability in these key areas.
127 Modifiable Cardiovascular Risk Profile in People with Mild Cognitive Symptoms Attending a Memory Service - an Opportunity to Promote Brain Health
Authors: Dookhy Joshi , McHale Cathy , Kennelly Sean , Coughlan Tara , Collins Ronan , Ryan Dan , O'Neill Desmond
Published: September 2019

Background

Current evidence strongly implicates the burden of vascular risk factors (VRF) in the development of stroke, cognitive decline and dementia. This effect is mediated through several mechanisms, including amyloidogenesis, chronic neuroinflamation, cerebral perfusion and white-matter changes. Vascular risk profiling is well-embedded in stroke and cardiac services, but less so in memory services.

Methods

A review of established modifiable VRF (hypercholesterolemia, Body Mass Index (BMI), hypertension, HbA1c, smoking and alcohol habits) of people with mild cognitive complaints (mild cognitive impairment and subjective memory decline) in a memory service was performed. Risk factors measured in clinic were classified as: systolic ≥140mmHg / diastolic ≥90mmHg hypertension; LDL cholesterol >3mmol/l; HbA1c >39mmol/mol; weekly alcohol >21units; smoking and BMI >24.9kg/m2. Data was recorded and analysed using Microsoft Excel.

Results

Thirty-seven people, including 16 females (mean age 71.4, range of 49-83 years), were reviewed. 13/37 (35%) were aged ≤69 years. A total of 91 VRFs were identified in the study population. 29/37 (78%) had ≥2 VRF present. 3/37 (8%) had five VRF. 18/37 (49%) had prior history of either stroke, vascular or heart disease.

Five of thirty-seven, (13.5%) and 13/37 (35%) were current and ex-smokers respectively, 2/37 (5%) consumed excess alcohol, 24/37 (65%) had elevated BMI and 11/37 (30%) had elevated LDL cholesterol. 21/37 (57%) had hypertension. Of these, 11/21 were known but poorly-controlled and 10/21 were identified de novo. All of the 32% (12/37) who had hyperglycaemia were de novo.

Conclusion

This study highlights the high prevalence of unidentified or poorly controlled VRF in people with mild cognitive symptoms attending a memory service. Given its importance to brain health and mitigation of future cognitive decline, a structured focus on identifying and managing these VRF in this setting is necessary. Exercise-based lifestyle programs should be embedded in post-diagnostic services for this population.
132 A Survey of Non-consultant Hospital Doctors’ Knowledge and Understanding of the Legal Status of Advance Care Directives in Ireland
Authors: Comber Ruth
Published: September 2019

Background

The legal status of advance care directives (ACDs) in Irish law, as they pertain to current clinical practice, is a relatively new topic to healthcare staff. This project aimed to assess current understanding in non-consultant hospital doctors (NCHDs).

Methods

An online survey was conducted with NCHDs across a range of disciplines to ascertain current knowledge of the legal parameters of ACDs. Descriptive analysis of data was conducted in Excel.

Results

The survey was completed by 183 NCHDs. Of respondents 93.99% (n=172) were familiar with the term advance care directive and 41.53% (n=76) had encountered one in clinical practice. Their current legal status in Ireland was not known to 58.47% (n=107). That to be considered legally binding an ACD must be in writing was understood by 63.39%, but 58.47% (n=107) were unsure if a solicitor is required to draft one. Refusal of medical treatment as an application for ACDs was appreciated by 79.78% (n=146), however 38.89% (n=73) erroneously believed medical intervention could be requested in an ACD, with a further 30.6% (n=56) unsure. Current guidance sets out that only specific situations may be contained within an ACD, however 77.6% (n=142) of respondents believed a general stipulation could be documented, 25.14% (n=46) did not know if cognitive function affected the legality of an ACD, 95.08% (n=174) of respondents would attend formal training on ACDs if provided by their place of work.

Conclusion

Despite being enshrined in current legislation the legal status of advance care directives, their definition and criteria to be considered legally binding are very poorly understood by NCHDs. Guidance and education are crucial to the future protection of both patients and doctors with regards the execution of advanced care directives as prescribed by law.
137 Does the Clinical Frailty Scale Predict Rehabilitation Potential in Older Patients?
Authors: D'Alton Maeve , Larkin Joanne , McKeag Avril , Coakley Grace , Nolan Emma , O'Connor Marie , Dolan Eamon
Published: September 2019

Background

The Clinical Frailty Scale (CFS) is widely used to assess frailty in older adults and reflects functional independence. We examined its use as an outcome measure in an offsite rehabilitation unit for patients over 65 transferred from an acute hospital following medical/surgical admission.

Methods

Patients were given a CFS score by consensus opinion from the multidisciplinary team on admission and on completion of rehabilitation. We included data on diagnosis, length of stay and discharge destination

Results

Thirty patients, with a mean age of 80, completed rehabilitation over a four-month period. The most common diagnosis was fracture of hip or pelvis (53%). Median CFS was 6 on admission and 5 on discharge (range 3-8). Twenty-one (70%) patients saw an improvement in CFS of an average of one point on the scale irrespective of admission score. Of those that improved, 81% were discharged directly home with no need for increased support services, compared with 11% of those who did not improve. Mean length of stay was significantly less in those with mild/moderate frailty (CFS 5-6) at admission versus severe frailty (31 vs 53.8 days, p<0.01).

Conclusion

Frailty score improved in the majority of patients undergoing rehabilitation, regardless of admission score; CFS alone did not predict rehabilitation potential, emphasising the importance of offering rehabilitation to frail older adults – better judged by experienced clinical assessment. CFS is a broad 9-point tool that can miss small improvements in physical function based on other objective scores e.g. FIM+FAM. Severe frailty was associated with longer length of stay in rehabilitation, possibly reflecting more complex discharge planning as well as rehabilitation progress in this group.
145 An Audit on Hip Fracture Rehabilitation Using a Community Integrated Care Programme
Authors: Sullivan Rachel , Khan Sarah , Gannon Elizabeth , Byrne Aoife , Spencer Michelle , Whelan Mairin , Nee Rory
Published: September 2019

Background

Teiripe sa Bhaile (TsaB) is an integrated rehabilitation programme that provides Early Supported Discharge (ESD) to patients following hip fractures. It involves weekly multidisciplinary domiciliary visits to patients under the guidance of a community geriatrician. ESD in hip fractures has been proven to be safe, more effective at improving functional recovery than inpatient rehab with a reduced average length of stay (LOS) (Chudyk 2009) and better outcomes in mobility and quality of life. (Langeland 2019)

Methods

A retrospective chart review was carried out on patients enrolled in TsaB since July 2018.  The Chartered Society of Physiotherapy for Hip Fracture Rehabilitation state that following discharge from hospital, rehabilitation should commence within 72 hours and all patients should receive two hours of rehabilitation per week until they have reached their goals. An appropriate outcome measure is recommended to measure progress against each rehab goal. The Functional Independence Measure (FIM) which looks at their level of assistance with Activities of Daily Living, was recorded pre and post completion of the programme.

Results

Fifteen patients completed TsaB over 3 to 8 week period. The male to female ratio was 3:1. The average age was 80.75 years. The average LOS in hospital post hip fracture was 54 days. The average LOS in hospital with TsaB was 14.8 days. This equates to 4 bed days saved per week. Each patient was seen within 72 hours of referral and received on average 3 hours per week of rehabilitation until their rehabilitation goals were achieved.

Average improvement in FIM was 36.35 (>20 is clinically significant). The average Rockwood frailty scale pre-rehabilitation was 5.6 (mild to moderately frail). This improved to 3.14 (managing symptoms) on discharge. No patients were readmitted within the 30 days post discharge from hospital.

Conclusion

TsaB is a home based integrated rehabilitation programme that enables patients to receive rehab in their homes and reduces the likelihood of complications such as hospital acquired infections and deconditioning.
165 Learning from Others: a Review of Dementia Registries and the Value of Dementia Data within the Irish Context
Authors: Hopper Louise , Bowen Christina
Published: September 2019

Background

Since the 1980’s, the number of established dementia registries worldwide has grown considerably and new registries continue to develop (e.g. Cuba, Netherlands, Greece and Australia). Ireland does not currently collect data relating to dementia in any systematic way. A National Dementia Registry model has been commissioned by the National Dementia Office (funded by Dormant Accounts through the Department of Health) to address this gap.

Methods

Despite a growth in dementia registry numbers (30+), no international standard has emerged, nor does Ireland have national guidelines in relation to patient registries. We commenced with a review of research, volunteer, epidemiological, and quality of care registries to examine similarities and differences in their design, governance, data collection, outputs and perceived value, so that we can mirror and learn from these and determine the possibilities for value creation in an Irish context.

Results

Key models have emerged along with a willingness to share experiences and support our learning (e.g. France, Spain, Sweden, Norway and USA). Common data includes patient characteristics, diagnostic work-up, diagnosis, treatment (point in time) and service provider details. There is a clear shift towards quality models that identify variation in best practice, follow the patient over time (only Sweden to date), and provide feedback on performance in an effort to stimulate quality improvement and motivate change. No jurisdiction has perfect conditions. The creation of a registry can itself drive the change required to enable it to add value to the health system.

Conclusion

Existing dementia registries evidence the value that a dementia registry provides, in particular the fostering of clinical best practice and improvement in patient outcomes. Notwithstanding the challenges of integrated data collection in Ireland, these registry models illustrate that the time is right to develop a national dementia registry. The value and importance in having dementia data cannot be underestimated.
Reversal of the Warburg phenomenon in chemoprevention of prostate cancer by sulforaphane
Authors: Singh Krishna B , Hahm Eun-Ryeong , Alumkal Joshi J , Foley Lesley M , Hitchens T Kevin , Shiva Sruti S , Parikh Rahul A , Jacobs Bruce L , Singh Shivendra V
Published: September 2019

Inhibition of metabolic re-programming represents an attractive approach for prevention of prostate cancer. Studies have implicated increased synthesis of fatty acids or glycolysis in pathogenesis of human prostate cancers. We have shown previously that prostate cancer prevention by sulforaphane (SFN) in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model is associated with inhibition of fatty acid metabolism. This study utilized human prostate cancer cell lines (LNCaP, 22Rv1 and PC-3), two different transgenic mouse models (TRAMP and Hi-Myc) and plasma specimens from a clinical study to explore the glycolysis inhibition potential of SFN. We found that SFN treatment: (i) decreased real-time extracellular acidification rate in LNCaP, but not in PC-3 cell line; (ii) significantly downregulated expression of hexokinase II (HKII), pyruvate kinase M2 and/or lactate dehydrogenase A (LDHA) in vitro in cells and in vivo in neoplastic lesions in the prostate of TRAMP and Hi-Myc mice; and (iii) significantly suppressed glycolysis in prostate of Hi-Myc mice as measured by ex vivo1H magnetic resonance spectroscopy. SFN treatment did not decrease glucose uptake or expression of glucose transporters in cells. Overexpression of c-Myc, but not constitutively active Akt, conferred protection against SFN-mediated downregulation of HKII and LDHA protein expression and suppression of lactate levels. Examination of plasma lactate levels in prostate cancer patients following administration of an SFN-rich broccoli sprout extract failed to show declines in its levels. Additional clinical trials are needed to determine whether SFN treatment can decrease lactate production in human prostate tumors.
Targeting lysosome function causes selective cytotoxicity in VHL-inactivated renal cell carcinomas
Authors: Bouhamdani Nadia , Comeau Dominique , Coholan Alexandre , Cormier Kevin , Turcotte Sandra
Published: September 2019

The inactivation of the tumor suppressor gene, von Hippel-Lindau (VHL), has been identified as the earliest event in renal cell carcinoma (RCC) development. The loss of heterogeneity by chromosome 3p deletion followed by inactivating mutations on the second VHL copy are events present in close to 90% of patients. Our study illustrates a lysosomal vulnerability in VHL-inactivated RCC in vitro. By investigating the mechanism of action of the previously identified STF-62247, a small bioactive compound known for its selective cytotoxic properties towards VHL-defective models, we present the promising approach of targeting truncal-driven VHL inactivation through lysosome disruption. Furthermore, by analyzing the open platform for exploring cancer genomic data (cbioportal), we uncover the high alteration frequency of essential lysosomal and autophagic genes in sequenced biopsies from clear cell RCC patient primary tumors. By investigating lysosome physiology, we also identify VHL-inactivated cells’ inability to maintain their lysosomes at the perinuclear localization in response to STF-62247-induced stress and accumulate cytoplasmic inclusion bodies in response to an inefficient lysosomal degradative capacity. Finally, by testing other known lysosomal-disrupting agents (LDAs), we show that these are selectively cytotoxic to cells lacking VHL functions. Our study builds a strong platform that could specifically link genetic clonal ccRCC evolution to lysosomal and trafficking vulnerabilities.
Bedaquiline for the Treatment of Multidrug-resistant Tuberculosis in the United States
Authors: Mase Sundari , Chorba Terence , Parks Samuel , Belanger Ann , Dworkin Felicia , Seaworth Barbara , Warkentin Jon , Barry Pennan , Shah Neha
Published: September 2019

Background

In 2012, the Food and Drug Administration approved use of bedaquiline fumarate as part of combination therapy for multidrug-resistant tuberculosis (MDR TB). We describe treatment outcomes, safety, and tolerability of bedaquiline in our case series.

Methods

Data on patients started on bedaquiline for MDR TB between September 2012 and August 2016 were collected retrospectively through 4 TB programs using a standardized abstraction tool. Data were analyzed using univariate methods. Adverse events were graded using the Common Terminology Criteria for Adverse Events.

Results

Of 14 patients, 7 (50%) had MDR, 4 (29%) had pre–extensively drug-resistant (XDR), and 3 (21%) had XDR TB. All had pulmonary TB, 5 (36%) had pulmonary and extrapulmonary TB, and 9/13 (69%) were smear positive. One patient (7%) had HIV coinfection, 5 (36%) had diabetes mellitus, and 5/14 (36%) had previous treatment TB. All patients were non–US-born and 5/14 (36%) had private insurance. All patients achieved sputum culture conversion within a mean of 71 days (26–116); 5 after starting bedaquiline. Twelve (86%) completed treatment and 1 (7%) moved out of the country. One patient (7%) had QTc prolongation >500 milliseconds and died 20 months after discontinuing bedaquiline of a cause not attributable to the drug. Common adverse events were peripheral neuropathy 7/14 (50%), not customarily associated with bedaquiline use, and QTc prolongation 6/14 (43%).

Conclusions

Of 14 patients, 1 (7%) had an adverse event necessitating bedaquiline discontinuation. Safety, culture conversion, and treatment completion in this series (7%) support use of bedaquiline for the treatment of MDR/XDR TB.
Safety, Tolerability, and Immunogenicity of Plasmodium falciparum Sporozoite Vaccine Administered by Direct Venous Inoculation to Infants and Young Children: Findings From an Age De-escalation, Dose-Escalation, Double-blind, Randomized Controlled Study in Western Kenya
Authors: Steinhardt Laura C , Richie Thomas L , Yego Reuben , Akach Dorcas , Hamel Mary J , Gutman Julie R , Wiegand Ryan E , Nzuu Elizabeth L , Dungani Allan , Kc Natasha , Murshedkar Tooba , Church L W Preston , Sim B Kim Lee , Billingsley Peter F , James Eric R , Abebe Yonas , Kariuki Simon , Samuels Aaron M , Otieno Kephas , Sang Tony , Kachur S Patrick , Styers David , Schlessman Kelly , Abarbanell Ginnie , Hoffman Stephen L , Seder Robert A , Oneko Martina
Published: September 2019

Background

The whole Plasmodium falciparum sporozoite (PfSPZ) vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous inoculation (DVI) with PfSPZ vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited.

Methods

We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (aged 5–9 years, 13–59 months, and 5–12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35 × 105, 2.7 × 105, 4.5 × 105, 9.0 × 105, and 1.8 × 106 PfSPZ, with the 2 highest doses given twice, 8 weeks apart. Solicited adverse events (AEs) were monitored for 8 days after vaccination, unsolicited AEs for 29 days, and serious AEs throughout the study. Blood taken prevaccination and 1 week postvaccination was tested for immunoglobulin G antibodies to P. falciparum circumsporozoite protein (PfCSP) using enzyme-linked immunosorbent assay.

Results

Rates of AEs were similar in vaccinees and controls for solicited (35.7% vs 41.5%) and unsolicited (83.9% vs 92.5%) AEs, respectively. No related grade 3 AEs, serious AEs, or grade 3 laboratory abnormalities occurred. Most (79.0%) vaccinations were administered by a single DVI. Among those in the 9.0 × 105 and 1.8 × 106 PfSPZ groups, 36 of 45 (80.0%) vaccinees and 4 of 21 (19.0%) placebo controls developed antibodies to PfCSP (P < .001).

Conclusions

PfSPZ vaccine in doses as high as 1.8 × 106 can be administered to infants and children by DVI, and was safe, well tolerated, and immunogenic.

Clinical Trials Registration

NCT02687373.
Tuberculosis, Human Immunodeficiency Virus, and the Association With Transient Hyperglycemia in Periurban South Africa
Authors: Kubjane Mmamapudi , Berkowitz Natacha , Goliath Rene , Levitt Naomi S , Wilkinson Robert J , Oni Tolu
Published: September 2019

Background

Diabetes mellitus (DM) increases tuberculosis (TB) risk. We assessed the prevalence of hyperglycemia (DM and impaired glucose regulation [IGR]) in persons with TB and the association between hyperglycemia and TB at enrollment and 3 months after TB treatment in the context of human immunodeficiency virus (HIV) infection.

Methods

Adults presenting at a Cape Town TB clinic were enrolled. TB cases were defined by South African guidelines, while non-TB participants were those who presented with respiratory symptoms, negative TB tests, and resolution of symptoms 3 months later without TB treatment. HIV status was ascertained through medical records or HIV testing. All participants were screened for DM using glycated hemoglobin and fasting plasma glucose at TB treatment and after 3 months. The association between TB and DM was assessed.

Results

Overall DM prevalence was 11.9% (95% confidence interval [CI], 9.1%–15.4%) at enrollment and 9.3% (95% CI, 6.4%–13%) at follow-up; IGR prevalence was 46.9% (95% CI, 42.2%–51.8%) and 21.5% (95% CI, 16.9%–26.3%) at enrollment and follow-up. TB/DM association was significant at enrollment (odds ratio [OR], 2.41 [95% CI, 1.3–4.3]) and follow-up (OR, 3.3 [95% CI, 1.5–7.3]), whereas TB/IGR association was only positive at enrollment (OR, 2.3 [95% CI, 1.6–3.3]). The TB/DM association was significant at enrollment in both new and preexisting DM, but only persisted at follow-up in preexisting DM in patients with HIV-1 infection.

Conclusions

Our study demonstrated high prevalence of transient hyperglycemia and a significant TB/DM and TB/IGR association at enrollment in newly diagnosed DM, but persistent hyperglycemia and TB/DM association in patients with HIV-1 infection and preexisting DM, despite TB therapy.
Prognostic value of the 12-lead surface electrocardiogram in sarcomeric hypertrophic cardiomyopathy: data from the REMY French register
Authors: Ledieu Nicolas , Larnier Louis , Auffret Vincent , Marie Coralie , Fargeau Dominique , Donal Erwan , Mirabel Mariana , Jeunemaitre Xavier , Puscas Tania , Marijon Eloi , Reynaud Amélie , Ritter Philippe , Lafitte Stephane , Mabo Philippe , Réant Patricia , Daubert Claude , Hagège Albert A ,   REMY Working Group of the French Society of Cardiology
Published: September 2019

Aims

To identify independent electrocardiogram (ECG) predictors of long-term clinical outcome based on standardized analysis of the surface ECG in a large multicentre cohort of patients with sarcomeric hypertrophic cardiomyopathy (HCM).

Methods and results

Retrospective observational study from the REMY French HCM clinical research observatory. Primary endpoint was a composite of all-cause mortality, major non-fatal arrhythmic events, hospitalization for heart failure (HF), and stroke. Secondary endpoints were components of the primary endpoint. Uni- and multivariable Cox proportional hazard regression analysis was performed to identify independent predictors. Among 994 patients with HCM, only 1.8% had a strictly normal baseline ECG. The most prevalent abnormalities were inverted T waves (63.7%), P-wave abnormalities (30.4%), and abnormal Q waves (25.5%). During a mean follow-up of 4.0 ± 2.0 years, a total of 272 major cardiovascular events occurred in 217 patients (21.8%): death or heart transplant in 98 (9.8%), major arrhythmic events in 40 (4.0%), HF hospitalization in 115 (11.6%), and stroke in 23 (2.3%). At multivariable analysis using ECG covariates, prolonged QTc interval, low QRS voltage, and PVCs of right bundle branch block pattern predicted worse outcome, but none remained independently associated with the primary endpoint after adjustment on main demographic and clinical variables. For secondary endpoints, abnormal Q waves independently predicted all-cause death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.23–4.47; P = 0.009] and prolonged QTc the risk of HF hospitalization (HR 1.006, 95% CI 1.001–1.011; P = 0.024).

Conclusion

The 12-lead surface ECG has no independent value to predict the primary outcome measure in patients with HCM. The 12-lead surface ECG has been widely used as a screening tool in HCM but its prognostic value remains poorly known. The value of baseline surface ECG to predict long-term clinical outcomes was studied in a cohort of 994 patients with sarcomeric HCM. The surface ECG has no significant additional value to predict outcome in this patient population
The second information revolution: digitalization brings opportunities and concerns for public health
Authors: McKee Martin , van Schalkwyk May C I , Stuckler David
Published: September 2019

The spread of the written word, facilitated by the introduction of the printing press, was an information revolution with profound implications for European society. Now, a second information revolution is underway, a digital transformation that is shaping the way Europeans live and interact with each other and the world around them. We are confronted with an unprecedented expansion in ways to share and access information and experiences, to express ourselves and communicate. Yet while these changes have undoubtedly provided many benefits for health, from information sharing to improved surveillance and diagnostics, they also open up many potential threats. These come in many forms. Here we review some the pressing issues of concern; discrimination; breaches of privacy; iatrogenesis; disinformation and misinformation or ‘fake news’ and cyber-attacks. These have the potential to impact negatively on the health and wellbeing of individuals as well as entire communities and nations. We call for a concerted European response to maximize the benefits of the digital revolution while minimizing the harms, arguably one of the greatest challenges facing the public health community today.
Data-adaptive spatio-temporal filtering of GRACE data
Authors: Prevost Paoline , Chanard Kristel , Fleitout Luce , Calais Eric , Walwer Damian , van Dam Tonie , Ghil Michael
Published: September 2019

Measurements of the spatio-temporal variations of Earth’s gravity field from the Gravity Recovery and Climate Experiment (GRACE) mission have led to new insights into large spatial mass redistribution at secular, seasonal and subseasonal timescales. GRACE solutions from various processing centres, while adopting different processing strategies, result in rather coherent estimates. However, these solutions also exhibit random as well as systematic errors, with specific spatial patterns in the latter.

In order to dampen the noise and enhance the geophysical signals in the GRACE data, we propose an approach based on a data-driven spatio-temporal filter, namely the Multichannel Singular Spectrum Analysis (M-SSA). M-SSA is a data-adaptive, multivariate, and non-parametric method that simultaneously exploits the spatial and temporal correlations of geophysical fields to extract common modes of variability.

We perform an M-SSA analysis on 13 yr of GRACE spherical harmonics solutions from five different processing centres in a simultaneous setup. We show that the method allows us to extract common modes of variability between solutions, while removing solution-specific spatio-temporal errors that arise from the processing strategies. In particular, the method efficiently filters out the spurious north–south stripes, which are caused in all likelihood by aliasing, due to the imperfect geophysical correction models and low-frequency noise in measurements.

Comparison of the M-SSA GRACE solution with mass concentration (mascons) solutions shows that, while the former remains noisier, it does retrieve geophysical signals masked by the mascons regularization procedure.
Integration of geological and seismological data in earthquakes occurrence models for Italy: towards a unified model for different forecast perspectives
Authors: Lombardi A M
Published: September 2019

The operational earthquake forecasting (OEF) is a procedure aimed at informing communities on how seismic hazard changes with time. This can help them live with seismicity and mitigate risk of destructive earthquakes. A successful short-term prediction scheme is not yet produced, but the search for it should not be abandoned. This requires more research on seismogenetic processes and, specifically, inclusion of any information about earthquakes in models, to improve forecast of future events, at any spatio-temporal-magnitude scale.

The short- and long-term forecast perspectives of earthquake occurrence followed, up to now, separate paths, involving different data and peculiar models. But actually they are not so different and have common features, being parts of the same physical process. Research on earthquake predictability can help to search for a common path in different forecast perspectives.

This study aims to improve the modelling of long-term features of seismicity inside the epidemic type aftershock sequence (ETAS) model, largely used for short-term forecast and OEF procedures. Specifically, a more comprehensive estimation of background seismicity rate inside the ETAS model is attempted, by merging different types of data (seismological instrumental, historical, geological), such that information on faults and on long-term seismicity integrates instrumental data, on which the ETAS models are generally set up. The main finding is that long-term historical seismicity and geological fault data improve the pseudo-prospective forecasts of independent seismicity.

The study is divided in three parts. The first consists in models formulation and parameter estimation on recent seismicity of Italy. Specifically, two versions of ETAS model are compared: a ‘standard’, previously published, formulation, only based on instrumental seismicity, and a new version, integrating different types of data for background seismicity estimation. Secondly, a pseudo-prospective test is performed on independent seismicity, both to test the reliability of formulated models and to compare them, in order to identify the best version. Finally, a prospective forecast is made, to point out differences and similarities in predicting future seismicity between two models.

This study must be considered in the context of its limitations; anyway, it proves, beyond argument, the usefulness of a more sophisticated estimation of background rate, inside short-term modelling of earthquakes.