A review of the enhanced CJD surveillance feasibility study in the elderly in Scotland, UK.

BACKGROUND: Variant Creutzfeldt - Jakob disease (vCJD) arose from dietary contamination with bovine-spongiform-encephalopathy (BSE). Because of concerns that vCJD-cases might be missed in the elderly, a feasibility study of enhanced CJD surveillance on the elderly was begun in 2016. Recruitment was lower than predicted. We describe a review of the challenges encountered in that study: identification, referral, and recruitment, and the effects of actions based on the results of that review. METHODS: Review was conducted in 2017. Study data for all eligible cases identified and referred from one participating service (Anne Rowling clinic (ARC)) was curated and anonymised in a bespoke database. A questionnaire was sent out to all the clinicians in medicine of the elderly, psychiatry of old age and neurology (including ARC) specialties in NHS Lothian, exploring possible reasons for low recruitment. RESULTS: Sixty-eight cases were referred from the ARC (March 2016-September 2017): 25% were recruited. Most cases had been referred because of diagnostic uncertainty. No difference was seen between those recruited and the non-recruited, apart from age and referrer. Twelve of 60 participating clinicians completed the questionnaire: only 4 had identified eligible cases. High workload, time constraints, forgetting to refer, unfamiliarity with the eligibility criteria, and the rarity of eligible cases, were some of the reasons given. Suggestions as to how to improve referral of eligible cases included: regular email reminders, feedback to referrers, improving awareness of the study, visible presence of the study team, and integration of the study with other research oriented services. These results were used to increase recruitment but without success. CONCLUSION: Recruitment was lower than predicted. Actions taken following a review at 21 months did not lead to significant improvement; recruitment remained low, with many families/patients declining to take part (75%). In assessing the failure to improve recruitment, two factors need to be considered. Firstly, the initial referral rate was expected to be higher because of existing patients already known to the clinical services, with later referrals being only newly presenting patients. Secondly, the unplanned absence of a dedicated study nurse. Searching digital records/anonymised derivatives to identify eligible patients could be explored.

An analysis of the construct validity and responsiveness of the ICECAP-SCM capability wellbeing measure in a palliative care hospice setting.

BACKGROUND: For outcome measures to be useful in health and care decision-making, they need to have certain psychometric properties. The ICECAP-Supportive Care Measure (ICECAP-SCM), a seven attribute measure (1. Choice, 2. Love and affection, 3. Physical suffering, 4. Emotional suffering, 5. Dignity, 6. Being supported, 7. Preparation) developed for use in economic evaluation of end-of-life interventions, has face validity and is feasible to use. This study aimed to assess the construct validity and responsiveness of the ICECAP-SCM in hospice inpatient and outpatient settings. METHODS: A secondary analysis of data collated from two studies, one focusing on palliative care day services and the other on constipation management, undertaken in the same national hospice organisation across three UK hospices, was conducted. Other quality of life and wellbeing outcome measures used were the EQ-5D-5L, McGill Quality of Life Questionnaire - Expanded (MQOL-E), Patient Health Questionnaire-2 (PHQ-2) and Palliative Outcomes Scale Symptom list (POS-S). The construct validity of the ICECAP-SCM was assessed, following hypotheses generation, by calculating correlations between: (i) its domains and the domains of other outcome measures, (ii) its summary score and the other measures' domains, (iii) its summary score and the summary scores of the other measures. The responsiveness of the ICECAP-SCM was assessed using anchor-based methods to understand change over time. Statistical analysis consisted of Spearman and Pearson correlations for construct validity and paired t-tests for the responsiveness analysis. RESULTS: Sixty-eight participants were included in the baseline analysis. Five strong correlations were found with ICECAP-SCM attributes and items on the other measures: four with the Emotional suffering attribute (Anxiety/depression on EQ-5D-5L, Psychological and Burden on MQOL-E and Feeling down, depressed or hopeless on PHQ-2), and one with Physical suffering (Weakness or lack of energy on POS-S). ICECAP-SCM attributes and scores were most strongly associated with the MQOL-E measure (0.73 correlation coefficient between summary scores). The responsiveness analysis (n = 36) showed the ICECAP-SCM score was responsive to change when anchored to changes on the MQOL-E over time (p < 0.05). CONCLUSIONS: This study provides initial evidence of construct validity and responsiveness of the ICECAP-SCM in hospice settings and suggests its potential for use in end-of-life care research.

Frailty assessment and risk prediction by GRACE score in older patients with acute myocardial infarction.

BACKGROUND: Risk prediction after myocardial infarction is often complex in older patients. The Global Registry of Acute Coronary Events (GRACE) model includes clinical parameters and age, but not frailty. We hypothesised that frailty would enhance the prognostic properties of GRACE. METHODS: We performed a prospective observational cohort study in two independent cardiology units: the Royal Infirmary of Edinburgh, UK (primary cohort) and the South Yorkshire Cardiothoracic Centre, Sheffield, UK (external validation). The study sample included 198 patients ≥65 years old hospitalised with type 1 myocardial infarction (primary cohort) and 96 patients ≥65 years old undergoing cardiac catheterisation for myocardial infarction (external validation). Frailty was assessed using the Clinical Frailty Scale (CFS). The GRACE 2.0 estimated risk of 12-month mortality, Charlson comorbidity index and Karnofsky disability scale were also determined for each patient. RESULTS: Forty (20%) patients were frail (CFS ≥5). These individuals had greater comorbidity, functional impairment and a higher risk of death at 12 months (49% vs. 9% in non-frail patients, p < 0.001). The hazard of 12-month all-cause mortality nearly doubled per point increase in CFS after adjustment for age, sex and comorbidity (Hazard Ratio [HR] 1.90, 95% CI 1.47-2.44, p < 0.001). The CFS had good discrimination for mortality by Receiver Operating Characteristic (ROC) curve analysis (Area Under the Curve [AUC] 0.81, 95% CI 0.72-0.89) and enhanced the GRACE estimate (AUC 0.86 vs. 0.80 without CFS, p = 0.04). At existing GRACE thresholds, the CFS resulted in a Net Reclassification Improvement (NRI) of 0.44 (95% CI 0.28-0.60, p < 0.001), largely through reductions in risk estimates amongst non-frail patients. Similar findings were observed in the external validation cohort (NRI 0.46, 95% CI 0.23-0.69, p < 0.001). CONCLUSIONS: The GRACE score overestimated mortality risk after myocardial infarction in these cohorts of older patients. The CFS is a simple guided frailty tool that may enhance prediction in this setting. These findings merit evaluation in larger cohorts of unselected patients. TRIAL REGISTRATION: Clinicaltrials.gov; NCT02302014 (November 26th 2014, retrospectively registered).

Exploring the costs, consequences and efficiency of three types of palliative care day services in the UK: a pragmatic before-and-after descriptive cohort study.

BACKGROUND: Palliative Care Day Services (PCDS) offer supportive care to people with advanced, progressive illness who may be approaching the end of life. Despite the growth of PCDS in recent years, evidence of their costs and effects is scarce. It is important to establish the value of such services so that health and care decision-makers can make evidence-based resource allocation decisions. This study examines and estimates the costs and effects of PCDS with different service configurations in three centres across the UK in England, Scotland and Northern Ireland. METHODS: People who had been referred to PCDS were recruited between June 2017 and September 2018. A pragmatic before-and-after descriptive cohort study design analysed data on costs and outcomes. Data on costs were collected on health and care use in the 4 weeks preceding PCDS attendance using adapted versions of the Client Service Receipt Inventory (CSRI). Outcomes, cost per attendee/day and volunteer contribution to PCDS were also estimated. Outcomes included quality of life (MQOL-E), health status (EQ-5D-5L) and capability wellbeing (ICECAP-SCM). RESULTS: Thirty-eight attendees were recruited and provided data at baseline and 4 weeks (centre 1: n = 8; centre 2: n = 8, centre 3: n = 22). The cost per attendee/day ranged from £121-£190 (excluding volunteer contribution) to £172-£264 (including volunteer contribution) across the three sites. Volunteering constituted between 28 and 38% of the total cost of PCDS provision. There was no significant mean change at 4 week follow-up from baseline for health and care costs (centre 1: £570, centre 2: -£1127, centre 3: £65), or outcomes: MQOL-E (centre 1: - 0.48, centre 2: 0.01, centre 3: 0.24); EQ-5D-5L (centre 1: 0.05, centre 2: 0.03, centre 3: - 0.03) and ICECAP-SCM (centre 1:0.00, centre 2: - 0.01, centre 3: 0.03). Centre costs variation is almost double per attendee when attendance rates are held constant in scenario analysis. CONCLUSIONS: This study highlights the contribution made by volunteers to PCDS provision. There is insufficient evidence on whether outcomes improved, or costs were reduced, in the three different service configurations for PCDS. We suggest how future research may overcome some of the challenges we encountered, to better address questions of cost-effectiveness in PCDS.

Phase 2 Randomised Controlled Trial and Feasibility Study of Future Care Planning in Patients with Advanced Heart Disease.

Future Care Planning (FCP) rarely occurs in patients with heart disease until close to death by which time the potential benefits are lost. We assessed the feasibility, acceptability and tested a design of a randomised trial evaluating the impact of FCP in patients and carers. 50 patients hospitalised with acute heart failure or acute coronary syndrome and with predicted 12 month mortality risk of >20% were randomly allocated to FCP or usual care for 12 weeks upon discharge and then crossed-over for the next 12 weeks. Quality of life, symptoms and anxiety/distress were assessed by questionnaire. Hospitalisation and mortality events were documented for 6 months post-discharge. FCP increased implementation and documentation of key decisions linked to end-of-life care. FCP did not increase anxiety/distress (Kessler score -E 16.7 (7.0) vs D 16.8 (7.3), p = 0.94). Quality of life was unchanged (EQ5D: E 0.54(0.29) vs D 0.56(0.24), p = 0.86) while unadjusted hospitalised nights was lower (E 8.6 (15.3) vs D 11.8 (17.1), p = 0.01). Qualitative interviews indicated that FCP was highly valued by patients, carers and family physicians. FCP is feasible in a randomised clinical trial in patients with acute high risk cardiac conditions. A Phase 3 trial is needed urgently.

Future Care Planning for patients approaching end-of-life with advanced heart disease: an interview study with patients, carers and healthcare professionals exploring the content, rationale and design of a randomised clinical trial.

OBJECTIVE: To explore the optimal content and design of a clinical trial of an end-of-life intervention for advanced heart disease with patients, carers and healthcare professionals. DESIGN: Qualitative interview and focus group study. SETTING: Community and hospital-based focus groups and interviews. PARTICIPANTS: Stable community-dwelling patients, informal carers (PC, n=15) and primary and secondary care based healthcare professionals (HCP, n=11). RESULTS: PC highlighted fragmentation of services and difficulty in accessing specialist care as key barriers to good care. They felt that time for discussion with HCP was inadequate within current National Health Service (NHS) healthcare systems. HCP highlighted uncertainty of prognosis, explaining mortality risk to patients and switching from curative to palliative approaches as key challenges. Patient selection, nature of the intervention and relevance of trial outcomes were identified by HCP as key challenges in the design of a clinical trial. CONCLUSIONS: PC and HCP expressed a number of concerns relevant to the nature and content of an end-of-life intervention for patients with advanced heart disease. The findings of this study are being used to support a phase II randomised clinical trial of Future Care Planning in advanced heart disease.

Prevention or treatment: the benefits of Trichomonas vaginalis vaccine.

Trichomoniasis (infection with Trichomonas vaginalis) is the most common non-viral sexually transmitted disease (STI) in the world. Although treatment is available, most cases occur in developing countries, where accessing healthcare is difficult and facilities are limited. Additionally, infection is often asymptomatic and as such goes untreated, creating reservoirs of T. vaginalis that allow the disease to spread within the community. Because of this there has been little success in controlling the incidence of trichomoniasis, especially amongst the underprivileged. The development of a vaccine against T. vaginalis could reduce the human costs (pregnancy complications, infertility), medical costs (repeated doctor visits, increased susceptibility to human immunodeficiency virus (HIV) infection), and societal costs (stigma of STI, cycles of untreated infection) associated with trichomoniasis.

Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis.

Infections with the sexually transmitted protozoan Trichomonas vaginalis are usually treated with metronidazole, a 5-nitroimidazole drug derived from the antibiotic azomycin. Metronidazole treatment is generally efficient in eliminating T. vaginalis infection and has a low risk of serious side effects. However, studies have shown that at least 5% of clinical cases of trichomoniasis are caused by parasites resistant to the drug. The lack of approved alternative therapies for T. vaginalis treatment means that higher and sometimes toxic doses of metronidazole are the only option for patients with resistant disease. Clearly, studies of the treatment and prevention of refractory trichomoniasis are essential. This review describes the mechanisms of metronidazole resistance in T. vaginalis and provides a summary of trichomonicidal and vaccine candidate drugs.