Nasal fentanyl alone plus buccal midazolam: an open-label, randomised, controlled feasibility study in the dying

Introduction: Many patients want to stay at home to die. They invariably become unable to take oral medication during their terminal phase. Symptoms are usually controlled by subcutaneous medications. There have been no studies on nasal fentanyl (NF) or buccal midazolam (BM) to control symptoms in the dying.Objective: To establish how best to conduct a definitive, randomised controlled trial (RCT) to determine whether NF and BM administered by families, for patients dying at home, lead to faster and better symptom control and fewer community nursing visits than standard breakthrough medication by healthcare professionals.Methods: This open-label mixed-method feasibility RCT compared the efficacy of NF and BM by family members to standard breakthrough medication by nurses for the terminally ill in a specialist palliative care unit. Partway through the study, a third observational arm was introduced where BM alone was used. The primary outcomes were whether recruitment and randomisation were possible, assessment of withdrawal and drop-out, and whether the methods were acceptable and appropriate.Results: Administration of NF and BM was acceptable to patients and families. Both were well tolerated. We were unable to obtain quality of life data consistently but did get time period data for dose-controlled symptoms.Conclusions: Study participation in a hospice population of the dying was acceptable. The results will help guide future community study planning

Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease

Objective:To assess low-density lipoprotein cholesterol (LDL-C) response in patients after initiation of statins, and future risk of CVD.Method:Prospective cohort study of 165,411 primary care patients, from the UK Clinical Practice Research Datalink, who were free from CVD prior to statin initiation, and had at least one pre-treatment LDL-C within 12 months prior to, and one post-treatment LDL-C within 24 months after, statin initiation. Based on current national guidelines, a less than 40% reduction in baseline LDL-cholesterol level within 24 months was classified as sub-optimal statin response. Cox proportional regression and competing-risks survival regression models were used to determine adjusted hazard ratios and sub-hazard ratios for incident CVD outcomes for LDL-C response to statins.Results: 84,609 (51.2%) patients had sub-optimal LDL-cholesterol response to initiated statin therapy within 24 months. During 1,077,299 person-years of follow-up (median follow-up 6.2 years), there were 22,798 CVD events (12,142 in sub-optimal responders and 10,656 in optimal responders). In sub-optimal responders, compared to optimal responders, the hazard ratio (95% CI) for incident CVD was 1.17 (1.13–1.20) and 1.22 (1.19–1.25) after adjusting for age and baseline untreated LDL-cholesterol level. Considering competing risks resulted in lower but similar sub-hazards ratios for both unadjusted 1.13 (1.10–1.16) and adjusted cumulative incidence function, 1.19 (1.16–1.23) of CVD.Conclusions:Optimal lowering of LDL-cholesterol is not achieved within two years in over half of patients in the general population initiated on statin therapy, and these patients will experience significantly increased risk of future cardiovascular disease

Performance and clinical utility of supervised machine-learning approaches in detecting familial hypercholesterolaemia in primary care

Familial hypercholesterolaemia (FH) is a common inherited disorder, causing lifelong elevated low-density lipoprotein cholesterol (LDL-C). Most individuals with FH remain undiagnosed, precluding opportunities to prevent premature heart disease and death. Some machine-learning approaches improve detection of FH in electronic health records, though clinical impact is under-explored. We assessed performance of an array of machine-learning approaches for enhancing detection of FH, and their clinical utility, within a large primary care population. A retrospective cohort study was done using routine primary care clinical records of 4,027,775 individuals from the United Kingdom with total cholesterol measured from 1 January 1999 to 25 June 2019. Predictive accuracy of five common machine-learning algorithms (logistic regression, random forest, gradient boosting machines, neural networks and ensemble learning) were assessed for detecting FH. Predictive accuracy was assessed by area under the receiver operating curves (AUC) and expected vs observed calibration slope; with clinical utility assessed by expected case-review workload and likelihood ratios. There were 7928 incident diagnoses of FH. In addition to known clinical features of FH (raised total cholesterol or LDL-C and family history of premature coronary heart disease), machine-learning (ML) algorithms identified features such as raised triglycerides which reduced the likelihood of FH. Apart from logistic regression (AUC, 0.81), all four other ML approaches had similarly high predictive accuracy (AUC > 0.89). Calibration slope ranged from 0.997 for gradient boosting machines to 1.857 for logistic regression. Among those screened, high probability cases requiring clinical review varied from 0.73% using ensemble learning to 10.16% using deep learning, but with positive predictive values of 15.5% and 2.8% respectively. Ensemble learning exhibited a dominant positive likelihood ratio (45.5) compared to all other ML models (7.0–14.4). Machine-learning models show similar high accuracy in detecting FH, offering opportunities to increase diagnosis. However, the clinical case-finding workload required for yield of cases will differ substantially between models

Does acupressure help reduce nausea and vomiting in palliative care patients? A double blind randomised controlled trial

Introduction: Nausea and vomiting are common symptoms for patients with advanced cancer. While there is evidence for acupuncture point stimulation for treatment of these symptoms for patients having anticancer treatment, there is little for when they are not related to such treatment.Objective: To determine whether acupressure at the pericardium 6 site can help in the treatment of nausea and vomiting suffered by palliative care patients with advanced cancer.Materials and methods: Double blind randomised controlled trial—active versus placebo acupressure wristbands. In-patients with advanced cancer in two specialist palliative care units who fitted either or both of the following criteria were approached: Nausea that was at least moderate; Vomiting daily on average for the prior 3 days.Results: 57 patients were randomised to have either active or placebo acupressure wristbands. There was no difference in any of the outcome measures between the two groups: change from baseline number of vomits; Visual Analogue Scale for ‘did acupressure wristbands help you to feel better?’; total number of as needed doses of antiemetic medication; need for escalation of antiemetics.Conclusions: In contrast to a previously published feasibility study, active acupressure wristbands were no better than placebo for specialist palliative care in-patients with advanced cancer and nausea and vomiting

Detection of familial hypercholesterolaemia: external validation of the FAMCAT clinical case-finding algorithm to identify patients in primary care

Background: The vast majority of individuals with familial hypercholesterolaemia (FH) in the general population remain unidentified worldwide. Recognising patients most at risk of having the condition, to enable targeted specialist assessment and treatment, could prevent major coronary morbidity and mortality. We evaluated the performance of a clinical case-finding algorithm for FH (FAMCAT), and compared it to currently recommended methods for FH detection in primary care.Methods: The FAMCAT regression equations were applied to a retrospective cohort of 747,000 patients, aged over 16 years with cholesterol assessed, who were randomly selected from 1500 primary care practices across the United Kingdom contributing to the QResearch® database, from 1 January 1999 to 1 September 2017. There were 1,219 cases of FH identified during this period. We compared the performance of FAMCAT to other established clinical case-finding approaches recommended internationally (Simon-Broome, Dutch Lipid Clinic Score Network, MEDPED, and cholesterols levels over 99th centile). Discrimination was assessed by area under the receiver operating curve (AUROC). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were provided. Findings: FAMCAT showed high levels of AUROC discrimination (0.832, 95% CI 0.820 – 0.845), performing significantly better than Simon-Broome criteria (0.694, 95% CI 0.681 – 0.703), Dutch Lipid Clinic Score (0.724, 95% CI 0.710 – 0.738), MEDPED (0.624, 95% CI 0.609 – 0.638), and screening cholesterols > 99th centile (0.581, 95% CI 0.570 – 0.591). Using a 1/500 probability threshold (prevalence of FH), FAMCAT achieved a sensitivity of 84% (1,028 predicted/1,219 observed cases) and specificity of 60% (443,949 predicted/746,993 observed non-cases), with a corresponding PPV of 0.34% and NPV of nearly 100%.Interpretation: FAMCAT identifies FH with significantly greater accuracy than currently recommended approaches, and should be considered for clinical case-finding of patients at highest likelihood of having FH in primary care

Clustering populations by health and social care with multiple long-term conditions: a cohort study - the English Longitudinal Study of Ageing (ELSA)

Background The integration of health and social care services is a potential solution for improving care, despite monetary constraints and increasing demand. How two or more multiple long-term conditions (MLTC) cluster, interact and associate with socioeconomic factors, and affect access to unscheduled primary healthcare services is understudied. Aim To cluster an MLTC population by health and social care, examine clusters, and quantify associations with health outcomes. Method A retrospective cohort study was conducted using the ELSA database (2002 to 2019) on 19802 participants aged ≥50 years. Ten major health conditions, and social care need, including difficulty in activities of daily living (ADL) and mobility, for example, were used to cluster MLTC by latent class modelling. Multivariate logistic regression models were used to establish further association. Results The mean age of the participants at baseline (wave 2) was about 66 years and 55% of participants were female, with more than 60% developing MLTC in their lifetime (waves 2 to 9). Of the five distinct latent clusters, cluster 5 was the most significant cluster composed of lung diseases, stroke, dementia, and high ADL and mobility difficulty scores. The majority of the participants were aged 70–79 years, female, and married. The odds of having a longer nursing home stay were 8.97 (95% confidence interval = 4.36 to 18.45), and death was 10% higher in this cluster compared to the highest probability cluster 4 in the maximally adjusted regression model. Conclusion This study identified MLTC clusters by social care need with the highest primary care demand. Targeting clinical practice to prevent MLTC progression for these groups may lessen future pressures on primary care demand

Hip fracture outcomes in patients with COPD

Hip fractures are common in patients with COPD and contemporary outcome data is needed. Patients admitted with a hip fracture to one acute trust (2010-2015) were assessed prospectively (UK National Hip Fracture Database audit) and mortality data collected. Of the 4020 patients, 16.2% had a recorded COPD diagnosis. Mortality was significantly greater in patients with COPD compared to non-COPD: 30-days (12.6% vs 7.8%) and 1-year (35.3% vs 25.3%), both p[less than] 0.001 and remained significant after adjustment (aOR at 1 year 1.44 95% CI1.18 -1.76). There is further excess mortality following a hip fracture in those with COPD

The changing clinical pattern of endemic Burkitt lymphoma in Western Africa: Experience from a tertiary center in Ghana

Abstract Background Burkitt lymphoma (BL) is the most common childhood cancer in Ghana, where the endemic variant is the predominant subtype and historically presents as a highly chemo-sensitive jaw tumor. This study aimed to update the current epidemiological characteristics of childhood BL in our institution. Procedure Patient data for all children diagnosed with BL and seen at Korle Bu Teaching Hospital between January 2007 and December 2012 were retrospectively analyzed. Results BL was diagnosed in 173 children

Statin treatment and LDL-cholesterol treatment goal attainment among individuals with familial hypercholesterolaemia in primary care

Objectives: Guidance recommends statin treatment in Familial Hypercholesterolaemia (FH) achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). We assessed statin prescribing rates and LDL-cholesterol treatment goal attainment among individuals with FH in primary care.Methods: Using primary care electronic health records from the UK Clinical Practice Research Datalink (CPRD), we identified adults with recorded diagnosis of FH, statin treatment, and measures of LDL-cholesterol prior to (baseline) and 12 months after initiating statin treatment. The percentage change in LDL-cholesterol was determined, and then baseline and treatment characteristics were assessed by LDL-cholesterol treatment goal attainment. Results: Of 3,064 adults (mean age 50.8 years) with recorded diagnosis of FH and repeat LDL-C measures, 50% reduction in LDL-cholesterol from baseline, was attained in 895 individuals (29.2%) in 12 months. Compared to those who did not attain this goal, these people were predominantly females, they were older at time of FH diagnosis (53.4 years vs 49.7 years) and first statin treatment (53.2 years vs 49.2 years); and had higher pre-treatment total cholesterol (8.20 (SD 1.38) mmol/l vs 7.57 (SD 1.39) mmol/l) and pre-treatment LDL-cholesterol (5.83 (SD 1.36) mmol vs 5.25 (SD 1.40) mmol/l). A higher proportion of individuals who attained the treatment goal were prescribed high and medium potency statins (24.3% and 71.7% versus 20.2% and 69.3%, respectively).Conclusions: Less than a third of individuals on statin treatment for FH in the community achieve recommended reductions in LDL-cholesterol. Greater awareness and optimisation of treatment for FH using higher potency statins is needed

Long-term body mass index changes in overweight and obese adults and the risk of heart failure, cardiovascular disease and mortality: a cohort study of over 260,000 adults in the UK

Background: Although obesity is a well-recognised risk factor for cardiovascular disease (CVD), the impact of long-term body mass index (BMI) changes in overweight or obese adults, on the risk of heart failure, CVD and mortality has not been quantified.Methods: This population-based cohort study used routine UK primary care electronic health data linked to secondary care and death-registry records. We identified adults who were overweight or obese, free from CVD and who had repeated BMI measures. Using group-based trajectory modelling, we examined the BMI trajectories of these individuals and then determined incidence rates of CVD, heart failure and mortality associated with the different trajectories. Cox-proportional hazards regression determined hazards ratios for incident outcomes. Results: 264,230 individuals (mean age 49.5 years (SD 12.7) and mean BMI 33.8kg/m2 (SD 6.1)) were followed-up for a median duration of 10.9 years. Four BMI trajectories were identified, corresponding at baseline, with World Health Organisation BMI classifications for overweight, class-1, class-2 and class-3 obesity respectively. In all four groups, there was a small, stable upwards trajectory in BMI (mean BMI increase of 1.06kg/m2 (± 3.8)). Compared with overweight individuals, class-3 obese individuals had hazards ratios (HR) of 3.26 (95% CI 2.98-3.57) for heart failure, HR of 2.72 (2.58-2.87) for all-cause mortality and HR of 3.31 (2.84-3.86) for CVD-related mortality, after adjusting for baseline demographic and cardiovascular risk factors. Conclusion: The majority of adults who are overweight or obese retain their degree of overweight or obesity over the long term. Individuals with stable severe obesity experience the worst heart failure, CVD and mortality outcomes. These findings highlight the high cardiovascular toll exacted by continuing failure to tackle obesity