Mortality rates and proximal causes of death in patients with Lewy body dementia versus Alzheimer's disease: A longitudinal study using secondary care mental health records.

BACKGROUND: Previous studies have shown reduced survival in Lewy body dementia (LBD) compared to Alzheimer's disease (AD), but the reasons for this are not known. We identified cause of death categories accounting for the reduced survival in LBD. METHODS: We linked cohorts of patients with dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and AD, with proximal cause of death data. We examined mortality by dementia group and hazard ratios for each death category by dementia group in males and females separately. In a specific focus on the dementia group with the highest mortality rate versus reference, we examined cumulative incidence to identify the main causes of death accounting for the excess deaths. RESULTS: Hazard ratios for death were higher in PDD and DLB compared to AD, for both males and females. PDD males had the highest hazard ratio for death across the dementia comparison groups (HR 2.7, 95% CI 2.2-3.3). Compared with AD, hazard ratios for "nervous system" causes of death were significantly elevated in all LBD groups. Additional significant cause-of-death categories included aspiration pneumonia, genitourinary causes, other respiratory causes, circulatory and a "symptoms and signs" category in PDD males; other respiratory causes in DLB males; mental disorders in PDD females; and aspiration pneumonia, genitourinary and other respiratory causes in DLB females. CONCLUSION: Further research and cohort development is required to investigate differences by age group, to extend cohort follow-up to the whole population and to investigate the risk-balance of interventions which may differ by dementia group.

Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study.

BACKGROUND: Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality than Alzheimer's disease (AD). The reasons for this are unclear, but antidementia drugs (including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit people with DLB and might improve outcomes. We investigated whether AChEIs and/or memantine were associated with reduced hospital admissions and mortality. METHODS AND FINDINGS: We performed a retrospective cohort study of those diagnosed with DLB between 1 January 2005 and 31 December 2019, using data from electronic clinical records of secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million), as well as linked records from national Hospital Episode Statistics (HES) data. Eligible patients were those who started AChEIs or memantine within 3 months of their diagnosis (cases) and those who never used AChEIs or memantine (controls). Outcomes included admission, length of stay, and mortality. Cox proportional hazard and linear regression models were used. Of 592 patients with DLB, 219 never took AChEIs or memantine, 100 took AChEIs only, and 273 took both AChEIs and memantine. The cohorts were followed up for an average of 896 days, 981 days, and 1,004 days, respectively. There were no significant differences in the cohorts' baseline characteristics, except for socioeconomic status that was lower in patients who never took AChEIs or memantine (χ2 = 23.34, P = 0.003). After controlling for confounding by sociodemographic factors (age, sex, marital status, ethnicity, socioeconomic status), antipsychotic use, antidepressant use, cognitive status, physical comorbidity, anticholinergic burden, and global health performance, compared with patients who never took AChEIs or memantine, patients taking AChEIs only or taking both had a significantly lower risk of death (adjusted hazard ratio (HR) = 0.67, 95% CI = 0.48 to 0.93, p = 0.02; adjusted HR = 0.64, 95% CI = 0.50 to 0.83, P = 0.001, respectively). Those taking AChEIs or both AChEIs and memantine had significantly shorter periods of unplanned hospital admission for physical disorders (adjusted coefficient -13.48, 95% CI = [-26.87, -0.09], P = 0.049; adjusted coefficient -14.21, 95% CI = [-24.58, -3.85], P = 0.007, respectively), but no difference in length of stay for planned admissions for physical disorders, or for admissions for mental health disorders. No significant additional associations of memantine on admission, length of stay, and mortality were found (all P > 0.05). The main limitation was that this was a naturalistic study and possible confounds cannot be fully controlled, and there may be selection bias resulting from nonrandom prescription behaviour in clinical practice. However, we mimicked the intention-to-treat design of clinical trials, and the majority of baseline characters were balanced between cohorts. In addition, our series of sensitivity analyses confirmed the consistency of our results. CONCLUSION: In this study, we observed that use of AChEIs with or without memantine in DLB was associated with shorter duration of hospital admissions and decreased risk of mortality. Although our study was naturalistic, it supports further the use of AChEIs in DLB.

Investigation of risk of dementia diagnosis and death in patients in older people's secondary care mental health services.

OBJECTIVES: Previous studies have shown increased rates of death and dementia in older people in specific serious mental illnesses (SMI) such as bipolar disorder or depression. We examined the rates of death and dementia in older people referred into a secondary care psychiatric service across a range of SMIs. METHODS: We used an anonymised dataset across 6 consecutive years with 28,340 patients aged 65 years and older from a single secondary care psychiatric trust in the United Kingdom. We identified deaths and incident dementia in patients with bipolar disorder/mania, schizophrenia, recurrent depression and anxiety disorders. We compared mortality and dementia rates between these diagnostic groups and in different treatment settings. We also examined mortality rates and dementia rates compared with general population rates. RESULTS: Patients with schizophrenia showed the highest hazard rate for death compared to other groups with SMIs (hazard ratio, 1.58; 95% confidence interval (CI), 1.18-2.1, with anxiety group the reference). Survival was reduced in patients referred to liaison psychiatry services. There were no significant differences between the SMI groups in terms of rates of dementia. However, risks of death and dementia were significantly increased compared to the general population (standardized mortality rates with 95% CI, 2.6(2.0-3.3), 3.5(2.6-4.5), 2.5(2.0-3.0) and 1.8 (1.4-2.2) and standardized dementia incidence rates with 95% CI, 2.7(1.5-4.1), 2.9(1.5-4.7), 3.8(2.6-5.2) and 4.3 (3.0-5.7) for bipolar disorder/mania, schizophrenia, recurrent depression and anxiety disorders respectively. CONCLUSIONS: Older adults referred into an old age psychiatry service show higher rates of dementia and death than those reported for the general population.

Fecal occult blood test performance indicators in warfarin-treated patients.

BACKGROUND: Antithrombotic drugs such as warfarin cause a general increase in bleeding tendency and therefore could influence fecal occult blood test results. METHODS: A population-based retrospective cohort study was conducted to investigate the performance of the fecal occult blood test for colorectal cancer screening in patients taking warfarin. The study population included 1356 tests performed in warfarin-treated patients and 64,088 tests in those not taking antithrombotics. Data on lower gastrointestinal evaluation were collected on 425 cases with a positive fecal occult blood test: all positives on warfarin and positive cases of a subsample of those tests in the group without antithrombotic treatment. RESULTS: The positivity rate of the fecal occult blood test in the warfarin group was found to be doubled (7.7% (95%CI, 6.3%-9.2%)) compared with those not taking antithrombotics (3.6% (95%CI, 3.4%-3.7%)) (P <.0001). No significant difference in the positive predictive value for carcinoma and significant adenomas was found comparing the warfarin group to the no-antithrombotic group. The detection rates of both clinically significant adenomas and findings not indicative of significant neoplasia were increased in the warfarin group (8.9/1000 and 32.5/1000 respectively) compared with the no-antithrombotic group (4.0/1000 and 11.3/1000) (P = .02 and P <.0001 respectively), whereas that of carcinoma was not found to be different (3.7/1000 in the warfarin group vs 3.3/1000, P = .85). CONCLUSIONS: Fecal occult blood test screening in warfarin users results in a higher, yet reasonable, positivity load and in a higher detection of premalignant lesions than in the general population. We consider fecal occult blood test screening appropriate for the warfarin-taking population.

The Medium-Term Impact of COVID-19 Lockdown on Referrals to Secondary Care Mental Health Services: A Controlled Interrupted Time Series Study.

To date, there is a paucity of information regarding the effect of COVID-19 or lockdown on mental disorders. We aimed to quantify the medium-term impact of lockdown on referrals to secondary care mental health clinical services. We conducted a controlled interrupted time series study using data from Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), UK (catchment population ~0.86 million). The UK lockdown resulted in an instantaneous drop in mental health referrals but then a longer-term acceleration in the referral rate (by 1.21 referrals per day per day, 95% confidence interval [CI] 0.41-2.02). This acceleration was primarily for urgent or emergency referrals (acceleration 0.96, CI 0.39-1.54), including referrals to liaison psychiatry (0.68, CI 0.35-1.02) and mental health crisis teams (0.61, CI 0.20-1.02). The acceleration was significant for females (0.56, CI 0.04-1.08), males (0.64, CI 0.05-1.22), working-age adults (0.93, CI 0.42-1.43), people of White ethnicity (0.98, CI 0.32-1.65), those living alone (1.26, CI 0.52-2.00), and those who had pre-existing depression (0.78, CI 0.19-1.38), severe mental illness (0.67, CI 0.19-1.15), hypertension/cardiovascular/cerebrovascular disease (0.56, CI 0.24-0.89), personality disorders (0.32, CI 0.12-0.51), asthma/chronic obstructive pulmonary disease (0.28, CI 0.08-0.49), dyslipidemia (0.26, CI 0.04-0.47), anxiety (0.21, CI 0.08-0.34), substance misuse (0.21, CI 0.08-0.34), or reactions to severe stress (0.17, CI 0.01-0.32). No significant post-lockdown acceleration was observed for children/adolescents, older adults, people of ethnic minorities, married/cohabiting people, and those who had previous/pre-existing dementia, diabetes, cancer, eating disorder, a history of self-harm, or intellectual disability. This evidence may help service planning and policy-making, including preparation for any future lockdown in response to outbreaks.

Evaluating a computer aid for assessing stomach symptoms (ECASS): study protocol for a randomised controlled trial.

BACKGROUND: For most cancers, only a minority of patients have symptoms meeting the National Institute for Health and Clinical Excellence guidance for urgent referral. For gastro-oesophageal cancers, the 'alarm' symptoms of dysphagia and weight loss are reported by only 32 and 8 % of patients, respectively, and their presence correlates with advanced-stage disease. Electronic clinical decision-support tools that integrate with clinical computer systems have been developed for general practice, although uncertainty remains concerning their effectiveness. The objectives of this trial are to optimise the intervention and establish the acceptability of both the intervention and randomisation, confirm the suitability and selection of outcome measures, finalise the design for the phase III definitive trial, and obtain preliminary estimates of the intervention effect. METHODS/DESIGN: This is a two-arm, multi-centre, cluster-randomised, controlled phase II trial design, which will extend over a 16-month period, across 60 general practices within the North East and North Cumbria and the Eastern Local Clinical Research Network areas. Practices will be randomised to receive either the intervention (the electronic clinical decision-support tool) or to act as a control (usual care). From these practices, we will recruit 3000 adults who meet the trial eligibility criteria and present to their GP with symptoms suggestive of gastro-oesophageal cancer. The main measures are the process data, which include the practitioner outcomes, service outcomes, diagnostic intervals, health economic outcomes, and patient outcomes. One-on-one interviews in a sub-sample of 30 patient-GP dyads will be undertaken to understand the impact of the use or non-use of the electronic clinical decision-support tool in the consultation. A further 10-15 GPs will be interviewed to identify and gain an understanding of the facilitators and constraints influencing implementation of the electronic clinical decision-support tool in practice. DISCUSSION: We aim to generate new knowledge on the process measures regarding the use of electronic clinical decision-support tools in primary care in general and to inform a subsequent definitive phase III trial. Preliminary data on the impact of the support tool on resource utilisation and health care costs will also be collected. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN12595588 .

The pattern of association between U.S. economic indicators and infant mortality rates at the state level.

This cross-sectional ecological study examines the pattern of association of state income and income inequality (measured by Gini coefficient) with state infant mortality rates (IMRs) in the U.S. Scatter plots and correlation coefficients were used to examine bivariate associations and bubble plots to examine three-way relationships. Infant mortality rate was positively associated with Gini (R=0.397, p=.004) and negatively with income (R=-0.482, p <.001). However using Black and White IMRs, the associations with Gini were non-significant, but with income remained significant. The bubble plot of Gini versus White IMR (income represented by bubble size) showed increasing IMR as Gini increases and income decreases, except for a subgroup of high-gini, high-income states with low IMRs. State income appears to be a stronger and more consistent predictor of U.S. IMRs for both Black and White races and can explain the pattern of association of White IMR with state Gini coefficient.

Scalable combinatorial tools for health disparities research.

Despite staggering investments made in unraveling the human genome, current estimates suggest that as much as 90% of the variance in cancer and chronic diseases can be attributed to factors outside an individual's genetic endowment, particularly to environmental exposures experienced across his or her life course. New analytical approaches are clearly required as investigators turn to complicated systems theory and ecological, place-based and life-history perspectives in order to understand more clearly the relationships between social determinants, environmental exposures and health disparities. While traditional data analysis techniques remain foundational to health disparities research, they are easily overwhelmed by the ever-increasing size and heterogeneity of available data needed to illuminate latent gene x environment interactions. This has prompted the adaptation and application of scalable combinatorial methods, many from genome science research, to the study of population health. Most of these powerful tools are algorithmically sophisticated, highly automated and mathematically abstract. Their utility motivates the main theme of this paper, which is to describe real applications of innovative transdisciplinary models and analyses in an effort to help move the research community closer toward identifying the causal mechanisms and associated environmental contexts underlying health disparities. The public health exposome is used as a contemporary focus for addressing the complex nature of this subject.

Exploration of preterm birth rates using the public health exposome database and computational analysis methods.

Recent advances in informatics technology has made it possible to integrate, manipulate, and analyze variables from a wide range of scientific disciplines allowing for the examination of complex social problems such as health disparities. This study used 589 county-level variables to identify and compare geographical variation of high and low preterm birth rates. Data were collected from a number of publically available sources, bringing together natality outcomes with attributes of the natural, built, social, and policy environments. Singleton early premature county birth rate, in counties with population size over 100,000 persons provided the dependent variable. Graph theoretical techniques were used to identify a wide range of predictor variables from various domains, including black proportion, obesity and diabetes, sexually transmitted infection rates, mother's age, income, marriage rates, pollution and temperature among others. Dense subgraphs (paracliques) representing groups of highly correlated variables were resolved into latent factors, which were then used to build a regression model explaining prematurity (R-squared = 76.7%). Two lists of counties with large positive and large negative residuals, indicating unusual prematurity rates given their circumstances, may serve as a starting point for ways to intervene and reduce health disparities for preterm births.

Excellent performance of Hemoccult Sensa in organised colorectal cancer screening.

BACKGROUND: Faecal occult blood (FOB) testing is the most commonly chosen approach in organised population-based colorectal cancer screening programmes throughout the world. Several FOB tests are available which differ in their test qualities. While immunological tests are gaining popularity due to their lower labour intensive analysis and higher standardisation, they are heat labile and more expensive. We studied the real-life experience of a large population-based, organised, screening programme in Israel which employs FOB testing with Hemoccult Sensa, a guaiac test with increased sensitivity that is similar to that of the immunological tests for cancer. METHODS: Clalit Health Services is the largest health care provider in Israel. All eligible insurees are actively invited to perform a free-of-charge, home-based, faecal occult blood test, using Hemoccult Sensa. All tests with positive results are followed up and information on colonoscopy, surgical procedures and pathology findings is collected. RESULTS: During an 18 month period (July 2007-December 2008) 382,792 FOBT tests (in 325,851 people) were performed by the target population, of them 85% Jews and 15% Arabs. Seven hundred and eighteen colorectal cancers and 2652 adenomas were detected. The overall test positivity rate in repeatedly-tested people was 4.2%. The overall detection rate of colorectal cancer in the subsequent tests was 1.7/1000 reflecting 91% of the expected period-incidence of CRC. 70% of the cancers were detected at stages Duke's B2 and lower. Left-sided cancers were detected at a significantly better stage than right-sided cancers (P<0.001). Detection rates among Arabs were somewhat lower than among Jews but the screening programme led to a meaningful increase in national incidence rate in this subgroup by detecting tumours that were otherwise asymptomatic. CONCLUSION: The Clalit organised colorectal cancer screening programme, using low cost Hemoccult Sensa, has reached the targets of very high detection rate of cancers, most of them at low stage while keeping a low positivity rate. This approach demonstrates an efficient field-tested alternative to other, more costly, screening options.

The longitudinal variability of serum 25(OH)D levels.

BACKGROUND: The extent to which a single serum 25(OH)D measurement represents long-term vitamin D status remains unclear. This study aims to assess the variability of serum 25(OH)D between tests taken at different time intervals. METHODS: Using the computerized database of the largest healthcare provider in Israel, we identified subjects in whom a serum 25(OH)D test was performed on at least two different occasions between January 2008 and September 2011 (n = 188,771). For these subjects we selected the first and the last dated tests, then we identified those who were not treated with supplements during the last 6 months before the first and before the last test (n = 94,418). Of these we analyzed subjects in whom the first and the last tests were performed in the same month of the year (n = 8881). RESULTS: The mean serum 25(OH)D level at the first test was 51.7 ± 24.0 nmol/L and was 56.7 ± 24.7 at the last test (P<0.001); the overall correlation was 0.63 (P < 0.001). For vitamin D status in two categories (<50 versus ≥ 50 nmol/L), the percentage of agreement between the first and last tests was 74.4%, and was 50.8% for vitamin D status in four categories (<30, 30-49.9, 50-74.9, and ≥ 75 nmol/L). The correlation decreased with increasing time between the tests ranging from 0.83 for tests done at the same year to 0.55 after 3 years. The more the first levels were higher or lower, the more likely subjects remain in their first category (≥ 50 versus <50 nmol/L). CONCLUSIONS: Long-term month specific serum 25(OH)D levels are relatively stable.

Unraveling seasonality in population averages: an examination of seasonal variation in glucose levels in diabetes patients using a large population-based data set.

It has been shown that the population average blood glucose level of diabetes patients shows seasonal variation, with higher levels in the winter than summer. However, seasonality in the population averages could be due to a tendency in the individual to seasonal variation, or alternatively due to occasional high winter readings (spiking), with different individuals showing this increase in different winters. A method was developed to rule out spiking as the dominant pattern underlying the seasonal variation in the population averages. Three years of data from three community-serving laboratories in Israel were retrieved. Diabetes patients (N = 3243) with a blood glucose result every winter and summer over the study period were selected. For each individual, the following were calculated: seasonal average glucose for all winters and summers over the period of study (2006-2009), winter-summer difference for each adjacent winter-summer pair, and average of these five differences, an index of the degree of spikiness in the pattern of the six seasonal levels, and number of times out of five that each winter-summer difference was positive. Seasonal population averages were examined. The distribution of the individual's differences between adjacent seasons (winter minus summer) was examined and compared between subgroups. Seasonal population averages were reexamined in groups divided according to the index of the degree of spikiness in the individual's glucose pattern over the series of seasons. Seasonal population averages showed higher winter than summer levels. The overall median winter-summer difference on the individual level was 8 mg/dL (0.4 mmol/L). In 16.9% (95% confidence interval [CI]: 15.6-18.2%) of the population, all five winter-summer differences were positive versus 3.6% (95% CI: 3.0-4.2%) where all five winter-summer differences were negative. Seasonal variation in the population averages was not attenuated in the group having the lowest spikiness index; comparison of the distributions of the winter-summer differences in the high-, medium-, and low-spikiness groups showed no significant difference (p = .213). Therefore, seasonality in the population average blood glucose in diabetes patients is not just the result of occasional high measurements in different individuals in different winters, but presumably reflects a general periodic tendency in individuals for winter glucose levels to be higher than summer levels.