Flexible parametric methods for calculating life expectancy in small populations.

BACKGROUND: Life expectancy is a simple measure of assessing health differences between two or more populations but current life expectancy calculations are not reliable for small populations. A potential solution to this is to borrow strength from larger populations from the same source, but this has not formally been investigated. METHODS: Using data on 451,222 individuals from the Clinical Practice Research Datalink on the presence/absence of intellectual disability and type 2 diabetes mellitus, we compared stratified and combined flexible parametric models, and Chiang's methods, for calculating life expectancy. Confidence intervals were calculated using the Delta method, Chiang's adjusted life table approach and bootstrapping. RESULTS: The flexible parametric models allowed calculation of life expectancy by exact age and beyond traditional life expectancy age thresholds. The combined model that fit age interaction effects as a spline term provided less bias and greater statistical precision for small covariate subgroups by borrowing strength from the larger subgroups. However, careful consideration of the distribution of events in the smallest group was needed. CONCLUSIONS: Life expectancy is a simple measure to compare health differences between populations. The use of combined flexible parametric methods to calculate life expectancy in small samples has shown promising results by allowing life expectancy to be modelled by exact age, greater statistical precision, less bias and prediction of different covariate patterns without stratification. We recommend further investigation of their application for both policymakers and researchers.

A scoping review of clusters of multiple long-term conditions in people with intellectual disabilities and factors impacting on outcomes for this patient group.

People with intellectual disabilities (ID) are vulnerable to multiple long-term conditions (MLTC). However, in the UK, there are no individual strategies tailored for them. This study synthesised evidence on prevalence of MLTC in people with ID alongside risk factors, outcomes and preventative strategies. The scoping review used the tool Abstrackr to search retrieved articles from three bibliographic databases. Of 933 articles initially screened and further identified, 20 papers met our inclusion criteria. Our findings revealed significant data on prevalence of MLTC in people with ID across the studies, but very limited data on clusters or patterns of co-occurrence in this population. The majority of papers explored risk factors and strategies for prevention of MLTC, but far fewer compared outcomes by MLTC. The identified gaps in the literature indicate the need for further research to identify clusters of MLTC and tailored prevention strategies to reduce poor outcomes in this population.

Immortal time bias for life-long conditions in retrospective observational studies using electronic health records.

BACKGROUND: Immortal time bias is common in observational studies but is typically described for pharmacoepidemiology studies where there is a delay between cohort entry and treatment initiation. METHODS: This study used the Clinical Practice Research Datalink (CPRD) and linked national mortality data in England from 2000 to 2019 to investigate immortal time bias for a specific life-long condition, intellectual disability. Life expectancy (Chiang's abridged life table approach) was compared for 33,867 exposed and 980,586 unexposed individuals aged 10+ years using five methods: (1) treating immortal time as observation time; (2) excluding time before date of first exposure diagnosis; (3) matching cohort entry to first exposure diagnosis; (4) excluding time before proxy date of inputting first exposure diagnosis (by the physician); and (5) treating exposure as a time-dependent measure. RESULTS: When not considered in the design or analysis (Method 1), immortal time bias led to disproportionately high life expectancy for the exposed population during the first calendar period (additional years expected to live: 2000-2004: 65.6 [95% CI: 63.6,67.6]) compared to the later calendar periods (2005-2009: 59.9 [58.8,60.9]; 2010-2014: 58.0 [57.1,58.9]; 2015-2019: 58.2 [56.8,59.7]). Date of entry of diagnosis (Method 4) was unreliable in this CPRD cohort. The final methods (Method 2, 3 and 5) appeared to solve the main theoretical problem but residual bias may have remained. CONCLUSIONS: We conclude that immortal time bias is a significant issue for studies of life-long conditions that use electronic health record data and requires careful consideration of how clinical diagnoses are entered onto electronic health record systems.

Comparing the number and length of primary care consultations in people with and without intellectual disabilities and health needs: observational cohort study using electronic health records.

BACKGROUND: In the United Kingdom, 15-min appointments with the general practitioner (GP) are recommended for people with complex health conditions, including intellectual disabilities and health needs, but we do not know whether this happens. AIMS: We compared number and length of primary care consultations (GP, nurse, other allied health, other) for people with and without intellectual disabilities and health needs. METHODS: Linked primary care data from the Clinical Practice Research Datalink (CPRD) in England were used to investigate face-to-face and telephone primary care consultations in 2017-2019. Health needs investigated were: epilepsy; incontinence; severe visual/hearing impairments; severe mobility difficulties; cerebral palsy; and percutaneous endoscopic gastrostomy feeding. Age and gender-standardized consultation rates per year (Poisson), duration of consultations, and the proportion of "long consultations" (≥15 min) were reported. RESULTS: People with intellectual disabilities (n = 7,794) had 1.9 times as many GP consultations per year as those without (n = 176,807; consultation rate ratio = 1.87 [95% confidence interval 1.86-1.89]). Consultation rates with nurses and allied healthcare professionals were also twice as high. Mean GP consultation time was 9-10 min regardless of intellectual disability/health need status. Long GP consultations were less common in people with intellectual disabilities (18.2% [17.8-18.7] vs. 20.9% [20.8-21.0]). Long consultations with practice nurses were more common in people with health needs, particularly severe visual loss. CONCLUSIONS: People with intellectual disabilities and/or health needs tend to have more, rather than longer, GP consultations compared with the rest of the population. We recommend further investigation into the role of practice nurses to support people with intellectual disabilities and health needs.

Comparative effectiveness of gliclazide modified release versus sitagliptin as second-line treatment after metformin monotherapy in patients with uncontrolled type 2 diabetes.

AIMS: To compare the effectiveness and safety of gliclazide modified release (MR) to sitagliptin as type 2 diabetes mellitus (T2D) treatments in a real-world patient population. MATERIALS AND METHODS: This retrospective cohort study used records from the UK Clinical Practice Research Datalink. The cohort consisted of adult patients with T2D newly treated with either gliclazide MR or sitagliptin as second-line treatment added to metformin and with a glycated haemoglobin (HbA1c) level of ≥7.0% (53 mmol/mol). Patients were 1:1 matched using high-dimensional propensity score matching and followed to determine the time taken to reach an HbA1c <7.0%. Secondary outcomes included time to HbA1c ≤6.5% (48 mmol/mol), time to ≥1% (11 mmol/mol) HbA1c reduction from baseline, treatment persistence and durability, and hypoglycaemic events. RESULTS: Among the 1986 patients included, those on gliclazide MR more likely achieved an HbA1c <7.0% [hazard ratio (HR): 1.35; 95% confidence interval (CI): 1.15-1.57], HbA1c ≤6.5% (HR: 1.51; 95% CI: 1.19-1.92) or had an HbA1c reduction ≥1% from baseline (HR: 1.11; 95% CI: 1.00-1.24) compared with patients on sitagliptin. Durability (log-rank P = .135) and persistence (P = .119) were similar between the two groups. Hypoglycaemic events were uncommon (23 total severe and non-severe events; incidence rate, 3.7 per 1000 patient years), with 4.7 and 2.6 events per 1000 patient years with gliclazide MR and sitagliptin treatment, respectively. CONCLUSIONS: In this real-world study, second-line gliclazide MR was more effective than sitagliptin in reducing HbA1c, with similar durability and persistence and low rates of hypoglycaemic events, in individuals with T2D on metformin treatment and HbA1c above the target of 7.0%.

Epidemiology of autism in adults across age groups and ability levels.

BACKGROUND: The epidemiology of autism in adults has relied on untested projections using childhood research. AIMS: To derive representative estimates of the prevalence of autism and key associations in adults of all ages and ability levels. METHOD: Comparable clinical diagnostic assessments of 7274 Adult Psychiatric Morbidity Survey participants combined with a population case-register survey of 290 adults with intellectual disability. RESULTS: The combined prevalence of autism in adults of all ages in England was 11/1000 (95% CI 3-19/1000). It was higher in those with moderate to profound intellectual disability (odds ratio (OR) = 63.5, 95% CI 27.4-147.2). Male gender was a strong predictor of autism only in those with no or mild intellectual disability (adjusted OR = 8.5, 95% CI 2.0-34.9; interaction with gender, P = 0.03). CONCLUSIONS: Few adults with autism have intellectual disability; however, autism is more prevalent in this population. Autism measures may miss more women with autism.

Incorporation of patient and public involvement in statistical methodology research: development of an animation.

BACKGROUND: Patient and Public Involvement and Engagement (PPIE) is important to all aspects of health research. However, there are few examples of successful PPIE in statistical methodology research. One of the reasons for this relates to challenges in the identification of individuals interested in statistical methodology research projects, and ambiguities over the importance of PPIE to these projects. METHODS: This project was conducted between August 2022 and August 2023. The aim is to report the process of the development of an accessible animation to describe what statistical methodology is and the importance of PPIE in statistical methodology research projects. For this, we combined storyboarding and scriptwriting with feedback from PPIE members and researchers. RESULTS: After three stages that incorporated feedback from the relevant stakeholders, we produced a final animation about PPIE in statistical methodology. The resulting animation used minimal text, simple animation techniques and was of short duration (< 3 min) to optimise the communication of the key messages clearly and effectively. CONCLUSIONS: The resulting animation provides a starting point for members of the public to learn about PPIE in statistical methodology research and for methodologists who wish to conduct PPIE. We recommend further work to explore ways in which members of the public can be more meaningfully involved in methodology research.

Patient and public involvement and engagement (PPIE) is when members of the public are directly involved in carrying out research projects. This is important because we as researchers want to make sure we are focusing on what matters most to patients, so that the research has as large an impact as possible. PPIE has typically been used in more applied research projects, such as clinical trials, but is equally as important in statistical methodology research, where we focus on making sure the statistical tools that we use in the applied projects are as good as possible. The aim of this project was to create a short animation that helps to explain the importance of PPIE in statistical methodology research projects. Researchers sometimes incorrectly assume that PPIE is less important in these projects as this type of research has a less obvious benefit to patients. The animation helps to further explain these concepts. It describes what statistical methodology research is and why involving members of the public is still important. This paper explains the process of developing the animation, including receiving feedback from members of the public to make sure the animation is accessible to as many people as possible. The result is a short, 3-min animation that is free to view on the NIHR website. This can be used by other researchers to help them when recruiting members of the public to their research projects.

Health Needs and Their Relationship with Life Expectancy in People with and without Intellectual Disabilities in England.

Health needs are common in people living with intellectual disabilities, but we do not know how they contribute to life expectancy. We used the Clinical Practice Research Datalink (CPRD) linked with hospital/mortality data in England (2017-2019) to explore life expectancy among people with or without intellectual disabilities, indicated by the presence or absence, respectively, of: epilepsy; incontinence; severe visual loss; severe visual impairment; severe mobility difficulties; cerebral palsy and PEG feeding. Life expectancy and 95% confidence intervals were compared using flexible parametric methods. At baseline, 46.4% (total n = 7794) of individuals with intellectual disabilities compared with 9.7% (total n = 176,807) in the comparison group had ≥1 health need. Epilepsy was the most common health need (18.7% vs. 1.1%). All health needs except hearing impairment were associated with shorter life expectancy: PEG feeding and mobility difficulties were associated with the greatest loss in life years (65-68% and 41-44%, respectively). Differential life expectancy attenuated but remained (≈12% life years lost) even after restricting the population to those without health needs (additional years expected to live at 10 years: 65.5 [60.3, 71.1] vs. 74.3 [73.8, 74.7]). We conclude that health needs play a significant role but do not explain all of the differential life expectancy experienced by people with intellectual disabilities.

Mortality disparities and deprivation among people with intellectual disabilities in England: 2000-2019.

BACKGROUND: The effect of policy initiatives and deprivation on mortality disparities in people with intellectual disabilities is not clear. METHODS: An electronic health record observational study of linked primary care data in England from the Clinical Practice Research Datalink and the Office for National Statistics deaths data from 2000 to 2019 was undertaken. All-cause and cause-specific mortality for people with intellectual disabilities were calculated by gender and deprivation status (index of multiple deprivation quintile) using direct age-standardised mortality rates (all years) and ratios (SMR; 2000-2009 vs 2010-2019). RESULTS: Among 1.0 million patients (n=33 844 with intellectual disability; n=980 586 general population without intellectual disability), differential mortality was consistently higher in people with intellectual disabilities and there was no evidence of attenuation over time. There was a dose-response relationship between all-cause mortality and lower deprivation quintile in the general population which was not observed in people with intellectual disabilities. Cause-specific SMR were consistent in both the 2000-2009 and 2010-2019 calendar periods, with a threefold increased risk of death in both males and females with intellectual disabilities (SMR ranges: 2.91-3.51). Mortality was highest from epilepsy (SMR ranges: 22.90-52.74) and aspiration pneumonia (SMR ranges: 19.31-35.44). SMRs were disproportionately high for people with intellectual disabilities living in the least deprived areas. CONCLUSIONS: People with intellectual disabilities in England continue to experience significant mortality disparities and there is no evidence that the situation is improving. Deprivation indicators may not be effective for targeting vulnerable individuals.

Safety of antidepressants in a primary care cohort of adults with obesity and depression.

BACKGROUND: Obesity, depressive disorders and antidepressant drugs are associated with increased mortality, cardiovascular disease, diabetes, fractures and falls. We explored outcomes associated with the most commonly prescribed antidepressants in overweight or obese people with depression. METHODS AND FINDINGS: We identified a cohort of overweight or obese adults (≥18 years) in primary care from the UK Clinical Practice Research Datalink, linked with hospital and mortality data, between 1 January 2000 and 31 December 2016 who developed incident depression to January 2019. Cox proportional hazards models and 99% confidence intervals were used to estimate hazard ratios (HR) for mortality, cardiovascular disease, diabetes, and falls/fractures associated with exposure to selective serotonin reuptake inhibitors (SSRIs), tricyclic (TCA)/other, combination antidepressants, citalopram, fluoxetine, sertraline, amitriptyline and mirtazapine, adjusting for potential confounding variables. In 519,513 adults, 32,350 (9.2 per 1,000 years) displayed incident depression and 21,436 (66.3%) were prescribed ≥1 antidepressant. Compared with no antidepressants, all antidepressant classes were associated with increased relative risks of cardiovascular disorders [SSRI HR: 1.32 (1.14-1.53), TCA/Other HR: 1.26 (1.01-1.58)], and diabetes (any type) [SSRI HR: 1.28 (1.10-1.49), TCA/Other: 1.52 (1.19-1.94)]. All commonly prescribed antidepressants except citalopram were associated with increased mortality compared with no antidepressants. However, prescription ≥1 year of ≥40mg citalopram was associated with increased mortality and falls/fractures and ≥1 year 100mg sertraline with increased falls/fractures. CONCLUSIONS: In overweight/obese people with depression, antidepressants may be overall and differentially associated with increased risks of some adverse outcomes. Further research is required to exclude indication bias and residual confounding.

Development, content validation, and reliability of the Assessment of Real-World Observational Studies (ArRoWS) critical appraisal tool.

PURPOSE: The objective was to develop and test a pragmatic critical appraisal tool, the Assessment of Real-World Observational Studies (ArRoWS), to quickly and easily assess the quality of real-world evidence studies using electronic health records. METHODS: The initial ArRoWS tool was developed by identifying items frequently found in existing validated assessment instruments and adapting these items to specifically assess real-world evidence studies. The tool was revised based on recommendations from an expert panel of 14 senior academic individuals specializing in epidemiology and content validity was measured. During March 2018-January 2019, 47 large, observational studies related to cardiometabolic medicine were identified through a search algorithm and assessed by three pairs of raters using the ArRoWS tool. RESULTS: The final version of the ArRoWS had 16 items including nine core items and seven study design-specific items with item-specific content validity indexes ranging from 0.64 to 1.00. The scale-level content validity index of the ArRoWS appraisal tool was 0.91. When the ArRoWS tool was pilot tested, the observed agreement between assessor pairs on whether the study provided high-quality real-world evidence was 85.7%, 68.8%, and 58.8%. The prevalence adjusted bias-adjusted kappa for the assessor pairs was 0.71, 0.38, and 0.18. CONCLUSION: The ArRoWS is a simple tool to standardize the assessment of real-world evidence studies.

Incidence of Depression and First-Line Antidepressant Therapy in People with Obesity and Depression in Primary Care.

OBJECTIVE: The aim of this study was to describe the age- and gender-specific incidence of depression, the dose-response relationship between BMI and risk of depression (Cox proportional hazards), and antidepressant drug prescribing in adults with overweight or obesity. METHODS: A retrospective electronic health record study using the Clinical Practice Research Datalink was conducted to identify adults with overweight and obesity (≥ 18 years) with incident depression (no prior depression diagnosis in their records), followed up from 2000 to 2019. RESULTS: Among 519,513 adults, incidence of depression was 9.2 per 1,000 person-years and was higher in women and in 40- to 59-year-old men who had severe obesity. Compared with having overweight, the hazard of depression increased with each BMI category as follows: 1.13 (30-34 kg/m2 ; 95% CI: 1.10-1.16), 1.34 (35-39 kg/m2 ; 1.29-1.40), 1.51 (40-44 kg/m2 ; 1.41-1.61), and 1.67 (45-49 kg/m2 ; 1.48-1.87), attenuating at BMI 50+ kg/m2 (1.54; 2.91-1.84). Antidepressants were prescribed as first-line therapy in two-thirds (66.3%) of cases. Prescriptions for fluoxetine reduced over time (20.4% [2000]; 8.8% [2018]), and prescriptions for sertraline increased (4.3% [2000]; 38.9% [2018]). CONCLUSIONS: We recommend guidance on antidepressant drug prescribing and specific services for people with obesity and depression that address both symptoms and behaviors.

Testing adults by questionnaire for social and communication disorders, including autism spectrum disorders, in an adult mental health service population.

OBJECTIVES: Autism is difficult to identify in adults due to lack of validated self-report questionnaires. We compared the effectiveness of the autism-spectrum quotient (AQ) and the Ritvo autism-Asperger's diagnostic scale-revised (RAADS-R) questionnaires in adult mental health services in two English counties. METHODS: A subsample of adults who completed the AQ and RAADS-R were invited to take part in an autism diagnostic observation schedule (ADOS Module 4) assessment with probability of selection weighted by scores on the questionnaires. RESULTS: There were 364 men and 374 women who consented to take part. Recorded diagnoses were most commonly mood disorders (44%) and mental and behavioural disorders due to alcohol/substance misuse (19%), and 4.8% (95% CI [2.9, 7.5]) were identified with autism (ADOS Module 4 10+). One had a pre-existing diagnosis of autism; five (26%) had borderline personality disorders (all female) and three (17%) had mood disorders. The AQ and RAADS-R had fair test accuracy (area under receiver operating characteristic [ROC] curve 0.77 and 0.79, respectively). AQ sensitivity was 0.79 (95% CI [0.54, 0.94]) and specificity was 0.77 (95% CI [0.65, 0.86]); RAADS-R sensitivity was 0.75 (95% CI [0.48, 0.93]) and specificity was 0.71 (95% CI [0.60, 0.81]). CONCLUSIONS: The AQ and RAADS-R can guide decisions to refer adults in mental health services to autism diagnostic services.

The relationship between symptoms of autism spectrum disorder and visual impairment among adults with intellectual disability.

The higher prevalence of autism reported in blind children has been commonly attributed to the confounding effects of an underlying intellectual disability. The aim of this study was to explore the relationship between symptoms of autism and blindness in adults with intellectual disability. We hypothesized that blindness can increase the probability of the autism phenotype, independent of known risk factors, that is, severity of intellectual disability and gender. A general population case register (population size of 0.7 million) was used to conduct two studies. The first study was on 3,138 adults with intellectual disability, using a validated autism risk indicator to study adults with visual impairment. This identified 386 adults with partial and complete visual impairment, both of which were associated with presence of high number of autistic traits (P < 0.001). The second study was only on those with congenital blindness using a standardized assessment tool, the Pervasive Developmental Disorder-Mental Retardation Scale. Those with hearing impairment or unilateral, partial, and acquired visual impairment were excluded. Control groups were randomly selected from those with normal hearing and vision. Prevalence of the autism phenotype was higher among those with congenital blindness (n = 46/60; 76.7%) than their controls (n = 36/67; 53.7%) and this association was statistically significant (adjusted odds ratio = 3.03; 95% confidence interval: 1.34-6.89; P = 0.008). Our results support the hypothesis that a congenital blindness independently affects psychosocial development and increases the probability of the autism phenotype. Early identification of autism could facilitate appropriate psychosocial interventions and educational opportunities to improve quality of life of people with blindness. Autism Res 2019, 12: 1411-1422. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Although autism has been commonly reported in those with blindness, it is generally attributed to an accompanying intellectual disability. Current study, however, revealed that congenital blindness is independently associated with symptoms of autism. In spite of its high prevalence, autism can be overlooked in those with intellectual disability and blindness. Improving diagnosis in this population should, therefore, be advocated through raising awareness of this association to facilitate early access to services.

Kidney symptom questionnaire: Development, content validation and relationship with quality of life.

BACKGROUND: Chronic kidney disease (CKD) is associated with a range of symptoms, even at early stages. The importance of patient symptom experience is increasingly recognised, but validated symptom scores are lacking. OBJECTIVES: This study aimed to refine an existing symptom questionnaire for use with patients not requiring renal replacement therapy (RRT), carry out content validity testing and explore convergent validity by comparing symptom scores with quality of life (QoL). DESIGN: A mixed-methods approach involving questionnaires, semi-structured interviews and a focus group. PARTICIPANTS: Patients with CKD not undergoing RRT and expert health professionals. APPROACH: Two hundred and nineteen patients completed an existing symptom questionnaire. The most commonly reported symptoms were identified, and descriptions refined in 11 semi-structured interviews. The questionnaire design was reviewed by a focus group. Content validity was established by a panel of expert health professionals. Seventy patients completed both the symptom questionnaire and a health-related QoL questionnaire (EQ-5D-5L). RESULTS: Thirteen common symptoms were identified. During the content validity phase, 13/16 experts responded (81%); 10/13 symptoms had 'excellent' or 'good' evaluation scores, and the content validity index of the whole questionnaire was 0.81, falling within the recommended threshold. Total symptom frequency scores, number of symptoms and the frequencies of 10/13 individual symptoms were all strongly associated with health-related QoL (EQ-5D-5L index score; p < 0.002 for all). CONCLUSION: This work has provided a new, validated symptom score for patients with CKD not requiring RRT for clinical management and research purposes.

Barriers and Facilitators to Healthy Lifestyle Changes in Minority Ethnic Populations in the UK: a Narrative Review.

Minority ethnic populations experience a disproportionate burden of health inequalities compared with the rest of the population, including an increased risk of type 2 diabetes (T2DM). The purpose of this narrative review was to explore knowledge and attitudes around diabetes, physical activity and diet and identify barriers and facilitators to healthy lifestyle changes in minority ethnic populations in the UK. The narrative review focused on three key research topics in relation to barriers and facilitators to healthy lifestyle changes in minority adult ethnic populations: (i) knowledge and attitudes about diabetes risk; (ii) current behaviours and knowledge about physical activity and diet; and (iii) barriers and facilitators to living a healthier lifestyle. Nearly all of the studies that we identified reported on South Asian minority ethnic populations; we found very few studies on other minority ethnic populations. Among South Asian communities, there was generally a good understanding of diabetes and its associated risk factors. However, knowledge about the levels of physical activity required to gain health benefits was relatively poor and eating patterns varied. Barriers to healthy lifestyle changes identified included language barriers, prioritising work over physical activity to provide for the family, cultural barriers with regard to serving and eating traditional food, different perceptions of a healthy body weight and fear of racial harassment or abuse when exercising. Additional barriers for South Asian women included expectations to remain in the home, fear for personal safety, lack of same gender venues and concerns over the acceptability of wearing 'western' exercise clothing. Facilitators included concern that weight gain might compromise family/carer responsibilities, desire to be healthy, T2DM diagnosis and exercise classes held in 'safe' environments such as places of worship. Our findings suggest that South Asian communities are less likely to engage in physical activity than White populations and highlight the need for health promotion strategies to engage people in these communities. There is a gap in knowledge with regard to diabetes, physical activity, diet and barriers to healthy lifestyle changes among other ethnic minority populations in the UK; we recommend further research in this area.

Symptom burden in patients with chronic kidney disease not requiring renal replacement therapy.

BACKGROUND: Although evidence shows that patients with end stage renal disease (ESRD) experience a high symptom burden which impacts on quality of life (QoL), less is known about patients with earlier stages of chronic kidney disease (CKD). This study aimed to explore symptom burden and potential contributing factors in patients with CKD Stage 1-5 not requiring renal replacement therapy (RRT). METHODS: Patients with CKD Stage 1-5 and not on RRT were asked to report their symptoms using the Leicester Uraemic Symptom Score (LUSS), a questionnaire which assesses the frequency and intrusiveness of 11 symptoms commonly reported by kidney patients. RESULTS: Symptoms were assessed in 283 CKD Stage 1-5 patients: 54% male, mean age 60.5 standard error± 1.0, mean eGFR 38ml/min/1.73m2. Some 96% (95% confidence interval 93.2-98.0) of participants reported experiencing at least one symptom, the median reported being six. Excessive tiredness (81%;76.0-85.6), sleep disturbance (70%;64.3-75.3) and pain in bones/joints (69%;63.4-74.6) were reported most commonly. Overall, few significant associations were found between biochemical markers of disease severity and symptom burden. Men tended to report fewer symptoms than women and South Asian patients often described experiencing symptoms with a greater severity. Older patients found musculoskeletal symptoms more intrusive whereas younger patients found reduced concentration more intrusive. CONCLUSIONS: Our findings suggest that patients with CKD stages 1-5 experience a multitude of symptoms that could potentially impact QoL. Using multidimensional tools like the LUSS, more exploration and focus could provide a greater opportunity for patient focussed symptom control from the earliest stages of CKD.

Bereaved carers' views of a hospice at home service.

INTRODUCTION: In recent years, there has been an increase in specialist palliative care services in the home. Despite this, there have been relatively few published evaluations of such care. METHODS: This is a qualitative study which used semistructured interviews to explore bereaved carers' views and experiences of a hospice at home (HAH) service in the East Midlands, UK. Eleven interviews were conducted and analysis followed the framework approach. RESULTS: Carers' views were divided into four themes: caring for someone at home; formal care provided by HAH; access to out-of-hours care; and provision of specialist equipment. CONCLUSIONS: Bereaved carers generally gave very positive accounts on care delivered by the HAH service. Shortcomings identified were the provision of out-of-hours care and the untimely supply and removal of specialist equipment. It is suggested that bereaved carers provide useful insights for qualitative evaluations of end-of-life services delivered in the home.

Changes over calendar time in the risk of specific first AIDS-defining events following HIV seroconversion, adjusting for competing risks.

BACKGROUND: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion. METHODS: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort. We compared results to those obtained from a cause-specific hazards model. RESULTS: Of 6,941, 2,021 (29%) developed AIDS and 437 (6%) died without AIDS. The risk of AIDS or death remained constant to 1996 then reduced; relative hazard = 0.89 (95% CI: 0.77-1.03); 0.90 (95% CI: 0.81-1.01); and 0.32 (95% CI: 0.28-0.37) for 1979-1990, 1991-1993, and 1997-2001, respectively, compared to 1994-1996. Significant risk reductions in 1997-2001 were observed in all but two AIDS-defining groups and death without AIDS in a competing risks model (with similar results from a cause-specific model). There was significant heterogeneity in the risk reduction across events; from 96% for cryptosporidiosis, to 17% for death without AIDS (P < 0.0001). CONCLUSION: These findings suggest that studies reporting a stable trend for particular AIDS diseases over the period 1979-2001 may not have accounted for the competing risks among other events or lack the power to detect smaller trends.