Patient preferences for treatment attributes in moderate-to-severe atopic dermatitis: a discrete choice experiment.

Purpose: Evidence on treatment preferences of patients with moderate-to-severe atopic dermatitis (AD) in the United States (US) is limited and an assessment of treatment preferences in this group is warranted.Materials and methods: An online discrete choice experiment survey was conducted (June 2023) among US adults with self-reported moderate-to-severe AD or experience with systemic therapy who had inadequate response to topical treatments. Preference weights estimated from conditional logistic regression models were used to calculate willingness to trade off and attributes' relative importance (RI).Results: Participants (N = 300; mean age: 45 years; 70% females; 52% systemic therapy experienced) preferred treatments with higher efficacy, lower risk of adverse events (AEs), and less frequent blood tests (p < .05). Treatment attributes, from high to low RI, were itch control (38%), risk of cancer (23%), risk of respiratory infections (18%), risk of heart problems (11%), sustained improvement in skin appearance (5%), blood test frequency (3%), and frequency and mode of administration (2%); together, AE attributes accounted for more than half of the RI.Conclusions: Participants preferred AD treatments that maximize itch control while minimizing AE risks, whereas mode of administration had little impact on preferences. Understanding patients' preferences may help improve shared decision-making, potentially leading to enhanced patient satisfaction with treatment, increased engagement, and better clinical outcomes.

Budget impact of capmatinib for adults with metastatic non-small cell lung cancer harboring a MET exon 14 skipping mutation in the United States.

AIMS: To estimate the budget impact of adding capmatinib, the first FDA approved MET inhibitor, to a US commercial or Medicare health plan for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have a mutation that leads to MET exon 14 (METex14) skipping. METHODS: Target population size was estimated using published epidemiology data. Clinical data were obtained from the GEOMETRY mono-1 capmatinib trial and published trials. Treatments in the market mix included crizotinib, pembrolizumab, ramucirumab, and chemotherapy. Uptake of capmatinib and testing rates were based on market research. All costs (drug acquisition and administration, pre-progression, progression, terminal care, adverse event, and testing) were estimated based on public sources (2020 USD). RESULTS: The number of patients eligible for capmatinib in the first three years was estimated to be 2-3 in a hypothetical 1 million member commercial plan and 34-44 in a hypothetical 1 million member Medicare plan each year. The estimated total budget impact ranged from $9,695 to $67,725 for a commercial plan and $141,350 to $985,695 for Medicare. With capmatinib included, a marginal per member per month budget impact was estimated (commercial: $0.0008 to $0.0056; Medicare: $0.0118 to $0.0821). Capmatinib inclusion resulted in lower medical costs (commercial: -$0.0003 to -$0.0007; Medicare: -$0.0037 to -$0.0106), partially offsetting increased drug costs ($0.0011 to $0.0064; $0.0154 to $0.0928, respectively), and were primarily driven by reductions in progression and terminal care costs (-$0.0003 to -$0.0009; -$0.0037 to -$0.0125, respectively). The results were most sensitive to capmatinib market share, capmatinib price, and treatment duration. LIMITATIONS: Certain assumptions were applied to the model to account for inputs with limited evidence. CONCLUSIONS: The estimated budget impact of including capmatinib for mNSCLC with a METex14 skipping mutation is minimal, and the increased drug costs were partially offset by savings in AEs, and progression-related and terminal care costs.

Cost-Effectiveness of Antihypertensive Therapy in Patients Older Than 80 Years: Cohort Study and Markov Model.

BACKGROUND: Blood pressure and antihypertensive treatment (AHT) generally increase with age, but there is uncertainty concerning the value of treatment at very advanced ages. OBJECTIVES: To estimate the cost-effectiveness of AHT in people aged 80 years and older. METHODS: A Markov model compared AHT with no blood pressure treatment for prevention of cardiovascular disease. Outcomes were new stroke, coronary heart disease, and diabetes, with falls included as a potential complication of AHT. Costs were evaluated from a health system perspective. Incidence, mortality, and costs of healthcare utilization were estimated from linked primary and secondary care electronic health records for 98 220 individuals aged 80 years and older. Clinical effectiveness estimates were from the Hypertension in the Very Elderly Trial. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In the base case, AHT was associated with an additional 725 quality-adjusted life-years (QALYs) and £4.3 million per 1000, with an incremental cost-effectiveness ratio (ICER) of £5977 per QALY. The ICER was most sensitive to the cost of falls and relative risk reduction in stroke incidence. Probabilistic sensitivity analysis gave 95% uncertainty intervals: £5057 to £8398 per QALY in men and £4955 to £8218 per QALY in women. AHT for secondary prevention in participants with coronary heart disease gave an ICER of £9903 per QALY. CONCLUSIONS: AHT is estimated to be cost-effective in individuals aged 80 years and older, even if health benefits are smaller or side effects costlier than in the base case. Benefits and harms for vulnerable subgroups require further evaluation.

Incidence and mortality of fractures by frailty level over 80 years of age: cohort study using UK electronic health records.

OBJECTIVE: This study aimed to estimate the association of frailty with incidence and mortality of fractures at different sites in people aged over 80 years. DESIGN: Cohort study. SETTING: UK family practices from 2001 to 2014. PARTICIPANTS: 265 195 registered participants aged 80 years and older. MEASUREMENTS: Frailty status classified into 'fit', 'mild', 'moderate' and 'severe' frailty. Fractures, classified into non-fragility and fragility, including fractures of femur, pelvis, shoulder and upper arm, and forearm/wrist. Incidence of fracture, and mortality within 90 days and 1 year, were estimated. RESULTS: There were 28 643 fractures including: non-fragility fractures, 9101; femur, 12 501; pelvis, 2172; shoulder and upper arm, 4965; and forearm/wrist, 6315. The incidence of each fracture type was higher in women and increased with frailty category (femur, severe frailty compared with 'fit', incidence rate ratio (IRR) 2.4, 95% CI 2.3 to 2.6). Fractures of the femur (95-99 years compared with 80-84 years, IRR 2.7, 95% CI 2.6 to 2.9) and pelvis (IRR 2.9, 95% CI 2.5 to 3.3) were strongly associated with age but non-fragility and forearm fractures were not. Mortality within 90 days was greatest for femur fracture (adjusted HR, compared with forearm fracture 4.3, 95% CI 3.7 to 5.1). Mortality was higher in men and increased with age (HR 5.3, 95% CI 4.3 to 6.5 in those over 100 years compared with 80-84 years) but was less strongly associated with frailty category. Similar associations with fractures were seen at 1-year mortality. CONCLUSIONS: The incidence of fractures at all sites was higher in women and strongly associated with advancing frailty status, while the risk of mortality after a fracture was greater in men and was associated with age rather than frailty category.

Determinants of health care costs in the senior elderly: age, comorbidity, impairment, or proximity to death?

Ageing is assumed to be accompanied by greater health care expenditures but the association is also viewed as a 'red herring'. This study aimed to evaluate whether age is associated with health care costs in the senior elderly, using electronic health records for 98,220 participants aged 80 years and over registered with the UK Clinical Practice Research Datalink and linked Hospital Episode Statistics (2010-2014). Annual costs of health care utilization were estimated from a two-part model; multiple fractional polynomial models were employed to evaluate the non-linear association of age with predicted health care costs while also controlling for comorbidities, impairments, and death proximity. Annual health care costs increased from 80 years (£2972 in men, £2603 in women) to 97 (men; £4721) or 98 years (women; £3963), before declining. Costs were significantly elevated in the last year of life but this effect declined with age, from £10,027 in younger octogenarians to £7021 in centenarians. This decline was steeper in participants with comorbidities or impairments; £14,500 for 80-84-year-olds and £6752 for centenarians with 7+ impairments. At other times, comorbidity and impairments, not age, were main drivers of costs. We conclude that comorbidities, impairments, and proximity to death are key mediators of age-related increases in health care costs. While the costs of comorbidity among survivors are not generally associated with age, additional costs in the last year of life decline with age.

'Fair innings' in the face of ageing and demographic change.

There are now 125 million people aged 80 years and over worldwide, projected by the United Nations to grow threefold by 2050. While increases in life expectancy and rapid increases in the older-age population are considered positive developments, the consequential future health care burden represents a leading concern for health services. We revisit Williams' 'fair innings' argument from 1997, in light of technological and demographic changes, and challenge the notion that greater longevity may impose an unfair burden on younger generations. We discuss perspectives on the equity-efficiency trade-off in terms of their implications for the growing over-80 population, as well as society in general. This includes questioning the comparison of treatment cost-effectiveness in younger vs. older populations when using quality-adjusted life years and the transience of life expectancies over generations. While recognising that there will never be a clear consensus regarding societal value judgements, we present empirical evidence on the very elderly that lends support to a stronger anti-ageist stance given current increases in longevity.

Evolution of the "fourth stage" of epidemiologic transition in people aged 80 years and over: population-based cohort study using electronic health records.

BACKGROUND: In the "fourth stage" of epidemiological transition, the distribution of non-communicable diseases is expected to shift to more advanced ages, but age-specific changes beyond 80 years of age have not been reported. METHODS: This study aimed to evaluate demographic and health transitions in a population aged 80 years and over in the United Kingdom from 1990 to 2014, using primary care electronic health records. Epidemiological analysis of chronic morbidities and age-related impairments included a cohort of 299,495 participants, with stratified sampling by five-year age group up to 100 years and over. Cause-specific proportional hazards models were used to estimate hazard ratios for incidence rates over time. RESULTS: Between 1990 and 2014, nonagenarians and centenarians increased as a proportion of the over-80 population, as did the male-to-female ratio among individuals aged 80 to 95 years. A lower risk of coronary heart disease (HR 0.54, 95% confidence interval [CI]: 0.50-0.58), stroke (0.83, 0.76-0.90) and chronic obstructive pulmonary disease (0.59, 0.54-0.64) was observed among 80-84 year-olds in 2010-2014 compared to 1995-1999. By contrast, the risk of type II diabetes (2.18, 1.96-2.42), cancer (1.52, 1.43-1.61), dementia (2.94, 2.70-3.21), cognitive impairment (5.57, 5.01-6.20), and musculoskeletal pain (1.26, 1.21-1.32) was greater in 2010-2014 compared to 1995-1999. CONCLUSIONS: Redistribution of the over-80 population to older ages, and declining age-specific incidence of cardiovascular and respiratory diseases in over-80s, are consistent with the "fourth stage" of epidemiologic transition, but increases in diabetes, cancer, and age-related impairment show new emerging epidemiological patterns in the senior elderly.

Declining blood pressure and intensification of blood pressure management among people over 80 years: cohort study using electronic health records.

BACKGROUND: Management of high blood pressure (BP) in people over 80 years is controversial, but there is limited information available concerning the uptake of hypertension treatment at this age. OBJECTIVE: To evaluate use of antihypertensive drugs and changes in SBP and DBP from 2001 to 2014 in men and women aged 80 years and over. METHODS: Cohort study using primary care electronic health records of 265 225 participants from the UK Clinical Practice Research Datalink. Records of BP and antihypertensive medications were analysed. Linear trends were estimated by frailty category in multiple regression models. RESULTS: Data were analysed for 116 401 men and 148 824 women. The proportion with BP recorded increased from 51% in 2001 to 78% in 2014. The proportion of patients prescribed antihypertensive medications increased from 64 to 76%. Mean SBP declined from 150 (SD 20) mmHg in 2001 to 135 (16) mmHg in 2014. In 'fit' participants, the decline in SBP was 12.4 (95% confidence interval 11.9-13.0) mmHg/decade in those treated for hypertension and 8.5 (7.8-9.1) mmHg in those not treated. The decline in SBP was smaller as frailty increased. The proportion of all participants with BP less than 140/90 mmHg increased from 14 to 44% in the study period. CONCLUSION: In octogenarians, BP treatment has intensified between 2001 and 2014. BP values have declined in both treated and untreated participants, with a substantial increase in the proportion achieving conventional BP targets.

Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of Age: Cohort Study Using Electronic Health Records.

BACKGROUND: Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ≥80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death. METHODS: A population-based cohort study was conducted using electronic health records of 144 403 participants ≥80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ≤5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportional-hazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death. RESULTS: During follow-up, 51 808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110 to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40-6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30-7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life. CONCLUSIONS: A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life.

Drug Utilization and Inappropriate Prescribing in Centenarians.

OBJECTIVES: To use primary care electronic health records (EHRs) to evaluate prescriptions and inappropriate prescribing in men and women at age 100. DESIGN: Population-based cohort study. SETTING: Primary care database in the United Kingdom, 1990 to 2013. PARTICIPANTS: Individuals reaching the age of 100 between 1990 and 2013 (N = 11,084; n = 8,982 women, n = 2,102 men). MEASUREMENTS: Main drug classes prescribed and potentially inappropriate prescribing according to the 2012 American Geriatrics Society Beers Criteria. RESULTS: At the age of 100, 73% of individuals (79% of women, 54% of men) had received one or more prescription drugs, with a median of 7 (interquartile range 0-12) prescription items. The most frequently prescribed drug classes were cardiovascular (53%), central nervous system (CNS) (53%), and gastrointestinal (47%). Overall, 32% of participants (28% of men, 32% of women) who received drug prescriptions may have received one or more potentially inappropriate prescriptions, with temazepam and amitriptyline being the most frequent. CNS prescriptions were potentially inappropriate in 23% of individuals, and anticholinergic prescriptions were potentially inappropriate in 18% of individuals. CONCLUSION: The majority of centenarians are prescribed one or more drug therapies, and the prescription may be inappropriate for up to one-third of these individuals. Research using EHRs offers opportunities to understand prescribing trends and improve pharmacological care of the oldest adults.

Longitudinal Trends in Hypertension Management and Mortality Among Octogenarians: Prospective Cohort Study.

The role of hypertension management among octogenarians is controversial. In this long-term follow-up (>10 years) study, we estimated trends in hypertension prevalence, awareness, treatment, and control among octogenarians, and evaluated the relationship of systolic blood pressure (SBP) ranges with mortality. Data were based on the English Longitudinal Study of Ageing (ELSA). Outcome measures were hypertension prevalence, awareness, treatment and control, and cardiovascular disease, and all-cause mortality events. Participants were separated into 8 categories of SBP values (<110, 110-119, 120-129, 130-139, 140-149, 150-159, 160-169, and >169 mm Hg). Among 2692 octogenarians, mean SBP levels declined from 147 mm Hg in 1998/2000 to 134 mm Hg in 2012/2013. The decline was of lower magnitude in the 50 to 79 years old subgroup (n=22007). Hypertension prevalence and awareness were 40% and 13%, respectively, higher among octogenarians than the 50 to 79 years of age subgroup, but hypertension treatment rates were similar (≈90%). Around 47% of the treated octogenarians achieved conventional BP targets (<140/90 mm Hg), increasing to 59% when assessed against revised targets (<150/90 mm Hg). All-cause mortality rates were higher (hazard ratio, 1.55; 95% confidence interval, 0.89-2.72) at lower extremes of SBP values (<110 mm Hg). The lowest cardiovascular disease and all-cause mortality risk among treated octogenarians was observed for an SBP range of 140 to 149 mm Hg (1.04, 0.60-1.78) and 160 to 169 mm Hg (0.78, 0.51-1.21). An increasing trend in hypertension awareness and treatment was observed in a large sample of community-dwelling octogenarians. The results do not support the view that more stringent BP targets may be associated with lower mortality.

Incidence and mortality of relapsing polychondritis in the UK: a population-based cohort study.

OBJECTIVE: Relapsing polychondritis is a rare disease characterized by cartilage inflammation. Our aim was to estimate the incidence, prevalence and mortality of relapsing polychondritis and describe the clinical features of relapsing polychondritis in a large population. METHODS: All participants diagnosed with relapsing polychondritis were sampled from the Clinical Practice Research Datalink. Prevalence and incidence rates for 1990-2012 were estimated. Relative mortality rates were estimated in a time-to-event framework using reference UK life tables. A questionnaire validation study assessed diagnostic accuracy. RESULTS: There were 117 participants with relapsing polychondritis ever recorded. Fifty (82%) of 61 cases were validated by a physician and unconfirmed cases were excluded. The analysis included 106 participants (42 men, 64 women) diagnosed with relapsing polychondritis. The mean age (range) at diagnosis in men was 55 (range 17-81) years and in women 51 (range 11-79) years. The median interval from first symptom to diagnosis was 1.9 years. The incidence of relapsing polychondritis between 1990 and 2012 was 0.71 (95% CI 0.55, 0.91) per million population per year. There were 19 deaths from any cause. There were 16 observed deaths eligible for survival analysis and 7.4 deaths expected for the UK population of the same age, sex and period. The standardized mortality ratio was 2.16 (95% CI 1.24, 3.51), P < 0.01. Respiratory disease, cardiac conditions and cancer were the most frequent causes of death. CONCLUSION: The incidence of relapsing polychondritis may be lower than previously estimated, and diagnostic misclassification and delay are common. Mortality in relapsing polychondritis is more than twice that of the general population.

Differences in Health at Age 100 According to Sex: Population-Based Cohort Study of Centenarians Using Electronic Health Records.

OBJECTIVES: To use primary care electronic health records (EHRs) to evaluate the health of men and women at age 100. DESIGN: Population-based cohort study. SETTING: Primary care database in the United Kingdom, 1990-2013. PARTICIPANTS: Individuals reaching the age of 100 between 1990 and 2013 (N = 11,084, n = 8,982 women, n = 2,102 men). MEASUREMENTS: Main categories of morbidity and an index of multiple morbidities, geriatric syndromes and an index of multiple impairments, cardiovascular risk factors. RESULTS: The number of new female centenarians per year increased from 16 per 100,000 in 1990-94 to 25 per 100,000 in 2010-13 (P < .001) and of male centenarians from four per 100,000 to six per 100,000 (P = .06). The most prevalent morbidities at the age of 100 were musculoskeletal diseases, disorders of the senses, and digestive diseases. Women had greater multiple morbidity than men (odds ratio (OR) = 1.64, 95% confidence interval (CI) = 1.42-1.89, P < .001). Geriatric syndromes, including falls, fractures, hearing and vision impairment, and dementia, were frequent; 30% of women and 49% of men had no recorded geriatric syndromes. Women had greater likelihood of having multiple geriatric syndromes (OR = 2.14, 95% CI = 1.90-2.41, P < .001). CONCLUSION: Fewer men than women reach the age of 100, but male centenarians have lower morbidity and fewer geriatric syndromes than women. Research using EHRs offers opportunities to understand the epidemiology of aging and improve care of the oldest old.

Evaluating pancreatitis in primary care: a population-based cohort study.

BACKGROUND: Pancreatitis is an important condition with significant mortality. Primary care may have an important role to play in its prevention, early diagnosis, and ongoing management. AIM: To evaluate incidence, case fatality, and clinical features of acute and chronic pancreatitis in a large population. DESIGN AND SETTING: Population-based cohort study using a primary care database in the UK from 1990 to 2013. METHOD: Use of general practice records from 16 491 patients diagnosed with pancreatitis. Age-standardised incidence rates and case fatality were estimated. Clinical features, aetiology, and patterns of recurrence were evaluated. RESULTS: Incidence of pancreatitis increased from 14.8 in 100 000 (1990-1994) to 31.2 in 100 000 (2010-2013) in males, and from 14.5 to 28.3 in 100 000 in females (2010-2013). Overall case fatality after diagnosis was 4.3% (95% CI = 4.0% to 4.6%) at 90 days and 7.9% (95% CI = 7.5% to 8.4%) at 365 days. In 1990-1994, 10% of patients with acute pancreatitis were recorded as heavy drinkers, increasing to 12% in 2010-2012; for patients with chronic pancreatitis the proportions were 13%, rising to 21%. Among patients who died in the 90 days after diagnosis, 92% consulted with their general practice in the 2 months before first diagnosis. CONCLUSION: The incidence of pancreatitis is increasing over time. Alcohol abuse may now account for at least one in eight cases of acute, and one in five cases of chronic pancreatitis. Consultations among those who subsequently died may have offered potential for earlier diagnosis and intervention.