Individualized Absolute Risk Calculations for Persons with Multiple Chronic Conditions: Embracing Heterogeneity, Causality, and Competing Events

Approximately 75% of adults over the age of 65 years are affected by two or more chronic medical conditions. We provide a conceptual justification for individualized absolute risk calculators for competing patient-centered outcomes (PCO) (i.e. outcomes deemed important by patients) and patient reported outcomes (PRO) (i.e. outcomes patients report instead of physiologic test results). The absolute risk of an outcome is the probability that a person receiving a given treatment will experience that outcome within a pre-defined interval of time, during which they are simultaneously at risk for other competing outcomes. This allows for determination of the likelihood of a given outcome with and without a treatment. We posit that there are heterogeneity of treatment effects among patients with multiple chronic conditions (MCC) largely depends on those coexisting conditions. We outline the development of an individualized absolute risk calculator for competing outcomes using propensity score methods that strengthen causal inference for specific treatments. Innovations include the key concept that any given outcome may or may not concur with any other outcome and that these competing outcomes do not necessarily preclude other outcomes. Patient characteristics and MCC will be the primary explanatory factors used in estimating the heterogeneity of treatment effects on PCO and PRO. This innovative method may have wide-spread application for determining individualized absolute risk calculations for competing outcomes. Knowing the probabilities of outcomes in absolute terms may help the burgeoning population of patients with MCC who face complex treatment decisions

Ethnic differences in respiratory impairment

Objective Spirometric Z scores by lambda-mu-sigma (LMS) rigorously account for age-related changes in lung function. Recently, the Global Lung Function Initiative (GLI) expanded LMS spirometric Z scores to multiple ethnicities. Hence, in aging populations, the GLI provides an opportunity to rigorously evaluate ethnic differences in respiratory impairment, including airflow limitation and restrictive pattern. Methods Using data from the Third National Health and Nutrition Examination Survey, including participants aged 40-80, we evaluated ethnic differences in GLI-defined respiratory impairment, including prevalence and associations with mortality and respiratory symptoms. Results Among 3506 white Americans, 1860 African Americans and 1749 Mexican Americans, the prevalence of airflow limitation was 15.1% (13.9% to 16.4%), 12.4% (10.7% to 14.0%) and 8.2% (6.7% to 9.8%), and restrictive pattern was 5.6% (4.6% to 6.5%), 8.0% 6.9% to 9.0%) and 5.7% (4.5% to 6.9%), respectively. Airflow limitation was associated with mortality in white Americans, African Americans and Mexican Americans - adjusted HR (aHR) 1.66 (1.23 to 2.25), 1.60 (1.09 to 2.36) and 1.80 (1.17 to 2.76), respectively, but associated with respiratory symptoms only in white Americans - adjusted OR (aOR) 2.15 (1.70 to 2.73). Restrictive pattern was associated with mortality but only in white Americans and African Americans - aHR 2.56 (1.84 to 3.55) and 3.23 (2.06 to 5.05), and associated with respiratory symptoms but only in white Americans and Mexican Americans-aOR 2.16 (1.51 to 3.07) and .12 (1.45 to 3.08), respectively. Conclusions In an aging population, we found ethnic differences in GLI-defined respiratory impairment. In particular, African Americans had high rates of respiratory impairment that were associated with mortality but not respiratory symptoms

Chronic obstructive pulmonary disease in older persons: A comparison of two spirometric definitions

SummaryBackgroundAmong older persons, we previously endorsed a two-step spirometric definition of chronic obstructive pulmonary disease (COPD) that requires a ratio of forced expiratory volume in 1sec to forced vital capacity (FEV1/FVC) below .70, and an FEV1 below the 5th or 10th standardized residual percentile (“SR-tile strategy”).ObjectiveTo evaluate the clinical validity of an SR-tile strategy, compared to a current definition of COPD, as published by the Global Initiative for Obstructive Lung Disease (GOLD-COPD), in older persons.MethodsWe assessed national data from 2480 persons aged 65–80 years. In separate analyses, we evaluated the association of an SR-tile strategy with mortality and respiratory symptoms, relative to GOLD-COPD. As per convention, GOLD-COPD was defined solely by an FEV1/FVC<.70, with severity staged according to FEV1 cut-points at 80 and 50 percent predicted (%Pred).ResultsAmong 831 participants with GOLD-COPD, the risk of death was elevated only in 179 (21.5%) of those who also had an FEV1<5th SR-tile; and the odds of having respiratory symptoms were elevated only in 310 (37.4%) of those who also had an FEV1<10th SR-tile. In contrast, GOLD-COPD staged at an FEV1 50–79%Pred led to misclassification (overestimation) in terms of 209 (66.4%) and 77 (24.6%) participants, respectively, not having an increased risk of death or likelihood of respiratory symptoms.ConclusionRelative to an SR-tile strategy, the majority of older persons with GOLD-COPD had neither an increased risk of death nor an increased likelihood of respiratory symptoms. These results raise concerns about the clinical validity of GOLD guidelines in older persons

Hereditary breast cancer and ancestry in the Madeira archipelago: An exploratory study

Access to genetic testing and counselling in remote areas such as the Madeira archipelago, in the Northern Atlantic Ocean, may be complex. Different counselling methods, including telegenetics, should be explored. In this study, we characterise the Hereditary Breast/Ovarian Cancer (HBOC) families with Madeira ancestry enrolled in our programme. Of a total of 3, 566 index patients tested between January 2000 and June 2018, 68 had Madeira ancestry and 22 were diagnosed with a pathogenic germline variant (PV). As in the whole group, BRCA2 PV were more frequent in Madeira patients (68.4%: c.9382C>T (26.3%), c.658_659del (21%), c.156_157insAlu (10.5%), c.793+1G>A (5.3%) and c.298A>T (5.3%). However, the most frequently diagnosed PV in Madeira patients was the BRCA1 c.3331_3334del (31.6%). BRCA1/2 detection rates were 27.9% and 10.5% for Madeira and the whole group, respectively. This study is the first characterisation of HBOC patients with Madeira ancestry. A distinct pattern of BRCA1/2 variants was observed, and the geographic clustering of BRCA1 c.3331_3334del variant may support the possibility of a founder mutation previously described in Northern Portugal. The high detection rate observed reinforces the need to reduce gaps in access to genetic testing in Madeira and other remote areas. According to current guidelines, timely identification of HBOC patients can contribute to their ongoing care and treatment

Development, Validation, and Assessment of an Ischemic Stroke or Transient Ischemic Attack-Specific Prediction Tool for Obstructive Sleep Apnea

BACKGROUND: Screening instruments for obstructive sleep apnea (OSA), as used routinely to guide clinicians regarding patient referral for polysomnography (PSG), rely heavily on symptomatology. We sought to develop and validate a cerebrovascular disease-specific OSA prediction model less reliant on symptomatology, and to compare its performance with commonly used screening instruments within a population with ischemic stroke or transient ischemic attack (TIA). METHODS: Using data on demographic factors, anthropometric measurements, medical history, stroke severity, sleep questionnaires, and PSG from 2 independently derived, multisite, randomized trials that enrolled patients with stroke or TIA, we developed and validated a model to predict the presence of OSA (i.e., Apnea-Hypopnea Index ≥5 events per hour). Model performance was compared with that of the Berlin Questionnaire, Epworth Sleepiness Scale (ESS), the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender instrument, and the Sleep Apnea Clinical Score. RESULTS: The new SLEEP Inventory (Sex, Left heart failure, ESS, Enlarged neck, weight [in Pounds], Insulin resistance/diabetes, and National Institutes of Health Stroke Scale) performed modestly better than other instruments in identifying patients with OSA, showing reasonable discrimination in the development (c-statistic .732) and validation (c-statistic .731) study populations, and having the highest negative predictive value of all in struments. CONCLUSIONS: Clinicians should be aware of these limitations in OSA screening instruments when making decisions about referral for PSG. The high negative predictive value of the SLEEP INventory may be useful in determining and prioritizing patients with stroke or TIA least in need of overnight PSG

An Official American Thoracic Society Workshop Report: Evaluation and Management of Asthma in the Elderly

Asthma in the elderly (&gt;65 yr old) is common and associated with higher morbidity and mortality than asthma in younger patients. The poor outcomes in this group are due, in part, to underdiagnosis and undertreatment. There are a variety of factors related to aging itself that affect the presentation of asthma in the elderly and influence diagnosis and management. Structural changes in the aging lung superimposed on structural changes due to asthma itself can worsen the disease and physiologic function. Changes in the aging immune system influence the cellular composition and function in asthmatic airways. These processes and differences from younger individuals with asthma are not well understood. Phenotypes of asthma in the elderly have not been clearly delineated, but it is likely that age of onset and overlap with chronic obstructive pulmonary disease impact disease characteristics. Physiologic tests and biomarkers used to diagnose and follow asthma in the elderly are generally similar to testing in younger individuals; however, whether they should be modified in aging has not been established. Confounding influences, such as comorbidities (increasing the risk of polypharmacy), impaired cognition and motor skills, psychosocial effects of aging, and age-related adverse effects of medications, impact both diagnosis and treatment of asthma in the elderly. Future efforts to understand asthma in the elderly must include geriatric-specific methodology to diagnose, characterize, monitor, and treat their disease

Diagnosing and managing sleep apnea in patients with chronic cerebrovascular disease: a randomized trial of a home-based strategy

Background Obstructive sleep apnea is common and associated with poor outcomes after stroke or transient ischemic attack (TIA). We sought to determine whether the intervention strategy improved sleep apnea detection, obstructive sleep apnea (OSA) treatment, and hypertension control among patients with chronic cerebrovascular disease and hypertension. Methods In this randomized controlled strategy trial intervention, patients received unattended polysomnography at baseline, and patients with OSA (apnea-hypopnea index ≥5 events/h) received auto-titrating continuous positive airway pressure (CPAP) for up to 1 year. Control patients received usual care and unattended polysomnography at the end of the study, to identify undiagnosed OSA. Both groups received 24-h blood pressure assessments at baseline and end of the study. “Excellent” CPAP adherence was defined as cumulative use of ≥4 h/night for ≥70% of the nights. Results Among 225 randomized patients (115 control; 110 intervention), 61.9% (120/194) had sleep apnea. The strategy successfully diagnosed sleep apnea with 97.1% (102/105) valid studies; 90.6% (48/53, 95% CI 82.7–98.4%) of sleep apnea was undiagnosed among control patients. The intervention improved long-term excellent CPAP use: 38.6% (22/57) intervention versus 0% (0/2) control (p < 0.0001). The intervention did not improve hypertension control in this population with well-controlled baseline blood pressure: intervention, 132.7 mmHg (±standard deviation, 14.1) versus control, 133.8 mmHg (±14.0) (adjusted difference, −1.1 mmHg, 95% CI (−4.2, 2.0)), p = 0.48). Conclusions Patients with cerebrovascular disease and hypertension have a high prevalence of OSA. The use of portable polysomnography, and auto-titrating CPAP in the patients’ homes, improved both the diagnosis and the treatment for sleep apnea compared with usual care but did not lower blood pressure

Infarct Location and Sleep Apnea: Evaluating the Potential Association in Acute Ischemic Stroke.

Background: The literature about the relationship between obstructive sleep apnea (OSA) and stroke location is conflicting with some studies finding an association and others demonstrating no relationship. Among acute ischemic stroke patients, we sought to examine the relationship between stroke location and the prevalence of OSA; OSA severity based on apnea-hypopnea index (AHI), arousal frequency, and measure of hypoxia; and number of central and obstructive respiratory events. Methods: Data were obtained from patients who participated in a randomized controlled trial (NCT01446913) that evaluated the effectiveness of a strategy of diagnosing and treating OSA among patients with acute ischemic stroke and transient ischemic attack. Stroke location was classified by brain imaging reports into subdivisions of lobes, subcortical areas, brainstem, cerebellum, and vascular territory. The association between acute stroke location and polysomnographic findings was evaluated using logistic regression for OSA presence and negative binomial regression for AHI. Results: Among 73 patients with complete polysomnography and stroke location data, 58 (79%) had OSA. In unadjusted models, no stroke location variable was associated with the prevalence or severity of OSA. Similarly, in multivariable modeling, groupings of stroke location were also not associated with OSA presence. Conclusions: These results indicate that OSA is present in the majority of stroke patients and imply that stroke location cannot be used to identify a group with higher risk of OSA. The results also suggest that OSA likely predated the stroke. Given this high overall prevalence, strong consideration should be given to obtaining polysomnography for all ischemic stroke patients

Diagnosing and Treating Sleep Apnea in Patients With Acute Cerebrovascular Disease

Background Obstructive sleep apnea ( OSA ) is common among patients with acute ischemic stroke and transient ischemic attack. We evaluated whether continuous positive airway pressure for OSA among patients with recent ischemic stroke or transient ischemic attack improved clinical outcomes. Methods and Results This randomized controlled trial among patients with ischemic stroke/transient ischemic attack compared 2 strategies (standard or enhanced) for the diagnosis and treatment of OSA versus usual care over 1 year. Primary outcomes were National Institutes of Health Stroke Scale and modified Rankin Scale scores. Among 252 patients (84, control; 86, standard; 82, enhanced), OSA prevalence was as follows: control, 69%; standard, 74%; and enhanced, 80%. Continuous positive airway pressure use occurred on average 50% of nights and was similar among standard (3.9±2.1 mean hours/nights used) and enhanced (4.3±2.4 hours/nights used; P=0.46) patients. In intention-to-treat analyses, changes in National Institutes of Health Stroke Scale and modified Rankin Scale scores were similar across groups. In as-treated analyses among patients with OSA, increasing continuous positive airway pressure use was associated with improved National Institutes of Health Stroke Scale score (no/poor, -0.6±2.9; some, -0.9±1.4; good, -0.3±1.0; P=0.0064) and improved modified Rankin Scale score (no/poor, -0.3±1.5; some, -0.4±1.0; good, -0.9±1.2; P=0.0237). In shift analyses among patients with OSA, 59% of intervention patients had best neurological symptom severity (National Institutes of Health Stroke Scale score, 0-1) versus 38% of controls ( P=0.038); absolute risk reduction was 21% (number needed to treat, 4.8). Conclusions Although changes in neurological functioning and functional status were similar across the groups in the intention-to-treat analyses, continuous positive airway pressure use was associated with improved neurological functioning among patients with acute ischemic stroke/transient ischemic attack with OS

Perfis municipais de risco a cheias e inundações para aplicação ao ordenamento do território em Portugal continental

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