Evaluation of Time to Benefit of Statins for the Primary Prevention of Cardiovascular Events in Adults Aged 50 to 75 Years: A Meta-analysis.

Importance: Guidelines recommend targeting preventive interventions toward older adults whose life expectancy is greater than the intervention's time to benefit (TTB). The TTB for statin therapy is unknown. Objective: To conduct a survival meta-analysis of randomized clinical trials of statins to determine the TTB for prevention of a first major adverse cardiovascular event (MACE) in adults aged 50 to 75 years. Data Sources: Studies were identified from previously published systematic reviews (Cochrane Database of Systematic Reviews and US Preventive Services Task Force) and a search of MEDLINE and Google Scholar for subsequently published studies until February 1, 2020. Study Selection: Randomized clinical trials of statins for primary prevention focusing on older adults (mean age >55 years). Data Extraction and Synthesis: Two authors independently abstracted survival data for the control and intervention groups. Weibull survival curves were fit, and a random-effects model was used to estimate pooled absolute risk reductions (ARRs) between control and intervention groups each year. Markov chain Monte Carlo methods were applied to determine time to ARR thresholds. Main Outcomes and Measures: The primary outcome was time to ARR thresholds (0.002, 0.005, and 0.010) for a first MACE, as defined by each trial. There were broad similarities in the definition of MACE across trials, with all trials including myocardial infarction and cardiovascular mortality. Results: Eight trials randomizing 65 383 adults (66.3% men) were identified. The mean age ranged from 55 to 69 years old and the mean length of follow-up ranged from 2 to 6 years. Only 1 of 8 studies showed that statins decreased all-cause mortality. The meta-analysis results suggested that 2.5 (95% CI, 1.7-3.4) years were needed to avoid 1 MACE for 100 patients treated with a statin. To prevent 1 MACE for 200 patients treated (ARR = 0.005), the TTB was 1.3 (95% CI, 1.0-1.7) years, whereas the TTB to avoid 1 MACE for 500 patients treated (ARR = 0.002) was 0.8 (95% CI, 0.5-1.0) years. Conclusions and Relevance: These findings suggest that treating 100 adults (aged 50-75 years) without known cardiovascular disease with a statin for 2.5 years prevented 1 MACE in 1 adult. Statins may help to prevent a first MACE in adults aged 50 to 75 years old if they have a life expectancy of at least 2.5 years. There is no evidence of a mortality benefit.

Making Medical Treatment Decisions for Unrepresented Patients in the ICU. An Official American Thoracic Society/American Geriatrics Society Policy Statement.

Background and Rationale: ICU clinicians regularly care for patients who lack capacity, an applicable advance directive, and an available surrogate decision-maker. Although there is no consensus on terminology, we refer to these patients as "unrepresented." There is considerable controversy about how to make treatment decisions for these patients, and there is significant variability in both law and clinical practice.Purpose and Objectives: This multisociety statement provides clinicians and hospital administrators with recommendations for decision-making on behalf of unrepresented patients in the critical care setting.Methods: An interprofessional, multidisciplinary expert committee developed this policy statement by using an iterative consensus process with a diverse working group representing critical care medicine, palliative care, pediatric medicine, nursing, social work, gerontology, geriatrics, patient advocacy, bioethics, philosophy, elder law, and health law.Main Results: The committee designed its policy recommendations to promote five ethical goals: 1) to protect highly vulnerable patients, 2) to demonstrate respect for persons, 3) to provide appropriate medical care, 4) to safeguard against unacceptable discrimination, and 5) to avoid undue influence of competing obligations and conflicting interests. These recommendations also are intended to strike an appropriate balance between excessive and insufficient procedural safeguards. The committee makes the following recommendations: 1) institutions should offer advance care planning to prevent patients at high risk for becoming unrepresented from meeting this definition; 2) institutions should implement strategies to determine whether seemingly unrepresented patients are actually unrepresented, including careful capacity assessments and diligent searches for potential surrogates; 3) institutions should manage decision-making for unrepresented patients using input from a diverse interprofessional, multidisciplinary committee rather than ad hoc by treating clinicians; 4) institutions should use all available information on the patient's preferences and values to guide treatment decisions; 5) institutions should manage decision-making for unrepresented patients using a fair process that comports with procedural due process; 6) institutions should employ this fair process even when state law authorizes procedures with less oversight.Conclusions: This multisociety statement provides guidance for clinicians and hospital administrators on medical decision-making for unrepresented patients in the critical care setting.

Managing grief and depression at the end of life.

Psychological distress is common in terminally ill persons and can be a source of great suffering. Grief is an adaptive, universal, and highly personalized response to the multiple losses that occur at the end of life. This response may be intense early on after a loss manifesting itself physically, emotionally, cognitively, behaviorally, and spiritually; however, the impact of grief on daily life generally decreases with time. Although pharmacologic interventions are not warranted for uncomplicated grief, physicians are encouraged to support patients by acknowledging their grief and encouraging the open expression of emotions. It is important for the physician to distinguish uncomplicated grief reactions from more disabling psychiatric disorders such as major depression. The symptoms of grief may overlap with those of major depression or a terminal illness or its treatment; however, grief is a distinct entity. Feelings of pervasive hopelessness, helplessness, worthlessness, guilt, lack of pleasure, and suicidal ideation are present in patients with depression, but not in those experiencing grief. Psychotherapy and antidepressant medications reduce symptoms of distress and improve quality of life for patients with depression. Physicians may consider psychostimulants, such as methylphenidate, for patients who have depression with a life expectancy of only days to weeks.

Prognostic indices for older adults: a systematic review.

CONTEXT: To better target services to those who may benefit, many guidelines recommend incorporating life expectancy into clinical decisions. OBJECTIVE: To assess the quality and limitations of prognostic indices for mortality in older adults through systematic review. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane, and Google Scholar from their inception through November 2011. STUDY SELECTION: We included indices if they were validated and predicted absolute risk of mortality in patients whose average age was 60 years or older. We excluded indices that estimated intensive care unit, disease-specific, or in-hospital mortality. DATA EXTRACTION: For each prognostic index, we extracted data on clinical setting, potential for bias, generalizability, and accuracy. RESULTS: We reviewed 21,593 titles to identify 16 indices that predict risk of mortality from 6 months to 5 years for older adults in a variety of clinical settings: the community (6 indices), nursing home (2 indices), and hospital (8 indices). At least 1 measure of transportability (the index is accurate in more than 1 population) was tested for all but 3 indices. By our measures, no study was free from potential bias. Although 13 indices had C statistics of 0.70 or greater, none of the indices had C statistics of 0.90 or greater. Only 2 indices were independently validated by investigators who were not involved in the index's development. CONCLUSION: We identified several indices for predicting overall mortality in different patient groups; future studies need to independently test their accuracy in heterogeneous populations and their ability to improve clinical outcomes before their widespread use can be recommended.

Approaching patients and family members who hope for a miracle.

A clinical problem may arise when caring for patients or their surrogates who prefer continued aggressive care based on the belief that a miracle will occur, despite a clinician's belief that further medical treatment is unlikely to have any meaningful benefit. An evidence-based approach is provided for the clinician by breaking this complex clinical problem into a series of more focused clinical questions and subsequently answering them through a critical appraisal of the existing medical literature. Belief in miracles is found to be common in the United States and is an important determinant of how decisions are made for those with advanced illness. There is a growing amount of evidence that suggests end-of-life outcomes improve with the provision of spiritual support from medical teams, as well as with a proactive approach to medical decision making that values statements given by patients and family members.