Publications

IMPORTANCE: Patients undergoing hemodialysis have an annual mortality rate exceeding 20%, comparable to many types of cancer. Past research has shown that patients with cancer overestimate their likelihood of survival relative to their physicians, but this relationship has not been examined in patients with noncancer diagnoses. Perceptions of prognosis and transplant candidacy may influence goals of care.

OBJECTIVES: To compare the perceptions of hemodialysis patients and their nephrologists concerning prognosis and the likelihood of transplant; to follow actual survival; and to explore the relationship between patients' expectations and their goals of care.

DESIGN: We completed a medical record abstraction to estimate 1-year mortality risk among patients who underwent dialysis at any time from November 1, 2010, through September 1, 2011. We then conducted in-person interviews with eligible patients whose predicted 1-year mortality, based on validated prognostic tools, was at least 20%. We also interviewed their nephrologists. We compared patients' and physicians' expectations about 1- and 5-year survival and transplant candidacy and measured the association between patients' expectations and goals of care. We then followed actual survival using Kaplan-Meier methods.

SETTING AND PARTICIPANTS: Two dialysis units in Boston. Two hundred seven patients undergoing hemodialysis included in the medical record review, with 62 eligible patients interviewed.

MAIN OUTCOMES AND MEASURES: Predicted 1-year mortality risk using validated prognostic tools; actual survival; patients' and physicians' expectations about 1-year survival and likelihood of transplant; and patients' goals of care.

RESULTS: Of the 207 hemodialysis patients, 72.5% had a predicted 1-year mortality of at least 20%. Of the 80 patients eligible for interview, 62 participated (response rate, 78%). Patients were significantly more optimistic than their nephrologists about 1- and 5-year survival (P < .001 for both) and were more likely to think they were transplant candidates (37 [66%] vs 22 [39%] [P = .008]). Of the 81% of patients reporting a 90% chance or greater of being alive at 1 year, 18 (44%) preferred care focused on extending life, even if it meant more discomfort, compared with 1 (9%) among patients reporting a lower chance of survival (P = .045). Actual survival was 93% at 1 year but decreased to 79% by 17 months and 56% by 23 months.

CONCLUSIONS AND RELEVANCE: Hemodialysis patients are more optimistic about prognosis and transplant candidacy than their nephrologists. In our sample, patients' expectations about 1-year survival were more accurate than those of their nephrologists, but their longer-term survival expectations dramatically overestimated even their 2-year survival rates. Patients' prognostic expectations are associated with their treatment preferences. Our findings suggest the need for interventions to help providers communicate effectively with patients about prognosis.

BACKGROUND: Heart failure (HF) is a leading cause of hospitalization and mortality. Plasma B-type natriuretic peptide (BNP) is an established diagnostic and prognostic ambulatory HF biomarker. We hypothesized that increased perioperative BNP independently associates with HF hospitalization or HF death up to 5 yr after coronary artery bypass graft surgery.

METHODS: The authors conducted a two-institution, prospective, observational study of 1,025 subjects (mean age = 64 ± 10 yr SD) undergoing isolated primary coronary artery bypass graft surgery with cardiopulmonary bypass. Plasma BNP was measured preoperatively and on postoperative days 1-5. The study outcome was hospitalization or death from HF, with HF events confirmed by reviewing hospital and death records. Cox proportional hazards analyses were performed with multivariable adjustments for clinical risk factors. Preoperative and peak postoperative BNP were added to the multivariable clinical model in order to assess additional predictive benefit.

RESULTS: One hundred five subjects experienced an HF event (median time to first event = 1.1 yr). Median follow-up for subjects who did not have an HF event = 4.2 yr. When individually added to the multivariable clinical model, higher preoperative and peak postoperative BNP concentrations each, independently associated with the HF outcome (log10 preoperative BNP hazard ratio = 1.93; 95% CI, 1.30-2.88; P = 0.001; log10 peak postoperative BNP hazard ratio = 3.38; 95% CI, 1.45-7.65; P = 0.003).

CONCLUSIONS: Increased perioperative BNP concentrations independently associate with HF hospitalization or HF death during the 5 yr after primary coronary artery bypass graft surgery. Clinical trials may be warranted to assess whether medical management focused on reducing preoperative and longitudinal postoperative BNP concentrations associates with decreased HF after coronary artery bypass graft surgery.

OBJECTIVE: Determination of biomarker and neuropathogenesis of postoperative cognitive change (POCC) or postoperative cognitive dysfunction.

BACKGROUND: POCC is one of the most common postoperative complications in elderly patients. Whether preoperative cerebrospinal fluid (CSF) β-amyloid protein (Aβ) to tau ratio, an Alzheimer disease biomarker, is a biomarker for risk of POCC remains unknown. We therefore set out to assess the association between preoperative CSF Aβ42 or Aβ40 to tau ratio and POCC.

METHODS: Patients who had total hip/knee replacement were enrolled. The CSF was obtained during the administration of spinal anesthesia. Cognitive tests were performed with these participants at 1 week before and at 1 week and 3 to 6 months after the surgery. Z scores of the changes from preoperative to postoperative on several key domains of the cognitive battery were determined. We then examined the association between preoperative CSF Aβ42/tau or Aβ40/tau ratio and the outcome measures described earlier, adjusting for age and sex.

RESULTS: Among the 136 participants (mean age = 71 ± 5 years; 55% men), preoperative CSF Aβ42/tau ratio was associated with postoperative Hopkins Verbal Learning Test Retention [Z score = 8.351; age, sex-adjusted (adj.) P = 0.003], and the Benton Judgment of Line Orientation (Z score = 1.242; adj. P = 0.007). Aβ40/tau ratio was associated with Brief Visuospatial Memory Test Total Recall (Z score = 1.045; adj. P = 0.044).

CONCLUSIONS: Preoperative CSF Aβ/tau ratio is associated with postoperative changes in specific cognitive domains. The presence of the Alzheimer's disease biomarker, specifically the Aβ/tau ratio, may identify patients at higher risk for cognitive changes after surgery.

OBJECTIVES: To determine whether a higher blood transfusion threshold would prevent new or worsening delirium symptoms in the hospital after hip fracture surgery.

DESIGN: Ancillary study to a randomized clinical trial.

SETTING: Thirteen hospitals in the United States and Canada.

PARTICIPANTS: One hundred thirty-nine individuals hospitalized with hip fracture aged 50 and older (mean age 81.5 ± 9.1) with cardiovascular disease or risk factors and hemoglobin concentrations of less than 10 g/dL within 3 days of surgery recruited in an ancillary study of the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair.

INTERVENTION: Individuals in the liberal treatment group received one unit of packed red blood cells and as much blood as needed to maintain hemoglobin concentrations at greater than 10 g/dL; those in the restrictive treatment group received transfusions if they developed symptoms of anemia or their hemoglobin fell below 8 g/dL.

MEASUREMENTS: Delirium assessments were performed before randomization and up to three times after randomization. The primary outcome was severity of delirium according to the Memorial Delirium Assessment Scale (MDAS). The secondary outcome was the presence or absence of delirium defined according to the Confusion Assessment Method (CAM).

RESULTS: The liberal group received a median two units of blood and the restrictive group zero units of blood. Hemoglobin concentration on Day 1 after randomization was 1.4 g/dL higher in the liberal group. Treatment groups did not differ significantly at any time point or over time on MDAS delirium severity (P = .28) or CAM delirium presence (P = .83).

CONCLUSION: Blood transfusion to maintain hemoglobin concentrations greater than 10 g/dL alone is unlikely to influence delirium severity or rate in individuals with hip fracture after surgery with a hemoglobin concentration less than 10 g/dL.

OBJECTIVES: To determine the extent to which bodily pain mediates the effect of obesity on disability and physical function.

DESIGN: Cross-sectional analysis.

SETTING: Population-based sample of residents in the greater Boston area.

PARTICIPANTS: Community-dwelling adults aged 70 and older (N=736).

MEASUREMENTS: Body mass index (BMI), obtained from measured height and weight, was categorized as normal weight (19.0-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obese (≥30.0 kg/m2). Main outcome measures were the Physical Component Summary of the Medical Outcomes Study 12-item Short-Form Survey (PCS), activity of daily living (ADL) disability, and Short Physical Performance Battery (SPPB) score. Chronic pain was assessed according to the number of weight-bearing joint sites that had pain (hips, knees, feet and pain all over).

RESULTS: Older obese adults had greater ADL disability and lower SPPB and PCS scores than their nonobese counterparts, although in sex-stratified adjusted analyses, obesity was adversely associated with outcomes only in women. Obesity was associated with greater number of pain sites; and more pain sites were associated with greater odds of disability. Mediation analysis suggests that pain is a significant mediator (22-44%) of the adverse effect of obesity on disability and physical function in women.

CONCLUSION: Bodily pain may be an important treatable mediator of the adverse effect of obesity on disability and physical function in women.

Anesthetics have been reported to promote Alzheimer's disease (AD) neuropathogenesis by inducing β-amyloid protein accumulation and apoptosis. Neuroinflammation is associated with the emergence of AD. We therefore set out to determine the effects of the common anesthetic isoflurane on the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, the proinflammatory cytokines, in vitro and in vivo, employing Western blot, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and reverse transcriptase polymerase chain reaction (RT-PCR). Here, we show that a clinically relevant isoflurane anesthesia increased the protein and messenger ribonucleic acid (mRNA) levels of TNF-α, IL-6, and IL-1β in the brain tissues of mice. The isoflurane anesthesia increased the amounts of TNF-α immunostaining positive cells in the brain tissues of mice, the majority of which were neurons. Furthermore, isoflurane increased TNF-α levels in primary neurons, but not microglia cells, of mice. Finally, isoflurane induced a greater degree of TNF-α increase in the AD transgenic mice than in the wild-type mice. These results suggest that isoflurane may increase the levels of proinflammatory cytokines, which may cause neuroinflammation, leading to promotion of AD neuropathogenesis.

BACKGROUND: The etiology of postoperative cognitive decline (POCD) remains to be determined. Anesthetic isoflurane, but not desflurane, may induce neurotoxicity. However, the functional consequences of these effects have not been assessed. We therefore performed a pilot study to determine the effects of isoflurane and desflurane on cognitive function in humans.

METHODS: The subjects included patients who had lower extremity or abdominal surgery under spinal anesthesia alone (S, n = 15), spinal plus desflurane anesthesia (SD, n = 15), or spinal plus isoflurane anesthesia (SI, n = 15) by randomization. Each of the subjects received cognitive tests immediately before and 1 week after anesthesia and surgery administered by an investigator who was blinded to the anesthesia regimen. POCD was defined using the scores from each of these tests.

RESULTS: We studied 45 subjects, 24 males and 21 females. The mean age of the subjects was 69.0 ± 1.9 years. There was no significant difference in age and other characteristics among the treatment arms. The mean number of cognitive function declines in the S, SD, and SI groups was 1.13, 1.07, and 1.40, respectively. POCD incidence after SI (27%), but not SD (0%), anesthesia was higher than that after S (0%), P = 0.028 (3-way comparison).

CONCLUSION: These findings from our pilot study suggest that isoflurane and desflurane may have different effects on postoperative cognitive function, and additional studies with a larger sample size and longer times of follow-up testing are needed.

BACKGROUND: Although postoperative atrial fibrillation (AF) is prevalent after cardiac surgery, the corresponding medication burden associated with this postoperative arrhythmia is unknown.

METHODS: We conducted a prospective study of 204 patients aged 60 or older (median age 73) undergoing cardiac surgery at two academic medical centers. We defined "AF at discharge" as AF that developed after surgery and was present on the day of discharge. We evaluated the prevalence of anticoagulant and antiarrhythmic use at discharge, and out to 1 year post-discharge. We investigated the association between age and prescription of both classes of medications at discharge.

RESULTS: Ninety-one (45%) patients developed new postoperative AF, which persisted at discharge in 28 (14%) patients. Thirty-four percent of patients with postoperative AF were discharged on warfarin, 62% were discharged on antiarrhythmic medication, and 25% were discharged on both. Eighty-two percent of those discharged on both were older than 72 years of age. Patients with AF present at discharge were more likely to be discharged on anticoagulant agents than patients whose AF resolved prior to discharge (54% versus 26%, p=0.01), and more likely to be discharged on antiarrhythmic agents than patients whose AF resolved prior to discharge, though not significantly so (73% versus 57%, p=0.2). At 12 months, the proportion of patients on antiarrhythmic and anticoagulant medications had still not returned to preoperative rates.

CONCLUSIONS: AF persists at hospital discharge in nearly one-third of affected patients. Cardiac surgery results in the initiation of anticoagulant and antiarrhythmic medications in many older patients annually, often concurrently. Our findings underscore the need for additional studies on the natural history of this arrhythmia and clinical trials investigating different management strategies after discharge. Such research will help to inform development of guidelines addressing duration of use for these medications, to aid physicians in these complicated post-discharge management decisions.

OBJECTIVE: There are approximately 8.5 million Alzheimer disease (AD) patients who need anesthesia and surgery care every year. The inhalation anesthetic isoflurane, but not desflurane, has been shown to induce caspase activation and apoptosis, which are part of AD neuropathogenesis, through the mitochondria-dependent apoptosis pathway. However, the in vivo relevance, underlying mechanisms, and functional consequences of these findings remain largely to be determined.

METHODS: We therefore set out to assess the effects of isoflurane and desflurane on mitochondrial function, cytotoxicity, learning, and memory using flow cytometry, confocal microscopy, Western blot analysis, immunocytochemistry, and the fear conditioning test.

RESULTS: Here we show that isoflurane, but not desflurane, induces opening of mitochondrial permeability transition pore (mPTP), increase in levels of reactive oxygen species, reduction in levels of mitochondrial membrane potential and adenosine-5'-triphosphate, activation of caspase 3, and impairment of learning and memory in cultured cells, mouse hippocampus neurons, mouse hippocampus, and mice. Moreover, cyclosporine A, a blocker of mPTP opening, attenuates isoflurane-induced mPTP opening, caspase 3 activation, and impairment of learning and memory. Finally, isoflurane may induce the opening of mPTP via increasing levels of reactive oxygen species.

INTERPRETATION: These findings suggest that desflurane could be a safer anesthetic for AD patients as compared to isoflurane, and elucidate the potential mitochondria-associated underlying mechanisms, and therefore have implications for use of anesthetics in AD patients, pending human study confirmation.

OBJECTIVES: To identify factors that influence the breast cancer treatment decisions of women aged 80 and older.

DESIGN: Medical record review.

SETTING: One academic primary care clinic and two community health centers in Boston.

PARTICIPANTS: Sixty-five women aged 80 and older diagnosed with breast cancer between 1994 and 2004 and followed through June 30, 2010.

MEASUREMENTS: Data were abstracted on breast cancer characteristics, comorbidities, treatments received, and outcomes. Notes from primary care physicians, oncologists, and breast surgeons were reviewed to determine factors involved in treatment decision-making.

RESULTS: Median age at diagnosis was 84.0 (interquartile range 82.0-86.3), 55 (84.6%) were non-Hispanic white, and 40 (61.5%) had at least one comorbidity. Nine women were diagnosed with ductal carcinoma in situ, 42 with a new primary invasive breast cancer, eight with a second primary, and six with a breast cancer recurrence. Sixty-three (96.9%) received some type of treatment. Fifty-six (86.2%) had at least one detailed physician note on treatment decision-making in their charts. The main categories found to influence participant, family, and physician treatment decision-making were tumor characteristics, ratio of treatment benefits to risks, logistics (e.g., transportation, finances), and participant age, health (including a concurrent diagnosis), and psychosocial characteristics. Family was involved in treatment discussions for 46 (70.8%) participants.

CONCLUSION: The quality of physician documentation about decision-making in these women was high. A great amount of thoughtful and complex decision-making involving patients, family, and physicians occurs after a woman aged 80 and older is diagnosed with breast cancer.