High doses or prolonged exposure to ketamine increase neuronal apoptosis in the developing brain, although effects on neural stem progenitor cells (NSPCs) remain unexplored. This study investigated dose- and time- dependent responses to ketamine on cell death and neurogenesis in cultured rat fetal cortical NSPCs.
University research laboratory
Sprague-Dawley (SD) rats
NSPCs were isolated from the cortex of SD rat fetuses on embryonic day 17 (E17). In dose-response experiments, cultured NSPCs were exposed to different concentrations of ketamine (0–100 μM) for 24 hours. In time-course experiments, NSPC cultures were exposed to 10 μM ketamine for different durations (0–48 hours).
Measurements and Main Results
Apoptosis and necrosis in NSPCs were assessed using activated caspase-3 immunostaining and lactate dehydrogenase (LDH) assays, respectively. Proliferative changes in NSPCs were detected using Bromo-deoxyuridine (BrdU) incorporation and Ki67 immunostaining. Neuronal differentiation was assessed using Tuj-1 immunostaining. Cultured NSPCs were resistant to apoptosis and necrosis following all concentrations and durations of ketamine exposure tested. Ketamine inhibited proliferation, with decreased numbers of BrdU-positive cells following ketamine exposure to 100 μM for 24 hours (P<0.005) or 10 μM for 48 hours (P<0.01), and reduced numbers of Ki67-positive cells following exposure to ketamine concentration higher than 10 μM for 24 hours (P<0.001) or at 10 μM for 48 hours (P<0.01). Ketamine enhanced neuronal differentiation, with all ketamine concentrations increasing Tuj-1-positive neurons (P<0.001) after 24-hours of exposure. This also occurred with all exposures to 10 μM ketamine for longer than 8 hours (P<0.001).
Clinically relevant concentrations of ketamine do not induce cell death in NSPCs via apoptosis or necrosis. Ketamine alters the proliferation and increases the neuronal differentiation of NSPCs isolated from the rat neocortex. These studies imply that ketamine exposure during fetal or neonatal life may alter neurogenesis and subsequent brain development.
ketamine; NMDA receptors; neural stem cells; apoptosis; necrosis; neurogenesis
To provide an updated overview of critical pertussis to the pediatric critical care community and describe a study of critical pertussis recently undertaken.
The six sites, seven hospitals of the Collaborative Pediatric Critical Care Research Network and 17 outside sites at academic medical centers with PICUs.
Despite high coverage for childhood vaccination, pertussis causes substantial morbidity and mortality in United States children, especially among infants. In pediatric intensive care units, Bordetella pertussis is a community-acquired pathogen associated with critical illness and death. The incidence of medical and developmental sequelae in critical pertussis survivors remains unknown, and the appropriate strategies for treatment and support remain unclear. The CPCCRN Critical Pertussis Study has begun to evaluate critical pertussis in a prospective cohort.
Research is urgently needed to provide an evidence base that might optimize management for critical pertussis, a serious, disabling, and too often fatal illness for United States children, and those in the developing world.
pertussis; respiratory failure; study design; outcomes; multiple organ system failure; advanced life support
Rapid advances have been made in the use of pharmacological analgesia and sedation for newborns requiring neonatal intensive care. Practical considerations for the use of systemic analgesics (opioids, non‐steroidal anti‐inflammatory agents, other drugs), local and topical anaesthetics, and sedative or anaesthetic agents (benzodiazepines, barbiturates, other drugs) are summarised using an evidence‐based medicine approach, while avoiding mention of the underlying basic physiology or pharmacology. These developments have inspired more humane approaches to neonatal intensive care. Despite these advances, little is known about the clinical effectiveness, immediate toxicity, effects on special patient populations, or long‐term effects after neonatal exposure to analgesics or sedatives. The desired or adverse effects of drug combinations, interactions with non‐pharmacological interventions or use for specific conditions also remain unknown. Despite the huge gaps in our knowledge, preliminary evidence for the use of neonatal analgesia and sedation is available, but must be combined with a clear definition of clinical goals, continuous physiological monitoring, evaluation of side effects or tolerance, and consideration of long‐term clinical outcomes.
Parents of children who die in the pediatric intensive care unit (PICU) often desire a follow-up meeting with the physicians who cared for their child. Our objective is to investigate critical care physicians’ experiences and perspectives regarding follow-up meetings with parents after a child’s death in the PICU.
Semi-structured, audio-recorded telephone interviews.
Six clinical centers affiliated with the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN).
Seventy critical care physicians (i.e., attendings and fellows) practicing or training at a CPCCRN clinical center between February 1, 2008 and June 30, 2008.
Measurements and Main Results
Twenty-three (33%) physicians reported never participating in a follow-up meeting with bereaved parents; 22 (31%) participated in 1-5; and 25 (36%) participated in more than 5. Of those with prior experience, 44 (94%) met with parents at the hospital and 40 (85%) met within 3 months of the death. Meeting content included discussing autopsy, parent questions, hospital course, cause of death, genetic risk, bereavement services, and legal or administrative issues; providing emotional support; and receiving parent feedback. Forty (85%) physicians perceived the meetings to be beneficial to families, and 35 (74%) to physicians. Barriers included time and scheduling, family and physician unwillingness, distance and transportation, language and cultural issues, parent anger, and lack of a system for meeting initiation and planning.
Critical care physicians have a wide range of experience conducting follow-up meetings with bereaved parents. Although physicians perceive benefits to follow-up meetings, barriers exist that interfere with their implementation in clinical practice.
bereavement; parent; critical care; communication; qualitative methods
Nosocomial infection / sepsis occurs in up to 40% of children requiring long stay intensive care. Zinc, selenium, glutamine, metoclopramide (a prolactin secretalogue), and or whey protein supplementation have been effective in reducing infection and sepsis in other populations. We evaluated whether daily nutriceutical supplementation with zinc, selenium, glutamine, and metoclopramide, compared to whey protein would reduce the occurrence of nosocomial infection / sepsis in this at-risk population.
Randomized double blinded comparative effectiveness trial.
Eight pediatric intensive care units in the NICHD Collaborative Pediatric Critical Care Research Network.
Two hundred and ninety three long stay intensive care patients (age 1–17 years) expected to require more than 72 hours of invasive care.
Patients were stratified according to immunocompromised status and center and then randomly assigned to receive daily enteral zinc, selenium, glutamine and IV metoclopramide (n = 149 ZSGM), or daily enteral whey protein (n = 144 WHEY) and IV saline, for up to 28 days of intensive care unit stay. The primary endpoint was time to development of nosocomial sepsis / infection. The analysis was intention to treat.
Measurements and Main Results
There were no differences by assigned treatment in the overall population with respect to time until the first episode of nosocomial infection / sepsis (median WHEY 13.2 days vs ZSGM 12.1 days, p=0.29 by log rank test) or the rate of nosocomial infection / sepsis (4.83/100 days WHEY vs. 4.99/100 days ZSGM, p = 0.81). Only 9% of the 293 subjects were immunocompromised and there was a reduction in rate of nosocomial infection / sepsis with ZSGM in this immunocompromised group (6.09/100 days WHEY vs 1.57/100 days ZSGM, p value = 0.011).
Compared with WHEY supplementation, ZSGM conferred no advantage in the immunecompetent population. Further evaluation of ZSGM supplementation is warranted in the immunocompromised long stay PICU patient.
Whey protein; zinc; selenium; glutamine; prolactin; nosocomial infection / sepsis
To investigate the extent of complicated grief symptoms and associated risk factors among parents whose child died in a pediatric intensive care unit.
Cross-sectional survey conducted by mail and telephone.
Seven children’s hospitals affiliated with the Collaborative Pediatric Critical Care Research Network from January 1, 2006, to June 30, 2008.
Two hundred sixty-one parents from 872 families whose child died in a pediatric intensive care unit 6 months earlier.
Assessment of potential risk factors, including demographic and clinical variables, and parent psychosocial characteristics, such as attachment style, caregiving style, grief avoidance, and social support.
Main Outcome Measure
Parent report of complicated grief symptoms using the Inventory of Complicated Grief. Total scale range is from 0 to 76; scores of 30 or higher suggest complicated grief.
Mean(SD)Inventory of Complicated Grief scores among parents were 33.7 (14.1). Fifty-nine percent of parents (95% confidence interval, 53%–65%) had scores of 30 or higher. Variables independently associated with higher symptom scores in multivariable analysis included being the biological mother or female guardian, trauma as the cause of death, greater attachment-related anxiety and attachment-related avoidance, and greater grief avoidance.
Parents who responded to our survey experienced a high level of complicated grief symptoms 6 months after their child’s death in the pediatric intensive care unit. However, our estimate of the extent of complicated grief symptoms may be biased because of a high number of nonresponders. Better understanding of complicated grief and its risk factors among parents will allow those most vulnerable to receive professional bereavement support.
Multicenter research has the potential to recruit participants with diverse racial, ethnic, and geographic backgrounds and is essential for understanding heterogeneity in bereavement. The National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) is a multicenter network charged with conducting research on the pathophysiology and management of critical illness in childhood. Among its research activities, the CPCCRN has undertaken research in parental bereavement because most childhood deaths in the United States occur in hospitals, primarily in critical care units.
The purpose of this paper is to discuss ethical and logistical issues found by the CPC-CRN to be problematic to multicenter research with bereaved parents and to explore research strategies that may be practicably implemented.
Ethical and logistical challenges encountered by the CPCCRN included issues of privacy; confidentiality; voluntariness; minimizing risks; working with multiple institutional review boards; researcher qualifications, training and support; and methods of data collection. Strategies to address these challenges included local recruitment of participants; flexibility in consent methods across sites; participant options for methods of data collection; involvement of local bereavement support services; central training of researchers with systematic monitoring and opportunitieas for support; and use of a secure Web-based collaborative workspace.
Multicenter parental bereavement research has distinct ethical issues that must be addressed by the logistics of the research plan. Greater attention to the issues identified may facilitate research to reduce adverse mental and physical health outcomes in a diverse population of bereaved individuals.
Through discourse analysis of transcribed interviews conducted over the phone with parents whose child died in the Pediatric Intensive Care Unit (PICU) (n = 51), this study uncovers parents’ perceptions of clinicians’ and their own communicative roles and responsibilities in the context of team-based care. We examine parents’ descriptions and narratives of communicative experiences they had with PICU clinicians, focusing on how parents use accounts to evaluate the communicative behaviors they report (n = 47). Findings indicate that parental perceptions of communicative responsibilities are more nuanced than assumed in previous research: Parents identified their own responsibilities as participating as part of the team of care, gathering information, interacting with appropriate affect, and working to understand complex and uncertain medical information. Complementarily, parents identified clinician responsibilities as communicating professionally, providing medical information clearly, managing parents’ hope responsibly, and communicating with appropriate affect. Through the accounts they provide, parents evaluate both parental and clinician role-responsibilities as fulfilled and unfulfilled. Clinicians’ management of prognostic uncertainty and parents’ struggles to understand that uncertainty emerged as key, complementary themes with practical implications for incorporating parents into the PICU care team. The study also highlights insights retrospective interview data bring to the examination of medical communication.
doctor-patient interaction; team communication; roles and responsibilities; parents’ perceptions; end-of-life; bereavement; discourse analysis
There is a commonly held belief that randomized, placebo-controlled trials in pediatric critical care should incorporate “rescue” therapy (open-label administration of active drug) when a child’s condition is deteriorating. The ethical, conceptual and analytic challenges related to “rescue” therapy in randomized trials can be misrepresented.
The ethical basis of “rescue” therapy, the equipoise concept, and intention-to-treat analysis are examined in the setting of a hypothetical randomized trial comparing corticosteroids versus placebo in pediatric septic shock.
The perceived need for “rescue” therapy may be partly motivated by the moral imperative to save a child’s life. However, allowing “rescue” therapy in a trial is misconceived and inconsistent with equipoise regarding the efficacy of the study drug. If “rescue” therapy is permitted, intention-to-treat analysis can only compare immediate versus delayed use of the study drug. When “rescue” therapy is beneficial, the observed treatment effect is substantially diminished from true effect of the study drug, leading to increased sample size and thereby placing more children at risk (18 “excess” placebo-arm deaths occur in our hypothetical example). Analysis of a trial incorporating “rescue” therapy cannot definitively assess overall efficacy of the agent, or distinguish beneficial or harmful treatment effects related to timing of drug use.
While a “rescue” therapy component in a randomized trial may be perceived as ethically desirable, inconsistency of “rescue” therapy with full equipoise may itself raise significant ethical concerns. Increased sample sizes expose more children to the risks of study participation, including death. Researchers should be aware that clinical trials designed with “rescue” therapy cannot definitively determine the beneficial or harmful effects of a treatment per se, and can only assess the effects of delayed versus immediate provision of the treatment.
clinical trials, randomized; critical care; corticosterone; equipoise; ethics; placebos; shock; septic; rescue therapy
Communicating bad news about a child’s illness is a difficult task commonly faced by intensive care physicians. Greater understanding of parents’ scope of experiences with bad news during their child’s hospitalization will help physicians communicate more effectively. Our objective is to describe parents’ perceptions of their conversations with physicians regarding their child’s terminal illness and death in the pediatric intensive care unit (PICU).
A secondary analysis of a qualitative interview study.
Six children’s hospitals in the National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.
Fifty-six parents of 48 children who died in the PICU 3–12 months before the study.
Parents participated in audio recorded semistructured telephone interviews. Interviews were analyzed using established qualitative methods.
Measurements and Main Results
Of the 56 parents interviewed, 40 (71%) wanted to provide feedback on the way information about their child’s terminal illness and death was communicated by PICU physicians. The most common communication issue identified by parents was the physicians’ availability and attentiveness to their informational needs. Other communication issues included honesty and comprehensiveness of information, affect with which information was provided, withholding of information, provision of false hope, complexity of vocabulary, pace of providing information, contradictory information, and physicians’ body language.
The way bad news is discussed by physicians is extremely important to most parents. Parents want physicians to be accessible and to provide honest and complete information with a caring affect, using lay language, and at a pace in accordance with their ability to comprehend. Withholding prognostic information from parents often leads to false hopes and feelings of anger, betrayal, and distrust. Future research is needed to investigate whether the way bad news is discussed influences psychological adjustment and family functioning among bereaved parents.
communication; critical care; physicians; parents; prognosis; death
To create a functional status outcome measure for large outcome studies that is well defined, quantitative, sufficiently rapid, reliable, minimally dependent on subjective assessments, and applicable to hospitalized pediatric patients across a wide spectrum of ages and inpatient environments.
Patients and Methods
The Functional Status Scale (FSS) was developed by a multidisciplinary consensus process. Domains of functioning included mental status, sensory, communication, motor, feeding, and respiratory categorized from normal (1) to very severe dysfunction (5). The Adaptive Behavior Assessment System (ABAS) II established construct validity and calibration within domains.
Seven institutions provided pediatric intensive care unit (PICU) patients within 24 hours of PICU discharge, high-risk non-PICU patients within 24 hours of admission, and technology-dependent children. Primary care nurses completed the ABAS II based on patient’s functioning when the FSS was completed. Patients from 10% of the study days were used to evaluate inter-rater reliability. Data were randomly split into estimation and validation sets. Statistical analyses included Pearson correlations, construct validity, linear regression analysis, receiver operating characteristic (ROC) curve analysis for discriminant validity, and the intraclass correlation for inter-rater reliability.
A total of 836 children with a mean FSS of 10.3 (standard deviation 4.4) were studied. Eighteen percent had the minimum possible FSS = 6, 44% had FSS ≥ 10, 14% had a FSS ≥ 15, and 6% had FSS scores ≥ 20. Each FSS domain was associated with mean ABAS II (p<.0001). Cells in each domain were collapsed and reweighted, which improved correlations with ABAS II from −0.58 to −0.62 in the estimation sample, and −0.60 to −0.63 in the validation sample (p<0.001 for improvements). Discrimination was very good for moderate and severe dysfunction (ABAS II categories) and improved with FSS weighting (area under the ROC curve > 0.8). Intraclass correlations of original and weighted total FSS were 0.95 and 0.94 respectively.
The FSS met our objectives and is well suited for large outcome studies.
Pediatrics; functional status; outcome assessment (health care); activities of daily living; adaptive behavior; health status indicators; health utilities index; treatment outcome; child
Despite implementation of CDC recommendations and bundled interventions for preventing catheter-associated blood stream infection, ventilator-associated pneumonia, or urinary catheter–associated infections, nosocomial infections and sepsis remain a significant cause of morbidity and mortality in critically ill children. Recent studies suggest that acquired critical illness stress-induced immune suppression (CRISIS) plays a role in the development of nosocomial infection and sepsis. This condition can be related to inadequate zinc, selenium, and glutamine levels, as well as hypoprolactinemia, leading to stress-induced lymphopenia, a predominant TH2 monocyte/macrophage state, and subsequent immune suppression. Prolonged immune dysfunction increases the likelihood of nosocomial infections associated with invasive devices. Although strategies to prevent common complications of critical illness are routinely employed (eg, prophylaxis for gastrointestinal bleeding, thrombophlebitis), no prophylactic strategy is used to prevent stress-induced immune suppression. This is the authors’ rationale for the pediatric CRISIS prevention trial (NCT00395161), designed as a randomized, double-blind, controlled clinical investigation to determine if daily enteral supplementation with zinc, selenium, and glutamine as well as parenteral metoclopramide (a dopamine 2 receptor antagonist that reverses hypoprolactinemia) prolongs the time until onset of nosocomial infection or sepsis in critically ill children compared to enteral supplementation with whey protein. If effective, this combined nutritional and pharmacologic approach may lessen the excess morbidity and mortality as well as resource utilization associated with nosocomial infections and sepsis in this population. The authors present the design and analytic plan for the CRISIS prevention trial.
critical care; nosocomial infection; prolactin; zinc; selenium; lymphocyte function
A systematic review of weaning and extubation for pediatric patients on mechanical ventilation.
Pediatric and Adult Literature, English language
Literature review using National Library of Medicine PubMed from January 1972 until April 2008, earlier cross-referenced article citations, the Cochrane Database of Systematic Reviews and the Internet.
Despite the importance of minimizing time on mechanical ventilation, only limited guidance on weaning and extubation is available from the pediatric literature. A significant proportion of patients being evaluated for weaning are actually ready for extubation, suggesting that weaning is often not considered early enough in the course of ventilation. Indications for extubation are even less clear, although a trial of spontaneous breathing would seem a prerequisite. Several indices have been developed in an attempt to predict weaning and extubation success but the available literature would suggest they offer no improvement over clinical judgment. Extubation failure rates range from 2–20% and bear little relationship to the duration of mechanical ventilation. Upper airway obstruction is the single most common cause of extubation failure. A reliable method of assessing readiness for weaning and predicting extubation success is not evident from the pediatric literature.
weaning; extubation; mechanical ventilation; respiratory support; spontaneous breathing
Problem Bloodstream infections associated with catheters were the most common nosocomial infections in one paediatric intensive care unit in 1994-7, with rates well above the national average.
Design Clinical data were collected prospectively to assess the rates of infection from 1994 onwards. The high rates in 1994-7 led to the stepwise introduction of interventions over a five year period. At quarterly intervals, prospective data continued to be collected during this period and an additional three year follow-up period.
Setting A 292 bed tertiary care children's hospital.
Key measures for improvement We aimed to reduce our infection rates to below the national mean rates for similar units by 2000 (a 25% reduction).
Strategies for change A stepwise introduction of interventions designed to reduce infection rates, including maximal barrier precautions, transition to antibiotic impregnated central venous catheters, annual handwashing campaigns, and changing the skin disinfectant from povidone-iodine to chlorhexidine.
Effects of change Significant decreases in rates of infection occurred over the intervention period. These were sustained over the three year follow-up. Annual rates decreased from 9.7/1000 days with a central venous catheter in 1997 to 3.0/1000 days in 2005, which translates to a relative risk reduction of 75% (95% confidence interval 35% to 126%), an absolute risk reduction of 6% (2% to 10%), and a number needed to treat of 16 (10 to 35).
Lessons learnt A stepwise introduction of interventions leading to a greater than threefold reduction in nosocomial infections can be implemented successfully. This requires a multidisciplinary team, support from hospital leadership, ongoing data collection, shared data interpretation, and introduction of evidence based interventions.
Relationships between plasma morphine concentrations and neonatal responses to endotracheal tube (ETT) suctioning are unknown in preterm neonates.
Ventilated preterm neonates (n=898) from 16 centres were randomly assigned to placebo (n=449) or morphine (n=449). After an i.v. loading dose (100 µg kg−1), morphine infusions [23–26 weeks postmenstrual age (PMA) 10 µg kg−1 h−1; 27–29 weeks 20 µg kg−1 h−1; and 30–32 weeks 30 µg kg−1 h−1] were established for a maximum of 14 days. Open-label morphine (20–100 µg kg−1) was given for pain or agitation. Morphine assay and neonatal response to ETT suctioning was measured at 20–28 and 70–76 h after starting the drug infusion and at 10–14 h after discontinuation of the study drug. The concentration–effect response was investigated using non-linear mixed effects models.
A total of 5119 data points (1598 measured morphine concentrations and 3521 effect measures) were available from 875 neonates for analysis. Clearance was 50% that of the mature value at 54.2 weeks PMA (CLmat50) and increased from 2.05 litre h−1 70 kg−1 at 24 weeks PMA to 6.04 litre h−1 70 kg−1 at 32 weeks PMA. The volume of distribution in preterm neonates was 190 litre 70 kg−1 (CV 51%) and did not change with age. There was no relationship between morphine concentrations (range 0–440 µg litre−1) and heart rate changes associated with ETT suctioning or with the Premature Infant Pain Profile.
A sigmoid curve describing maturation of morphine clearance is moved to the right in preterm neonates and volume of distribution is increased compared with term neonates. Morphine does not alter the neonatal response to ETT suctioning.
anaesthesia, paediatric; anaesthetic–analgesic regimens; analgesics opioid, morphine; model, pharmacodynamic; model, pharmacokinetic
To investigate parents' perspectives on the desirability, content and conditions of a physician-parent conference after their child's death in the pediatric intensive care unit (PICU).
Audio-recorded telephone interviews were conducted with 56 parents of 48 children. All children died in the PICU of one of six children's hospitals in the National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network 3-12 months prior to the study.
Only 7 (13%) parents had a scheduled meeting with any physician to discuss their child's death; 33 (59%) wanted to meet with their child's intensive care physician. Of these, 27 (82%) were willing to return to the hospital to meet. Topics that parents wanted to discuss included the chronology of events leading to PICU admission and death, cause of death, treatment, autopsy, genetic risk, medical documents, withdrawal of life support, ways to help others, bereavement support, and what to tell family. Parents sought reassurance and the opportunity to voice complaints and express gratitude.
Many bereaved parents want to meet with the intensive care physician after their child's death. Parents seek to gain information and emotional support, and to give feedback about their PICU experience.
bereavement; grief; critical care; communication; interview
This one-arm pilot study investigated the effect of tai chi on cognition in elders with cognitive impairment. Although no significant difference existed between pre- and post-test performance on all cognition measures, a dose-response relationship was demonstrated between attendance and some cognition measures.
We previously demonstrated that parents whose children die in a pediatric intensive care unit (PICU) have a high level of complicated grief symptoms 6 months after the death. In this study, we investigate the change in the extent of complicated grief symptoms among these parents between 6 and 18 months postdeath and identify factors predicting improvement.
One hundred thirty-eight parents of 106 children completed surveys at 6 and 18 months. Surveys included the Inventory of Complicated Grief (ICG), measures of grief avoidance, attachment, caregiving and social support, and demographics. Multivariable analysis was performed using generalized estimating equations to identify characteristics independently associated with improvement in ICG score.
ICG scores were 33.4 ± 13.6 at 6 months and 28.0 ± 13.5 at 18 months, representing an improvement in ICG score of 5.4 + 8.0 (95% confidence interval [CI] 4.1–6.8, p < 0.001). Variables independently associated with greater improvement in ICG score included traumatic death and greater grief avoidance. Variables independently associated with less improvement included being the biological parent and having more responsive caregiving. Parents with one or two surviving children had more improvement in ICG score than those with no surviving children whereas parents with three or more surviving children had less improvement.
Complicated grief symptoms decrease among parents between 6 and 18 months after their child's death in the PICU; however, high symptom levels persists for some. Better understanding of the trajectory of complicated grief will allow parents at risk for persistent distress to receive professional support.
This article reports a pilot study of the effect of tai chi (TC), a pharmacological adjunct and mild aerobic exercise, on osteoarthritic knee pain in elders with cognitive impairment (CI). The TC program included a warm-up, 12-form Sun-style TC, and a cool-down period, for a total of 20-40 minutes per session, twice a week for 15 weeks. The results showed no significant differences in knee pain after the TC intervention in 7 elders with CI. However, more minutes of TC attendance were related to improved pain scores (Spearman's rho = .78, P <.05). Greater accuracy in TC performance was also correlated with improvements in pain scores (Spearman's rho = .70, P = .08). Of 4 elders who participated in TC practice regularly (more than 20 sessions), 3 showed clinically important improvements, but 3 elders who participated in no sessions or only a few sessions showed no improvement.