Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer's disease (MCI and dementia) in primary care: a review and synthesis.

The critical role of primary care clinicians (PCCs) in Alzheimer's disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early signs of cognitive deficits (i.e. MCI due to AD and mild AD dementia). A timely AD diagnosis is particularly important for optimizing patient care and enabling the appropriate use of anticipated DMTs. An accelerating challenge for PCCs and AD specialists will be to respond to innovations in diagnostics and therapy for AD in a system that is not currently well positioned to do so. To overcome these challenges, PCCs and AD specialists must collaborate closely to navigate and optimize dynamically evolving AD care in the face of new opportunities. In the spirit of this collaboration, we summarize here some prominent and influential models that inform our current understanding of AD. We also advocate for timely and accurate (i.e. biomarker-defined) diagnosis of early AD. In doing so, we consider evolving issues related to prevention, detecting emerging cognitive impairment and the role of biomarkers in the clinic.

Regional tissue oxygenation in asymptomatic neonates at high risk for neonatal abstinence syndrome and impact of non-pharmacologic interventions: A case report.

BACKGROUND: Improving neonatal abstinence syndrome (NAS) management is an important concern, and objective measures of its physiologic impact remain elusive. We sought to determine whether near-infrared spectroscopy (NIRS)-derived tissue oxygenation (rSO2) and fractional tissue oxygen extraction (FTOE) demonstrated physiologically plausible changes correlating with standard NAS scoring. METHODS: Thirty subjects (mean 39 weeks' GA and 3 127 g BW) underwent cerebral and peripheral muscle NIRS monitoring on Days of Life (DOL) Three, Five, and Seven. We examined correlations between NAS scores and FTOE and assessed the impact of non-pharmacologic swaddling and cuddling. RESULTS: No statistically significant correlations between NAS scores and FTOE were observed; however, plausible trends were demonstrated between NAS scores and cerebral measurements. Buprenorphine-exposed babies (57%) showed significantly lower FTOE when swaddled (DOL7). CONCLUSIONS: Tissue oxygenation monitoring demonstrates potential to provide objective, clinically relevant physiologic information on infants at risk for NAS. Further study is required to determine whether NIRS-derived measures could assist in individualizing NAS care.

Indomethacin dosing strategy and neonatal patent ductus arteriosus closure.

BACKGROUND: Few studies exist that have evaluated the effects of indomethacin dosing frequency as a factor associated with successful patent ductus arteriosus closure in very low birth weight neonates. The objective of this study is to determine if indomethacin dosing strategy is associated with efficacy for initial patent ductus arteriosus management in very low birth weight neonates. METHODS: This retrospective review compared every 12 hour and every 24 hour indomethacin regimens primarily for efficacy in initial patent ductus arteriosus management, defined as an absence of repeat medical and/or surgical treatment, and secondarily for safety in both univariate and multivariate models. RESULTS: One hundred three very low birth weight neonates were included: 56 (54%) received every 12 hour and 47 (46%) underwent every 24 hour indomethacin dosing. Repeat medical and/or surgical patent ductus arteriosus treatment rates were similar between groups. Less ligation of the patent ductus arteriosus occurred with every 12 hour versus every 24 hour dosing (11% vs. 26%, p = 0.05), though this effect was mitigated controlling for birth weight and gestational age. Renal function, respiratory outcomes, feeding outcomes, length of stay, and mortality were similar between groups. CONCLUSIONS: Neither the every 12 hour nor the every 24 hour indomethacin regimen demonstrated inferior efficacy or safety for initial management of patent ductus arteriosus. Further prospective analysis of indomethacin dosing strategy is warranted.

Identifying Better Outcome Measures to Improve Treatment of Agitation in Dementia: A Report from the EU/US/CTAD Task Force.

For the second time in the past 3 years, the EU-US CTAD Task Force addressed challenges related to designing clinical trials for agitation in dementia, which is one of the most disruptive aspects of the condition for both patients and caregivers. Six recommendations emerged from the Task Force meeting: 1 - Operationalizing agitation criteria established by the IPA; 2 - Combining clinician- and caregiver-derived outcomes as primary outcome measures; 3 - Using global ratings to define clinically meaningful effects and power studies; 4 - Improving the accuracy of caregiver reports by better training and education of caregivers; 5 - Employing emerging technologies to collect near real-time behavioral data; and 6 - Utilizing innovative trial designs and increasing the use of biomarkers to maximize the productivity of clinical trials for neuropsychiatric symptoms.

Quetiapine to treat agitation in dementia: a randomized, double-blind, placebo-controlled study.

In this 10-week, double-blind, fixed-dose study, elderly institutionalized patients with dementia and agitation were randomized (3:3:2) to quetiapine 200mg/day, 100mg/day, or placebo. The primary endpoint was change in Positive and Negative Syndrome Scale (PANSS)-Excitement Component (EC) scores at endpoint, analysed using last observation carried forward (LOCF) and observed cases (OC) approaches. Other efficacy measures were the Clinical Global Impression of Change (CGI-C), and response rates (percentage with > or =40% reduction [PANSS-EC]; "much" or "very much improved" [CGI-C]), Neuropsychiatric Inventory-Nursing Home version (NPI-NH), and Cohen-Mansfield Agitation Inventory (CMAI). The key safety measure was incidence of adverse events; change in Mini-Mental State Examination (MMSE) was also assessed. Baseline characteristics of 333 participants (quetiapine 200mg/day, n=117; quetiapine 100mg/day, n=124; placebo, n=92) and completion rates (63-65%) were comparable among groups. Compared with placebo, quetiapine 200mg/day was associated with clinically greater improvements in PANSS-EC (LOCF, p=0.065; OC, p=0.014 [ANCOVA]), CGI-C (LOCF, p=0.017; OC, p=0.002 [ANOVA]), and CGI-C response rates (LOCF, p=0.002; OC, p<0.001 [Chi-square test]). Quetiapine 100mg/day did not differentiate from placebo on these measures. There were no between-group differences in NPI-NH or CMAI. Incidences of cerebrovascular adverse events, postural hypotension, and falls were similar among groups. MMSE did not change in any group. Mortality was numerically higher in the quetiapine groups; rates were not statistically different from placebo. The results of this study suggest that quetiapine 200mg/day was effective and well-tolerated for treating agitation associated with dementia. However, caution should be exercised given the concerns regarding increased mortality with atypical antipsychotics in this vulnerable patient population.

Effects of sodium bicarbonate correction of metabolic acidosis on regional tissue oxygenation in very low birth weight neonates.

OBJECTIVE: To determine the effects of sodium bicarbonate (NaHCO3) correction of metabolic acidosis on cardiopulmonary, laboratory, and cerebral, renal and splanchnic regional oxygen saturation (rSO2) and fractional tissue oxygen extraction (FTOE) in extremely premature neonates during the first postnatal week. STUDY DESIGN: Observational cohort data were collected from 500 to 1250 g neonates who received NaHCO3 'half' corrections (0.3 * Weight (kg) * Base Deficit (mmol l(-1))) for presumed renal losses. RESULT: Twelve subjects with normal blood pressure and heart rate received 17 NaHCO3 corrections. Mean (±s.d.) gestational age was 27±2 week and birth weight was 912±157 g. NaHCO3 corrections provided a mean (±s.d.) 4.5±1.0 ml kg(-1) fluid bolus, shifted mean (±s.d.) base deficit from 7.6±1.8 to 3.4±2.1 mmol l(-1) (P<0.05), and increased median (±s.d.) pH from 7.23±0.06 to 7.31±0.05 (P<0.05). No significant changes in blood pressure, pulse oximetry, PCO2, lactate, sodium, blood urea nitrogen, creatinine or hematocrit were observed. Cerebral, renal and splanchnic rSO2 (74%, 66% and 44%, respectively, at baseline) and FTOE (0.21, 0.29 and 0.52, respectively, at baseline) were unchanged following NaHCO3 correction. CONCLUSION: NaHCO3 infusions decreased base deficits and increased pH though produced no discernible effects or benefits on cardiopulmonary parameters including rSO2 and FTOE. These findings warrant further prospective evaluation in larger populations with more significant metabolic acidosis to determine the utility of tissue oxygenation monitoring in differentiating metabolic acidosis due to oxygen delivery/consumption imbalance versus renal bicarbonate losses.

Fenfluramine challenge test as a marker of serotonin activity in patients with Alzheimer's dementia and agitation.

BACKGROUND: Changes in serotonin (5-HT) have been described in both Alzheimer's disease (AD) and aggressive/agitated behaviors. This paper explores a possible association between 5-HT deficits and agitation in AD, using prolactin response to d,1-fenfluramine administration as a probe for 5-HT activity. METHODS: Five AD patients with agitation and 5 without agitation received a 60-mg oral dose of d,1-fenfluramine. Prolactin levels were obtained at baseline, and 2 and 3 hours following administration. RESULTS: Change in prolactin levels from baseline to 3 hours was significantly larger among the agitated than the nonagitated Alzheimer's patients. Further, there was a positive and significant correlation between change in prolactin levels from baseline and level of agitation. CONCLUSIONS: These findings suggest an association between 5-HT responsiveness and agitation in AD.

A 24-week randomized trial of controlled-release physostigmine in patients with Alzheimer's disease.

OBJECTIVE: To evaluate the safety and efficacy of controlled-release physostigmine, an acetylcholinesterase inhibitor, in patients with probable AD of mild to moderate severity. METHODS: A prospective, 24-week, randomized, multicenter, double-blind, parallel group study of patients was conducted. The study enrolled 475 patients at 24 sites. Patients met criteria for probable AD and were randomized to one of three arms: placebo, controlled-release (CR) physostigmine 30 mg daily, or CR physostigmine 36 mg daily. Dosage was escalated by a forced upward titration during the first 6 to 9 weeks of the trial, then maintained at a constant dose to 24 weeks. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of Change-Plus with caregiver input (CIBIC+). Secondary outcome measures included the Clinical Global Impression of Change (CGIC), the Geriatric Evaluation by Relatives Rating Instrument, and an Instrumental Activities of Daily Living Scale. RESULTS: In an intent-to-treat population, the last observation carried forward analysis revealed a 2.9-point ADAS-Cog (p = 0.002) difference between physostigmine and placebo-treated patients for both dosages, and a 0.26 to 0.31-point difference on the CIBIC+ (p = 0.048). There were no significant differences on the secondary outcome measures except for a difference on the CGIC when analyzed by use of the Cochran-Mantel-Haenszel statistic (p = 0.014). There were significant increases in gastrointestinal side effects including nausea, vomiting, diarrhea, anorexia, dyspepsia, and abdominal pain for patients on either dose of physostigmine, resulting in a high dropout rate. Agitation was decreased significantly. There was no evidence of cardiac rhythm disturbance or liver function abnormalities. CONCLUSION: CR physostigmine enhanced cognitive and global function. It is relatively safe for the treatment of cognitive dysfunction secondary to AD. However, in light of the gastrointestinal side effects, a lower starting dose and a flexible titration schedule might lead to a more favorable adverse event profile in the clinical arena.

Underlying mechanisms of psychosis and aggression in patients with Alzheimer's disease.

It is well known that serotonergic function is related to aggression. Patients with Alzheimer's disease exhibit aggressive behavior, and alterations in their serotonergic function have been identified. Recent clinical trials involving new antipsychotic agents, such as risperidone, which has both serotonergic and dopaminergic activity, have demonstrated the efficacy and safety of these drugs in treating the psychosis and aggressive behavior associated with dementia.

Agitation as a possible expression of generalized anxiety disorder in demented elderly patients: toward a treatment approach.

Symptoms of generalized anxiety disorder are commonly observed in elderly persons and especially in those suffering from dementia. In the demented elderly, these symptoms are often defined as agitation. Approximately 60% of demented persons will present with symptoms of agitation at some point during the course of their illness. The presence of agitation has devastating consequences for the patient and the caregiver. This paper reviews some of the existing literature with regard to the etiology and treatment of agitation in the demented elderly. Agitated behaviors are generally divided in three categories (verbal agitation physically nonaggressive agitation, and aggressive agitation). It is suggested that each category may have a different etiology and treatment; verbal agitation is often related to underlying medical conditions, physically nonaggressive behavior responds to behavioral treatment, and aggressive agitation is more likely to respond to a combination of behavioral and pharmacologic treatment.

Efficacy and adverse effects of clozapine in four elderly psychotic patients.

BACKGROUND: Clozapine is an atypical antipsychotic agent that is effective in refractory schizophrenic patients. Older patients may have various psychotic manifestations that may not be responsive to typical neuroleptic therapy. There may also be patient-specific factors--declines in reserve capacity and homeostasis, and age-related changes in the pharmacokinetics and pharmacodynamics of drugs--in older patients that increase their susceptibility to the side effects of psychotropic medications. While clozapine has few extrapyramidal side effects, it has other side effects that may be problematic in the older population. METHOD: In our geropsychiatric unit, clozapine was prescribed for four patients over the age of 65 years. All patients were either experiencing psychotic symptoms refractory to other antipsychotic medications or had relative contraindications to a typical neuroleptic. Two of the four were chronic schizophrenics, and three of the four also presented with dementia. RESULTS: Two of the four patients did eventually receive relief of psychotic symptoms from clozapine. All four experienced events after initiation of clozapine therapy, which included falls (2 patients), symptomatic bradycardia (2 patients), and delirium (1 patient). All these adverse effects occurred on doses ranging from 6.25 to 37.50 mg/day, and the three patients with moderate-to-severe dementia experienced these severe adverse effects after administration of the first dose. CONCLUSION: Clozapine may be a useful drug for older patients with psychotic symptoms; however, at current dosage recommendations, adverse events may occur, especially on first dose. Well-designed studies need to be performed to assess the effectiveness and dosage ranges for this population.

Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group.

BACKGROUND: We report the findings from the first large, double-blind, placebo-controlled study conducted to evaluate the efficacy and safety of risperidone in the treatment of psychotic and behavioral symptoms in institutionalized elderly patients with dementia. METHOD: 625 patients (67.8% women; mean age = 82.7 years) with DSM-IV diagnoses of Alzheimer's disease (73%), vascular dementia (15%), or mixed dementia (12%) and significant psychotic and behavioral symptoms were included. Each patient was randomly assigned to receive placebo or 0.5 mg/day, 1 mg/day, or 2 mg/day of risperidone for 12 weeks. The primary outcome measure was the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD). RESULTS: The study was completed by 70% of the patients. Baseline Functional Assessment Staging scores were 6 or 7 in more than 95% of the patients, indicating severe dementia. At endpoint, significantly greater reductions in BEHAVE-AD total scores and psychosis and aggressiveness subscale scores were seen in patients receiving 1 and 2 mg/day of risperidone than in placebo patients (p = .005 and p < .001, respectively). At week 12, 0.5 mg/day of risperidone was superior to placebo in reducing BEHAVE-AD aggression scores (p = .02). More adverse events were reported by patients receiving 2 mg/day of risperidone than 1 mg/day. The most common dose-related adverse events were extrapyramidal symptoms, somnolence, and mild peripheral edema. The frequency of extrapyramidal symptoms in patients receiving 1 mg/day of risperidone was not significantly greater than in placebo patients. CONCLUSION: Risperidone significantly improved symptoms of psychosis and aggressive behavior in patients with severe dementia. Results show that 1 mg/day of risperidone is an appropriate dose for most elderly patients with dementia.

A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting.

OBJECTIVES: To evaluate the safety and efficacy of donepezil in the management of patients with Alzheimer's disease (AD) residing in nursing home facilities. DESIGN: Twenty-four-week, randomized, multicenter, parallel-group, double-blind, placebo-controlled trial. SETTING: Twenty-seven nursing homes across the United States. PARTICIPANTS: Two hundred eight nursing home patients with a diagnosis of probable or possible AD, or AD with cerebrovascular disease; mean Mini-Mental State Examination (MMSE) score 14.4; mean age 85.7. MEASUREMENTS: The primary outcome measure was the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). Secondary efficacy measures were the Clinical Dementia Rating (Nursing Home Version)-Sum of the Boxes (CDR-SB), MMSE, and the Physical Self-Maintenance Scale (PSMS). Safety was monitored by physical examinations, vital signs, clinical laboratory tests, electrocardiograms (ECGs), and treatment-emergent adverse events (AEs). RESULTS: Eighty-two percent of donepezil- and 74% of placebo-treated patients completed the trial. Eleven percent of donepezil- and 18% of placebo-treated patients withdrew because of AEs. Mean NPI-NH 12-item total scores improved relative to baseline for both groups, with no significant differences observed between the groups at any assessment. Mean change from baseline CDR-SB total score improved significantly with donepezil compared with placebo at Week 24 (P < .05). The change in CDR-SB total score was not influenced by age. Differences in mean change from baseline on the MMSE favored donepezil over placebo at Weeks 8, 16, and 20 (P < .05). No significant differences were observed between the groups on the PSMS. Overall rates of occurrence and severity of AEs were similar between the two groups (97% placebo, 96% donepezil). Gastrointestinal AEs occurred more frequently in donepezil-treated patients. In general, AEs were similar in older and younger donepezil-treated patients, with the majority of patients experiencing only AEs that were transient and mild or moderate in severity. Weight loss was reported as an AE more frequently in older patients, although a loss at last visit of >or=7% of screening weight occurred at the same rate in older and younger patients (9% of donepezil- and 6% of placebo-treated patients). No significant differences between groups in vital sign changes, bradycardia, or rates of clinically significant laboratory or ECG abnormalities were observed. CONCLUSION: Patients treated with donepezil maintained or improved in cognition and overall dementia severity in contrast to placebo-treated patients who declined during the 6-month treatment period. The safety and tolerability profile was comparable with that reported in outpatient studies of donepezil. These findings also suggest that advanced age, comorbid illnesses, and high concomitant medication usage should not be barriers to donepezil treatment. Given the apparent improvement in behavior in the placebo group, and the high use of concomitant medications in both groups, the impact of donepezil on behavior in the nursing home setting is unresolved and merits further investigation. In summary, effects on cognition, overall dementia severity, and safety and tolerability findings are consistent with previous findings in outpatients and support the use of donepezil in patients with AD who reside in nursing homes.

Acute desensitization of lymphocyte beta-adrenergic-stimulated adenylate cyclase in old age and Alzheimer's disease.

The effect of prior incubation with a single concentration of isoproterenol (10(-4) M) for 2 hours at 37 degrees C on isoproterenol-stimulated cyclic AMP accumulation in intact lymphocytes from young, old and subjects with Alzheimer's disease was studied. In lymphocytes from all three subjects groups prior incubation of cells with isoproterenol resulted in a significant reduction of cyclic AMP accumulation upon subsequent stimulation with isoproterenol.

Behavioral Intensive Care Unit (BICU): a new concept in the management of acute agitated behavior in elderly demented patients.

Intensive care units were developed in response to the perceived need for increased monitoring in critically ill medical patients. The same principle applies to elderly patients with severe agitated behaviors. These patients can be served by the Geriatric Behavioral Intensive Care Unit (BICU). The uniqueness of the program results from the application of a behavioral and environmental approach to the treatment of agitated behavior. The underlying strategy in the treatment process is to enhance the patient's ability to adapt to his or her home environment. Preliminary results have been encouraging, showing positive outcomes in diverse areas such as low level of institutional placement, patient quality of life, and caregiver symptoms of burden and depression.

Treatment of agitation in patients with dementia.

This article attempts to summarize some of the pertinent literature in the context of the authors' clinical experience and suggests that a comprehensive psychiatric and medical evaluation, as well as a combined behavioral/environmental approach together with appropriate pharmacotherapy, are important tools in the management of this complicated clinical challenge.

Effectiveness of a continuum of care using brief and partial hospitalization for agitated dementia patients.

OBJECTIVE: A behavioral intensive care unit was originally designed as a 21-day inpatient program for treating agitation among demented patients, one of the most common behavioral disorders in this group. Due to the need to dramatically reduce length of stay and create alternative care environments, the original model was modified into an integrated continuum of care blending inpatient and outpatient care and partial hospitalization that reduced hospitalization from 21 to an average of seven days. This quasiexperimental study compared the effectiveness of the inpatient and continuum-of-care programs and conducted cost analyses. METHODS: Subjects were inpatients diagnosed with both dementia and agitation. Outcomes of 68 patients treated in the inpatient program were compared with those of 110 patients treated in the continuum of care. The primary outcome measure was patients' score on the Cohen-Mansfield Agitation Inventory, which provides a total agitation score and scores on three factors describing agitated behavior--physically aggressive behavior, verbally aggressive behavior, and nonaggressive behavior. RESULTS: A statistically significant reduction in agitation was found for patients treated in both programs, with no significant difference in outcome between programs. Patients in both programs showed significant improvements in physical aggression, verbal aggression, and nonaggressive behavior. The cost-effectiveness analysis revealed clear advantages for the continuum-of-care program, especially in the area of aggressive behaviors. CONCLUSIONS: The data suggest that the restructured program is an effective and economically feasible intervention.

Behavioral and psychological signs and symptoms of dementia: a practicing psychiatrist's viewpoint.

Alzheimer's disease typically presents with two often overlapping syndromes, one cognitive, the other behavioral. The behavioral syndrome is characterized by psychosis, aggression, depression, anxiety, agitation, and other common if less well-defined symptoms subsumed under the umbrella entity "behavioral and psychological symptoms of dementia" (BPSD), itself divided into a number of subsyndromes: psychosis, circadian rhythm (sleepwake) disturbance, depression, anxiety, and agitation, it is BPSD with its impact on care providers that ultimately precipitates the chain of events resulting in long-term institutional care. The treatment challenge involves eliminating unmet medical needs (undiagnosed hip fracture and asymptomatic urinary tract infection or pneumonia). Pharmacologic intervention relies on risperidone and, increasingly cholinesterase inhibitors for the control of psychosis (but with response rates of only 65% at tolerable doses), olanzapine and risperidone for anxiety, and carbamazepine and valproic acid for agitation. However, evidence increasingly favors nonpharmacologic interventions, to the extent that these should now be considered as the foundation of BPSD treatment. Problem behaviors are viewed as meaningful responses to unmet needs in the therapeutic milieu. Because the progression and impact of BPSD varies between patients, interventions must be explored, designed, implemented, and assessed on an individual basis. They include: family support and education, psychotherapy reality orientation, validation therapy, reminiscence and life review, behavioral interventions, therapeutic activities and creative arts therapies, environmental considerations (including restraint-free facilities), behavioral intensive care units, and workplace design and practices that aid the ongoing management of professional caregiver stress.

Quiescent variability of cerebral, renal, and splanchnic regional tissue oxygenation in very low birth weight neonates.

OBJECTIVE: In extremely premature neonates, data concerning the normal baseline variability of near-infrared spectroscopy (NIRS)-derived regional oxygen saturation (rSO2) are lacking. We sought to determine: 1) the quiescent variability of cerebral, renal, and splanchnic rSO2 in clinically stable, undisturbed very low birth weight neonates and 2) the effects of different data averaging epochs on site-specific variability. STUDY DESIGN: In this prospective, observational study, neonates between 500 and 1250 g underwent seven days of continuous, real-time cerebral, renal, and splanchnic NIRS monitoring starting within the first seventy-two postnatal hours. Demographic, cardiopulmonary, bedside care, and rSO2 data were collected. rSO2 variability was analyzed utilizing data from quiescent periods identified using pre-specified stability criteria. Between- and within-monitoring site comparisons of data averaging methods were made utilizing ANOVA. RESULT: Twenty-four subjects (GA 27 ± 0.3 wk, birth weight 988 ± 34 g; mean ± SEM) were monitored. Coefficients of variation (CoVar = SD/mean) were calculated for each monitoring site using varied data averaging epochs. CoVar was lowest for cerebral, intermediate for renal, and highest for splanchnic rSO2 (P < 0.01). For renal and splanchnic sites, shorter epochs (5- and 15-min) resulted in significantly smaller CoVars [P < 0.01 and P < 0.05, respectively]. Splanchnic variability was highly dependent on epoch length, ranging from 16% over 5 min to 23% over 60 min. CONCLUSION: 1) rSO2 variability differs significantly between monitoring sites and 2) shorter data sampling epochs decrease rSO2 variability. These observations may assist clinicians in operationally defining minimally significant departures to enable medical decision making utilizing this monitoring technique.

A delicate subject: The impact of cultural factors on neonatal and perinatal decision making.

The neonatal intensive care unit (NICU) is a high-stress environment for both families and health care providers that can sometimes make appropriate medical decisions challenging. We present a review article of non-medical barriers to effective decision making in the NICU, including: miscommunication, mixed messages, denial, comparative social and cultural influences, and the possible influence of perceived legal issues and family reliance on information from the Internet. As examples of these barriers, we describe and discuss two cases that occurred simultaneously in the same NICU where decisions were influenced by social and cultural differences that were misunderstood by both medical staff and patients' families. The resulting stress and emotional discomfort created an environment with sub-optimal relationships between patients' families and health care providers. We provide background on the sources of conflict in these particular cases. We also offer suggestions for possible amelioration of similar conflicts with the twin goals of facilitating compassionate decision making in NICU settings and promoting enhanced well-being of both families and providers.