Jacqueline Stack

Rating chronic medical illness burden in geropsychiatric practice and research: Application of the Cumulative Illness Rating Scale

Reliable quantitative ratings of chronic medical illness burden have proved to be difficult in geropsychiatric practice and research. Thus, the purpose of the study was to demonstrate the feasibility and reliability of a modified version of the Cumulative Illness Rating Scale (CIRS; Linn et al., 1968) in providing quantitative ratings of chronic illness burden. The modified CIRS was operationalized with a manual of guidelines geared toward the geriatric patient and for clarity was designated the CIRS(G). A total of 141 elderly outpatient subjects (two medical clinic groups of 20 each, 45 recurrent depressed subjects, 21 spousally bereaved subjects, and 35 healthy controls) received comprehensive physical examinations, reviews of symptoms, and laboratory testing. These data were then used by nurse practitioners, physicians assistants, and geriatric psychiatrists to compute CIRS(G) ratings of chronic illness burden. As hypothesized, analysis of variance demonstrated significant differences among groups with respect to total medical illness burden, which was highest among medical clinic patients and lowest in control subjects. Good interrater reliability (i.e., intraclass correlations of 0.78 and 0.88 in a subsample of 10 outpatients and a separate group of 10 inpatients, respectively) was achieved for CIRS(G) total scores. Among medical clinic patients, a significant correlation was found, as expected, between CIRS(G) chronic illness burden and capability as quantified by the Older Americans Activities of Daily Living Scale; and between CIRS(G) scores and physicians global estimates of medical burden. Finally, with repeated measures of illness burden approximately 1 year from symptom baseline, significant rises were detected, as expected. The current data suggest that the CIRS(G) can be successfully applied in medically and psychiatrically impaired elderly subjects, with good interrater reliability and face validity (credibility).

Allelic Variation in the Serotonin Transporter Promoter Affects Onset of Paroxetine Treatment Response in Late-Life Depression

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.

Intraventricular Hemorrhage and Neurodevelopmental Outcomes in Extreme Preterm Infants

OBJECTIVE: Not many large studies have reported the true impact of lower-grade intraventricular hemorrhages in preterm infants. We studied the neurodevelopmental outcomes of extremely preterm infants in relation to the severity of intraventricular hemorrhage. METHODS: A regional cohort study of infants born at 23 to 28 weeks’ gestation and admitted to a NICU between 1998 and 2004. Primary outcome measure was moderate to severe neurosensory impairment at 2 to 3 years’ corrected age defined as developmental delay (developmental quotient >2 SD below the mean), cerebral palsy, bilateral deafness, or bilateral blindness. RESULTS: Of the 1472 survivors assessed, infants with grade III–IV intraventricular hemorrhage (IVH; n = 93) had higher rates of developmental delay (17.5%), cerebral palsy (30%), deafness (8.6%), and blindness (2.2%). Grade I–II IVH infants (n = 336) also had increased rates of neurosensory impairment (22% vs 12.1%), developmental delay (7.8% vs 3.4%), cerebral palsy (10.4% vs 6.5%), and deafness (6.0% vs 2.3%) compared with the no IVH group (n = 1043). After exclusion of 40 infants with late ultrasound findings (periventricular leukomalacia, porencephaly, ventricular enlargement), isolated grade I–II IVH (n = 296) had increased rates of moderate-severe neurosensory impairment (18.6% vs 12.1%). Isolated grade I–II IVH was also independently associated with a higher risk of neurosensory impairment (adjusted odds ratio 1.73, 95% confidence interval 1.22–2.46). CONCLUSIONS: Grade I–II IVH, even with no documented white matter injury or other late ultrasound abnormalities, is associated with adverse neurodevelopmental outcomes in extremely preterm infants.

Open-trial response to antidepressant treatment in elderly patients with mixed depression and cognitive impairment

We report open-trial antidepressant response in 16 inpatients with mixed symptoms of depression and cognitive impairment, compared to 16 elderly depressives without cognitive impairment. Criteria for adequate treatment specified a steady-state plasma nortriptyline level of 50-150 ng/ml for 4 consecutive weeks or a minimum of six treatments with electroconvulsive therapy. Ten of 16 mixed-symptom patients showed a drop in Hamilton depression ratings greater than or equal to 50% during treatment. Similarly, Blessed dementia ratings declined significantly; the % change in Blessed dementia ratings was significantly correlated with improvement in Hamilton depression ratings. By contrast, Folstein mini-mental state scores did not change significantly during treatment. Six of 16 (37.5%) patients showed resolution of cognitive impairment with adequate treatment of depression. Mixed-symptom patients diagnosed as suffering from major depression (with cognitive impairment) showed more robust pre-post treatment differences, particularly in Hamilton, Folstein, and Blessed dementia scores, than did mixed patients diagnosed as having primary degenerative dementia (with depression). In cognitively intact elderly depressives, the mean % change in Hamilton ratings was 72% (4.3), not significantly different from mean % change in mixed-symptom patients (57.4 +/- 29.9). The proportion of intact depressives showing a reduction greater than or equal to 50% in Hamilton depression ratings was significantly greater (93.8%) than in the mixed group (62.5%). In both groups, 81.3% of patients (13 of 16 in each cell) had a final Hamilton rating less than or equal to 10. These data suggest that elderly patients with mixed depression and cognitive impairment respond to treatment similar to that used in cognitively intact elderly depressives. A controlled study of antidepressant treatment in mixed-symptom patients is warranted.

Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants

BACKGROUNDnThe safest ranges of oxygen saturation in preterm infants have been the subject of debate.nnnMETHODSnIn two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial.nnnRESULTSnAfter 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P=0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P=0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P=0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P=0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P=0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P=0.001).nnnCONCLUSIONSnUse of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).

What is the optimal duration of a short-term antidepressant trial when treating geriatric depression?

Background: To determine the optimal duration of an antidepressant trial in elderly patients, the authors examined the probability of eventually responding to treatment based on early improvement. Methods: Four hundred seventy-two elderly patients with major depression (nonpsychotic, nonbipolar) were treated under protocolized conditions for up to 12 weeks and assessed weekly with the Hamilton Rating Scale for Depression. The probability of full response after 12 weeks of treatment was calculated in patients who had not fully responded after periods of treatment that lasted for 4 to 10 weeks. Results: Most of the patients who had shown a partial improvement after 4 weeks of treatment became full responders after 4 or more additional weeks of treatment. By contrast, only a few of those who were nonresponders became full responders even after up to 8 additional weeks of treatment. Conclusions: After 4 weeks of treatment, it is possible to reliably identify a subgroup of elderly patients with depression who are more likely to benefit from a change in their treatment than from a few additional weeks of treatment with the same agent.

Sleep deprivation effects in older endogenous depressed patients

In a drug-free group of 15 older endogenous depressed inpatients, all-night sleep deprivation (SD) was associated with a significant decrease in Hamilton depression scores and in Profile of Mood States self-ratings of depression. Six of 15 patients (40%) were responders to SD, as evidenced by greater than or equal to 30% improvement in Hamilton ratings. While symptomatic improvement was short-lived (8 of 15 patients worsened after 1 night of recovery sleep), five patients showed further improvement after 1 night of recovery sleep. The final two patients had an increase in Hamilton ratings after sleep deprivation, with a return to baseline values after 1 night of recovery sleep. Responders (but not nonresponders) showed significant improvement in sleep latency, sleep efficiency, and slow wave sleep during recovery sleep (as did controls). The SD Hamilton depression rating (at 9 a.m. after all-night sleep deprivation) showed a significant inverse correlation with the increase in slow wave sleep (SWS) minutes and in SWS % from baseline to first recovery night. Responders also had significantly larger increases in SWS minutes than did nonresponders (53.8 vs. 7 minutes). Similarly, the % change in Hamilton depression ratings was predicted by baseline Stage 4 sleep. These findings suggest that there is a mutual interaction between the process of sleep regulation and the symptoms of depression. They also confirm a prediction from the two-process model of sleep regulation--namely, that improved sleep initiation and maintenance and increased SWS, attained by SD, are associated with clinical improvement.

Electroencephalographic sleep in unipolar depressive subtypes: support for a biological and familial classification.

A tripartite classification of unipolar disease based on family history has been proposed by Winokur. In this study, we sought to investigate whether the familial pure depressive disorder (FPDD) and the sporadic depressive disorder (SDD) populations could be differentiated on the basis of baseline EEG sleep as effected by a tricyclic pharmacological probe. A subject group consisting of 26 females and 10 males yielding 18 FPDD/SDD pairs matched for age was selected. Both groups of patients demonstrated a considerable amount of sleep continuity disturbance with an overall sleep efficiency of 80.5 per cent in the pure depressive (FPDD) group and 83 per cent in the sporadic (SDD) group. Examination of the rapid eye movement (REM) sleep variables revealed the usual shortened REM latency as well as increased REM activity and REM density changes. However, the only significant difference between the two groups on baseline was the presence of more stage 3 and 4 sleep in the sporadic group, but stage 3 and 4 sleep was found in less than 40 per cent of the total sample. In contrast, analysis of the first two nights of EEG sleep on 50 mg of amitriptyline demonstrated several significant findings between the two groups. While considerable REM sleep suppression occurred in both groups, REM activity, REM intensity, and the number of REM periods were significantly more suppressed in the pure group than the sporadic group. Application of these variables led to a successful discrimination of 75 per cent of all the cases. These findings suggest a hyper-reactivity of sleep in patients with FPDD to a pharmacological probe.

Surfactant protein B deficiency: Clinical, histological and molecular evaluation

Abstract: Congenital alveolar proteinosis due to surfactant protein B deficiency is an inherited disease which results in severe respiratory failure in term infants soon after birth. The pathophysiologic basis of this disease is now known to be an inability to synthesise adequate quantities of normally functioning surfactant protein B. We report a male infant with fatal respiratory failure of neonatal onset, and histopathological features typical of those seen in congenital alveolar proteinosis. Molecular analysis of genomic DNA revealed two mutations, the ‘common’ 121ins2 mutation in exon 4, and a novel 2bp frameshift mutation in exon 5. We believe this is the first Australian case of surfactant protein B deficiency confirmed by molecular analysis.

Early Intervention to Preempt Major Depression Among Older Black and White Adults

OBJECTIVEnThe study objective was to assess the efficacy of problem-solving therapy for primary care (PST-PC) for preventing episodes of major depression and mitigating depressive symptoms of older black and white adults. The comparison group received dietary coaching.nnnMETHODSnA total of 247 participants (90 blacks, 154 whites, and three Asians) with subsyndromal depressive symptoms were recruited into a randomized depression prevention trial that compared effects of individually delivered PST-PC and dietary coaching on time to major depressive episode and level of depressive symptoms (Beck Depression Inventory) over two years. Cumulative intervention time averaged 5.5-6.0 hours in each study arm.nnnRESULTSnThe two groups did not differ significantly in time to major depressive episodes, and incidence of such episodes was low (blacks, N=8, 9%; whites, N=13, 8%), compared with published rates of 20%-25% over one year among persons with subsyndromal symptoms and receiving care as usual. Participants also showed a mean decrease of 4 points in depressive symptoms, sustained over two years. Despite greater burden of depression risk factors among blacks, no significant differences from whites were found in the primary outcome.nnnCONCLUSIONSnBoth PST-PC and dietary coaching are potentially effective in protecting older black and white adults with subsyndromal depressive symptoms from developing episodes of major depression over two years. Absent a control for concurrent usual care, this conclusion is preliminary. If confirmed, both interventions hold promise as scalable, safe, nonstigmatizing interventions for delaying or preventing episodes of major depression in the nations increasingly diverse older population.