The Effect of Multiple Assessments on Delirium Detection: a Pilot Study.

BACKGROUND: Delirium is characterized by fluctuating attention or arousal, with high prevalence in the orthopaedic ward. Our aim was to: 1) establish the prevalence of delirium on an orthopaedic ward, and 2) compare delirium prevalence using a single geriatrician assessment vs. multiple 3D-CAM (3-Minute Diagnostic Interview for Confusion Assessment Method) assessments during the day. We hypothesized that multiple assessments would increase the detection rate due to the fluctuating nature of delirium. METHODS: Comparative study conducted at an academic hospital in Hamilton, Ontario. Participants included patients 65 years and older admitted to the orthopaedic ward (n=55). After a geriatrician made the first assessment of delirium by 3D-CAM on each patient, teams with specialized geriatrics training re-assessed participants up to four times. Delirium rates based on first assessment were compared to cumulative end-of-day rates to determine if detection increased with multiple assessments. RESULTS: The prevalence of delirium was 30.9% (17 participants) using multiple assessments. Of these cases, 13 (76.4%) were detected in the initial geriatrician assessment. In patients with hip fractures, 70.6% (12 of 17) were identified as delirious by multiple assessments. CONCLUSION: As symptoms fluctuate, multiple daily CAM assessments may increase the identification of delirium in orthopaedic inpatients.

Bias in beliefs about the self is associated with depressive but not anxious mood.

BACKGROUND: Biases in beliefs about the self are associated with psychopathology and depressive and anxious mood, but it is not clear if both negative and positive beliefs are associated with depression or anxiety. We examined these relationships in people who present with a wide range of depressive and anxious mood across diagnostic categories. METHODS: We probed positive and negative beliefs about the self with a task in which 74 female participants with either affective disorder (depression and/or anxiety), borderline personality disorder or no psychiatric history indicated the degree to which 60 self-related words was "like them" or "not like them". Depressive and anxious mood were assessed with the Beck Depression Inventory-II and the Beck Anxiety Inventory. RESULTS: The participants with no psychiatric history (n=25) reported a positive bias in their beliefs about the self, the participants with affective disorder (n=23) reported no bias, and the participants with BPD (n=26) reported a negative bias. Two hierarchical multiple regressions demonstrated that the positive and negative beliefs contributed additively to the ratings of depression (corrected for anxiety), but did not contribute to the ratings of anxiety (corrected for depression). LIMITATIONS: Despite the apparent small sample size, the regression analyses indicated adequate sampling. Anxiety is a much more heterogeneous condition than is depression, so it may be difficult to find relevant self-descriptors. Only measures of endorsement were used. CONCLUSIONS: Biases in beliefs about the self are associated with depressed, but not anxious mood, across diagnostic categories.

The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom's Macroglobulinemia.

CXCR4(WHIM) somatic mutations are common Waldenstrom's Macroglobulinemia (WM), and are associated with clinical resistance to ibrutinib. We engineered WM cells to express the most common WHIM (Warts, Hypogammaglobulinemia, Infections and Myelokathexis), CXCR(S338X) mutation in WM. Following SDF-1a stimulation, CXCR4(S338X) WM cells exhibited decreased receptor internalization, enhanced and sustained AKT kinase (AKT) and extracellular regulated kinase (ERK) signaling, decreased poly (ADP-ribose) polymerase and caspase 3 cleavage, and decreased Annexin V staining versus CXCR4 wild-type (WT) cells. CXCR4(S338X)-related signaling and survival effects were blocked by the CXCR4 inhibitor AMD3100. SDF-1a-treated CXCR4(S338X) WM cells showed sustained AKT and ERK activation and decreased apoptotic changes versus CXCR4(WT) cells following ibrutinib treatment, findings which were also reversed by AMD3100. AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance. Enhanced bone marrow pAKT staining was also evident in CXCR4(WHIM) versus CXCR4(WT) WM patients, and remained active despite ibrutinib therapy in CXCR4(WHIM) patients. Last, CXCR4(S338X) WM cells showed varying levels of resistance to other WM relevant therapeutics, including bendamustine, fludarabine, bortezomib and idelalisib in the presence of SDF-1a. These studies demonstrate a functional role for CXCR4(WHIM) mutations, and provide a framework for investigation of CXCR4 inhibitors in WM.

Detection of MYD88 L265P in peripheral blood of patients with Waldenström's Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance.

MYD88 L265P is highly prevalent in Waldenstrom's Macroglobulinemia (WM) and IgM monoclonal gammopathy of unknown significance (MGUS). We investigated whether MYD88 L265P could be identified by peripheral blood (PB) allele-specific PCR. MYD88 L265P was detected in untreated WM (114/118; 96.6%); previously treated WM (63/102; 61.8%); and IgM MGUS (5/12; 41.7%) but in none of 3 hyper-IgM or 40 healthy individuals. Median PB MYD88 L265P ΔCt was 3.77, 7.24, 10.89, 12.33 and 14.07 for untreated WM, previously treated WM, IgM MGUS, hyper-IgM and healthy individuals, respectively (P<0.0001). For the 232 IgM MGUS and WM patients, PB MYD88 L265P ΔCt moderately correlated to bone marrow (BM) disease (r=-0.3553; P<0.0001), serum IgM (r=-0.3262; P<0.0001) and hemoglobin (r=0.3005; P<0.0001) levels. PB MYD88 L265P ΔCt and serum IgM correlated similarly with BM disease burden. For positive patients, PB MYD88 L265P ΔCt was <6.5 in 100/114 (88%) untreated WM, and >6.5 in 4/5 (80%) IgM MGUS patients (P=0.0034). Attainment of a negative PB MYD88 L265P mutation status was associated with lower BM disease (P=0.001), serum IgM (P=0.019) and higher hemoglobin (P=0.004) levels in treated patients. These studies show the feasibility for detecting MYD88 L265P by PB examination, and the potential for PB MYD88 L265P ΔCt use in the diagnosis and management of WM patients.

Characterization of familial Waldenstrom's macroglobulinemia.

BACKGROUND: Familial clustering of B-cell disorders among Waldenström's macroglobulinemia (WM) patients has been reported, though the frequency and any differences in disease manifestation for familial patients remain to be defined. PATIENTS AND METHODS: We therefore analyzed clinicopathological data from 257 consecutive and unrelated WM patients. Forty-eight (18.7%) patients had at least one first-degree relative with either WM (n = 13, 5.1%), or another B-cell disorder including non-Hodgkin's lymphoma (n = 9, 3.5%), myeloma (n = 8, 3.1%), chronic lymphocytic leukemia (n = 7, 2.7%), monoclonal gammopathy of unknown significance (n = 5, 1.9%), acute lymphocytic leukemia (n = 3, 1.2%) and Hodgkin's disease (n = 3, 1.2%). Patients with a familial history of WM or a plasma cell disorder (PCD) were diagnosed at a younger age and with greater bone marrow involvement. RESULTS: Deletions in 6q represented the only recurrent structural chromosomal abnormality and were found in 13% of patients, all non-familial cases. Interphase FISH analysis demonstrated deletions in 6q21-22.1 in nearly half of patients, irrespective of familial background. CONCLUSIONS: The above results suggest a high degree of clustering for B-cell disorders among first-degree relatives of patients with WM, along with distinct clinical features at presentation based on familial disease cluster patterns. Genomic studies to delineate genetic predisposition to WM are underway.

Too many pre-discharge home assessment visits for older patients? A postal questionnaire survey.

OBJECTIVE: To investigate current practice of pre-discharge home assessment visits for older patients. DESIGN: Postal questionnaire survey. SETTING: NHS Trust hospitals in the United Kingdom. SUBJECTS: Occupational therapy departments in 265 NHS Trust hospitals which admit acutely ill older patients. MAIN OUTCOME MEASURES: The number of pre-discharge home visits done, who went, and therapy time spent on home visits. RESULTS: Of 265 NHS Trusts contacted, 239 (90%) replied. Of 238 units, 155 (65%) do between 11 and 40 visits per month, with 25 (11%) doing more than 60. The equivalent of one day per week or more is spent doing home visits by Senior I occupational therapists in 107 (45%) units and by Senior II staff in 126 (53%) units. Carers or relatives, unqualified occupational therapists, social workers and home care managers accompany the patient and occupational therapist on most home visits. CONCLUSION: Therapy perception is that pre-discharge home assessment visits are increasing in number, complexity and involvement of professional time despite little evidence for their effectiveness. Controlled trials are required to assess which patients are likely to benefit.

Developmental pathways from child maltreatment to peer rejection.

Using a prospective longitudinal design, rejection by peers, aggressive behavior, and social withdrawal were examined among a representative community sample of 107 maltreated children and an equal number of non-maltreated children. Results revealed that chronic maltreatment was associated with heightened risk of rejection by peers. Chronically maltreated children were more likely to be rejected by peers repeatedly across multiple years from childhood to early adolescence. Maltreatment chronicity was also associated with higher levels of children's aggressive behavior, as reported by peers, teachers, and children themselves. Aggressive behavior accounted in large part for the association between chronic maltreatment and rejection by peers. Socially withdrawn behavior was associated with peer rejection, but did not account for the association between chronic maltreatment and peer rejection. These results held for both girls and boys, followed from childhood through early adolescence. Moreover, the links among chronic maltreatment, aggressive behavior, and peer rejection were already established by early school age. Implications of these results for developmental theory and intervention are discussed.

Screening for cognitive impairment and dementia in the elderly.

OBJECTIVE: To review the evidence available to support or refute the recommendation to screen for cognitive impairment (cognitive deficits which do not affect daily function) and dementia in primary care. DATA SOURCES: Medline search using terms listed at the end of this article; consultation with experts in the field; review of other published recommendations. STUDY SELECTION: There were no articles which described a randomized controlled trial of screening versus no screening. Studies were therefore chosen which aided in the definition; natural history; interventions and outcomes including possible negative effects. DATA SYNTHESIS: No systematic synthesis was performed. Background papers were circulated to a panel of experts prior to the Canadian Consensus Conference on Dementia and conclusions endorsed by consensus. CONCLUSIONS: 1. There is insufficient evidence to recommend for or against screening for cognitive impairment or dementia. (C); 2. Memory complaints should be evaluated and the individual followed to assess progression. (B); 3. When caregivers or informants describe cognitive decline in an individual, these observations should be taken very seriously; cognitive assessment and careful follow-up are indicated. (A) (See Appendix).

Pathways from child maltreatment to internalizing problems: perceptions of control as mediators and moderators.

Using a prospective longitudinal design, we examined internalizing problems and perceptions of control in a community sample of 785 children, 59 of whom had been maltreated. Children's internalizing problems and perceptions of control were measured via self-report at annual assessments in third grade through seventh grade (modal ages 9-13 years). Children's experiences of multiple types of maltreatment were rated based on social service records, using a standard coding system. Results of longitudinal analyses examining the roles of specific types of maltreatment (neglect, harsh parenting, and sexual abuse) revealed that neglect and sexual abuse were each associated with more internalizing problems, especially among children who experienced both these maltreatment types. Neglected children reported higher levels of perceived external control than other children did. Sexual abuse was associated with higher levels of perceived external control, but only among children who had also been neglected. Results of mediation analyses showed that higher levels of perceived external control accounted substantially for associations between specific maltreatment types and children's internalizing problems. Results of moderator analyses revealed that, among maltreated children, greater perceived internal control predicted fewer internalizing problems, suggesting that perceived internal control functioned as a protective factor. Children maltreated early in life were less likely to have this protective characteristic. Results are discussed in terms of their implications for understanding the developmental consequences of specific and co-occurring types of maltreatment.

Infective discitis as an uncommon but important cause of back pain in older people.

CASE REPORTS: two elderly patients (aged 70 and 80 years) presented with severe back pain and restriction of spinal movements. Inflammatory markers were raised and in each case computed tomography findings confirmed infective discitis. One patient improved with antibiotics but the second developed paraplegia, a recognized complication of discitis. CONCLUSION: the association of back pain, restricted spinal movements and raised inflammatory markers should act as 'red flags', alerting the clinician to the presence of serious, but potentially treatable pathology.

The recognition, assessment and management of dementing disorders: conclusions from the Canadian Consensus Conference on Dementia.

OBJECTIVE: To develop evidence based consensus statements on which to build clinical practice guidelines for primary care physicians toward the recognition, assessment and management of dementing disorders and to disseminate and evaluate the impact of these statements and guidelines built on these statements. OPTIONS: Structured approach to assessment, including recommended laboratory tests, choices for neuroimaging and referral, management of complications (especially behavioural problems and depression) and use of cognitive enhancing agents. POTENTIAL OUTCOMES: Consistent and improved clinical care of persons with dementia; cost containment by more selective use of laboratory investigations; neuroimaging and referrals; and appropriate use of cognitive enhancing agents. EVIDENCE: Authors of each background paper were entrusted to perform a literature search, discover additional relevant material, including references cited in retrieved articles, consult with other experts in the field and then synthesize information. Standard rules of evidence were applied. Based on this evidence, consensus statements were developed by a group of experts, guided by a steering committee of 8 individuals, from the areas of Neurology, Geriatric Medicine, Psychiatry, Family Medicine, Preventive Health Care and Health Care Systems. VALUES: Recommendations have been developed with particular attention to the context of primary care, and are intended to support family physicians in their ongoing assessment and care of patients with dementia. BENEFITS HARM AND COSTS: Potential for improved clinical care of people with dementia. A dissemination and evaluation strategy will attempt to measure the impact of the recommendations. RECOMMENDATIONS: Forty-eight recommendations are offered that address the following aspects of dementia care: early recognition; importance of careful history and examination in making a positive diagnosis; essential laboratory tests; rules for neuroimaging and referral; disclosure of diagnosis; importance of monitoring and providing support to caregivers; cultural aspects; detection and treatment of depression; observation and management of behavioural disturbances; detection and reporting of unsafe motor vehicle driving; genetic factors and opportunities for preventing dementia; pharmacological treatment with particular emphasis on cognitive enhancing agents. VALIDATION: Four other sets of consensus statement or guidelines have been published recently. These recommendations are generally congruent with our own consensus statements. The consensus statements have been endorsed by relevant bodies in Canada.

The effectiveness of predischarge home assessment visits: a systematic review.

OBJECTIVE: To evaluate the effectiveness of predischarge home assessment visits for elderly patients. DESIGN: Systematic review. METHODS: A computer-aided search was conducted using the databases of Medline and Cinahl. Any studies investigating predischarge home assessment visits were included in the analysis. RESULTS: No randomized controlled trials were found. Only five studies (two retrospective surveys, three observational surveys) were identified. In four of these, a possible benefit for home visiting was suggested. CONCLUSIONS: Little evidence exists for the effectiveness of predischarge home assessment visits. Further research is needed to establish their value.

Peer relationships and self-esteem among children who have been maltreated.

A prospective longitudinal design was employed to assess risks associated with maltreatment in a representative community sample of 107 maltreated children and an equal number of nonmaltreated comparison children. Heightened difficulties in peer relationships and self-esteem were associated with greater severity and chronicity of maltreatment. For example, children who experienced chronic maltreatment were less well-liked by peers. Type of maltreatment was also related to specific aspects of children's adjustment. For instance, sexual abuse predicted low self-esteem, but not problems in peer relationships. Emotional maltreatment, on the other hand, was related to difficulties in peer relationships, but not to low self-esteem. Thus, the best predictions of specific aspects of children's adjustment were provided by considering timing, type, and severity of maltreatment. For some groups of maltreated children, having a good friend was associated with improvement over time in self-esteem.

Families of the lesbian baby boom: children's contact with grandparents and other adults.

In an exploratory study of 37 lesbian-mother families, the frequency of children's contact with adults in their extended family and friendship networks was found to counter stereotypes of such children as isolated from parents' families of origin. Children were more likely to have regular contact with relatives of the biological than nonbiological mother. Mothers rated those in regular contact with grandparents as having fewer behavior problems, and those in more regular contact with unrelated adults rated themselves more positively on general well-being.

Psychosocial adjustment among children conceived via donor insemination by lesbian and heterosexual mothers.

This study examined the relations among family structure (e.g., number of parents, parental sexual orientation), family process (e.g., parents' relationship satisfaction, interparental conflict), and the psychological adjustment of children who had been conceived via donor insemination. The 80 participating families, all of whom had conceived children using the resources of a single sperm bank, included 55 families headed by lesbian and 25 families headed by heterosexual parents. Fifty families were headed by couples and 30 by single parents. Participating children averaged 7 years of age. Results showed that children were developing in normal fashion, and that their adjustment was unrelated to structural variables such as parental sexual orientation or the number of parents in the household. These results held true for teacher reports as well as for parent reports. Variables associated with family interactions and processes were, however, significantly related to indices of children's adjustment. Parents who were experiencing higher levels of parenting stress, higher levels of interparental conflict, and lower levels of love for each other had children who exhibited more behavior problems.

Retrospective study of radiotherapy for lung cancer in patients aged 75 years and over.

BACKGROUND: Radiotherapy is widely used in the management of lung cancer but there are few data on its use in elderly patients. METHODS: Retrospective review of case notes of all patients aged 75 years and over referred to a regional centre for radiotherapy with a diagnosis of lung cancer over 1 year. RESULTS: Of 149 patients referred, full information was available on 144 (97%); age range 75-93 years (mean 79). Main referral sources were chest physicians [68 (44%)], general physicians [40 (28%)] and geriatricians [20 (14%)]; all patients were accepted for radiotherapy. One hundred and thirty-four (93%) had palliative treatment with most [129 (90%)] receiving 1-5 fractions over 1 week and 117 (81%) having treatment as an outpatient. Palliation appeared good for haemoptysis but less effective for the more common symptoms of dyspnoea and cough. Side effects were reported by 25 patients (18%) and were usually mild. CONCLUSION: Radiotherapy for lung cancer in this selected group of elderly patients is well tolerated with responses similar to those in younger patients.

A continuing medical education strategy for care of the elderly by the surgical specialties.

As the absolute numbers and percentage of older people rises in Canada, surgeons are required to treat an increasing number of elderly patients. Recognizing the need to enhance the quality of health care for these people by continuing medical education of health care professionals, the Canadian Medical Association sponsored an invitational workshop in May 1992. The workshop group addressing surgery and its specialties identified three essential underprinnings: knowledge of the aging process (altered physiology and response to illness); decision analysis for interventions (risks, benefits and ethical dimensions); and communication skills. Three priorities for continuing education were recommended: improving knowledge of the physiologic changes that impact on the recovery of elderly patients from surgery; management of postoperative care; and improved knowledge and skills in prescribing medications for older surgical patients. Strategies to implement these priorities are outlined.