Premature death in adults with 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disease with a prevalence of 1/4000. Variable expression of congenital and later onset features contributes to its under-recognition. Longevity in those surviving childhood is believed to be normal but data are limited. METHODS: We prospectively followed 264 subjects; 102 adults (>17 years) with 22q11.2DS (44 male (M), 58 female (F); mean (SD) age 33.6 (10.9) years) and their 162 unaffected siblings (77 M, 85 F; mean age 36.1 (12.2) years). We compared survival between groups using Kaplan-Meier estimates. RESULTS: Twelve (11.8%; 4 M, 8 F) individuals with 22q11.2DS and no siblings died (p<0.0001). Survival to ages 40 and 50 years was 89.9% and 73.9%, respectively. Median age at death was 41.5 (range 18.1-68.6) years. Deaths included two (7.7%) of 26 subjects with neither major congenital heart disease (CHD) nor schizophrenia. Four of six sudden and unexpected deaths occurred in individuals with no major CHD. There was no evidence of cancer or coronary artery disease or family history of sudden death in the 12 patients who died, six of whom had autopsies. DISCUSSION: Individuals with 22q11.2DS who survive childhood have diminished life expectancy and increased risk of sudden death not attributable to any single factor. Some sudden and/or premature deaths observed in the general population may represent undiagnosed 22q11.2DS. Increased recognition of the syndrome by family doctors, specialists and coroners will be essential to facilitate the tissue studies needed to determine underlying mechanisms.

Occurrence and correlates of fatigue in psoriatic arthritis.

OBJECTIVE: To determine the relationship between fatigue and disease-related and psychosocial variables in psoriatic arthritis (PsA). METHOD: 499 patients attending the University of Toronto PsA Clinic were administered the modified fatigue severity scale (mFSS). At the time of mFSS administration, clinical and laboratory measures of disease activity and damage were recorded. Linear regression models were used to examine the cross-sectional relationship between disease-related and psychosocial variables and mFSS scores. RESULTS: At least moderate fatigue occurred in 49.5% of patients and severe fatigue in 28.7%. Univariately the vast majority of variables were significantly associated with mFSS scores. The final multivariate model was composed of female sex, the medical outcome survey short form 36 (SF-36) pain and mental health scales, the number of fibromyalgia tender points, the health assessment questionnaire (HAQ) and "ever used" methotrexate, and explained 54.5% of the variation in mFSS scores. The SF-36 mental health scale played the largest role in the multivariate model, uniquely accounting for 6.6% of the variation in the fatigue severity scale. The disease-related factors significant at the univariate level did not achieve statistical significance in the context of HAQ and pain measures. CONCLUSION: Fatigue is a common symptom in PsA, and is associated, in a multivariate model, with pain, female sex, physical functional disability, medication status and psychological distress. Fatigue appears to provide some information that does not overlap with the core set of outcome domains in PsA.

Did the pattern of practice in the prescription of palliative radiotherapy for the treatment of uncomplicated bone metastases change between 1999 and 2005 at the rapid response radiotherapy program?

AIMS: Since 1999, randomised clinical trials and meta-analyses have reported equal efficacy of pain relief from single- and multiple-fraction radiotherapy for bone metastases. A number of factors, including limited radiotherapy resources, waiting times, and patient convenience, suggest single fraction to be the treatment of choice for patients. However, international patterns of practice indicate that multiple fractions are still commonly used. This study examined whether dose-fractionation schemes used for the treatment of bone metastases at the Rapid Response Radiotherapy Program (RRRP) at the Odette Cancer Centre have changed since 1999. MATERIALS AND METHODS: A retrospective review of the prospective RRRP database and hospital records were conducted for all patients treated with palliative radiotherapy for uncomplicated bone metastases at the RRRP in 1999 (or baseline), 2001, 2004 and from 1 January to 31 July 2005. Data were collected on patient demographics and clinical characteristics. RESULTS: Of the 693 patients, 65 and 35% were prescribed single fraction (predominantly single 8 Gy) and multiple fractions (predominantly 20 Gy/five fractions), respectively. The administration of single treatments generally increased over time, from 51% in 1999 to 66% in 2005 (P=0.0001). On the basis of multiple logistic regression analyses, patients were more likely to be prescribed single-fraction radiotherapy if they had prostate cancer, had a poorer performance status, were treated to the limbs, hips, shoulders, pelvis, ribs, scapula, sternum, or clavicle (compared with the spine), were treated by a radiation oncologist who had been trained in earlier years, and who were treated after 1999. CONCLUSIONS: Between 1999 and 2005, the use of single-fraction radiotherapy increased, corresponding to publications showing equal efficacy of pain relief between single and multiple fractions in the management of uncomplicated bone metastases. However, about a third of patients still received multiple fractions.

Elevated rates of schizophrenia in a familial sample with mental illness and intellectual disability.

BACKGROUND: It is unknown whether intellectual disability (ID) is more familially related to psychotic mood disorders or schizophrenia. L. S. Penrose's large sample of families with two or more members admitted to psychiatric hospitals provided a unique opportunity to investigate the familial relationship between mild ID, schizophrenia and psychotic affective disorders. METHOD: There were 183 affected relative pairs comprising probands with mild ID (95 male, 88 female) and their first or second degree relatives with schizophrenia or psychotic affective disorder. RESULTS: There were nearly twice as many relatives with a diagnosis of schizophrenia (n = 121) as relatives with affective disorders (n = 62) among the intellectually impaired probands. This excess of schizophrenia was statistically significant, even after accounting for the increased risk of hospitalization for schizophrenia (P = 0.005), and was fairly constant across the different relative types. First-degree relatives with either mental illness were more likely to be parents (n = 77) than siblings (n = 51) or children (n = 3), but there was no excess of mother-son pairs. CONCLUSIONS: These results suggest a stronger familial relationship of ID with schizophrenia than psychotic affective disorder, and lend some support to the neurodevelopmental hypothesis of schizophrenia.

Postmaturity in a genetic subtype of schizophrenia.

OBJECTIVE: To determine whether postmaturity (gestation > 41 weeks), small for gestational age (SGA), and other pregnancy and birth complications that may elevate risk for neurodevelopmental disorders, are associated with elevated risk for schizophrenia in 22q11 Deletion Syndrome (22qDS), a genetic subtype of schizophrenia. METHOD: Antepartum and intrapartum features were examined in 20 adults with 22qDS-schizophrenia and three comparison groups: newborn encephalopathy (n = 164) and healthy newborn controls (n = 400) from Badawi et al.'s (Br Med J 1998, 317: 1549) study, and 16 non-psychotic 22qDS adults (22qDS-NP). RESULTS: Postmaturity (OR 13.0, 95% CI 3.95, 42.77; P < 0.001) and SGA (OR 3.59, 95% CI 1.23, 10.5; P = 0.03) were more prevalent in 22qDS-SZ than controls. Postmaturity was non-significantly more prevalent in 22qDS-SZ than in newborn encephalopathy (P = 0.06) or 22qDS-NP (P = 0.2). SGA showed similar rates in the two 22qDS groups and newborn encephalopathy, but was more prevalent in 22qDS-NP than controls (P = 0.05). CONCLUSION: The results suggest that postmaturity may be associated with expression of schizophrenia in a 22qDS subtype of schizophrenia. SGA may be a non-specific marker of neurodevelopmental disturbance.

Understanding successful community living by individuals with serious and persistent mental illness.

34 volunteers diagnosed as chronically mentally ill were administered a questionnaire to evaluate what factors were important in preventing rehospitalization. The volunteers were divided into two groups based on their relapse history. Analysis showed the nonrelapse group were more likely to attribute factors such as in-home therapy, taking medication, and having fun with friends than did the group who had experienced at least one relapse in the past 24 months.

Euroscreen 2: towards community policy on insurance, commercialization and public awareness.

The project Euroscreen 2 has examined genetic screening and testing with particular reference to implications for insurance, commercialization through marketing of genetic tests direct to the public, and issues surrounding raising public awareness of these and other developments in genetics, including the practical experiment of a Gene Shop. This paper provides a snapshot of the three year project. The study group's work included monitoring developments in different European countries and exploring possibilities for regulation in insurance and commercialization together with public attitudes to regulation. The success or failure of different strategies is not independent of public awareness. Exploration of policy, however, also requires examination of fundamental concepts such as solidarity and geneticization.

Health-related quality of life of patients with psoriatic arthritis: a comparison with patients with rheumatoid arthritis.

OBJECTIVE: To compare health-related quality of life (QOL) between patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA), using the Medical Outcomes Study Short Form health survey (SF-36) and the Health Assessment Questionnaire (HAQ). METHODS: Both the SF-36 and the HAQ were administered to 107 PsA patients attending the University of Toronto Psoriatic Arthritis Clinic between January 1 and December 31, 1994, and to 43 RA patients attending a University of Toronto-affiliated RA clinic during the same period. Standardized assessments of disease activity and severity were also performed at each clinic visit. Logistic regression analysis was used to compare health-related QOL between PsA and RA. RESULTS: Both patient populations experienced lower physical health compared with that of a general population sample. The RA patients demonstrated more active inflammatory disease at the time of assessment than the PsA patients. The PsA patients were younger, and more were men. Logistic regression analyses showed that patients with PsA reported higher levels of vitality than patients with RA, even after adjusting for the observed differences in clinical and demographic characteristics. PsA patients, however, reported more role limitations due to emotional problems and more bodily pain after adjusting for the difference in vitality and other covariates. CONCLUSIONS: Although both patient populations experienced reduced QOL, there were some meaningful differences in how the 2 conditions affect health-related QOL. Further, it appeared that there may be unique disabilities associated with the psoriasis dimension of PsA.

Comparison of hemodynamic responses to social and nonsocial stress: evaluation of an anger interview.

Hemodynamic responses to an anger interview and cognitive and physical stressors were compared, and the stability of associated hemodynamic reactions examined. Participants experienced control, handgrip, counting, and mental arithmetic tests and an anger interview on two occasions. Systolic and diastolic blood pressure, heart rate, stroke volume, and cardiac output were measured. Total peripheral resistance was also derived. The anger interview produced larger, more sustained changes in blood pressure in both sessions than the other stressors. These changes were largely a consequence of increased peripheral resistance. Consistent with previous findings, handgrip was associated with a resistance-type reaction whereas arithmetic was associated with a cardiac output-type reaction. There was low-to-modest stability of hemodynamic reactions to the interview. Further research is necessary to optimize its utility in studies of cardiovascular function. Nevertheless, the findings underscore the ability of ecologically relevant stressors to provoke unique configurations of cardiovascular activity.

The effectiveness of day treatment with persistently mentally ill in rural areas.

PURPOSE/METHOD: This study investigated the effectiveness of day treatment programmes in rural Minnesota by comparing 2 groups in terms of yearly rates of re-hospitalization. RESULTS: It was found that the group that responded positively to day treatment was much less likely to be re-hospitalized. Their rates of re-hospitalization were much lower than the state of Minnesota. The other group that dropped out of day treatment has a re-hospitalization rate as much as 10 times higher. CONCLUSION: This demonstrates the cost effectiveness of day treatment programmes.

Methods for assessing responsiveness: a critical review and recommendations.

A review of the literature suggests there are two major aspects of responsiveness. We define the first as "internal responsiveness," which characterizes the ability of a measure to change over a prespecified time frame, and the second as "external responsiveness, " which reflects the extent to which change in a measure relates to corresponding change in a reference measure of clinical or health status. The properties and interpretation of commonly used internal and external responsiveness statistics are examined. It is from the interpretation point of view that external responsiveness statistics are considered particularly attractive. The usefulness of regression models for assessing external responsiveness is also highlighted.

The relationship between patient satisfaction with health and clinical measures of function and disease status in patients with psoriatic arthritis.

OBJECTIVE: To investigate whether patient satisfaction with health is a distinct aspect of clinical or health status in a sample of patients with psoriatic arthritis (PsA). METHODS: One hundred sixty-nine consecutive outpatients attending the University of Toronto PsA Clinic completed the Arthritis Impact Measurement Scales II (AIMS2), which includes both a global rating of patient satisfaction with health and a scale that assesses satisfaction with functioning in 12 health domains. Clinical, laboratory, and radiological assessments of function, pain, inflammation, and damage were also performed according to a standard protocol. RESULTS: Logistic regression analysis indicated that the AIMS2 global ratings of patient satisfaction with health were not associated with traditional clinical measures of inflammation and damage, but were associated with American College of Rheumatology (ACR) functional class and number of fibromyalgia tender points. Patient satisfaction was also related to annual family income and use of retinoids or corticosteroids. Similarly, linear regression analysis showed that scores on the AIMS2 satisfaction scale were unrelated to traditional clinical measures of inflammation and damage, with the exception of total number of actively inflamed joints. ACR functional class, annual family income, and comorbidity were also related to scores on the satisfaction scale. CONCLUSION: Patient satisfaction with health appears to be relatively independent of traditional clinical measures of physical functioning, pain, and disease status.

Validity assessment of the disabilities of arm, shoulder, and hand questionnaire (DASH) for patients with psoriatic arthritis.

OBJECTIVE: To determine whether patients' perception of their functional ability, as measured by the disabilities of arm, shoulder. and hand (DASH) questionnaire, correlates with clinical measures of articular status in patients with psoriatic arthritis (PsA). METHODS: Patients attending the University of Toronto Psoriatic Arthritis Clinic between June and August 1997 were asked to complete a DASH questionnaire during their visits. Clinical assessments were performed according to a standard protocol including number of actively inflamed joints, total number of damaged joints, and grip strength. Spearman rank correlations were used to examine the relationship between clinical measures and the DASH questionnaire. RESULTS: Fifty consecutive patients, 28 men and 22 women, (mean age 49.2 yrs, mean disease duration 13 yrs) were included. DASH scores correlated with clinical measures of upper extremity function including right grip strength (r = -0.47, CI -0.67, -0.21) and number of active joints in the upper limbs (r = 0.65, CI 0.46, 0.79). As expected, the correlation between DASH scores and total number of active joints (r = 0.40, CI 0.14, 0.61) was lower than that between DASH scores and number of active joints in the upper limbs. The DASH was unrelated to clinical damage. CONCLUSION: DASH is a valid instrument for assessing upper extremity function and inflammatory disease activity in patients with PsA.

Insight in severe mental illness: implications for treatment decisions.

This article reviews recent research related to impaired insight in schizophrenia and its consequences for cognitive, behavioral, legal, and treatment compliance issues affecting this population. It discusses efforts to find the neurobiological basis for lack of insight and the various structures or circuits of the brain that have been implicated. In the search for a more reliable and valid measure of insight for treatment decisions, the development of various assessment instruments is summarized. Impaired insight is shown to be related to a poorer course of the illness and noncompliance with necessary treatment. The implications of these findings for treatment decisions, legal interventions, and ongoing treatment monitoring are discussed.

Agreement: the origin of ethical action.

The health care setting is an interweaving of human concerns. What is needed in this arena is an ethic--a guidance system centered on, and relevant to, these concerns. Such an ethic must be derived from, and appropriate to, the health care setting and the practice of health care professionals. This is established by the health care professional/patient agreement. This article will describe how a practice-based, symphonological ethic--an ethic based on agreement--can be brought to bear on the adversities faced by nurses and any other health care professional in any setting.

Responsiveness of health status instruments to changes in articular status and perceived health in patients with psoriatic arthritis.

OBJECTIVE: To compare the responsiveness of the Health Assessment Questionnaire (HAQ), Arthritis Impact Measurement Scale 2 (AIMS2), and Medical Outcome Study Short Form Health Survey (SF-36) to changes in articular status and perceived health in outpatients with psoriatic arthritis (PsA). METHODS: The 3 health status instruments were administered in random order on 2 occasions, about 12-18 months apart, to 70 patients attending the University of Toronto psoriatic arthritis clinic. Standardized assessments of disease activity, disease severity, and general health perceptions were also performed at each clinic visit. To assess responsiveness we used: (1) linear regression analyses to relate change scores for perceived health, the number of actively inflamed, and damaged joints to change scores for selected dimensions of the HAQ, AIMS2, and SF-36; (2) logistic regression analyses to relate both improvement in disease activity and disease progression to health status change scores; and (3) standardized response means (SRM). RESULTS: There were 43 men and 27 women with a mean age of 46 years and arthritis duration of 13 years. Univariate regression analyses showed that the individual instruments were responsive to perceived changes in health, but relatively insensitive to detect changes in articular status. Multivariate regression analyses, in which the common dimensions of the instruments were jointly entered, indicated the SF-36 was equally or more responsive to changes in number of actively inflamed joints, clinical improvement in disease activity, and perceived health than the HAQ and AIMS2. The SRM analysis also suggested that the SF-36 was the most responsive. CONCLUSION: The SF-36 proved equally or more responsive to short term changes in perceived health and inflammatory disease activity; however, none of the instruments showed responsiveness to disease progression.