Risk factors for tardive dyskinesia in a large population of youths and adults.

This study was designed to identify predisposing factors for tardive dyskinesia (TD) in youths and adults within a large, predominantly developmentally disabled and mentally ill population. The findings support previously reported risk factors for TD, including increasing age, use of anticholinergic medication for those over 40 years old, and long duration of neuroleptic exposure for those over 18 years of age. Higher cumulative levels of "typical" neuroleptic dosage decreased the risk for TD for those over 18. Novel findings included the benefit of personality disorder in individuals 18 to 40 years old and the strong risk factor of profound mental retardation in all age groups. These findings reveal further complex interactions to the risk factors for TD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Late acute rejection and subclinical noncompliance with cyclosporine therapy in heart transplant recipients

BACKGROUND: Although noncompliance with immunosuppressive medication is recognized as a critical behavioral risk factor for late acute rejection episodes and graft loss after transplantation, little is known about the degree of subclinical cyclosporine noncompliance, its associated risk for acute late rejection episodes (>1 year after transplantation), and its determinants in heart transplant recipients. METHODS: The convenience sample of this longitudinal study included 101 European heart transplant recipients (87 men and 14 women), with a median age of 56 (Q1 = 50, Q3 = 61) and a median posttransplantation status of 3 (range 1 to 6) years. Subclinical cyclosporine noncompliance was measured during a 3-month period with electronic event monitoring. Selected sociodemographic, behavioral, cognitive, emotional, health, and treatment-related determinants of medication noncompliance were measured by using instruments with established psychometric properties or by patient interviews. With the use of iterative partitioning methods of cluster analysis, including nonstandardized electronic event monitoring compliance parameters, patients were categorized by degree of subclinical cyclosporine noncompliance into a 3-cluster solution. RESULTS: Overall compliance was high, with a median medication taking compliance of 99.4%. The 3 derived clusters, that is, excellent compliers (84%), minor subclinical noncompliers (7%), and moderate subclinical noncompliers (9%), differed significantly by degree of subclinical noncompliance (p < .0001) and showed a 1.19%, 14.28%, and 22.22% incidence of late acute rejections (p = .01), respectively. The 3 groups also differed in terms of former medication noncompliance (p = .02), appointment noncompliance (p = .03), and perceived self-efficacy with medication taking (p = .04). CONCLUSIONS: Although in absolute numbers cyclosporine compliance in this sample was high, minor deviations from dosing schedule were associated with an increased risk for acute late rejection episodes. This suggests a pivotal role of patient compliance in successful long-term outcome after transplantation.     

The effect of gender and age at onset of depression on mortality

BACKGROUND: Depression has a marked negative impact on geriatric patient mortality and morbidity. The risk factors and exact reasons for these effects are not well understood. METHOD: Seeking to better define the factors, we retrospectively analyzed the effects of gender and age at onset of affective disorder in a naturalistic study of 192 geriatric patients consecutively admitted to a large midwestern tertiary care center between 1980 and 1987 for the treatment of unipolar depression. RESULTS: After controlling for age at index admission, patients with an onset of depression before age 40 suffered significantly (p < .05) less mortality in follow-up than those with onset after age 40. When effects of gender are examined, the effects of age at onset are most profound in women, with a threefold increase in the rate of death in the cohort with age at onset of depression after 70 years when compared to those with onset before age 40. CONCLUSION: These results and those of others suggest that depressed elderly women with no previous history of affective disorder are at a markedly increased risk compared with elderly women with a history of affective illness for morbidity and mortality and that a significant proportion of elderly depressed patients are admitted to a psychiatric hospital for a depression that is secondary to serious medical illness.     

Costs of cancer research: financial and personal

INTRODUCTION: The HLA-A2 allele has recently been considered as a risk factor in AD by advancing the age at onset of the disease, especially in subjects who were homozygous for the apoE epsilon4 allele. MATERIAL AND METHODS: We examined the distribution of apoE genotypes and A2 allele as a function of age at onset in 109 patients with sporadic and familial AD. RESULTS: In the early onset (< or =60 years) and late onset (>75 years) AD groups, there was, respectively, a 2.2 year and a 2.7 year earlier onset in the A2 positive cases. Age effect was not apparent in the middle onset (61-75 years) AD group. The effect of A2 allele on the age at onset was not different between familial and sporadic AD cases. The presence or absence of the A2 allele did not modify mean age at onset in the groups homozygous and heterozygous for epsilon4, and in cases with no epsilon4 alleles. CONCLUSION: Though the sample size was small, there is a trend in favor of an A2 effect on age at onset. Additionally, there is no evidence of interaction between A2 and apoE epsilon4 alleles on age at onset of AD.     

Reciprocal influences in children's and families' adaptation to early childhood wheezing.

Objective: The objective of the present study was to demonstrate the reciprocal relationships between family adaptation to illness and children's medication use over time among children who presented with wheezing illness in infancy but have varying illness outcomes by age 4. Design: A longitudinal design and latent growth curve models (LGM) were used to predict change in family and caregiver adaptation to illness and children's medication use over three years among 140 infants with wheezing, among families from low socioeconomic, multi-ethnic backgrounds. Main Outcome Measures: One LGM predicted level and change (slope) of family adaptation to illness from children's baseline medication use. The second LGM predicted level and change (slope) of children's medication use from baseline family adjustment to illness. In both models, illness severity, caregivers' psychological resources, and emergency department use were covaried with the independent variable. Results: Two latent growth models were found to adequately fit the data and demonstrate full reciprocal relations between family adaptation to illness and children's medication use while accounting for baseline variables. Baseline measures of caregiver psychological functioning and illness severity were also significant predictors of family adaptation and children's medication use over time. The two models were not statistically different for children with and without active asthma at 4 years of age. Conclusion: Findings support the reciprocal effects model of child and family influences on pediatric illness and underscore the importance of early indicators of individual and family functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ABC Schizophrenia Study: a preliminary overview of the results

The ABC Schizophrenia Study, a large-scale epidemiological and neurobiological research project commenced in 1987, initially pursued two aims: (1) to elucidate the possible causes of the sex difference in age at first admission for schizophrenia and (2) to analyse the early course of the disorder from onset until first contact and its implications for further course and outcome. First, transnational case-register data (for Denmark and Germany) were compared, second, a population-based sample of first-episode cases of schizophrenia (n = 232) were selected and third, the results obtained were compared with data from the WHO Determinants of Outcome Study by using a systematic methodology. A consistent result was a 3-4 years higher age of onset for women by any definition of onset, which was not explainable by social variables, such as differences in the male-female societal roles. A sensitivity-reducing effect of oestrogen on central D2 receptors was identified as the underlying neurobiological mechanism in animal experiments. Applicability to humans with schizophrenia was established in a controlled clinical study. A comparison of familial and sporadic cases showed that in cases with a high genetic load, the sex difference in age of onset disappeared due to a clearly reduced age of onset in women, whereas in sporadic cases it increased. To analyse early course retrospectively, a semistructured interview, IRAOS, was developed. The early stages of the disorder were reconstructed in comparison with age- and sex-matched controls from the same population of origin. The initial signs consisted mainly of negative and affective symptoms, which accumulated exponentially until the first episode, as did the later emerging positive symptoms. Social disability appeared 2-4 years before first admission on average. In early-onset cases, social course and outcome, studied prospectively over 5 years, was determined by the level of social development at onset through social stagnation. In late-onset cases, decline from initially high social statuses occurred. Socially negative illness behaviour contributed to the poor social outcome of young men. Symptomatology and other proxy variables of the disorder showed stable courses and no sex differences. Further aspects tested were the sequence of onset and the influence of substance abuse on the course of schizophrenia, primary and secondary negative symptoms, structural models and symptom clusters from onset until 5 years after first admission.     

Calcium stores in cultured fibroblasts and their changes with Alzheimer''s disease

Digital movement analysis (DMA) is a new instrumental approach to assessing oral tardive dyskinesia (TD) by means of digital image processing of a video signal, tracking five paper dots placed around the patient's mouth. A total of 40 schizophrenic patients, 30 with and 10 without TD, were examined twice (with a 3-month interval) with this new device. The patients were further examined with two TD rating scales: the St. Hans Rating Scale for extrapyramidal syndromes (SHRS) and the Abnormal Involuntary Movement Scale (AIMS). The schizophrenic patients accepted the instrumental assessment without any anxiety or resistance. The internal reliability of the apparatus was high, with correlation coefficients of 0.80-0.99. The DMA TD values correlated with the SHRS and AIMS scores with correlation coefficients of 0.48-0.73 indicating an acceptable, although not strong, concurrent validity. Fluctuations occurred from the first to the second examination independent of medication. For these fluctuations no correlation was found between DMA values and rating scores. Finally, the DMA device was able to detect perioral tremor as a sign of parkinsonism. It has been concluded that DMA is a useful supplement to classical TD rating, although further validity evaluation is warranted.     

Takayasu's arteritis as a cause of renovascular hypertension in a non-Asian population

Takayasu's disease (TD) is a chronic inflammatory arteritis which affects the aorta and its main branches and occasionally the pulmonary artery. Its cause is not known. Clinical manifestations are due to the intensity and location of arterial inflammation in the acute phase, as well as chronic arterial stenosis over time; 50% of patients have hypertension. Although TD appears to be more common in Asia, increasing numbers of patients of different races are observed in Western countries. The most important pathogenetic mechanism of hypertension seems to be through renal artery stenosis. We show here seven Caucasian hypertensive patients with TD and renovascular stenosis and arterial hypertension. One case was diagnosed in the acute phase of the disease, while in the others diagnosis was established in an advanced occlusive phase. Basic diagnosis was established by angiographic study, with biopsy confirmation in two cases. All patients had at least three of the six criteria listed as diagnostic of TD (by the American College of Reumatology). All patients had the following criteria: age of disease onset before 40 years (symptoms or findings related to TD), vascular bruits in different areas and all patients also had aortic and renal arterial stenosis with some lesions of the main aortic branches. Six of them had claudication of the extremities. We describe their clinical, analytical and angiographic features and also the therapeutic approach. We discuss the aetiopathogenic mechanisms of hypertension in this disease and suggest that TD is not an unusual cause of vasculorenal hypertension.     

New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests

BACKGROUND: In April, 1996, ten cases of Creutzfeldt-Jakob disease (CJD) with an apparently new clinicopathological phenotype were published and it was suggested that these new variant cases (nvCJD) might be causally linked to bovine spongiform encephalopathy (BSE). There have now been 21 cases of nvCJD in the UK and one case in France. We report clinical features and diagnostic test results of the first 14 cases of nvCJD in the UK. METHODS: Case ascertainment of CJD was mainly by direct referral from neurologists and neuropathologists. Clinical and investigate details were obtained by interview with patients' relatives and by examination of case notes. Ten cases in this report were examined while alive. Prion protein (PrP) gene analysis was carried out with informed consent from the patient or from a relative. The diagnosis of nvCJD was established histologically. FINDINGS: Eight cases were women. Mean age at onset of symptoms was 29 (16-48) years and the median duration of illness was 14 (9-35) months. All patients had early psychiatric symptoms, most often depression, and 13 were seen by a psychiatrist early in the clinical course. Eight patients developed early sensory symptoms which were persistent and often painful. Neurological signs, including ataxia and involuntary movements, developed in all cases and towards the end of the illness, most had akinetic mutism. The electroencephalogram was abnormal in most patients but typical periodic complexes of CJD were not seen in any case. Cerebral imaging was usually normal or showed non-specific abnormalities; in two cases magnetic-resonance imaging scans showed high signal in the thalamus. INTERPRETATION: Clinical features in these cases are similar and relatively distinct from other forms of CJD, suggesting that this is a new clinical phenotype consistent with a single strain of infectious agent. There is, however, some overlap with atypical cases of sporadic CJD, and the diagnosis of nvCJD remains dependent on neuropathological confirmation.     

Community outbreak of psittacosis in a rural Australian town

BACKGROUND: Health authorities in Victoria, Australia were notified of three men from a rural town with atypical pneumonia, admitted to hospital over 8 days. Initial serological testing suggested Chlamydia psittaci as the cause. We did a case-control study to find risk factors for psittacosis. METHODS: We searched for cases of pneumonia or severe flu-like illness through family physicians and the regional hospital. We selected three controls per case from the region's electoral roll. We collected blood for serological tests and administered questionnaires to all cases and controls. FINDINGS: We found 16 cases of psittacosis and one died. Most cases were clustered within a small geographical area, with a median age of 58 years (range 23-76), 15 (94%) of whom were male. Keeping, handling, or feeding domestic or wild birds was not associated with illness. Cases spent a median of 17.5 h per week in their garden, compared with a median of 5.2 h for controls (p=0.04) and were more likely to have mowed lawns during the 3 weeks before onset of illness than controls (odds ratio 4.81 [95% CI 1.08-33.37]). INTERPRETATION: We showed that psittacosis outbreaks are not limited to direct contact with birds and pose new challenges for disease control. Modifications may be needed to work outdoors to decrease the risk of psittacosis.     

Septicemia in the newborn due to gram-negative bacilli. Risk factors, clinical symptoms, and hematologic changes

The case histories of 17 newborns developing septic shock due to gram-negative bacilli were studied for pre- and perinatal risk factors, clinical symptoms, and hematologic changes. Immaturity, resuscitation procedures, and hypothermia on admission were found to be the risk factors most frequently preceding septicemia. A skin color fading and changing from reddish-pink to yellow-green was the most early noticeable clinical symptom in all patients. The total leukocyte counts as well as the relative proportion of bands increased significantly at the onset of illness. When septicemia advanced, a marked drop of leukocytes was found, while the relative proportion of bands increased further. Only 1 in 12 cases showed a decrease in the platelet counts at the height of septicemia. A procedure for the early diagnosis of a neonatal septicemia is proposed: (1) Registration of perinatal risk factors. (2) With perinatal risk factors a skilled and attentive clinical observation is necessary. Particular attention should be paid to changes of skin color. (3) White blood cell picture: (a) every day in patients with perinatal risk factors and (b) every 6 h in patients showing suspicious symptoms.     

Obsessive-compulsive disorder in children and adolescents

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common psychiatric condition that usually emerges during childhood or adolescence. Over 80% of individuals with OCD have their onset before age 18 years. Epidemiologic studies suggest a prevalence of 1-2% for adolescents. METHOD: This article reviews current knowledge of paediatric OCD in the following areas: age of onset, nosology and classification, subtypes, prevalence, aetiology, pathophysiology, assessment, prognosis and treatment. RESULTS: Essential components of treatment include long-term commitment, care management and illness education. Specific components of treatment include cognitive-behavioural therapy, parent behaviour management training and medication. CONCLUSIONS: The most effective treatments are selective serotonin reuptake inhibitors (e.g. fluvoxamine, sertraline) and exposure/response prevention.     

The long-term effect of day care rehabilitation on individuals with dementia

In the treatment of senile dementia, rehabilitation rather than drugs, could result in more positive long-term effects. A Day Care program designed for individuals with Senile Dementia of the Alzheimer type (SDAT) and Vascular Dementia (VD:MID and BD), activates the brain through memory training, creative arts therapy, physical activity, and social interaction. The objective of this study is to determine if Day Care can modify the patients intellectual decline or even alter the natural course of the dementing illness. 135 SDAT and 213 VD patients were studied over three years. ADL (Activities of Daily Living) measurements were evaluated by the Barthel Index and cognitive measurements by the NM-scale. The Wilcoxon test and the Sign test were carried out using the BI and NM-scale scores. These results indicated a decline or arrest in the progression of SDAT and VD as determined by the multiple logistical models. The 8 variables (risk factors, medication, age at onset, self-rehabilitation, family support, sex, grade of dementia and Day Care) influence on the survival curves was calculated using the Kaplan-Meire Life table method. The Cox proportional hazard analysis was then used to examine the relationship between the 8 variables and dementia. The significantly positive results from these four analyses of the ADL and cognitive measurements indicate that Day Care programs clearly retards the progression of intellectual decline in dementia patients and improves the quality of life (QOL) in all cases. In VD patients the mortality rate was notably decreased through Day Care. These results make one consider the benefits of introducing such programs into society as a strong treatment against the onset of dementia developing into severe, dehabilitating dementia. However a healthy diet, a physically and mentally active life, as well as early diagnosis, are the best preventions against dementia.     

Personality and risk of cancer in men with coronary heart disease

BACKGROUND: Virtually all individuals with Down syndrome (DS) have neuropathologic changes characteristic of Alzheimer's disease (AD) beginning at 40 years of age. Few studies have examined factors that influence age at onset of AD in DS. We investigated whether sex differences in age at onset and risk of AD among adults with DS are similar to those observed in the general population and whether the effect of sex on risk of AD is modified by apolipoprotein E (APOE) genotype. METHODS: A community-based sample of 111 adults with cytogenetically confirmed DS (34 to 71 years of age) was ascertained through the New York State Developmental Disabilities system. A semistructured interview with caregivers and review of medical records was used to ascertain the presence or absence of AD. APOE genotyping was carried out without knowledge of the subject's medical history or clinical diagnosis. RESULTS AND CONCLUSIONS: Both male gender and the presence of an APOE epsilon4 allele were associated with an earlier onset of AD. Compared with women, men with DS were three times as likely to develop AD. Compared with those with the APOE 3/3 genotype, adults with DS with the 3/4 or 4/4 genotypes were four times as likely to develop AD. No individual with an APOE epsilon2 allele developed AD. No evidence of interaction of sex and APOE genotype was found in risk of AD. The higher risk of AD in men may be related to differences in hormonal function between men and women with DS that are distinct from those in the general population.     

Glaucoma after macular hole surgery

OBJECTIVE: The study aimed to report incidence and to assess risk factors of postoperative glaucoma in patients with stage 3 idiopathic macular hole treated with pars plana vitrectomy, removal of posterior hyaloid membrane, and perfluoropropane gas tamponade. DESIGN: The author performed a retrospective chart review and statistical analysis of risk factors of postoperative glaucoma by using chi-square statistics, Fisher's exact test, and logistic regression. PARTICIPANTS: Forty consecutive patients with stage 3 idiopathic macular hole who were operated on between January 1994 and December 1995 were studied. INTERVENTION: A pars plana vitrectomy, removal of posterior hyaloid membrane, and 14% perfluoropropane gas tamponade were done to all patients. MAIN OUTCOME MEASURES: Preoperative and postoperative intraocular pressure measurements were performed. RESULTS: Twenty-one (52%) of 40 patients experienced transient intraocular pressure elevation to more than 30 mmHg. Nine (22%) had pressure elevation within 2 to 4 hours, 6 (15%) in 24 hours, and 6 (15%) in 1 week after surgery. Three patients, including one with a history of preoperative ocular hypertension, required extended topical antiglaucoma medication. Factors of age, race, gender, lens status, preoperative intraocular pressure (all preoperative intraocular pressure were 25 mmHg or less), and success in closure of macular hole were not to any statistically significant degree associated with postoperative pressure elevation. CONCLUSION: Glaucoma is a significant complication after stage 3 macular hole surgery even without adjunctive therapy. Usually happening within the first postoperative week, elevation of intraocular pressure in most cases is transient and can be controlled by medication. However, extended medication might become necessary in some cases.     

Increasing the colloid osmotic pressure of cardiopulmonary bypass prime and normothermic blood cardioplegia minimizes myocardial oedema and prevents cardiac dysfunction

Various mutations in the fibroblast growth factor receptor 3 (FGFR3) gene have recently been reported in thanatophoric dysplasia (TD). We examined the clinical, radiographic, and histologic findings in 91 cases from the International Skeletal Dysplasia Registry and correlated them with the specific FGFR3 mutation. Every case of TD examined had an identifiable FGFR3 mutation. Radiographically, all of the cases with the Lys650Glu substitution demonstrated straight femora with craniosynostosis, and frequently a cloverleaf skull (CS) was demonstrated. In all other cases, the femora were curved, and CS was infrequently present but was occasionally as severe as TD with the Lys650Glu substitution. Histopathologically, all of the cases shared similar abnormalities, but cases with the Lys650Glu substitution had better preservation of the growth plate. Cases with the Tyr373Cys substitution tended to have more severe radiographic manifestations than the Arg248Cys cases, but there was overlap in the phenotypic spectrum between them. One common classification of TD distinguishes affected infants based on the presence or absence of CS. In contrast, and as originally proposed by Langer et al. [1987: Am J Med Genet 3: 167-179], our data suggest that TD can be divided into at least two groups (TD1 and TD2) based on the presence of straight or curved femora. The variable presence of CS and severity of the radiologic and histologic findings in the other substitutions may be due to other genetic, environmental, or stochastic factors.     

Medication adherence in rheumatoid arthritis patients: older is wiser

OBJECTIVES: To create a profile of individuals nonadherent to their medications in an age-stratified sample (ages 34-84) of community-dwelling rheumatoid arthritis patients. The relative contributions of age, cognitive function, disability, emotional state, lifestyle, and beliefs about illness to nonadherence were assessed. DESIGN: A direct observation approach was used in conjunction with structural equation modeling. All participants were administered a preliminary assessment battery. Medications were then transferred to vials with microelectronic caps that recorded medication events for all medications for the next 4 weeks. PARTICIPANTS AND SETTING: A volunteer sample of 121 community-dwelling rheumatoid arthritis (RA) patients were recruited from newspaper ads, posters, and via informal physician contact from private rheumatology practices in Atlanta and Athens, Georgia. Written verification of the RA diagnosis and a disease severity rating were obtained from personal physicians before patients were enrolled in the study. Patients were tested in a private physician's office, and their medication adherence was monitored electronically for a month in their every-day work and home settings. MEASUREMENTS AND RESULTS: Structural equation modeling techniques were used to develop a model of adherence behavior. Cognitive and psychosocial measures were used to construct latent variables to predict adherence errors. The model of medication adherence explained 39% of the variance in adherence errors. The model demonstrated that older adults made the fewest adherence errors, and middle-aged adults made the most. A busy lifestyle, age, and cognitive deficits predicted nonadherence, whereas coping with arthritis-related moods predicted adherence. Illness severity, medication load, and physical function did not predict adherence errors. Omission of medication accounted for nearly all errors. CONCLUSION: Despite strong evidence for normal, age-related cognitive decline in this sample, older adults had sufficient cognitive function to manage medications. A busy lifestyle and middle age were more determinant of who was at risk of nonadherence than beliefs about medication or illness. Thus, practicing physicians should not assume that older adults have insufficient cognitive resources to manage medications and that they will be the most likely to make adherence errors. Very busy middle-aged adults seem to be at the greatest risk of managing medications improperly.     

Phenotype-genotype studies in kuru: implications for new variant Creutzfeldt-Jakob disease

The PRNP polymorphic (methionine/valine) codon 129 genotype influences the phenotypic features of transmissible spongiform encephalopathy. All tested cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been homozygous for methionine, and it is conjectural whether different genotypes, if they appear, might have distinctive phenotypes and implications for the future "epidemic curve" of nvCJD. Genotype-phenotype studies of kuru, the only other orally transmitted transmissible spongiform encephalopathy, might be instructive in predicting the answers to these questions. We therefore extracted DNA from blood clots or sera from 92 kuru patients, and analyzed their codon 129 PRNP genotypes with respect to the age at onset and duration of illness and, in nine cases, to detailed clinical and neuropathology data. Homozygosity at codon 129 (particularly for methionine) was associated with an earlier age at onset and a shorter duration of illness than was heterozygosity, but other clinical characteristics were similar for all genotypes. In the nine neuropathologically examined cases, the presence of histologically recognizable plaques was limited to cases carrying at least one methionine allele (three homozygotes and one heterozygote). If nvCJD behaves like kuru, future cases (with longer incubation periods) may begin to occur in older individuals with heterozygous codon 129 genotypes and signal a maturing evolution of the nvCJD "epidemic." The clinical phenotype of such cases should be similar to that of homozygous cases, but may have less (or at least less readily identified) amyloid plaque formation.