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Relationship between Alzheimer's disease severity and patient participation in decisions about their medical care.

To examine the relationships between Alzheimer's disease (AD) severity and patient participation in decisions about their medical care, we performed a cross-sectional study of 74 caregivers' ratings of the degree to which AD patients participate in making decisions about their medical care. The majority of the caregivers reported that they made the final decisions about medical care (n = 48, 64%), one-quarter (n = 19, 26%) reported an equal role, and a small proportion (n = 7, 9%) reported that the patient made the final decisions. Multivariate models showed that the significant predictors of the patient's participation in decisions about medical care were measures of dementia severity: Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Patients with mild-stage disease (CDR = 1 or MMSE > or = 20) are involved in decision making largely in a collaborative role with the caregiver. Beyond mild-stage disease, the clinician can largely expect that the caregiver is making the final decisions. These results illustrate how and when caregivers can expect changes in their decision making role.

Adult↗

Confidence in controlling a SARS outbreak: experiences of public health nurses in managing home quarantine measures in Taiwan.

BACKGROUND: Taiwan experienced one of the most serious outbreaks of severe acute respiratory syndrome (SARS) during the 2003 epidemic. Public health nurses faced unprecedented challenges in implementing an extensive quarantine policy to prevent disease spread. Their professional confidence, however, was shattered during the SARS crisis. This paper assesses factors related to public health nurses' confidence in managing community SARS control programs. METHODS: In May 2003, we sent structured questionnaires to all 361 health centers in Taiwan and asked the public health nurses responsible for epidemic control to complete. A total of 312 completed surveys were returned for a response rate of 86.4%. Descriptive methods and logistic regression were used to analyze the data. RESULTS: Most public health nurses (71.9%) expressed a general lack of confidence in handling the SARS epidemic. Confidence was significantly associated with perceived epidemic severity (OR, 0.58; 95% CI: 0.35-0.99), daily epidemic updates (OR, 2.26; 95% CI: 1.28-3.98), and number of cases in the community (OR, 2.21; 95% CI: 1.13-4.31). CONCLUSION: Nurses' individual risk perception and prompt update of epidemic information significantly affect levels of professional confidence, a key factor influencing quarantine implementation success. Strategies to promote productive interagency collaboration and advocate participatory policy making involving health workers at all levels are needed to control effectively infectious disease outbreaks.

Adult↗

Role of global surveillance in combating bacterial resistance.

In recent years, one of the more alarming aspects of clinical microbiology has been the dramatic increase in the incidence of antibacterial resistance among pathogens causing nosocomial as well as community-acquired infections. Numerous antibacterial agents have lost their in vitro activity as a result of selective pressure exerted by antibacterial usage. There is a general consensus on the fact that emergence and spread of resistance may be delayed by improving hygiene measures, reducing inappropriate use of antibacterials, and adopting successful empirical therapy based on sound epidemiological data. As a consequence, worldwide international studies of antibacterial resistance surveillance have been established. Surveys such as the Alexander Project and the SENTRY Programme supply high quality data to participating countries, stimulate collaboration and provide the educational information required for clinical decision-making that may result in improved cure rates.

Anti-Bacterial Agents↗

Hypertension in four African-origin populations: current 'Rule of Halves', quality of blood pressure control and attributable risk of cardiovascular disease.

OBJECTIVE: To assess the public health burden from high blood pressure and the current status of its detection and management in four African-origin populations at emerging or high cardiovascular risk. DESIGN: Cross-site comparison using standardized measurement and techniques. SETTING: Rural and urban Cameroon; Jamaica; Manchester, Britain. SUBJECTS: Representative population samples in each setting. African-Caribbeans (80% of Jamaican origin) and a local European sample in Manchester. MAIN OUTCOME MEASURES: Cross-site age-adjusted prevalence; population attributable risk. RESULTS: Among 1,587 men and 2,087 women, age-adjusted rates of blood pressure > or =160 or 95 mmHg or its treatment rose from 5% in rural to 17% in urban Cameroon, despite young mean ages, to 21% in Jamaica and 29% in Caribbeans in Britain. Treatment rates reached 34% in urban Cameroon, and 69% in Jamaican- and British-Caribbean-origin women. Sub-optimal blood pressure control (> 140 and 90 mmHg) on treatment reached 88% in European women. Population attributable risks (or fractions) indicated that up to 22% of premature all-cause, and 45% of stroke mortality could be reduced by appropriate detection and treatment. Additional benefit on just strokes occurring on treatment could be up to 47% (e.g. in both urban Cameroon men and European women) from tighter blood pressure control on therapy. Cheap, effective therapy is available. CONCLUSION: With mortality risk now higher from non-communicable than communicable diseases in sub-Saharan Africa and elsewhere, systematic measurement, detection and genuine control of hypertension once treated can go hand-in-hand with other adult health programmes in primary care. Cost implications are not great. The data from this collaborative study suggest that such efforts should be well rewarded.

Adult↗

Intracellular cross-talk between thyrotropin receptor and A1 adenosine receptor in regulation of phospholipase C and adenylate cyclase in COS-7 cells transfected with their receptor genes.

COS-7 cells were transiently transfected with human thyrotropin receptor (TSHR) and dog A1 adenosine receptor (A1R) cDNA. TSH stimulated both inositol phosphate production and cyclic AMP (cAMP) accumulation in the cells. An A1 agonist, N6-(L-2-phenylisopropyl)adenosine (PIA), which is ineffective alone, significantly enhanced TSH-induced inositol phosphate production, but insignificantly inhibited TSH-induced cAMP accumulation was revealed by short-term treatment with the protein kinase C inhibitors, staurosporine and K252a, or long-term treatment with 12-myristate 13-acetate, suggesting that endogenous protein kinase C inhibits the A1R-mediated inhibition of the TSHR-adenylate cyclase system. In staurosporine-treated cells, the stimulatory and inhibitory permissive actions of PIA on TSH-induced phospholipase C and adenylate cyclase activation respectively were completely reversed by pretreatment with pertussis toxin whereas intrinsic TSH-induced effects were hardly affected by the toxin. The cross-talk between the signalling pathway for TSHR and that for A1R was not detected in a mixture of cells expressing either TSHR or A1R. We conclude that a single species of A1R, via pertussis-toxin-sensitive GTP-binding proteins, not only inhibits adenylate cyclase but also stimulates phospholipase C in collaboration with an activated TSHR within a single cell expressing both types of receptor.

Adenylate Cyclase Toxin↗

Biochemical Society Special Lecture. Nitrate- and nitrite-responsive sensors NarX and NarQ of proteobacteria.

Nitrate and nitrite are efficient respiratory oxidants for anaerobic growth. In Escherichia coli, the homologous nitrate reductase (Nar) two-component regulatory systems NarX-NarL and NarQ-NarP collaborate to control anaerobic respiratory gene expression in response to nitrate and nitrite. Several other species classified in the gamma and beta subdivisions of the proteobacteria contain only a single Nar two-component regulatory pair. This raises questions concerning the physiology of anaerobic respiration as well as the evolution, function and cross-regulation of two-component regulatory systems. Here, I focus on the sensor histidine kinases NarX and NarQ, and present a comparison of the deduced NarX and NarQ primary sequences from a broad sampling of proteobacteria. This comparison defines shared features, including a large central region of unknown function that appears to be unique to this family of sensor kinases. I then consider the phylogenetic distribution of narX and narQ genes in relation to anaerobic respiratory enzyme repertoire and physiological function. One noteworthy observation is that narXL genes are specifically associated with the structural genes for membrane-bound nitrate reductase, narGHJI, whereas organization and linkage of the narQ and narP genes is quite variable. I conclude with some speculative thoughts on the evolutionary and functional divergence of the NarX-NarL and NarQ-NarP regulatory systems. Overall, this analysis aims to provide a basis for future hypothesis and experimentation in this area.

Amino Acid Sequence↗

Prevalence of risk factors for trachoma in a rural locality of north-western Ethiopia.

BACKGROUND: In Ethiopia, the prevalence of blindness has been estimated to be 1.5%. According to a survey done in collaboration with WHO in 1981, the leading cause of blindness in Ethiopia was trachoma (42%) followed by cataract (29%). The problem is mainly seen in the rural areas of the country. OBJECTIVE: To determine the prevalence and associated risk factors of trachoma in a rural locality of north-western Ethiopia. DESIGN: Cross-sectional survey. SUBJECTS: One thousand seven hundred and eighteen individuals participated in the study. MAIN OUTCOME MEASURES: Grades of trachoma--the WHO simplified method of clinical signs was used to determine the various grades of trachoma. RESULTS: The overall prevalence rate of trachoma of the locality was 59.2% while the prevalence rate of active trachoma was found to be 52.4%. Higher frequency of trachoma was observed among females aged 15 years and above than males of the corresponding age group, and this finding was statistically significant (chi2-test, p < 0.001). Child care-taking among women, habits and frequency of face washing, presence of cooking places in living rooms and sharing of same rooms with animals have been found to be highly associated with trachoma (p < 0.001). CONCLUSION: Based on the results of this study, the following recommendations are made, among others: (i) the development of a system aimed at educating and convincing the people to maintain high personal and environmental hygiene and; (ii) the strengthening of the nearby health centres to incorporate activities like correction of lid deformities to prevent further loss of eye vision due to corneal damage are recommended.

Adolescent↗

Evaluation of enzyme-linked immunosorbent assay of cleanup for thin-layer chromatography of aflatoxin B1 in corn, peanuts, and peanut butter.

A simple, rapid enzyme-linked immunoassay (ELISA) was used to evaluate the performance of each step (extraction, filtration, solvent partition, and silica gel column chromatography) of a solvent-efficient thin-layer chromatographic (TLC) method which is undergoing interlaboratory collaborative study for the determination of aflatoxin B1 in corn, raw peanuts, and peanut butter. The apparent average recoveries using the ELISA method were about 30 to 50% higher than those using the TLC method if only the amount of B1 added to the samples was used in the calculations. After the cross-reaction of the antibody with other aflatoxins added to the samples was considered, the amounts recovered approached the levels of aflatoxins added in all 3 commodities tested. With no cleanup treatment, ELISA recoveries at aflatoxin B1 levels above 7.5 ng/g were 84, 79, and 103% for corn, raw peanuts, and peanut butter, respectively. The coefficients of variation were between 5.2 and 25.2%. With each cleanup step in the TLC method, ELISA detected a progressive decrease in recovery from 150.5 to 105.3% (before correction for the presence of other aflatoxins) or from 93.5 to 65.4% (after correction for other aflatoxins) of B1 added to the samples. The ELISA data support the conclusion obtained from previous studies that cleanup treatments were not necessary in the ELISA. When large amounts of other aflatoxins are present, an understanding of the cross-reactivity of antibody with other aflatoxins in the ELISA is essential for final interpretation of the data.

Aflatoxin B1↗

Clinical audit of the process of referral to genitourinary medicine of patients found to be chlamydia positive in a family planning service.

This paper describes a collaborative audit between a large family planning and genitourinary medicine (GUM) service undertaken to ensure that all women presenting for termination of pregnancy (TOP) or IUD fitting were offered screening for chlamydia, were informed of a positive result, and were subsequently referred to GUM for full sexual health screening and contact tracing. Over a six month period in 1996 1072 patients were seen for either TOP (763) or W1) fitting (309) and of these 999 were offered a test which was performed in 988. Overall 38 positive tests were reported (3.8 per cent) but only two of 259 patients tested prior to lUD fitting were found to have chlamydia (<0.8 per cent). Only 27 of these 38 women (74 per cent) had information recorded in their notes that they had been given their result and 24 patients (63 per cent) were seen in GUM. The audit uncovered problems with documentation and cross-referencing of information which largely accounted for the failure to reach some of the standards set. An action plan has been formulated in an attempt to improve this aspect of the screening service. If more widespread screening for chlamydia is to be effectively implemented as recommended by the 31st RCOG Study Group on the Prevention of Pelvic Infection, then it is of importance that workable local protocols are in place including arrangements for partner notification and treatment. This will involve close collaboration between a range of specialities working in the sexual health field.

Chlamydia Infections↗

Validation of the MOS SF-36 for quality of life assessment of patients with systemic lupus erythematosus in Singapore.

OBJECTIVE: To assess the reliability and construct validity of the Medical Outcomes Study Short Form 36 Health Survey (SF-36) in a multiracial cohort of Asian patients with lupus in Singapore. METHODS: A cross sectional study was performed on 118 English speaking patients with lupus attending a specialist rheumatology unit between March and August 1996. Patients completed a questionnaire containing the UK standard version of the SF-36 twice within a 14 day period. All patients were assessed for disease activity using the British Isles Lupus Assessment Group score (BILAG), and for disease related damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (DI). Relationships between SF-36, BILAG, and DI scores were studied using Spearman's rank correlation. Internal consistency of the SF-36 was assessed using Cronbach's alpha, and stability using the repeatability coefficient of Bland and Altman. RESULTS: SF-36 subscales showed high internal consistency, with Cronbach's alpha coefficient ranging from 0.84 to 0.94. Test-retest reliability was acceptable, with Spearman's rank correlation >0.70 for all subscales except role-physical, and mean differences in test scores of <2 points for 5 of 8 subscales. SF-36 subscale scores were weakly correlated with BILAG scores (Spearman's p -0.37 to 0.15) and SLICC/ACR DI scores (Spearman's p -0.25 to 0.23), suggesting divergent construct validity of the SF-36. CONCLUSION: These data suggest the SF-36 is a reliable and valid measure of the quality of life of patients with lupus in Singapore.

Cohort Studies↗

Immunological relevance of CREG matching in cadaver kidney transplantation.

BACKGROUND: On the basis of cross-reactive antibodies that react with different human leukocyte antigens (HLA) with shared epitopes, HLA-A and -B antigens can be assigned to cross-reactive groups (CREG). In the context of renal transplantation, it has been reported that matching for CREG results in improved graft outcome and reduces the requirement for rejection treatment. Because CREG matching also improves the equity of kidney distribution to ethnic minorities, a CREG-based cadaver kidney allocation policy was introduced in the United States a few years ago. METHODS: The authors reexamined the immunologic relevance of matching according to CREG using the data of the international Collaborative Transplant Study. A total of 91,917 patients who received a first cadaver kidney transplant between 1991 and 2002 formed the basis of this analysis. RESULTS: The authors found that the underlying impact of matching for HLA antigens accounts entirely for the observed positive effect of CREG matching. For patients with a particular HLA antigen match grade, matching for CREG had no advantageous effect on graft outcome or rejection treatment. An immunologic basis for CREG matching could thus not be found in this large analysis of cadaver kidney transplants. CONCLUSIONS: The findings indicate that CREG matching for kidney allocation is conceptually flawed from an immunologic viewpoint.

Cadaver↗

Body composition in systemic lupus erythematosus.

The objectives were to determine the body composition, and the effects of disease and corticosteroid therapy on body composition, in a population of female patients with systemic lupus erythematosus (SLE). All female SLE patients managed through a single centre were invited to participate in a cross-sectional study of body composition. Data were collected by standardized interview and examination, and review of medical records. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Eighty-two subjects were evaluated, 30 of whom were post-menopausal. Univariate linear regression analysis revealed a significant association of reduced fat-free mass with SLE severity [as measured by the Systemic Lupus International Collaborative Clinics (SLICC)] (P = 0.020), a history of corticosteroid exposure (P = 0.043) and age (P = 0.048). Reduced total body bone mineral density (BMD) was also significantly associated with SLICC (P < 0.001) and corticosteroid exposure (P = 0.017), and with age (P < 0.001), post-menopausal status (P = 0.003) and the duration of menopause (P < 0.001). Stepwise multiple linear regression analysis revealed a significant association between fat-free mass and total body, lumbar spine and femoral neck BMD (P = 0.007, P = 0.025, P = 0.003, respectively). Fat mass was significantly associated only with lumbar spine BMD (P = 0.008). In this SLE population, disease severity and corticosteroid exposure were independently associated with a negative effect both on total body BMD and on fat-free mass. Fat-free mass was a significant predictor of lumbar spine, femoral neck and total body BMD.

Absorptiometry, Photon↗

A proposal for a pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index based on the analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus.

OBJECTIVE: To devise a modified version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) for use in children and adolescents with systemic lupus erythematosus (SLE), based on the frequency and distribution of damage in patients with juvenile-onset SLE and the sources of damage that are most suitable for inclusion in a pediatric damage index. METHODS: In this cross-sectional study, damage was assessed through the SDI. Clinical assessments included evaluation of growth failure and delayed puberty, which were believed to be important sources of damage that are not incorporated in the SDI but should be included in a pediatric version of the instrument. RESULTS: A total of 1,015 patients with juvenile-onset SLE in 39 countries were enrolled in the study. Of these, 405 patients (39.9%) had an SDI score of > or =1 (mean +/- SD score 0.8 +/- 1.4). Renal damage (13%), neuropsychiatric damage (10.7%), and musculoskeletal damage (10.7%) were observed most frequently, followed by ocular damage (8.2%) and skin damage (7.6%). Growth failure and delayed puberty were recorded in 15.3% and 11.3% of patients, respectively. A pediatric version of the SDI was devised, with inclusion of growth failure and delayed puberty as new domains. CONCLUSION: We propose a modified version of the SDI for use in patients with juvenile-onset SLE. This new instrument warrants prospective validation in other populations of patients seen in different clinical or research settings.

Adolescent↗

Tumorigenesis in p27/p53- and p18/p53-double null mice: functional collaboration between the pRb and p53 pathways.

Mice lacking both p18(Ink4c) and p27(Kip1) develop a tumor spectrum similar to pRb(+/-) mice, and loss of p53 function accelerates tumorigenesis in pRb(+/-) mice. We hypothesized that codeletion of either p18 or p27 in conjunction with p53 deletion will also accelerate tumorigenesis. Mice lacking both p18 and p53 develop several tumors not reported in either single null genotype, including hepatocellular carcinoma, testicular choriocarcinoma, hemangiosarcoma, leiomyosarcoma, fibrosarcoma, and osteosarcoma. Mice lacking both p27 and p53 exhibit a decreased lifespan and develop unique tumors, including papillary carcinoma of the colon, hemangiosarcoma, and leiomyosarcoma. In both p18/p53 and p27/p53 double null genotypes, the incidence and spectra of tissues that develop lymphoma are also increased, as compared to the single null genotypes. The development of p27/p53 double null colon tumors correlates with secondary changes in cell-cycle protein expression and CDK (cyclin-dependent kinase) activity, perhaps contributing to the progression of colorectal cancer. We concluded that p18 and p27 can, not only functionally collaborate with one another, but also can independently collaborate with p53 to modulate the cell cycle and suppress tumorigenesis in a tissue-specific manner.

Animals↗

Buprenorphine and methadone in the treatment of opioid dependence: methods and design of the COBRA study.

Buprenorphine and methadone are the two established substitution drugs licensed in many countries for the treatment of opioid dependence. Little is known, however, about how these two drugs are applied and how they work in clinical practice. In this paper we present the aims, methods, design and sampling issues of a collaborative multi-stage epidemiological study (COBRA) to address these issues. Based on a nationally representative sample of substitution physicians, the study is designed as an observational, naturalistic study, consisting of three major parts. The first part was a national survey of substitution doctors (prestudy, n = 379 doctors). The second part was a cross-sectional study (n = 223 doctors), which consisted of a target-week assessment of 2,694 consecutive patients to determine (a) the severity and problem profiles and treatment targets; (b) the choice and dosage scheme of the substitution drug; (c) past and current interventions, including treatment of comorbid hepatitis C; and (d) cross-sectional differences between the two drugs with regard to comorbidity, clinical course, acceptance/compliance and social integration. The third part consists of a prospective-longitudinal cohort study of 48 methadone-treated and 48 buprenorphine-treated patients. The cohort is followed up over a period of 12 months to investigate whether course and outcome of the patients differ by type or treatment received in terms of clinical, psychosocial, pharmaco-economic and other related measures. The response rate among substitution doctors was 57.1%; that among eligible patients was 71.7%. Comparisons with the federal registers reveal that the final samples of doctors and patients may be considered nationally representative with regard to regional distribution, training, type of setting as well as the frequency of patients treated with buprenorphine or methadone. The COBRA study provides a unique comprehensive database, informing about the natural allocation and intervention processes in routine care and about the course and outcome of patients treated with buprenorphine or methadone.

Buprenorphine↗

Studies on IgE production in mice. I. Spontaneous suppression of IgE production in SJA/9 mice.

IgE levels after Nippostrongylus brasiliensis infestation were high in all strains of mice examined except in the SJA/9 strain. However, surface IgE levels on B cells were not different from those observed in the SJL strain. Most surface IgE-bearing cells also had surface IgM molecules. We suggest that the surface IgE-bearing cells are precursors of IgE-producing cells. In adoptive transfer, hapten-specific IgE antibody was produced when hapten-primed cells from SJA/9 mice were transferred together with cells from SJL donors infested with N. brasiliensis but not when the cells were from SJA/9 donors. It is suggested that the lack of collaboration between hapten-primed B cells and cells from infested mice is a genetic trait of the SJA/9 strain.

Animals↗

The prevalence of anemia among clients of family planning clinics in Egypt.

A hospital-based study of the prevalence of anemia among clients of family planning clinics in Egypt was carried out in collaboration with a number of university hospitals. The study aimed to estimate the prevalence of anemia among the clients of family planning clinics and to determine the underlying risk factors for developing anemia in this population, with special emphasis on the role played by different contraceptive methods. The study was designed as a cross-sectional study and was carried out in seven family planning clinics of Alexandria, Mansoura, Cairo, Al-Azhar, Ein Shams, El Minia, and Assiut University Hospitals during August 1993 to March 1994. A total of 1039 clients of family planning services who fulfilled the selection criteria were recruited in the study. A standardized interview questionnaire was used to record pertinent information on study subjects. As well, laboratory investigations were made to determine the hemoglobin level and the presence of bilharzial infection. The prevalence of anemia in the studied population reached 49.6%, with variations among centers. Anemia was more prevalent among urban compared to rural residents (55.7% and 42.0%, respectively). Anemia was more common in Lower Egypt, followed by urban governorates and Upper Egypt. Other independent determinants associated with high prevalence of anemia included: young age (20-39 years), lack of obesity, heavy menstrual periods, low parity, use of the intrauterine device (IUD), low intake of iron-rich foods, and bilharzial infection. Use of IUD were significantly associated with the highest prevalence of anemia among all contraceptive users (64.9%), and IUD users had the lowest level of hemoglobin compared to nonusers or users of other methods. Given the increasing prevalence of IUD use in Egypt, a major recommendation of this study would be to introduce the prescription of iron supplementation tablets as part of IUD services provided in family planning clinics, both to new users and to current users. Other recommendations include early treatment of menstrual disturbances and parasitic infections (including schistosomiasis), as well as improvement of the nutritional status of women at high risk for developing anemia, through mass media campaigns addressing dietary patterns and the health benefits of intake of iron-rich, inexpensive food items.

Adolescent↗