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Usefulness of AgNOR counts in diagnosing epithelial dysplasia.

BACKGROUND: Diagnosis of epithelial dysplasia has traditionally been subjective, and there is a need for a quantifiable and useful test. METHODS: In a double blind study, clinical leukoplakias from 52 people were diagnosed for presence (DLK) or absence (NDLK) of epithelial dysplasia using hematoxylin and eosin (H&E) stain as a gold standard criterion, and results were compared against their mean silver stainable nucleolar organizer region (AgNOR) counts. We used mean AgNOR count cut-point of 2.37 from our prior report as the diagnostic threshold (mean >or= 2.37 being DLK and mean < 2.37 being NDLK). RESULTS: The two methods (H&E and AgNOR) disagreed in 37% of the diagnoses. Both NDLK and DLK had high AgNOR counts. P-AgNOR was non-contributory for diagnosing epithelial dysplasia. CONCLUSIONS: Mean AgNOR count can be a useful tool in definitive diagnosis of epithelial dysplasia.

Analysis of Variance↗

Four-year longitudinal study of conduct disorder in boys: patterns and predictors of persistence.

A prospective study of conduct disorder (CD) was conducted using 4 annual structured diagnostic interviews of 171 clinic-referred boys, their parents, and their teachers. Only about half of the 65 boys who met criteria for CD in Year 1 met criteria again during the next year, but 88% met criteria for CD again at least once during the next 3 years. For most boys with CD, the number of symptoms fluctuated above and below the diagnostic threshold from year to year but remained relatively high. Lower socioeconomic status, parental antisocial personality disorder (APD), and attention-deficit hyperactivity disorder were significant correlates of CD in Year 1, but the interaction of parental APD and the boy's verbal intelligence predicted the persistence of CD symptoms over time (i.e., only boys without a parent with APD and with above-average verbal intelligence clearly improved).

Child↗

Two-year stability and change of schizotypal, borderline, avoidant, and obsessive-compulsive personality disorders.

The authors examined the stability of schizotypal (STPD), borderline (BPD), avoidant (AVPD) and obsessive-compulsive (OCPD) personality disorders (PDs) over 2 years of prospective multiwave follow-up. Six hundred thirty-three participants recruited at 4 collaborating sites who met criteria for 1 or more of the 4 PDs or for major depressive disorder (MOD) without PD were assessed with semistructured interviews at baseline, 6, 12, and 24 months. Lifetable survival analyses revealed that the PD groups had slower time to remission than the MDD group. Categorically, PD remission rates range from 50% (AVPD) to 61% (STPD) for dropping below diagnostic threshold on a blind 24-month reassessment but range from 23% (STPD) to 38% (OCPD) for a more stringent definition of improvement. Dimensionally, these findings suggest that PDs may be characterized by maladaptive trait constellations that are stable in their structure (individual differences) but can change in severity or expression over time.

Adult↗

Serum ferritin assay and bone-marrow iron stores in patients on maintenance hemodialysis.

Fifty-five patients on maintenance hemodialysis underwent bone-marrow aspirations for evaluation of iron stores that were to be compared to concomitant measurements of hematocrit, red blood cell volume, serum iron concentration, total iron binding capacity, transferrin saturation, and serum ferritin concentration. In 42 patients (76.4%), the bone marrow iron stores were found to be absent or deficient. Mean hematocrit for the total group was 26.4%, and red blood cell volume measurement showed a mean value of 41.1% of predicted normal. Results also indicated that serum ferritin was the best predictor of iron storage levels, with diagnostic thresholds of 80 to 350 ng/ml derived from statistical analysis of the data. Other hematologic parameters studied had significantly less correlation with bone-marrow iron stores.

Adult↗

Impaired glucose tolerance and impaired fasting glycaemia: the current status on definition and intervention.

A workshop was convened by the International Diabetes Federation to review the latest information relating to the risks associated with impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG) for future diabetes and cardiovascular disease (CVD). The workshop sought to address three questions: (i) are the current definitions of IGT and IFG appropriate; (ii) are IFG and IGT risk factors, risk markers or diseases; (iii) what interventions (if any) should be recommended for people with IFG and IGT? The determinants of elevated fasting glucose and 2-h plasma glucose in an oral glucose tolerance test (2-HPG) levels differ. Raised hepatic glucose output and a defect in early insulin secretion are characteristic of the former, and peripheral insulin resistance is most characteristic of the latter. Therefore, it is not surprising that the concordance between the categories of IFG and IGT is limited. In all prevalence studies to date only half or less of people with IFG have IGT, and even a lower proportion (20-30%) with IGT also have IFG. In the majority of populations studied, IGT is more prevalent than IFG, and there is a difference in phenotype and gender distribution between the two categories. IFG is substantially more common amongst men and IGT slightly more common amongst women. The prevalence of IFG tends to plateau in middle age whereas the prevalence of IGT rises into old age. Both IFG and IGT are associated with a substantially increased risk of developing diabetes, with the highest risk in people with combined IFG and IGT. Because IGT is commoner than IFG in most populations it is more sensitive (but slightly less specific) for identifying people who will develop diabetes. In most populations studied, 60% of people who develop diabetes have either IGT or IFG 5 years or so before, with the other 40% having normal glucose tolerance at that time. The limited published data suggest that both isolated IFG (I-IFG) and isolated IGT (I-IGT) are similarly associated with cardiovascular risk factors, such as hypertension and dyslipidaemia, with the highest risk in those with combined IFG and IGT. However, some data have suggested that I-IGT is more strongly associated with hypertension and dyslipidaemia (features of the metabolic syndrome) than I-IFG. In unadjusted analyses both IFG and IGT are associated with CVD and total mortality. In separate analyses for fasting and 2-HPG adjusted for other cardiovascular risk factors (from the DECODE study) there remains a continuous relationship between 2-HPG and mortality, but an independent relationship with fasting glucose is only found above 7.0 mmol/l. Glycated haemoglobin (HbA1c) levels are continuously and positively associated with CVD and total mortality independent of other CVD risk factors. Life style interventions, including weight loss and increased physical activity, are highly effective in preventing or delaying the onset of diabetes in people with IGT. Two randomized controlled trials of individuals with IGT found that life style intervention studies reduce the risk of progressing to diabetes by 58%. The oral hypoglycaemic drugs metformin and acarbose have also been shown to be effective, but less so than the life style measures. Similar data do not yet exist for the effectiveness of such interventions in people with I-IFG. Larger studies are required to evaluate the effects of interventions on cardiovascular outcomes in people with IGT. Cost effective strategies to identify people with IGT for intervention should be developed and evaluated. The use of simple risk scores to assess who should undergo an oral glucose tolerance test is one promising approach, although these will need to be population-specific. In conclusion, IGT and IFG differ in their prevalence, population distribution, phenotype, and risk of total mortality and CVD. The consensus of the workshop was: 1. The diagnostic thresholds for all categories of glucose intolerance should be revisited in the light of the latest evidence. There was no clear consensus (with current evidence) on whether IFG and IGT should be classified as diseases, but they clearly represent risk factors and risk markers for diabetes and CVD, respectively. 2. Both IGT and IFG are similarly associated with an increased risk of diabetes, but IGT is more strongly associated with CVD outcomes. 3. Risks are higher when IGT and IFG coexist. 4. Life style interventions are highly effective in delaying or preventing the onset of diabetes in people with IGT and may reduce CVD and total mortality, but the latter requires formal testing.

Blood Glucose↗

The prevalence of dementia in older people in an urban population of Korea: the Seoul study.

OBJECTIVES: To estimate prevalence of dementia and its subtypes in older people in Seoul, a metropolitan area of Korea, and compare these findings with estimates reported for other populations. DESIGN: The study employed a two-stage design for case identification. Initially, the Mini-Mental State Examination in the Korean version (MMSE-KC) of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessment packet was administered to all participants. Two hundred seventeen persons sampled from three levels of performance on MMSE-KC underwent the second-stage clinical evaluation based on the Korean Version of the CERAD assessment packet. SETTING: The study was conducted in an urban community setting. PARTICIPANTS: Six hundred forty-three persons aged 65 and over participated in the study. MEASUREMENTS: Dementia was defined using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic features of dementia. RESULTS: Dementia prevalence ranged from 2.6% in persons aged 65 to 69 to 32.6% in persons aged 85 and older. Age-standardized prevalence was 8.2% for dementia, 5.4% for Alzheimer's disease, and 2.0% for vascular dementia. The prevalence estimates, which excluded very mild cases (clinical dementia rating index 0.5), were approximately 5.3% for dementia and 4.3% for Alzheimer's disease. CONCLUSION: The prevalence of dementia in older people in Seoul appears to be somewhat lower than in rural areas of Korea. Considering the difficulties involved in establishing a diagnostic threshold for dementia, actual differences in dementia prevalence between Asian populations are probably minimal.

Aged↗

Dysglycemia: a key cardiovascular risk factor.

Although diabetes is a strong independent risk factor for cardiovascular events, this risk is not confined to glucose levels above the diagnostic threshold for diabetes. Rather, there is now a growing consensus that the risk of cardiovascular events rises progressively as the fasting and postprandial glucose levels rise from the clearly normal range right into the diabetes range. Hence, dysglycemia (i.e., any elevated fasting or glucose level) is a progressive, continuous risk factor for cardiovascular events. In this respect it resembles every other well-established and progressive cardiovascular risk factor, such as age, LDL cholesterol, systolic and diastolic blood pressure, degree of smoking, albumin excretion, and body mass index. Whether or not strategies designed to normalize glucose levels in people with either diabetes or lesser degrees of dysglycemia will also reduce cardiovascular risk remains to be established. The results of several large international trials of glucose lowering in dysglycemic individuals should clarify the cardiovascular benefits of such an approach within the next few years.

Aged↗

Comparative effects of a high-intensity interval warm-up and salbutamol on the bronchoconstrictor response to exercise in asthmatic athletes.

Approximately half of all asthmatics become refractory to exercise-induced bronchoconstriction (EIB) with repeated challenges. Exercise refractoriness has been utilized by asthmatic athletes to reduce the bronchoconstrictor response to exercise prior to competition, and this has led to the observation that some asthmatic athletes can "run through" their asthma. The main aim of this study was to investigate the efficacy of short high-intensity, repeated warm-ups compared with salbutamol (a commonly used inhaled beta (2)-agonist) on the severity of EIB. Eight moderately trained (.VO(2peak), 51.9 +/- 2.3 ml . kg (-1) . min (-1)) recreational asthmatic athletes with documented EIB were tested under 4 experimental conditions: 1) control (CON) condition; 2) an interval warm-up (WU) consisting of 8 x 30-sec runs at peak treadmill speed, with 45-sec recovery between each sprint; 3) inhaling 200 microg of salbutamol (Ventolin, GlaxoSmithKline, Uxbridge, Middlesex, U.K.) (IH); and 4) combining both the WU and IH session. All 4 experimental sessions were followed by an exercise challenge test (85-90 % predicted maximum heart rate for 8 min). Pulmonary function was measured pre-exercise and at 1, 5, 10, 15 min postexercise. The mean maximum percent fall in pre- to postexercise forced expiratory volume in 1-sec (FEV (1)) for all 8 asthmatic subjects during the EIB screening test (CON session) was - 18.25 +/- 4.01 %. The mean maximum percent decrease in postexercise FEV (1) significantly decreased (p < 0.05) to only - 9.1 +/- 0.6 % following the WU condition, which is below the EIB diagnostic threshold of a 10 % fall in postexercise FEV (1). The IH and WU + IH condition resulted in a substantial postexercise bronchodilation as shown by a significant increase (p < 0.05) in the mean maximum percent change in postexercise FEV (1) following the IH (+ 8.9 +/- 6.1 %) and WU + IH (+ 15.2 +/- 4.6 %) condition. Similar changes as a result of experimental condition were observed for FEF (25-75 %). These data indicate that repeated high-intensity warm-ups can lessen the bronchoconstrictor response to exercise. In addition, combining the interval warm-up with salbutamol prior to exercise resulted in substantial bronchodilation and conferred a greater protective effect against developing EIB than either intervention alone.

Adolescent↗

Contrasting effect of similar effective regurgitant orifice area in mitral and tricuspid regurgitation: a quantitative Doppler echocardiographic study.

We compared the effect of similar effective regurgitant orifice (ERO) areas in tricuspid regurgitation (TR) and mitral regurgitation (MR) on hemodynamics and volume overload, and examined the impact on grading of TR and MR severity. In a prospective study, 95 patients with TR in sinus rhythm were compared with 95 patients with MR in sinus rhythm matched for ERO area, age, and body surface area. We found that similar ERO area was associated with decreased volume overload in TR compared with MR. There were more women with TR than with MR, but comparison stratified by sex confirmed that regurgitant volume (RVol) was smaller in TR than in MR for similar ERO area. However, patients with systolic venous flow reversal (hepatic for TR and pulmonary for MR) had lower RVol but similar ERO area in TR compared with MR. Therefore, optimal diagnostic thresholds for severe regurgitation (maximum sum of sensitivity and specificity) in TR and MR were different for RVol (45 and 60 mL/beat, respectively) but similar for ERO area (40 mm(2)). We conclude that similar ERO areas induce less RVol in TR than in MR because of the decreased driving force in TR, but have similar consequences with regard to venous flow reversal. Therefore, a similar ERO area grading scheme can be used, and an ERO area of 40 mm(2) or greater is consistent with severe regurgitation in both TR and MR.

Aged↗

Value of early blood Th-1 cytokine determination in predicting severity of acute pancreatitis.

BACKGROUND: Early evaluation of the severity of acute pancreatitis (AP) requires measurement of many variables within 48 h after admission. Septic complications (SC) are frequent, and preliminary studies have highlighted the value of prophylactic antibiotherapy; however, single and reliable predictive markers of sepsis are not yet available. The aim of this study was to assess the value of determining early blood Th-1 cytokines and their natural antagonists (interleukin-6 (IL-6), IL-1, IL-1ra, and the soluble form of tumor necrosis factor (sTNF) receptors RI and RII) to predict the severity and SC during AP. METHODS: Thirty-seven patients with AP were prospectively included; 25 of them had severe AP, including 8 with SC. Serum cytokines were measured 48 h and 72 h after the onset of AP with an enzyme-linked immunosorbent assay. The optimal severity or SC diagnostic thresholds was determined using receiver operative curves. RESULTS: Severe AP in accordance with the Atlanta criteria were better predicted by C-reactive protein and IL-6 serum determination, albeit these levels could not predict absolutely the death of two patients. In severe AP cases (n = 25) the IL-1 to IL-1-ra ratio was lower in cases further complicated by sepsis ((6+/-4) 10(-3) versus (34+/-13) 10(-3), P < 0.05); moreover, sTNF RI (2497+/-270 pg/ml versus 2133+/-611 pg/ml, P < 0.05) and RII (3751+/-400 pg/ml versus 3045+/-509 pg/ml, P < 0.05) were higher in AP characterized by further SC. The IL-1 to IL-1-ra ratio and IL-1 concentration were dramatically decreased within the first 48 h ((0.4+/-0.4) 10(-3) versus (30+/-11) 10(-3), P < 0.05, and 0.3+/-0.3 versus 15+/-3 ng/l, P < 0.05) in patients with further infection of the pancreatic necrosis (n = 3). The SC diagnosis was better anticipated by an IL-1 to IL-1-ra ratio lower than 5 x 10(-3) or by an sTNF RI higher than 1750 pg/ml and sTNF RII higher than 2750 pg/ml, and the infection of the pancreatic necrosis by an IL-1 concentration <2 ng/l or an IL-1 to IL-1-ra ratio <2 x 10(-3). CONCLUSION: Besides severity markers, IL-1, IL-1-ra, and sTNF RI and RII should be considered in base-line AP assays and, if confirmed by larger studies, could help to screen patients at risk for SC and candidates for prophylactic antibiotherapy with a good negative predictive value.

Acute Disease↗

The use of skin delayed-type hypersensitivity as an adjunct test to diagnose brucellosis in cattle: a review.

Brucellosis, caused by bacteria of the genus Brucella, is a contagious disease that causes economic loss to owners of domestic animals due to loss of progeny and milk yield. Because cattle, sheep, goats, and to a lesser extent pigs are considered to be the source of human brucellosis, serological tests have been used to screen domestic animals for antibodies against Brucella. Although the serological tests helped to eradicate brucellosis in many countries, serological tests are not always adequate to detect latent carriers of Brucella. Therefore, the use of the skin delayed-type hypersensitivity (SDTH) test, which is independent of circulating antibodies, might improve the diagnosis of brucellosis. In the literature, however, there are conflicting reports as to the value of the SDTH test for the diagnosis of brucellosis. Some studies consider the test unreliable, whereas others advocate its use because it detects brucellosis earlier than serological tests. The objectives of this study were therefore to assess the characteristics of the SDTH test, to select a Brucella strain that will yield a suitable brucellin for use in the field, and to determine whether the use of serological tests in combination with the SDTH test improves the detection of brucellosis. The results of this study clearly show that the SDTH test detects latent carriers of Brucella and confirms brucellosis in cattle with ambiguous serological test results. Brucellins prepared from smooth or mucoid strains of Brucella are better suited for use in the field than brucellins prepared from rough strains because they detect brucellosis in cattle with acute as well as chronic infection. The SDTH test is highly specific (99.3% specificity), and repeated testing of naive cattle or cattle infected with microorganisms that serologically cross-react with Brucella does not sensitize cattle to subsequent SDTH tests. However, it is possible that some naive cattle may serologically react to the injection of brucellin. The effect of these serological reactions on the sero-diagnosis of brucellosis is limited, because cattle may only now and then react serologically either with the serum agglutination test (SAT) or the complement fixation test (CFT). Nevertheless, cattle infected with microorganisms that serologically cross-react with Brucella may test seropositive for brucellosis 4 to 7 weeks after injection of brucellin, depending on the cross-reacting microorganism. The value of the SDTH test for the diagnosis of brucellosis was demonstrated after an outbreak of brucellosis. When the SDTH test was used in combination with SAT and CFT at diagnostic threshold > or =2 mm or > or =1 mm (increase in skinfold thickness), respectively, 39/44 (88%) or 42/44 (95%) of the infected cattle were detected compared with only 27/44 (61%) when SAT and CFT were used. When cattle in areas of low prevalence or in areas free from brucellosis are tested with the SDTH test an increase > or =2 mm in skinfold thickness should be considered indicative of infection. When the control and eradication of brucellosis is based on test-and-slaughter, an increase of > or =1 mm in skinfold thickness should be considered indicative of infection. Repeated serological testing complemented with the SDTH test in this programme will shorten the quarantine (movement control) period of a suspect herd, limiting the financial loss incurred during outbreaks of the disease. Consequently, since the SDTH test usually does not interfere with the serological diagnosis and can safely be used to establish the infection status of cattle in a suspect herd, it is opportune to consider adding the SDTH test to the procedure currently used to diagnose brucellosis in individual animals.

Animals↗

Detection and estimation of avian infectious bronchitis virus antigen by a novel indirect liquid-phase blocking enzyme-linked immunosorbent assay using chicken and rabbit affinity purified immunoglobulins.

An indirect liquid-phase blocking (LPB) enzyme-linked immunosorbent assay (ELISA) using chicken and rabbit affinity purified immunoglobulin G (IgG) has been developed to detect and estimate avian infectious bronchitis virus (IBV) antigen concentration directly in infected allantoic fluid. The method is based on the principle of binding of specific IgG to the test IBV antigen and the assay of unbound IgG on an antigen-coated ELISA plate. The immunoglobulins are chicken N-terminal S2 peplomeric protein-specific IgG isolated by immunoaffinity chromatography on synthetic peptide coupled to CNBr-activated Sepharose 4B or rabbit polyclonal IgG purified from the serum using Protein A Sepharose 4B. The assay detected all tested IBV strains and field isolates propagated in chicken embryos. Signal to noise ratios were calculated from LPB ELISA absorbance units and a diagnostic threshold was established from the signal to noise ratio frequency distribution of samples positive or negative for IBV by virus titration or reverse transcription polymerase chain reaction. The relative sensitivity of the test ranged between 10(5) and 10(6) median egg infectious doses (EID(50)) for chicken IgG and between 10(3) and 10(4) EID(50) for rabbit IgG, depending on the test strain. The assay is simple and takes less than 3 h to perform. It does not require expensive reagents and can be readily adapted to monitor the IBV antigen concentration in allantoic fluids during propagation of vaccine strains or in samples of freeze-dried, live-attenuated IBV vaccines.

Animals↗

Bilateral photoplethysmography studies of the leg arterial stenosis.

A newly developed portable multi-channel photoplethysmography (PPG) device has been used for comparative studies of 20 healthy control subjects and 45 patients with diagnosed arterial stenosis in a leg. The peripheral blood pulsations were detected simultaneously at four body sites-the same fingers and toes of both arms and legs. The PPG pulses recorded at the periphery of the stenotic leg, if compared with those of the healthy leg, were much weaker, with delayed arrival as a consequence of increased pulse wave transit time (PWTT) due to higher vascular resistance. The specific PWTT delays for the occluded legs were in the range of 20-80 ms, while in the case of healthy subjects the leg PPG signals arrived without delays or with smaller time-shifts not exceeding 14 ms. The reference bilateral PPG signals detected at the fingertips did not show any notable PWTT delays in both groups. Parallel measurements of local blood pressures by means of the oscillometry method with subsequent calculation of the ankle-brachial index were performed. Convincing correlation between the bilateral differences in the local blood pressure (a routine tool for diagnostics of leg stenosis) and in the corresponding PWTT delay (Pearson's coefficient r = 0.93), as well as between the PWTT delay and the ankle-brachial index (r = -0.96) has been established. From the point of view of PWTT delay, the average value of leg stenosis diagnostic threshold was established to be in the range of 23 +/- 9 ms, with full reliability above 32 ms. The obtained data may find further applications in alternative methodologies for detection and/or assessment of arterial occlusions in human extremities.

Adult↗

Are even impaired fasting blood glucose levels preoperatively associated with increased mortality after CABG surgery?

AIMS: Impaired fasting glucose (IFG) below the diagnostic threshold for diabetes mellitus (DM) is associated with macrovascular pathology and increased mortality after percutaneous coronary interventions. The study goal was to determine whether pre-operative fasting blood glucose (fB-glu) is associated with an increased mortality after coronary artery bypass grafting (CABG). METHODS AND RESULTS: During 2001-03, 1895 patients underwent primary CABG [clinical DM (CDM) in 440/1895; complete data on fB-glu for n=1375/1455]. Using pre-operative fB-glu, non-diabetics were categorized as having normal fB-glu (<5.6 mmol/L), IFG (5.6< or =fB-glu<6.1 mmol/L), or suspected DM (SDM) (> or =6.1 mmol/L). fB-glu was normal in 59%. The relative risks of 30 day and 1 year mortality compared with patients with normal fB-glu was 1.7 [95% confidence interval (CI): 0.5-5.5] and 2.9 (CI: 0.8-11.2) with IFG, 2.8 (CI: 1.1-7.2) and 1.9 (CI: 0.5-6.3) with SDM vs. 1.8 (CI: 0.8-4.0) and 1.6 (CI: 0.6-4.3) if CDM, respectively. The receiver operator characteristic area for the continuous variable fB-glu and 1 year mortality was 0.65 (P=0.002). CONCLUSION: The elevated risk of death after CABG surgery known previously to be associated with CDM seems also to be shared by a group of similar size that includes patients with IFG and undiagnosed DM.

Aged↗

Treatments for late life depression in primary care--a systematic review.

BACKGROUND: Depression is common among older people. It is associated with increased mortality and use of health services. We could identify no prior systematic review of treatment for depression in either primary care attenders or population samples of older people. OBJECTIVES: The aim of this study was to carry out a systematic review of trials of treatments for depression of patients over 60 years of age in primary care or population samples. METHODS: We searched Medline, Embase, Cinahl, the Cochrane Library, Psyclit, BIDS--Social Science and BIDS--Science Citation Indices for trials of drug treatment, interpersonal psychotherapy, cognitive behavioural psychotherapy, counselling and social interventions for late life depression in English, French or German published between 1980 and June 1999. RESULTS: Of the studies identified, only two were of patients over 60 years of age and met all inclusion criteria for content and quality. Three further studies that were not restricted to but included patients over the age of 60 years also fulfilled our criteria. We found no studies of psychological therapies for depression in older people. With few exceptions, studies were limited to older people who reached a diagnostic threshold and excluded those with 'subcase level depression'. CONCLUSION: There is little evidence of effectiveness for a variety of treatment approaches for depression in older people in primary care, particularly in those with less severe depression. As older people take more medication, making contra-indications to the use of antidepressant drugs more likely, there is a pressing need for studies of the efficacy of non-pharmacological interventions in primary care settings.

Age Factors↗

The "close-in" or ultra high-risk model: a safe and effective strategy for research and clinical intervention in prepsychotic mental disorder.

The development of a new frontier for research and early intervention in psychotic disorders is highly dependent on the construction of synergistic clinical infrastructures. This has catalyzed great progress in the recognition, enhanced treatment, and study of first episode psychosis, and the task is even more challenging when the boundaries are extended to include the earliest clinical phase of illness, the prodromal or prepsychotic phase. This article describes the conceptual and practical building blocks for the construction of service models for intervention in the postonset clinical phase prior to the attainment of current diagnostic thresholds. This is best regarded as indicated prevention, a form of very early secondary prevention, which involves a blend of immediate clinical care combined with research-oriented preventive intervention. The experience of the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne across several stages of growth is described and contrasted with that of several emerging centers in Europe and North America. The progress to date, the lessons learned, and the unresolved challenges and opportunities are detailed. It is concluded that service models can be developed that are acceptable and helpful to young people and their families, and that create a unique environment for the study of the transition to frank psychotic disorder. The ultimate clinical utility and general safety of this approach and the range of effective treatments remain unclear, and will be determined by more extensive research. Such research must be conducted in a logical and rigorous manner with the best designs possible, sensitive to input from consumers and caregivers and to ethical considerations.

Academies and Institutes↗

A family study of schizotypal disorder.

Direct, blind interviews were used to study the risk for and prevalence of DSM-III-R Axis I and II disorders in 93 first-degree relatives of outpatients with schizotypal personality disorder (SPD) and outpatients with other personality disorders. Risks for SPD (at a slightly loosened diagnostic threshold) and schizoid personality disorder were significantly higher in the families of probands with SPD. Schizophrenia was present only among relatives of probands with SPD, accounting for a morbid risk of 4.1 percent. Neither familial risks for mood and anxiety disorders nor the prevalence of other Axis II disorders significantly differed in the two groups of relatives. It is suggested that SPD is a familial disorder representing a phenotypic expression of liability to schizophrenia.

Adolescent↗

Utility of Gram's stain and efficacy of quantitative cultures for posttraumatic pneumonia: a prospective study.

OBJECTIVE: This prospective trial examined the efficacy of using bronchoalveolar lavage (BAL) for the diagnosis of pneumonia (PN) and the utility of Gram's stain (GS) for dictating empiric therapy. SUMMARY BACKGROUND DATA: Posttraumatic nosocomial PN remains a significant cause of morbidity and mortality. However, its diagnosis is elusive, especially in multiply injured patients. The systemic inflammatory response syndrome of fever, leukocytosis, and a hyperdynamic state is common in trauma patients, especially patients with pulmonary contusion. Bronchoscopy with BAL with quantitative cultures of the lavage effluent may distinguish between PN and systemic inflammatory response syndrome, and GS of the lavage effluent may guide empiric therapy before quantitative culture results. METHODS: Mechanically ventilated trauma patients with a clinical diagnosis of PN (fever, leukocytosis, purulent sputum, and new or changing infiltrate on chest radiograph) underwent bronchoscopy with BAL. Effluent was sent for GS and quantitative cultures. The diagnostic threshold for PN was > or =10(5) colony-forming units (CFU)/mL, and antibiotics were continued. Antibiotics were stopped for < 10(5) CFU/mL and the diagnosis of systemic inflammatory response syndrome was made. Causative organisms for PN were compared to GS. RESULTS: Over a 2-year period, 232 patients underwent 443 bronchoscopies with BAL (71% men, 29% women; mean age, 41). The mean injury severity score was 30. Sixty percent of the patients had pulmonary contusion, and 59% were cigarette smokers. The overall incidence of PN was 39% and was no different regardless of the number of BALs a patient had. The false-negative rate of BAL was 7%. GS identified gram-positive organisms in 80% of patients with gram-positive PN and 40% of patients with gram-negative PN. GS identified gram-negative organisms in 52% of patients with gram-positive PN and 77% with gram-negative PN. The duration of the intensive care unit stay relative to the timing of BAL was beneficial for guiding empiric therapy. BAL in week 1 primarily identified Haemophilus influenzae and gram-positive organisms; Acinetobacter sp. and Pseudomonas sp. were more common after week 1. CONCLUSIONS: Bronchoscopy with BAL is an effective method to diagnose PN and avoids prolonged, unnecessary antibiotic therapy. Empiric therapy should be adjusted to the duration of the intensive care unit stay because the causative bacteria flora changes over time. GS of BAL effluent correlates poorly with quantitative cultures and is not reliable for dictating empiric therapy.

Adult↗