Combination Of Clinical Data Research Articles

Detection of Invasive Pulmonary Aspergillosis in Haematological Malignancy Patients by using Lateral-flow Technology

Invasive pulmonary aspergillosis (IPA) is a leading cause of morbidity and mortality in haematological malignancy patients and hematopoietic stem cell transplant recipients1. Detection of IPA represents a formidable diagnostic challenge and, in the absence of a 'gold standard', relies on a combination of clinical data and microbiology and histopathology where feasible. Diagnosis of IPA must conform to the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycology Study Group (EORTC/MSG) consensus defining "proven", "probable", and "possible" invasive fungal diseases2. Currently, no nucleic acid-based tests have been externally validated for IPA detection and so polymerase chain reaction (PCR) is not included in current EORTC/MSG diagnostic criteria. Identification of Aspergillus in histological sections is problematic because of similarities in hyphal morphologies with other invasive fungal pathogens3, and proven identification requires isolation of the etiologic agent in pure culture. Culture-based approaches rely on the availability of biopsy samples, but these are not always accessible in sick patients, and do not always yield viable propagules for culture when obtained. An important feature in the pathogenesis of Aspergillus is angio-invasion, a trait that provides opportunities to track the fungus immunologically using tests that detect characteristic antigenic signatures molecules in serum and bronchoalveolar lavage (BAL) fluids. This has led to the development of the Platelia enzyme immunoassay (GM-EIA) that detects Aspergillus galactomannan and a 'pan-fungal' assay (Fungitell test) that detects the conserved fungal cell wall component (1 →3)-β-D-glucan, but not in the mucorales that lack this component in their cell walls1,4. Issues surrounding the accuracy of these tests1,4-6 has led to the recent development of next-generation monoclonal antibody (MAb)-based assays that detect surrogate markers of infection1,5. Thornton5 recently described the generation of an Aspergillus-specific MAb (JF5) using hybridoma technology and its use to develop an immuno-chromatographic lateral-flow device (LFD) for the point-of-care (POC) diagnosis of IPA. A major advantage of the LFD is its ability to detect activity since MAb JF5 binds to an extracellular glycoprotein antigen that is secreted during active growth of the fungus only5. This is an important consideration when using fluids such as lung BAL for diagnosing IPA since Aspergillus spores are a common component of inhaled air. The utility of the device in diagnosing IPA has been demonstrated using an animal model of infection, where the LFD displayed improved sensitivity and specificity compared to the Platelia GM and Fungitell (1 → 3)-β-D-glucan assays7. Here, we present a simple LFD procedure to detect Aspergillus antigen in human serum and BAL fluids. Its speed and accuracy provides a novel adjunct point-of-care test for diagnosis of IPA in haematological malignancy patients.

Rapid and simple IgG specific test for the exclusion of heparin induced thrombocytopenia (HIT)

The exclusion of heparin induced thrombocytopenia (HIT) is required for selecting the most appropriate anticoagulation therapy in affected patients. It requires the combination of clinical data with the detection of antibodies directed against platelet factor 4 (PF4) in complex with polyanions (PA) such as heparin. We developed a lateral flow immunoassay (LFIA) for PF4/PA complex specific IgG antibodies based on gold nanoparticles. Unlike most other assays, the initial immune reaction takes place in the liquid phase. The sensitivity of the assay has been adjusted with clinical samples aiming in the reliable detection of sera which are positive in a functional platelet activation assay. Sera from 60 patients with suspected HIT were investigated. LFIA identified correctly all samples (n=20) which were positive in a functional assay (HIPA) and an IgG specific ELISA. It correlated with ELISA, but false positive results were less frequent (7 samples were negative with LFIA and HIPA but positive with ELISA). The LFIA may be a suitable tool for the rapid exclusion of HIT within 10 min.

Mathematical framework for human SLE Nephritis: disease dynamics and urine biomarkers

BackgroundAlthough the prognosis for Lupus Nephritis (LN) has dramatically improved with aggressive immunosuppressive therapies, these drugs carry significant side effects. To improve the effectiveness of these drugs, biomarkers of renal flare cycle could be used to detect the onset, severity, and responsiveness of kidney relapses, and to modify therapy accordingly. However, LN is a complex disease and individual biomarkers have so far not been sufficient to accurately describe disease activity. It has been postulated that biomarkers would be more informative if integrated into a pathogenic-based model of LN.ResultsThis work is a first attempt to integrate human LN biomarkers data into a model of kidney inflammation. Our approach is based on a system of differential equations that capture, in a simplified way, the complexity of interactions underlying disease activity. Using this model, we have been able to fit clinical urine biomarkers data from individual patients and estimate patient-specific parameters to reproduce disease dynamics, and to better understand disease mechanisms. Furthermore, our simulations suggest that the model can be used to evaluate therapeutic strategies for individual patients, or a group of patients that share similar data patterns.ConclusionsWe show that effective combination of clinical data and physiologically based mathematical modeling may provide a basis for more comprehensive modeling and improved clinical care for LN patients.

Use of population health data to refine diagnostic decision-making for pertussis

To improve identification of pertussis cases by developing a decision model that incorporates recent, local, population-level disease incidence. Retrospective cohort analysis of 443 infants tested for pertussis (2003-7). Three models (based on clinical data only, local disease incidence only, and a combination of clinical data and local disease incidence) to predict pertussis positivity were created with demographic, historical, physical exam, and state-wide pertussis data. Models were compared using sensitivity, specificity, area under the receiver-operating characteristics (ROC) curve (AUC), and related metrics. The model using only clinical data included cyanosis, cough for 1 week, and absence of fever, and was 89% sensitive (95% CI 79 to 99), 27% specific (95% CI 22 to 32) with an area under the ROC curve of 0.80. The model using only local incidence data performed best when the proportion positive of pertussis cultures in the region exceeded 10% in the 8-14 days prior to the infant's associated visit, achieving 13% sensitivity, 53% specificity, and AUC 0.65. The combined model, built with patient-derived variables and local incidence data, included cyanosis, cough for 1 week, and the variable indicating that the proportion positive of pertussis cultures in the region exceeded 10% 8-14 days prior to the infant's associated visit. This model was 100% sensitive (p<0.04, 95% CI 92 to 100), 38% specific (p<0.001, 95% CI 33 to 43), with AUC 0.82. Incorporating recent, local population-level disease incidence improved the ability of a decision model to correctly identify infants with pertussis. Our findings support fostering bidirectional exchange between public health and clinical practice, and validate a method for integrating large-scale public health datasets with rich clinical data to improve decision-making and public health.

Is CT Still Useful in the Study Protocol of Retinoblastoma?

Intralesional calcium deposition is considered a key element for differentiating retinoblastoma from simulating lesions. Our aim was to assess whether MR imaging associated with ophthalmologic investigations (ophthalmoscopy and ultrasonography) could replace CT in the detection of diagnostic intralesional calcifications in retinoblastoma. Ophthalmoscopic findings, MR images, CT scans, and histologic examination of 28 retinoblastomas from 23 consecutive children (11 males, 12 females; age range at admission, 1-35 months; mean age, 11 months; median age, 9 months) were retrospectively evaluated. Ultrasonography was performed in 18 patients with 21 retinoblastomas. MR imaging included T2-weighted spin-echo and gradient-echo images, fluid-attenuated inversion recovery images, and T1-weighted spin-echo images with and without contrast enhancement. Clinical data were integrated with MR imaging data to evaluate the utility of both approaches to discover calcifications; particularly, a correlation between intralesional signal-intensity void spots on MR imaging and hyperattenuating areas on CT scans was performed. Ophthalmoscopy detected calcifications in 12 of 28 eyes (42.85%). Ultrasonography detected calcifications in 20 of 21 eyes (95.23%). CT showed hyperattenuating intralesional areas consistent with calcifications in 27 of 28 eyes (96.42%). MR imaging showed intralesional signal-intensity void spots in 25 of 28 eyes (89.28%). All spots detected with MR imaging matched the presence of calcifications on CT scans. Gradient-echo T2*-weighted and fast spin-echo T2-weighted images showed the highest degree of correlation with CT. When we put together ophthalmoscopy, ultrasonography, and MR imaging data, no calcifications detected on CT were missed, and the differential diagnosis was thorough. A combination of clinical data and MR images may remove potentially harmful ionizing radiation from the study protocol of retinoblastoma.

Highest accuracy of combined consensus clinical criteria and SNRPN gene molecular markers in diagnosis of Prader-Willi syndrome in Thai patients

Prader-Willi Syndrome (PWS) is a complex human genetic disease arising from a loss of paternal allele expression of imprinting genes on chromosome 15q11-q13. Normally the CpG islands at this site are heavily methylated in the maternal allele, but unmethylated in the paternal allele and therefore activated in gene expression. only the methylated allele should present in pws patients when methylation-specific pcr (msp) is analyzed. This paper reports an analysis of PWS in Thai patients using consensus diagnostic criteria based on a combination of clinical data, basic G-banding and fluorescence in situ hybridization (FISH) cytogenetics, PCR-based methylation assay, and bisulfite sequencing of the CpG islands of SNRPN to confirm 15q deletion or the methylation pattern of the SNRPN promoter and exon 1. Lack of complete clinical reports or inadequacy of the minimum laboratory support required had made it difficult to diagnose PWS, Angelman syndrome and other microdeletion disorders. Accuracy of 100% was obtained for diagnosis of the PWS study patients using the minimum requirements necessary. A total of 20 patients were diagnosed as PWS based on clinical criteria and the scoring tool for PWS, and the same approach was applied to four separate patients with some unmatched criteria but phenotypic similarity to PWS. Findings showed that 70% of those clinically diagnosed as PWS patients (14/20) had a deletion at 15q11-q13 according to FISH, while all 20 patients showed MSP positive of SNRPN gene. Six cases (30%) without a paternal deletion were confirmed to have maternal uniparental disomy (mUPD) of PWS by MSP and methylation sequencing approaches. Noteworthy, two of the six cases with mUPD were 3.5 year-old twins. None of the five cases with scores lower than the reported consensus criteria showed positive G-band, FISH or MSP results. We demonstrate here the high power of combining clinical findings, FISH and MSP in definitive diagnosis of PWS and in distinguishing between the two major different types of molecular mechanisms. No false positives or false negatives were observed in our analysis.

The amylase-to-creatinine clearance ratio--a non-specific response to acute illness?

It was felt that the apparent specificity of the amylase-to-creatine clearance ratio (ACCR) in several previous studies of pancreatitis might reflect a failure to utilize adequately ill control subjects. The ACCR and the renal clearances of beta 2-microglobulin (B2-m), similarly related to creatinine (BCCR) as well as the urinary concentration of albumin, were compared in 27 patients with acute pancreatitis, 8 with a perforated peptic ulcer and 7 with mild biliary colic, during the first 5 days in hospital. Acute pancreatitis was graded as mild (6), moderate (14) or severe (7), using a combination of clinical data, diagnostic peritoneal lavage and multiple criteria. Further assessment of the severity of the acute illness was obtained from measurement of C-reactive protein (C-RP). Lowest C-RP levels were found in the patients with mild pancreatitis and biliary colic, and highest levels in the patients with severe pancreatitis and perforated ulcer (P less than 0.002). Similarly, ACCR and BCCR levels were significantly lower in the two mild groups than in the two severe ones (P less than 0.01 and less than 0.002 respectively), although plasma amylase was raised only in patients with pancreatitis and plasma B2-m was similar in all groups. Electrophoresis of urine showed dense bands of tubuloprotein in patients from both severe groups. Urine albumin was higher in severe pancreatitis than in perforated ulcer (P less than 0.1), perhaps indicating a more specific glomerular lesion in pancreatitis. Thus a rise in amylase clearance appeared to be related to the severity of the acute illness, and may be a component of a non-specific tubuloproteinuria. In this study patients with a perforated peptic ulcer had increases in ACCR similar to those seen in patients with severe pancreatitis, and we are therefore doubtful whether ACCR has any role in the clinical diagnosis of pancreatic disease.

Association of C-reactive protein and myocardial perfusion in patients with ST-elevation acute myocardial infarction

This study sought to evaluate the relation between C-reactive protein (CRP) on admission of patients with acute myocardial infarction (AMI) and myocardial perfusion as defined by postintervention angiographic myocardial blush grade (MBG) and their impact on subsequent mortality. The patient population comprised 191 consecutive patients with AMI undergoing PTCA within 12 h of symptom onset on a native vessel. Patients were divided based on the CRP level on admission (Rolf Greiner BioChemica, Germany, cutpoint for the assay CRP: 5 mg/l) into a group with elevated CRP (≥5 mg/l) and a group with normal CRP. Angiographic myocardial blush grade (MBG) after revascularization of the infarct-related artery was determined to evaluate myocardial reperfusion. Revascularization of the infarct-related artery was successful in 176 (92.6%) patients. The frequency of impaired perfusion (MBG 0-2) was higher in the elevated CRP group than in the normal CRP group (74.5% versus 59.7%, respectively, p = 0.046). Elevated CRP on admission was an independent predictor of impaired myocardial perfusion (MBG 0-2, OR 1.92, 95% CI 1.02–4.01, p = 0.042) in addition to age >70 years. Elevated CRP (OR 2.64, 95% CI 1.26–5.53, p = 0.009) and MBG 0–2 (OR 4.58; 95% 1.73–12.20, p = 0.002) were independent predictors of mortality during a 22.4 ± 15.3 months follow-up in addition to heart rate on admission >100 beats/min (OR 3.07; 95% CI 1.30–7.25, p = 0.009). In sequential Cox models, the predictive power of clinical data and MBG for mortality (model chi-squared 18.3) was strengthened by the inclusion of CRP levels (model chi-squared 24.3). In conclusion, there is a relation between elevated admission CRP and impaired reperfusion in the myocardium subtended to the infarct-related artery. The combination of clinical data, myocardial reperfusion levels after primary angioplasty for AMI and admission CRP increases the predictive value for subsequent survival.

Leprosy in Britain: 50 years experience in Liverpool

Leprosy is a chronic infection that presents with varying dermal and neurological symptoms, and which can lead to extensive disability and morbidity, often with accompanying social stigma. To review the patients presenting to the Liverpool School of Tropical Medicine (LSTM) between 1946 and 2003, looking specifically at country of birth and of infection, details of clinical presentation, diagnosis, management and reactions. Retrospective record review. We retrieved all available clinical records for patients seen between 1946 and 2003 (n = 50), consisting of letters, hospital and LSTM casenotes, and some radiographs and photographs. Any history of tuberculosis or diabetes was recorded. Most patients (64%) were born in the Indian subcontinent, and most were thought to have contracted the disease there (62%). Features at presentation included anaesthetic skin lesions in 19 (36%), hypopigmentation in 15 (30%), and peripheral nerve enlargement in 25 (50%). Diagnoses were made by a combination of clinical data and biopsy (60%), and slit skin smears were positive for acid-fast bacilli in 61% of multibacillary patients. Initial presentation was with a leprosy reaction in five cases (10%), and reactions were documented in 42% of all patients. Treatments were varied, progressing from traditional Eastern medicine to the WHO-approved multidrug therapy in use today, with prophylaxis for children and close contacts. Leprosy remains an important diagnosis to consider in patients with a history of work or travel in the tropics, and is a diagnosis with far-reaching medical, social and emotional consequences.

Prognostic significance of advanced neuromonitoring after traumatic brain injury using neural networks.

While the therapeutic impact of tissue oxygenation (PtiO2) supplementing ICP-monitoring is proven by several clinical studies, its prognostic value is not well studied. In the following study artificial neural networks (ANN) were used to analyze the accuracy of outcome prediction after traumatic brain injury (TBI) for different combinations of clinical data and parameters derived from neuromonitoring. The total group included 95 patients suffering from TBI. For all patients clinical data (age, GCS, pupillary response etc.) were recorded and outcome was classified using Glasgow outcome scale after 6 months. In a first step a subgroup of 60 patients was chosen to train a neural network to predict outcome based only on clinical data. In a second step the resting 35 patients all having continuous neuromonitoring with automatic data storage of ICP and PtiO2 were chosen. Different network models were composed using the former clinical model plus up to three additional input units for the following parameters: (a) relative number of ICP > 40 mmHg, (b) relative number of PtiO2 < 5 mmHg and (c) relative number of ICP > 30 mmHg with simultaneous PtiO2 < 10 mmHg. For each model the following time periods were analyzed: day 1-2, day 1-3 and day 1-4 after trauma and additionally day 1-4 after trauma plus last day of neuromonitoring. Pure clinical data allowed to predict outcome with 74.3% accuracy. A combination of clinical data with ICP (a) significantly increased the confidence levels of outcome prediction in all time periods (p < 0.05) with accuracy rates rising up to 82.9% for the longer time periods. The combination of clinical data and ICP & PtiO2 (c) lead to comparable results. In contrast, no significant increases were observed in the early time periods when combining clinical data with PtiO2 (b) while accuracy rates rose up to 80% for extended time periods after trauma. A combination of all parameters lead to results lying between the above results. The results indicate that prediction of outcome can be improved by combining clinical and neuromonitoring data. The prognostic value of ICP might be superior to that of PtiO2.

Value of routine diagnostic criteria of bullous pemphigoid.

The clinical, histologic, and direct (DIF) and indirect (IIF) immunofluorescence findings are used in a critical, although arbitrary, manner in the routine diagnostic process of bullous pemphigoid (BP). Our purpose was to estimate their relative value. In the present retrospective study, a follow-up of at least 18 months was used as a prerequisite for the final diagnosis of BP (63 patients) and controls (n=159). The clinical, histologic, DIF, and IIF diagnostic criteria of BP were found to vary independently of each other. Positive DIF was the most sensitive (90.5%) typical for BP histology and positive IIF were the most specific (99%). Immunopathologic tests were the most valuable, especially in the atypical varieties of BP. Nearly 25% of patients in this group would have been misdiagnosed if IF tests had not been performed. Atypical cases (40%) seemed to represent a clinical continuum over the whole spectrum of the disease. Patients with exclusively immunoglobulin G (IgG) and C3 basal membrane zone (BMZ) deposits were significantly more often seropositive than the rest of the DIF-positive cases; however, the class of BMZ immunoreactants varied according to the site of biopsy. C3 was almost invariably deposited at the BMZ of DIF-positive patients. When Igs were also present, they were only exceptionally (5% of cases) of greater fluorescence intensity than C3. The combination of clinical data plus one positive immunopathologic test provide the best combination of sensitivity and specificity (98%), and seem to be most appropriate in defining patient populations for study purposes. The relationship between the classes of immunoreactants should be better evaluated with reference to the site of skin biopsy. It may be suggested, however, that the likelihood of BP existence is very low when in vivo C3 is absent or of lower intensity of fluorescence than the concomitant Ig(s).

Clinical aspects of perinatal hypoxic-ischemic brain injury

Perinatal hypoxic-ischemic cerebral injury is a significant cause of neurological morbidity and mortality in childhood. It is often difficult to determine the precise timing of such injury. Data from epidemiological and neuropathological studies have identified several maternal and fetal risk factors that seem to be associated with suspected prenatal brain injury. Hypoxic-ischemic cerebral injury that originates earlier in gestation may result in few, if any, clinical abnormalities during the newborn period. Clinical abnormalities may also be difficult to recognize in the premature newborn, and greater reliance must be placed on other adjunctive investigations, eg, neuroimaging. In contrast, term infants who sustain acute, intrapartum hypoxic-ischemic insult of sufficient magnitude to result in long-term sequelae invariably show recognizable encephalopathy during the newborn period. A combination of clinical data and adjunctive investigations during the neonatal period is a powerful predictive tool for long-term outcome.

Practical issues in conducting multinational, multicenter trials managed by Contract Research Organisations

Large multinational, multicenter trials are increasingly being performed during Phase III of the clinical development of a psychotropic drug to demonstrate the efficacy of the new therapeutic agent in the shortest possible time. The testing of the new drug therapy under a common protocol, foreseeing the combination of clinical data collected across countries for a joint evaluation, is becoming more frequent in drug development. Usually, Sponsors use the services of Contract Research Organisations (CROs) to undertake and manage such large multinational, multicenter trials.The Sponsor who is setting up large definitive CRO-managed studies with psychotropics may anticipate to encounter issues along the following lines: Psychiatric Practice, Organization and Logistics, Data Integration and Manpower.

Using routinely collected data for clinical research

Clinical research involving prospective data collection in randomized controlled trials is not always feasible. Increasingly, hospitals are developing large clinical databases that are waiting to be mined. We have developed a computer program, ClinQuery, that facilitates such exploration and analysis. We have also shown in a series of studies that the use of clinical data is a powerful tool in health services research. In some cases, we have shown that coded data are inaccurate and that alternative clinical data are preferable. In other cases, a combination of clinical data and coded discharge diagnoses is preferable.

Predictive importance of clinical findings and a predischarge exercise test in patients with suspected unstable coronary artery disease

The prognostic information of clinical variables and a predischarge exercise test was studied in 400 patients (282 men, 118 women) admitted to the coronary care unit with suspected unstable coronary artery disease, that is, recurring chest pain of new onset, increasing anginal pain in formerly stable angina pectoris or suspected nontransmural acute myocardial infarction. Forty-nine coronary events occurred in the 276 men who performed the exercise test during the following year, whereas only 5 coronary events occurred among the 118 women. The only variable of prognostic importance in women was nontransmural myocardial infarction. In men, the clinical variables increasing age, duration of angina, ST-or T-segment changes on the rest electrocardiogram and increasing angina or nontransmural myocardial infarction as inclusion criteria were associated with increased occurrence of coronary artery bypass surgery, transmural myocardial infarction or cardiac death. Findings of ST-segment depression, limiting chest pain or low rate-pressure product during the exercise test were of greater value than any clinical variable in prediction of coronary artery bypass surgery, transmural myocardial infarction or cardiac death. Within all clinical sub-groups of men, the results of the exercise test had an additive predictive value for future coronary events. Combinations of clinical data and exercise test results enabled the best identification of patients with high or low risk for coronary events.

Improved confidence of outcome prediction in severe head injury

An analysis of clinical signs, singly or in combination, multimodality evoked potentials (MEP's), computerized tomography scans, and intracranial pressure (ICP) data was undertaken prospectively in 133 severely head-injured patients to ascertain the accuracy, reliability, and relative value of these indicants individually, or in various combinations, in predicting one of two categories of outcome. Erroneous predictions, either falsely optimistic (FO) or falsely pessimistic (FP), were analyzed to gain pathophysiological insights into the disease process. Falsely optimistic predictions occurred because of unpredictable complications, whereas FP predictions were due to intrinsic weakness of the indicants as prognosticators. A combination of clinical data, including age, Glasgow Coma Scale (GCS) score, pupillary response, presence of surgical mass lesions, extraocular motility, and motor posturing predicted outcome with 82% accuracy, 43% with over 90% confidence. Nine percent of predictions were FO and 9% FP. The GCS score alone was accurate in 80% of predictions, but at a lower level of confidence (25% at the over-90% level), with 7% FO and 13% FP. Computerized tomography and ICP data in isolation proved to be poor prognostic indicants. When combined individually with clinical data, however, they increased the number of predictions made with over 90% confidence to 52% and 55%, respectively. Data from MEP's represented the most accurate single prognostic indicant, with 91% correct predictions, 25% at the over-90% confidence level. There were no FP errors associated with this indicant. Supplementation of the clinical examination with MEP data yielded optimal prognostic power, an 89% accuracy rate, with 64% over the 90% confidence level and only 4% FP errors. The clinical examination remains the strongest basis for prognosticating outcome in severe head injury, but additional studies enhance the reliability of such predictions.

Combined Use of Milk Progesterone Profiles, Clinical Examination and Oestrus Observation for the Study of Fertility in the Post-Partum Period of Dairy Cows

Three different criteria were used to study the fertility of 50 cows: 1. Clinical investigation of ovaries and uterus at two-weekly intervals. 2. Daily observation of oestrus, three times a day. 3. Determination of milk progesterone every second or every third day. From the combination of clinical data and progesterone profiles it was found that 26% of the animals were abnormal according to both criteria. This group could be subdivided into three categories: delayed start (later than day 30 after parturition) of luteal activity (12%), prolonged (lasting longer than 20 days) luteal activity (6%) and irregular luteal activity (8%). Three animals (6%) which were clinically diagnosed to be abnormal (retained placenta or peritonitis) had normal progesterone profiles. On the other hand, one animal (2%) which appeared to be clinically normal had an abnormal progesterone profile. Two animals with follicular cysts were treated with Nymfalon (progesterone + HCG), one with a pyometra was treated with Cloprostenol (PGF2α) and one cow showing anoestrus was treated with GnRH. In all these cows the effectiveness of the treatment was confirmed by the corresponding progesterone profile. From the combined data of oestrus observations and progesterone profiles it was found that 48% of the animals showed at least one silent oestrus (the start of the first progesterone rise was not taken into consideration). 27% of a total of 110 oestrous periods, as expected from the progesterone profiles (excluding the start of the first progesterone rise), were apparently silent, since they were not observed despite frequent oestrus observations. One animal was never seen in oestrus, although there was some (delayed) luteal activity. Although 88% of the animals had started luteal activity earlier than day 30 after parturition, only 36% had shown oestrus at that time.

Management Strategies for Urinary and Vaginal Infections

Detailed history, physical examination, laboratory and follow-up data were obtained from 821 women coming to a primary care clinic over a two-year period with the symptoms of urinary tract (UTI) or vaginal infection. Using all available information, each patient retrospectively was given one of several mutually exclusive diagnoses. Vaginitis without UTI was diagnosed in 70% of patients, UTI without vaginitis in 12%, UTI and vaginitis in 2%. The conditional probability of the several possible diagnoses was calculated, given various combinations of clinical data; a diagnosis of vaginitis was twice as likely as a diagnosis of UTI in a patient with dysuria. On the basis of these calculations we identified efficient clinical strategies for when to perform a pelvic examination, a urinalysis, and a urine culture, and when to diagnose UTI presumptively on the basis of urinalysis.

THE SIMPLIFICATION OF A CLINICAL DATA BASE: APPLICATION TO GALLSTONE PATIENTS

In patients with gallstones, recommendations for cholecystectomy depend on evidence of abnormality in the cholecystogram. Symptoms and signs, usually related as a syndrome, are employed to identify patients who should have a cholecystogram. Triplet combinations of clinical data from gallstone patients and controls were examined to find which combination was the best discriminator between diseased and non-diseased, and between those who should be investigated radiologically and those who need not. The cholecystogram was confirmed as the best overall discriminator, but right costal margin pain by itself was as efficient as any triplet. The performance of a cholecystogram on all patients with right costal margin pain is as efficient a system for identifying patients with gallstones as the consideration of any quantity of clinical data.