The effect of zymosan and the protective effect of various antioxidants on fracture healing in rats.

AIM: To investigate the effects of free oxygen radicals and various antioxidants on bone healing after experimental formation of fracture. MATERIALS AND METHODS: Fifty male rats were used and divided into five groups (ten rats in each). The right forelimbs of the rats were broken by bimanual compression method. One hour before this procedure, 5 ml/kg of intraperitoneal (i.p.) physiologic saline were given to the control Group 1. All 40 rats in the experimental Groups 2, 3, 4 and 5 were treated with i.p. zymosan at a dosage of 100 mg/kg to induce the production of free radicals by stimulating NADPH oxidase in polymorphonuclear leukocytes. Zymosan induction was stopped on the fifth post-fracture day. In addition to the zymosan, i.p. 1 g/kg/day of dimethyl sulfoxide were given to the animals in Group 3, 50 mg/kg/d of Ginko biloba Extract (EGb 761) in Group 4 and 500 mg/kg/day of vitamin C in Group 5. Radiographs of the fractures of all animals were obtained to assess callus formation, remodeling and bridging bone formation under ether anesthetics on postfracture day 7, 14 and 21. All rats were euthanized on day 22, and sections of the radius and ulna were examined both histologically with light and electron microscopy and ultrastructurally. Statistical analysis was made with Kruskal-Wallis variance analyze test and comparison between groups was performed by Dunn's multiple comparison test. RESULTS: An impairment of bone healing was observed in Group 2 inducted with purely zymosan. Variable results were obtained for bone healing in the groups treated with various antioxidants. There was very significant difference of fracture healing between Groups 1 and 2 both histologically and radiologically (P < 0.001). There was significant difference between Groups 2 and 5 radiologically (P < 0.05). CONCLUSION: Free oxygen radicals demonstrate a negative effect on fracture healing and vitamin C (an antioxidant) partially prevents the negative effect of zymosan on fracture healing.

Once tired, always tired? Limitations in function over time of tired patients in Dutch general practice.

OBJECTIVE: To gain insight into limitations in function over time of general-practice patients who presented and were diagnosed with "tiredness". METHODS: In a routine family-practice electronic register based on use of the International Classification of Primary Care (ICPC), 684 patients were identified who presented (in 1997 or 1998) with the complaint tiredness, who were given the same symptom diagnosis, and who still had this diagnosis on 1 August 1999. A questionnaire (WONCA/COOP charts, HAD Scale, recent medical care, tiredness and attribution) was sent to these 684 "cases" and 858 controls. In a logistic regression analysis (16 dichotomous variables), we constructed five models for optimizing sensitivity and specificity for the detection of patients with an episode of care for "tiredness". RESULTS: We received 385 fully completed questionnaires of cases, on average 19 (7~31) months after the start of their episode of care for "tiredness". The results of the 1997 and 1998 cases were similar. Cases did considerably worse than did the 385 optimally matched controls: e.g., seriously limited by tiredness: 52% of cases vs 32% of controls; poor overall health: 35% of cases vs 20% of controls; HAD Scale scores indicating anxiety or depression: about 20% of cases vs about 10% of controls. Highest sensitivity (70%) was reached by including poor overall health, recent medical care and HAD Scale depression score >10 in the model; and highest specificity (65%) by including poor overall health and a HAD Scale anxiety score >7. CONCLUSION: Patients who present with tiredness and receive the same diagnosis have a high probability of suffering from substantial limitations in function in the years following diagnosis. Their limitations are more serious than those of controls, but no indication is found for a specific limitation. The indicators are strongly related and concentrate around "poor overall health".

Contrast-enhanced dynamic magnetic resonance imaging findings of hepatocellular carcinoma and their correlation with histopathologic findings.

PURPOSE: To investigate the correlations of contrast-enhanced magnetic resonance (MR) imaging findings of large (> 5 cm) hepatocellular carcinomas with tumor size and histopathologic findings. MATERIALS AND METHODS: MR imaging was performed in 30 patients with a histopathologic diagnosis of hepatocellular carcinoma. The imaging protocol included non-contrast, hepatic arterial, portal venous and late phases. The signal intensities relative to the liver, enhancement patterns and the morphologic features of the lesions were evaluated in relation to size and degree of differentiation. RESULTS: On histopathologic examination, 12 of 30 (40%) tumors were well-differentiated (grade 1), 6 of 30 (20%) were moderately differentiated (grades 2 and 3) and 12 of 30 (40%) were poorly differentiated (grade 4). Tumor size, tumor boundry, serum alpha-fetoprotein level and portal vein invasion were found to have statistically significant correlations with the degree of differentiation (p < 0.05). Portal vein invasion, capsule formation and tumor surface characteristics showed statistically significant correlations with tumor size (p < 0.05). CONCLUSION: MR imaging findings of hepatocellular carcinomas larger than 5 cm are partially dependent on tumor size and degree of differentiation.

[The clinical relationship between symptoms and the final diagnosis in general practice, determined by means of posterior probabilities calculated on the basis of the Transition Project]. / Het klinisch verband tussen klachten en uiteindelijke diagnosen in de huisartspraktijk, vastgesteld met achterafkansen berekend op grond van het Transitieproject.

OBJECTIVE: To determine how, with the aid of the database of the Transition Project (www.transitionproject.nl), one can calculate posterior probabilities for general practice that provide insight into the clinical significance of the simultaneous occurrence of two events (a symptom and a diagnosis, or two diseases) in general practice. DESIGN: Descriptive. METHOD: The use of the 'International classification of primary care' (ICPC) to code both the patient's reason for encounter and the diagnosis of the general practitioner in the Transition Project has resulted in a database for the period 1985-2002 with a total of 201,127 patient-years, in which the posterior probability of a diagnosis in the presence of a complaint or symptom is available in the form of an odds ratio. Also in the case of the simultaneous occurrence of 2 episodes of care (comorbidity) in a patient it is now possible to determine whether the ratio between the prior and the posterior probability indicates a clinically relevant relationship or that it is a chance finding. Such posterior probabilities have been calculated for the conditions otitis media, hypertension in diabetes mellitus, shortness of breath and heart failure. In the calculation ofthe prior and posterior probabilities, only 'certain' diagnoses were used. RESULTS: For the diagnosis 'otitis media' in the age group 0-4 years, otalgia had the highest posterior probability (odds ratio: 15.77), with discharge from the ear taking second place (odds ratio: 8.59). 'Fever' contributed almost nothing. The odds ratio for hypertension in 45-74-year-old women with diabetes mellitus was 3.42. When the symptom was 'shortness of breath', the prior probability of heart failure in the age group 45-64 years was relatively low (2.0) but the posterior probability was relatively high (24.2). In this way, the combination of prior and posterior probabilities can provide support for the clinical work of the general practitioner. As a predictive variable for heart failure in the age group 65-74 years, 'ankle oedema' played an important role while 'fatigue' contributed nothing to the diagnosis. It was apparent from the database that the care for patients with heart failure often coincided with that for chronic diseases such as diabetes mellitus, hypertension, ischaemic heart disease, chronic obstructive pulmonary disease and atrial fibrillation. But the question whether there is a clinically relevant relationship could only be answered on the basis of the posterior probabilities: the highest odds ratio's were found for 'atrial fibrillation/atrial flutter' (32.5), 'chronic obstructive pulmonary disease' (22.5) and 'chronic skin ulcer' (20.2). CONCLUSION: The calculation of prior and posterior probabilities on the basis of the database of the Transition Project makes it possible for general practitioners to determine the clinical relevance of their observations.

Nutritional deficiency in Dutch primary care: data from general practice research and registration networks.

OBJECTIVE: To explore incidence and prevalence rates of nutritional deficiency in adults in general practice. METHODS: Six Dutch general practice research and registration networks supplied incidence and prevalence rates of nutritional deficiency by the International Classification of Primary Care (ICPC) or 'E-list' labels ('loss of appetite, feeding problem adult, iron, pernicious/folate deficiency anaemia, vitamin deficiencies and other nutritional disorders, weight loss'). In case of disease-related nutritional deficiency, we asked whether this was labelled separately ('co-registered') or included in the registration of the underlying disease. RESULTS: 'Iron deficiency anaemia' had highest incidence (0.3-8.5/1000 person years), and prevalence rates (2.8-8.9/1000 person years). Nutritional deficiency was mostly documented in the elderly. In two networks 'co-registration' was additional, two only documented the underlying disease and two did not specify 'co-registration'. No clear difference was found between networks considering the difference in 'co-registration'. CONCLUSION: Nutritional deficiency is little documented in general practice, and generally is not registered separately from the underlying disease.

Chest radiography and thoracic computed tomography findings in children who have family members with active pulmonary tuberculosis.

OBJECTIVE: The chest radiography and TCT findings in children who had contacted with adult family members with active pulmonary tuberculosis were compared. The contributions of thoracic computed tomography to the diagnosis of tuberculosis were investigated. METHODS AND MATERIAL: The children who were 0-16 years old (n=173) and children of families with an adult member which was diagnosed as pulmonary tuberculosis were evaluated. The children were considered in two groups based on the absence (n=125) or presence (n=48) of complaints and/or ambiguous symptoms such as lack of appetite, mild cough, sweating, history of lung infection, low body weight and those with suspicious chest radiography findings (12 cases) were included in this study. Asymptomatic patients (n=125) did not undergo TCT. Patients who had positive PPD skin tests only received isoniazid. If the TCT demonstrated enlarged lymph nodes or parenchymal lesions, minimally active pulmonary tuberculosis was diagnosed and antituberculous treatment was given. RESULTS AND DISCUSSIONS: TCT revealed lymph node enlargement or parenchymal lesions in 39 children (81.2%). Of the 12 children whose CXRs revealed suspicious lymph node enlargement and/or infiltration, five had normal findings in TCT whereas the initial findings were confirmed in the remaining seven. These data suggest that there is a correlation between the presence of ambiguous symptoms in exposed children and TCT findings; chest radiography and TCT findings do not yield parallel findings. All the patients who received anti-TB treatment were resolved in the control examinations. CONCLUSION: In this study there is a correlation between presence of ambiguous symptoms and TCT findings, but the chest radiography and TCT findings do not yield harmony in exposed children with ambiguous symptoms (suspicious tuberculosis cases). These observations should be considered in children with symptoms similar to those of exposed children, but with no definite history of exposure. If similar TCT findings observed in such patients, treatment for tuberculosis should be considered.

Tiredness in Dutch family practice. Data on patients complaining of and/or diagnosed with "tiredness".

BACKGROUND: Research including patients from the entire tiredness spectrum in family practice is needed. OBJECTIVES: Our aim was to provide routine family practice data on (i) relationships between the RFE (reason for encounter) and the diagnosis "tiredness"; (ii) duration, number of encounters and family physician's (FP's) interventions in episodes of care of tiredness; and (iii) sex/age and co-morbidity of patients diagnosed with "tiredness". METHODS: Routine episode of care data from the Transition Project, coded comprehensively with the International Classification of Primary Care (ICPC), were used. (i) A 16 year database (1985-2000, 58 FPs, 504 145 episodes of care, 168 550 patient years) for calculating "prior probabilities" with (diagnostic) odds ratios. (ii) A "basic population" extracted from that 16 year database of patients listed for an entire 4 year period (1997-2000; n = 12 292). RESULTS: The RFE tiredness resulted in a variety of diagnoses, but most frequently (43%) in "tiredness". Most odds ratios were low or negative. Of episodes of care of tiredness, 90% started with the RFE tiredness; 72% required one encounter only, and 90% lasted <6 months. In the 4 year period, 21% of patients first presented with tiredness, and 12% were diagnosed with tiredness; both groups were skewed towards women. Average co-morbidity in tired patients (16.6) was higher than in other visiting patients (10.4), and contained more tiredness-related conditions. FPs' interventions were mainly blood test, physical exam and advice; few referrals occurred. CONCLUSIONS: For many diagnoses, the RFE tiredness hardly contributes to the Bayesian posterior probability. FPs react differently to the RFE tiredness in cases in which they diagnose the patient with "tiredness" from how they react in other cases. The characteristics of ICPC and the Dutch health care system resulted in a full integration of tiredness as an RFE and as a freestanding episode of care in the context of family practice.

The March 2002 update of the electronic version of ICPC-2. A step forward to the use of ICD-10 as a nomenclature and a terminology for ICPC-2.

The electronic version of the second edition of the International Classification of Primary Care, ICPC-2-E, available on the website of Family Practice since 2000, needed an update of the mapping with ICD-10 as a nomenclature and, consequently, of some of its criteria. This is now being made available, together with the full four-digit conversion structure between the two systems, in an electronic form, allowing the use of the alphabetical index of ICD-10 in several languages to be used as a terminology for ICPC-2. In this contribution, we discuss the considerations for preparing this new mapping structure, and its potential use in future electronic patient records in family practice.

Severity of episodes of care assessed by family physicians and patients: the DUSOI/WONCA as an extension of the International Classification of Primary Care (ICPC).

OBJECTIVES: The DUSOI/WONCA is included in the second edition of the International Classification of Primary Care (ICPC-2), as an extension to assess the severity of episodes of care. We studied (i) family physician's (FPs') assessment of three DUSOI/WONCA parameters per episode of care; (ii) how these relate to patient and episode of care characteristics, and to the interventions that occur; and (iii) how FPs' and patients' assessment of severity compare. METHODS: Twelve FPs participated and coded patient and encounter data with ICPC. Also, they answered three DUSOI/WONCA questions, that were also answered (after the consultation) by 300 patients. Odds ratios were calculated for the relationships of the severity elements to patient and episode characteristics, and interventions. The relative agreement between FPs' and patients' ratings of severity was assessed. RESULTS: In 2033 consultations, 2860 episodes of care were documented, with a subset of 411 with a paired assessment by patient and FP. Patients appeared to be less hindered by symptoms/ complaints than the FPs thought, and less optimistic about the prognosis without care than the FP. Clear relationships existed between the FPs' assessment of severity and the patient, encounter and episode of care characteristics. Substantial agreement existed between FPs' and patients' assessment of severity. CONCLUSIONS: This study confirms the feasibility for FPs routinely to code the separate elements of severity for episodes of care, simultaneously using ICPC and DUSOI/WONCA. The studied elements of severity all provide relevant information: the interventions that occurred all related to them in a logical fashion. The FP-patient agreement on severity is satisfactory, also in the sense that it seems realistic to include these elements of severity as a topic in the communication with the patient.

The probability of specific diagnoses for patients presenting with common symptoms to Dutch family physicians.

OBJECTIVE: Our goal was to develop reliable data on the probability of specific diagnoses among patients of family physicians (FPs) presenting with common symptoms. STUDY DESIGN: A group of 54 Dutch FPs recorded the reasons for encounter, diagnoses, and interventions for all episodes of care between 1985 and 1995. Diagnoses could be modified during the episode of care, and a modified diagnosis was applied to all episode data. POPULATION: We used the listed patient populations of the 54 Dutch FPs, representing 93,297 patient years, 236,027 episodes of care, and 267,897 patient encounters. OUTCOMES MEASURED: The top 20 diagnoses related to 4 selected presenting symptoms (cough, shortness of breath, general weakness/tiredness, and low back symptom/complaints without radiation), per 100 patients, with 95% confidence intervals, stratified by age. In the standard tables, age-specific cells with fewer than 10 observations were excluded. RESULTS: The availability of an accurate estimate of prior (pretest) probabilities for common symptoms/complaints has great potential value for family practice as an academic discipline and for family physicians in that it can support their medical decision making. Stratifying data by age groups increases the clinical relevance of the prior probabilities. CONCLUSIONS: Though collected by Dutch FPs, the data in our study have a high face validity for other clinicians. Still, FPs in other countries should give priority to collecting their own probability databases.

Advantages of long observation in episode-oriented electronic patient records in family practice.

From 1985-2000, 58 Dutch family physicians (FPs) of the Transition Project collected ICPC-coded data on 47, 2451 episodes of care, first in paper records for direct encounters only, later with a complete electronic patient record (EPR) for all (direct and indirect) encounters. Based on these data, the effects of a long observation period and the inclusion of all encounters (both direct and indirect) in the EPR were studied. Long observation periods in EPRs appear to have important advantages for patient documentation and the assessment of the content of family practice. Comparison of data from a one-year versus a four-year observation period showed a shift in utilization rates. In a long observation period, visiting patients appeared to make less demand on care, while the content of the FP's care for selected chronic diseases was reflected more realistically. The inclusion of all indirect encounters in an EPR (as compared to the previous inclusion of direct encounters only) resulted in more than twice the number of coded entries per listed patient, and thus led to a major shift in perspective on the FP's involvement in patient care.

ICPC-2-E: the electronic version of ICPC-2. Differences from the printed version and the consequences.

BACKGROUND: In 1998, ICPC-2 was published as a book. In the process of translating the book, and preparing an electronic version of chapter 10 (the actual classification), ICPC-2 proved to contain many errors and inconsistencies. Particularly, major problems were identified in the conversion between ICPC-2 and ICD-10, which could lead to major errors when used in electronic patient records. OBJECTIVES: We prepared an electronic version of chapter 10 of ICPC-2, ICPC-2-E, with all necessary corrections, to be published on the Oxford University Press web site as a part of this article. METHODS: Errors and inconsistencies were redressed, including particularly those in the con-version structure with all consequences on the level of inclusion and exclusion criteria, through a process of careful checking. RESULTS AND CONCLUSION: ICPC-2-E, the electronic version of chapter 10 of ICPC-2, is specifically to be used in an electronic patient record and for research purposes. It is to be used together with the first nine chapters of ICPC-2, since the book is indispensable to make a correct use of ICPC.

[Post-traditional medicine. Negotiating about the complaint, diagnosis and therapy]. / Posttraditionele geneeskunde. Onderhandelen over klacht, diagnose en therapie.

Dutch health care is developing in the direction of posttraditional medicine: a dynamic system of demand and supply, in which the media, information technology and a more active attitude of the patient play a part. The nature of the complaint/diagnosis combination affects the degree to which therapy is or is not evidence-based and can be medically justified. Randomized studies and guidelines in itself do not lead to a more purposeful application of treatment. Patients persistently request interventions that are not medically justified, but rather have various non-medical aims. Physicians can regard demands of this nature as an encroachment on their authenticity and find it difficult to decide whether or not to comply with them.

Patients with chronic alcohol abuse in Dutch family practices.

Routine data from the Dutch Transition project on 236 027 episodes of care collected by 54 family physicians (FPs) for 93 297 patient years in their listed practices and classified with the International Classification of Primary Care, were used to analyse chronic alcohol abuse episodes of care in Dutch family practices. Data on 332 episodes are presented. In a subsample with a 4-year registration period, 70 patients were identified. Important reasons for an encounter are the patient's explicit presentation of the problem and the FPs' initiatives. FPs show considerable sensitivity to psychosocial problems, including alcohol abuse. It is concluded that over the years registered FPs actively deal with chronic alcohol abuse in approximately 2% of all visiting men aged 25-64 years. In an average Dutch family practice with 2200 listed patients, approximately 20 patients are known by the FP to have chronic alcohol abuse. Real life studies in registered family practice populations are necessary to better establish how patients with abundant alcohol consumption as a risk factor develop the chronic alcohol abuse episode of care, and what FPs can do to prevent this effectively.

[Patients with fatigue in family practice: prevalence and treatment]. / Prevalentie en behandeling van vermoeide patiënten in de huisartspraktijk; gegevens uit het transitieproject.

OBJECTIVE: To gain insight into the prevalence and treatment of severe fatigue in general practice. DESIGN: Secondary data analysis. METHOD: By means of an episode-oriented morbidity registration by 54 GPs throughout the Netherlands over the period 1985-1994 it was established how often in the course of one year 'fatigue' was listed as the reason for consultation, what diagnoses were then made, how long episodes of care because of 'fatigue' lasted and what interventions took place (n = 93,297). Of the patients with a care episode because of 'fatigue' lasting at least 6 months, age, sex, comorbidity and consumption of care were established; for this purpose use was also made of a file containing data on 4 years in succession (n = 9630). RESULTS: Per annum, 92 per 1000 listed patients consulted the GP because of fatigue. Somatic or psychic diagnoses were made in 27.7 per 1000 patients listed. The episode of care lasted 4 weeks at most in 86% and at least 6 months in approximately 4%. The GPs' management of patients with 'fatigue' included physical examination in 63% and blood testing in 34%, conversation in 35%, prescription of medication in 24% and referral to a specialist in 3%. Of the 97 patients with fatigue lasting longer than 6 months, 61% had a chronic disease or psychic problems. CONCLUSION: Fatigue is frequently encountered in general practice, but the estimate that one per 1000 listed patients meets the criteria of the chronic fatigue syndrome looks a little high. It appears that GPs, in accordance with recommendations, mostly adopt a policy of wait and see.

Gender differences in general practice consultations: methodological challenges in epidemiological research.

BACKGROUND: Women consult their GP more often than men do. The distribution of complaints and diagnoses are different for women and men patients. Although several findings on gender differentials on mortality and health care consumption are rather consistent across studies, detailed findings and subsequent conclusions diverge in several important fields. OBJECTIVES: Our aim was to explore methodological aspects of research on gender differences in general practice. METHODS: We reviewed empirical studies within this field, aiming to identify methodological and interpretative intricacies which deserve special attention in epidemiological research on GP consultations. RESULTS AND CONCLUSIONS: We found that descriptive and explanatory levels of research are frequently confused. Simple questions, answers and explanations are commonly raised for complex issues within a poorly defined theoretical explanatory framework. There is a need to assess relevant approaches for various purposes, and to develop more uniform conceptual terms. Findings from one level are often transferred to another, incompatible level. Epidemiological issues must be considered, especially matters related to denominator level and standardization/confounders-not in order to decide which level represents 'reality', but to clarify the consequences of different measures for different research questions. The contents of the core variables and the potentials for bias should be discussed in order to provide a sound basis for future explanatory studies.

Mental health problems in primary care. A research agenda.

BACKGROUND: The North American Primary Care Research Group (NAPCRG) Task Force on Mental Health Problems was commissioned to explore critical research and policy issues in mental health and to develop a primary care research agenda for review and action by NAPCRG. This paper presents the key findings and recommendations of the task force. METHODS: As co-chairpersons of the task force, we performed a comprehensive review of the primary care mental health literature using MEDLINE searches with manual follow-up and personal communications with many active researchers in the field. Task force members participated in the editing and refinement of this paper through electronic mail and a series of face-to-face meetings. CONCLUSIONS: Rapid changes in the US health care environment threaten to undo the integration of mental and physical health that is at the heart of primary care. It will be necessary for the primary care leaders in the mental health field to step forward to guide policymakers, purchasers, and the public as primary care is reengineered for the next generation. Efforts to use episode of care and comorbidity recording within electronic medical record systems, particularly in cooperation with managed care corporations or primary care research networks, may represent the most effective strategy for promoting the integration of mental health services into primary care. The most promising area for original research may be the exploration of common mental health problems in the context of routine primary care practice.

The classification of mental disorders in primary care: a guide through a difficult terrain.

BACKGROUND: Primary care physicians traditionally have a strong interest in the mental health of their patients. Three classification systems are available for them to diagnose, label, and classify mental disorders: 1) The ICD-10 approach with three options, 2) The DSM-IV approach with two options, and 3) the ICPC approach with two options. This article lists important similarities and differences between the systems to help potential users choose the option that best meets their needs. METHODS: Definitions for depressive disorder, anxiety disorder, and somatization disorder are compared on five characteristics of classification: 1. the domain, 2. the scope, 3. the nature of the definitions, 4. focus on episodes of care, and 5. clinical guidelines. RESULTS: Primary care physicians and psychiatrists have different perspectives, reflected in different classifications. Each system has specific possibilities and limitations with regard to the diagnosis of mental disorders. For common mental disorders it is possible, however, to choose codes from one system while maintaining compatibility with the other two. Comparability as to the diagnostic content of the different classes, however, is more difficult to establish. The available classification systems give both primary care physicians and psychiatrists options to diagnose, label, and to classify mental disorders from their own perspective, but once a system has been chosen the clinical comparability of a patient with the same diagnosis in other systems is limited. CONCLUSION: Compatibility among systems can be optimized by strictly following a number of rules. The conversion between ICPC and ICD-10 (and consequently DSM-IV) allows simultaneous use of ICPC and ICD-10 as a classification and DSM-IV as the standard nomenclature. This is of particular interest for computer based patient records in primary care. The clinical comparability of the same diagnosis in different systems however is limited by the characteristics of the different system.