How to use polarity thinkingTM to manage tensions between accountability and learner agency when using a multipurpose portfolio?

Portfolios are often implemented to target multiple purposes, e.g. assessment, accountability and/or self-regulated learning. However, in educational practice, it appears to be difficult to combine different purposes in one portfolio, as interdependencies between the purposes can cause tensions. This paper explored directions to manage tensions that are inextricably linked to multipurpose portfolio use. We used a systems thinking methodology, that was based on the polarity thinkingTM framework. This framework provides a step-by-step approach to chart a polarity map® that can help to balance the tensions present in specific settings. We followed the steps of the framework to chart a polarity map for multipurpose portfolio use. Based on literature and our prior research, we selected one overarching polarity: accountability and learner agency. This polarity seems responsible for multiple tensions related to multipurpose portfolio use. We formulated values (potential benefits) and fears (tensions that can arise) of the two poles of this polarity. Then, we organised a session with stakeholders who work with the portfolio of the Dutch General Practice speciality programme. Together we formulated action steps and early warnings that can help to balance accountability and learner agency during multipurpose portfolio use. In addition to previous recommendations concerning portfolio use, we advocate that it is important to create a shared frame of reference between all involved with the multipurpose portfolio. During this process, the acknowledgement and discussion of tensions related to multipurpose portfolio use are vital.

It Is Smart to Set Treatment Goals, But Are Set Treatment Goals SMART? A Qualitative Assessment of Goals Described in the Assessment of the Burden of COPD Tool.

The Assessment of the Burden of COPD (ABC) tool facilitates shared decision-making and goal setting to develop a personalized care plan. In a previous trial (RCT), the ABC tool was found to have a significant effect on patients' Health-related Quality of Life (HRQoL). In this exploratory study we used data from the intervention group of the RCT to investigate if patients with health-related goals had an improved HRQoL compared to those without goals, and if the quality and types of goals differed for those who have a clinically meaningful improvement in HRQoL. We hypothesized that the quality and the type of the goal described in the ABC tool, relates to an improved HRQoL. We assessed the quality of the goals according to the Specificity, Measurability, Achievability, Relevance and Timeliness (SMART) criteria, and coded and counted each type of goal. We found that having a goal or not, did not differ significantly for those who had a clinically meaningful improved HRQoL versus those who had not, nor was the quality or type of goal significantly different. The most common types of goals were exercise more, smoke less, and improve weight. Based on the results, we speculate that when a clinically meaningful improvement in HRQoL is achieved, it is not related to a single component (i.e. goal setting as part of shared decision-making) but that the different components of the ABC tool (visualization of burden, shared decision making, utilization of tailored evidence based interventions, and regular monitoring of progress) may have a synergistic effect on disease cognition and/or behavior change. Noteworthy, the sample size was small while the calculated effect size was moderate, making it unlikely to find a significant effect.

European Society of ColoProctology: guideline for haemorrhoidal disease.

AIM: The goal of this European Society of ColoProctology project was to establish a multidisciplinary, international guideline for haemorrhoidal disease (HD) and to provide guidance on the most effective (surgical) treatment for patients with HD. METHODS: The development process consisted of six phases. In phase one we defined the scope of the guideline. The patient population included patients with all stages of haemorrhoids. The target group for the guideline was all practitioners treating patients with haemorrhoids and, in addition, healthcare workers and patients who desired information regarding the treatment management of HD. The guideline needed to address both the diagnosis of and the therapeutic modalities for HD. Phase two consisted of the compilation of the guideline development group (GDG). All clinical members needed to have affinity with the diagnosis and treatment of haemorrhoids. Further, attention was paid to the geographical distribution of the clinicians. Each GDG member identified at least one patient in their country who could read English to comment on the draft guideline. In phase three review questions were formulated, using a reversed process, starting with possible recommendations based on the GDG's knowledge. In phase four a literature search was performed in MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews. The search was focused on existing systematic reviews addressing each review question, supplemented by other studies published after the time frame covered by the systematic reviews. In phase five data of the included papers were extracted by the surgical resident (RT) and checked by the methodologist (JK) and the GDG. If needed, meta-analysis of the systematic reviews was updated by the surgical resident and the methodologist using Review Manager. During phase six the GDG members decided what recommendations could be made based on the evidence found in the literature using GRADE. RESULTS: There were six sections: (i) symptoms, diagnosis and classification; (ii) basic treatment; (iii) outpatient procedures; (iv) surgical interventions; (v) special situations; (vi) other surgical techniques. Thirty-four recommendations were formulated. CONCLUSION: This international, multidisciplinary guideline provides an up to date and evidence based summary of the current knowledge of the management of HD and may serve as a useful guide for patients and clinicians.

Interprofessional Pulmocheck care pathway: An innovative approach to managing pediatric asthma care in the Netherlands.

OBJECTIVES: Under-diagnosis and suboptimal asthma control in children persists. An innovative care pathway was developed by a hospital department of pediatrics with the aim to detect pulmonary problems in children and provide appropriate treatment possibilities through systematic feedback towards the referring primary care physician. Primary care physicians can use this pathway to refer children with asthma-like symptoms for a one-day assessment. Goals are to measure the usage of the pathway by primary care general practitioners (GPs), the outcomes in terms of new diagnoses of asthma, the reduction in regular referrals, generated recommendations/therapy and the adequacy of asthma follow-up. METHODS: We collected all feedback letters sent to the GP concerning children who underwent the Pulmocheck in 2010, 2011 and 2012. Furthermore, all GPs, who had referred a child to the Pulmocheck in this period and that subsequently was diagnosed with asthma and was further managed in primary care, were sent a follow-up questionnaire in 2014. RESULTS: There were 121 referrals from 51 GPs in 3 years to this pathway. In 59.5% of these referrals a new diagnosis of asthma was established. In 90.9% one or more changes in clinical management were advised. The response rate to the follow-up questionnaires was 65.7% of which 4.8% of the children with new established asthma were reviewed four times or more in the follow-up period, 17.4% two times, 65.2% once, and in 8.7% were not followed. CONCLUSIONS: The specialty pediatric asthma care pathway revealed a high number of children with newly diagnosed asthma, but was also helpful to exclude this diagnosis. However, the referral rate of GPs to this pathway was low, but in the children, that were referred several changes in the clinical management were advised and the frequency of monitoring of the children with diagnosed asthma was not in accordance with the asthma guidelines.

Effectiveness of video- versus text-based computer-tailored smoking cessation interventions among smokers after one year.

BACKGROUND: In western countries, smoking prevalence rates are high among smokers unmotivated to quit and those with a lower socioeconomic status (LSES). Multiple computer tailoring and the use of audio-visual aids may improve such interventions and increase cessation in LSES smokers. This study assessed the 12-month effectiveness of a video- and text-based computer-tailored intervention. METHODS: A randomized controlled trial in the Netherlands was used in which smokers were allocated to the video-based condition (VC) (N=670), the text-based condition (TC) (N=708) or the control condition (CC) (brief generic text advice) (N=721). After 12months, self-reported prolonged abstinence was assessed and biochemically verified in respondents indicating to have quit smoking. Three analysis strategies were used to assess the effects: (1) multiple imputation (MI); (2) intention-to-treat (ITT); (3) complete case analysis (CC). RESULTS: VC was more effective in prolonged abstinence compared to CC (odds ratio (OR)=1.90, p=.005) and the text-based condition (OR=1.71, p=.01). VC was furthermore more effective than TC. No differences were found for SES and motivational levels. Results were similar when using ITT and CC. For our secondary outcome seven-day point prevalence abstinence; however, neither VC (OR=1.17, p=.34) or TC (OR=0.91, p=.52) outperformed the CC. CONCLUSION: The video-based computer-tailored intervention was effective in obtaining substantial long-term abstinence compared to the text-based version and a brief generic text advice.

How to encourage smokers to participate in web-based computer-tailored smoking cessation programs: a comparison of different recruitment strategies.

The reach, retention and costs of four strategies aimed to recruit smokers for participation in a computer-tailored smoking cessation intervention was explored. The study was part of a randomized controlled trial whereby 832 respondents were randomized to three conditions. Smokers were invited by general practitioners (GPs), newspapers, Internet and other strategies (i.e. mailing organizations) to take part. ANOVA's/Chi-square tests explored sample differences. Logistic regression analyses investigated differences between the samples regarding retention and smoking behaviour. Smokers recruited via GPs (N = 144) had a lower educational level and suffered more from chronic obstructive pulmonary disease compared with respondents recruited via Internet (N = 307) (χ(2) = 11.554, df = 3, P = 0.009). Less motivated respondents recruited by GPs were more likely to return to study compared with the less motivated respondents recruited by 'other recruitment' strategies (χ(2) = 6.416, df = 3, P = 0.093). Highly addicted respondents recruited from newspapers (N = 213) were less likely to make a quit attempt compared with highly addicted respondents recruited by GPs (OR = 0.334, P = 0.035). Females from newspapers were less likely to remain abstinent compared with the GP sample (OR = 0.337, P = 0.005). Recruitment via GPs showed highest costs. Recruitment strategy influenced the type of smokers. Group differences were associated with different patterns of quitting.

[Systemic reactions to orally applied metal alloys]. / Systemische reacties op in de mond toegepaste metaallegeringen.

Orally applied metal alloys can cause undesirable physical effects. A distinction needs to be made in this respect between local and systemic reactions and toxic and immunological reactions. A case is presented which illustrates this problem. In this case, the application of orthodontic appliances was probably the trigger for an exacerbation of nickel allergy. The oral exposure to nickel resulted in hand eczema. The patient was also exposed to nickel by single-unit fixed dental prostheses, a removable dental prosthesis, and food, as a result of which removal of the orthodontic appliances did not result in complete healing. Therefore, the single-unit fixed dental prostheses also had to be removed and food had to be prepared henceforward in nickel free pans.

Palladium-induced Th2 cytokine responses reflect skin test reactivity.

Recently, a crucial role of Th2 responses in nickel allergic contact dermatitis (ACD) was demonstrated. As palladium allergy is an issue of growing interest, the diagnostic potential of Th2 parameters for palladium sensitization was investigated. Palladium (Na(2) [PdCl(4)])-induced lymphocyte proliferation (LPT), Th1 and Th2 cytokine production were correlated with skin test (ST) reactivity in 16 positive and 21 negative controls. Furthermore, the diagnostic potential of these assays was evaluated using receiver operating characteristics (ROC) analysis. For comparison, same experiments were carried out for nickel (NiSO(4)). Correlation coefficients between palladium ST reactivity and IFN-γ, LPT, IL-5, and IL-13 were 0.34, 0.51, 0.69, and 0.78, and overall test accuracies were 68%, 81%, 89%, and 95%, respectively. Both palladium- and nickel-mediated Th2 responses tightly correlate with ST reactivity, supporting recent findings on the crucial role of Th2 involvement in ACD. Therefore, these assays may have great potential as diagnostic tools for future in vitro sensitization testing.

Learning from complex elderly care: a qualitative study on motivating residents in family medicine.

BACKGROUND: More and more patients need complex care, especially the elderly. For various reasons, this is becoming increasingly difficult. The onus is essentially on family physicians to provide this care and family medicine residency programs should therefore prepare their residents for this task. We know from self-determination theory (SDT) that motivation plays a key role in learning and that in order to boost motivation, fulfillment of 3 basic psychological needs - for autonomy, competence, and relatedness - is crucial. As residents often lack motivation, residency programs face the important challenge to motivate them to learn about and engage in complex elderly care. How to do so, however, is not yet sufficiently understood. METHODS: We conducted a qualitative multi-institutional case study across four universities in Belgium and the Netherlands. In the period between June, 2015, and May, 2019, we triangulated information from semi-structured interviews, document analysis, and observations of educational moments. Guided by SDT concepts, the analysis was performed iteratively by a multidisciplinary team, using ATLAS.ti, version 8. In this process, we gained more insights into residents' motivation to learn complex elderly care. RESULTS: We scrutinized 1,369 document pages and 4 films, observed 34 educational moments, and held 41 semi-structured interviews. Although we found all the 3 basic psychological needs postulated by SDT, each seemed to have its own challenges. First, a tension between the need to guide residents and to encourage their independent learning complicated fulfillment of the need for autonomy. Second, the unpredictability of complex care led to reduced feelings of competence. Yet, guidelines and models could help residents to capture and apprehend its complexity. And third, family medicine practice, patients, and educational practice, by either satisfying or thwarting the need for relatedness, were identified as key mediators of motivation. By setting the right example and encouraging residents to discuss authentic dilemmas and switch their health care approach from cure to care, educators can boost their motivation. CONCLUSION: Our study has demonstrated that the degree of perceived autonomy, guidance by the education program, use of authentic dilemmas, as well as involvement of group facilitators can aid the process of motivation. TRIAL REGISTRATION: NVMO, ERB number 482.

COPD screening in general practice using a telephone questionnaire.

Chronic obstructive pulmonary disease (COPD) is a growing health problem, and an underestimated and underdiagnosed disease in primary care. The aim of this survey was to study the feasibility of detecting undiagnosed COPD patients in the general practice population with the aid of a telephone questionnaire. The study was held in 2 general practices in the Netherlands. During 2 weeks, all patients registered with these 2 practices and aged between 40 and 75 years were contacted through a call center. Persons known with a previous history or diagnosis of COPD or asthma or comorbidity were excluded from the telephone list. The telephone interview used the Respiratory Health Screening Questionnaire (DB Price, 2006). Based on the score on this instrument, respondents were classified as having a low, moderate or high risk of having COPD. Smoking behaviour and BMI were also recorded. Patients with medium and high risk for COPD were invited for spirometry, performed by 2 experienced registered nurses. The results of the telephone interview and spirometric findings were assessed by the attending GP, who established the final diagnosis. The call center reached 1032 persons, 813 of whom answered the questions. The percentage of smokers was 49.2%, with an average number of pack-years of 17.9 (SD = 17); mean BMI was 26.1. Spirometry and analysis by the GP showed that 15.7% of the medium-risk group had previously undiagnosed COPD, versus 39.6% of the high-risk group. The number of undiagnosed COPD patients in the general practice population is considerable. Case finding can focus on moderate- and high-risk groups after telephone risk assessment.

A TASMAN Expedition: Development of a Questionnaire to Assess Specific Self-Management Abilities.

Introduction: Self-management (SM) is a core component of well-being and perceived health for patients with chronic obstructive pulmonary disease (COPD). Most theories on SM share that self-efficacy, illness-perception and coping are determinants of SM behavior. Optimal support to improve SM should be tailored to the individual patient's level of these determinants as SM abilities vary between patients. To tailor SM support, it is therefore necessary to assess the scores on these determinants. Unfortunately, no such instrument exists for clinical use. Therefore, the first goal of this study was to verify presumed correlations between SM and the determinants thereof. The second goal was to develop an instrument to assess the SM abilities. Methods: In this cross-sectional, observational study, COPD patients completed the General Self-Efficacy Scale (GSES), Brief Illness Perception Questionnaire (B-IPQ) and the Utrecht Proactive Coping Competence measure (UPCC) as well as the Self-Management Ability Scale (SMAS-30). Correlations between the questionnaires were assessed and a principal component analysis (PCA) was performed to identify the best-fitting items in the three independent variables related to SM. These items were used to create an instrument to assess SM abilities. Results: Hundred COPD patients (58 males, 41 females, 1 unknown) were included. The correlation between SM and self-efficacy, illness perception on concerns and proactive coping was moderate and significant (r=0.318, p<0.01; r=-.230, p<0.05; r=.426, p<0.01, respectively). PCA identified six UPCC items and nine GSES items that met the predefined criteria. These items were supplemented with the B-IPQ concerns item to establish the new instrument to assess SM abilities.

[Nausea; article for education and training purposes]. / Misselijkheid.

Nausea is a common presenting symptom in medical care with a broad differential diagnosis. In this teaching article we provide practical information on many aspects of nausea including pathophysiology and differential diagnosis, history and physical examination, and diagnostic tests and treatment. This was done by means of answering several questions from the daily practice of general practitioners, specialists in internal medicine and surgeons. In a patient with nausea a provisional diagnosis can be made based on medical history, careful history-taking and age. Diagnostic testing is only performed on clinical suspicion and depends on the provisional diagnosis and presence of alarm symptoms. Tailored medical treatment of nausea is based on the provisional diagnosis and on the mechanism of action of the intended antiemetic agent.

Reactivity to sodium tetrachloropalladate (Na2[PdCl4]) compared to PdCl2 and NiCl2 in lymphocyte proliferation tests.

BACKGROUND: For patch testing, replacement of the commonly used palladium dichloride (PdCl2) by sodium tetrachloropalladate (Na2[PdCl4]) was recently demonstrated to improve test accuracy and show a significant correlation with nickel (Ni), supporting the concept of cross-reactivity between Pd and Ni. A promising alternative to metal allergy patch testing is the in vitro lymphocyte proliferation test (LTT). OBJECTIVES: The aim of this study was to test whether Na2[PdCl4] is also more sensitive for diagnosing Pd allergy with a standardized LTT. PATIENTS/METHODS: After determining optimal nontoxic and nonmitogenic concentrations for Na2[PdCl4], blood samples from 105 patients with clinical suspicion of metal allergy were tested with an LTT called memory lymphocyte immuno stimulation assay for Na2[PdCl4], PdCl2 and NiCl2. Reaction profiles were analysed for concordant positive reactions. RESULTS: Using the conventional cut-off of stimulation index > or = 3, 74.3% showed a positive reaction to NiCl2, 15.2% to PdCl2 and 28.6% to Na2[PdCl4]. All positive results to PdCl2 were covered by Na2[PdCl4]. From the 30 positive reactions to Na2[PdCl4], 26 (87%) were concordant for NiCl2 reactivity. CONCLUSION: In LTT, the use of Na2[PdCl4] results in more positive reactions in Pd allergy testing which are in concordance with positive reactions to PdCl2 and NiCl2.

Expression of TNF-receptor associated factor 2 correlates with poor progression-free survival time in ABC-like primary nodal diffuse large B-cell lymphomas.

AIMS: Tumour necrosis factor (TNF)-receptor associated factor 2 (TRAF2) is an adaptor molecule involved in nuclear factor (NF)-kappaB activation, which is characteristic of in vitro activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL) and may result in expression of anti-apoptotic genes and poor response to chemotherapy. TRAF2 also has direct anti-apoptotic properties via interference with the apoptosis signalling cascade. The aim was to determine whether TRAF2 is preferentially expressed in ABC-like DLBCL, and whether expression correlates with clinical outcome. METHODS AND RESULTS: TRAF2 was expressed in nine of 20 tested ABC-like DLBCLs and in only one of 13 tested germinal centre B-lymphocyte (GCB)-like DLBCLs. High TRAF2 expression was correlated with high International Prognostic Index at time of presentation, high chance of relapse and short progression-free survival time in 44 tested DLBCLs. Furthermore, when analysis was restricted to ABC-like DLBCL only, TRAF2 expression was significantly associated with poor progression-free survival time. CONCLUSIONS: TRAF2 might be involved in activation of NF-kappaB in a subset of ABC-like DLBCL, and its expression is associated with a particularly poor outcome in primary nodal DLBCL patients. Because of its possible effect on to chemotherapy resistance, resistance, TRAF2 might be an attractive candidate as a molecular target for TRAF2+ DLBCL.

Rome III vs Rome IV criteria for irritable bowel syndrome: A comparison of clinical characteristics in a large cohort study.

BACKGROUND: The Rome criteria for irritable bowel syndrome (IBS) have been revised and are expected to apply only to the subset of Rome III IBS subjects with abdominal pain as predominant symptom, occurring at least once a week. The aim of this study was to determine the percentage of Rome III IBS subjects that fulfills Rome IV criteria and to evaluate differences between Rome IV-positive and Rome IV-negative subjects. METHODS: Four hundred and four Rome III IBS subjects completed a 14-day end-of-day symptom diary, the Gastrointestinal Symptom Rating Scale (GSRS), Hospital Anxiety and Depression Scale, and RAND 36-item Short-Form Health Survey (SF-36). Diary-based surrogate Rome IV criteria were defined as occurrence of abdominal pain at least 1 day each week with a severity of ≥2 (mild; definition 1) or ≥3 (considerable; definition 2). KEY RESULTS: Using surrogate Rome IV criteria, 353 (87.4%, definition 1) and 249 (61.6%, definition 2) subjects were defined as Rome IV positive. These patients were more often female, younger, and recruited from secondary/tertiary care compared with Rome IV-negative subjects. They also presented with higher abdominal pain scores and gastrointestinal (GI) symptom severity on both end-of-day diary and GSRS, higher psychological symptom scores, and lower quality of life compared with Rome IV-negative subjects. CONCLUSIONS AND INFERENCES: The Rome IV IBS population likely reflects a subgroup of Rome III IBS patients with more severe GI symptomatology, psychological comorbidities, and lower quality of life. This implies that results from Rome III IBS studies may not be directly comparable to those from Rome IV IBS populations.

The contribution of an asthma diagnostic consultation service in obtaining an accurate asthma diagnosis for primary care patients: results of a real-life study.

Previous studies showed that general practitioners have problems in diagnosing asthma accurately, resulting in both under and overdiagnosis. To support general practitioners in their diagnostic process, an asthma diagnostic consultation service was set up. We evaluated the performance of this asthma diagnostic consultation service by analysing the (dis)concordance between the general practitioners working hypotheses and the asthma diagnostic consultation service diagnoses and possible consequences this had on the patients' pharmacotherapy. In total 659 patients were included in this study. At this service the patients' medical history was taken and a physical examination and a histamine challenge test were carried out. We compared the general practitioners working hypotheses with the asthma diagnostic consultation service diagnoses and the change in medication that was incurred. In 52% (n = 340) an asthma diagnosis was excluded. The diagnosis was confirmed in 42% (n = 275). Furthermore, chronic rhinitis was diagnosed in 40% (n = 261) of the patients whereas this was noted in 25% (n = 163) by their general practitioner. The adjusted diagnosis resulted in a change of medication for more than half of all patients. In 10% (n = 63) medication was started because of a new asthma diagnosis. The 'one-stop-shop' principle was met with 53% of patients and 91% (n = 599) were referred back to their general practitioner, mostly within 6 months. Only 6% (n = 41) remained under control of the asthma diagnostic consultation service because of severe unstable asthma. In conclusion, the asthma diagnostic consultation service helped general practitioners significantly in setting accurate diagnoses for their patients with an asthma hypothesis. This may contribute to diminish the problem of over and underdiagnosis and may result in more appropriate treatment regimens. ASTHMA: SERVICE HELPS GENERAL PRACTITIONERS MAKE ACCURATE DIAGNOSES: A consultation service can help general practitioners more accurately diagnose asthma and select the appropriate treatments for their patients. Researchers in The Netherlands, led by Frank Smeenk from Catharina Hospital in Eindhoven, describe an asthma diagnostic consultation service they created to support GPs in their diagnostic process for patients suspected of having asthma. Over a four-year period, the service received a total of 659 referrals and only confirmed the diagnosis of asthma in 275 cases. Another 20 patients had asthma overlapping with chronic obstructive pulmonary syndrome. The service also picked up other diseases, such as rhinitis, that general practitioners had missed. Overall, because of the consultation service and its revised diagnoses, more than half of all patients adjusted their medications. Most patients required only a single consultation and could then be referred back to their physicians.

Association between exhaled inflammatory markers and asthma control in children.

The relationship between exhaled inflammatory markers and asthma control in children is unclear. To explore the association between inflammatory markers in exhaled breath (fractional nitric oxide (FeNO), volatile organic compounds (VOCs), cytokines/chemokines) and asthma control. To assess whether exhaled inflammatory markers are able to discriminate between children with persistently controlled/uncontrolled asthma. 96 asthmatic children were followed-up in a one-year observational study. Every 2 months, the following parameters were assessed: asthma control, FeNO, lung function (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), exhaled VOCs, and cytokines/chemokines in exhaled breath condensate (EBC). Random Forest was used to analyse the relationship between exhaled inflammatory markers and asthma control. For each model, patients were randomly selected for a training set and validation set. To assess the accuracy of the classification models, receiver operating characteristic-curves (ROC-curves) were generated. No significant association was found between the exhaled inflammatory markers (FeNO, markers in EBC, VOCs) and asthma control (area under the ROC-curve 49%). However, 15 exhaled VOCs could discriminate between subgroups of children with persistently controlled and uncontrolled asthma during all clinical visits (area under the ROC-curve 86%). Adding FeNO and markers in EBC to this model, did not lead to a more accurate classification (area under the ROC-curve 87%). There was no association between exhaled inflammatory markers and asthma control in children. However, children with persistently controlled or uncontrolled asthma during the 12 month study period could be discriminated by a set of VOCs.

Clinical items not helpful in differentiating viral from bacterial lower respiratory tract infections in general practice.

OBJECTIVE: Incorrect and unnecessary antibiotic prescribing enhancing bacterial resistance rates might be reduced if viral and bacterial lower respiratory tract infections (LRTI) could be differentiated clinically. Whether this is possible is often doubted but has rarely been studied in general practice. STUDY DESIGN AND SETTING: This was an observational cohort study in 15 general practice surgeries in the Netherlands. RESULTS: Etiologic diagnoses were obtained in 112 of 234 patients with complete data (48%). Viral pathogens were found as often as bacterial pathogens. Haemophilus (para-) influenzae was most frequently found. None of the symptoms and signs correlated statistically significantly with viral or bacterial LRTI. Erythrocyte sedimentation rate >50 (odds ratio [OR] 2.3-3.3) and C-reactive protein (CRP) >20 (OR 2.1-4.6) were independent predictors for viral LRTI and bacterial LRTI when compared with microbiologically unexplained LRTI. CONCLUSION: Extensive history-taking and physical examination did not provide items that predict viral or bacterial LRTI in adult patients in daily general practice. We could not confirm CRP to differentiate between viral and bacterial LRTI.

Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal diffuse large B-cell lymphomas.

Clinical outcome in diffuse large B-cell lymphoma (DLBCL) remains unpredictable, despite the identification of clinical prognostic parameters. Here, we investigated in pretreatment biopsies of 70 patients with DLBCL whether numbers of activated cytotoxic T-lymphocytes (CTLs), as determined by the percentage of CD3-positive lymphocytes with granzyme B (GrB) expression, have similar prognostic value as found earlier in Hodgkin's lymphoma and anaplastic large-cell lymphoma and whether loss of major histocompatibility complex (MHC)-I molecules or expression of the GrB antagonist protease inhibitor 9 (PI9) may explain immune escape from CTL-mediated cell death. Independent of the International Prognostic Index (IPI), the presence of >/=15% activated CTLs was strongly associated with failure to reach complete remission, with a poor progression-free and overall survival time. Downregulation of MHC-I light- and/or heavy-chain expression was found in 41% of interpretable cases and in 19 of 56 interpretable cases PI9 expression was detected. We conclude that a high percentage of activated CTLs is a strong, IPI independent, indicator for an unfavorable clinical outcome in patients with primary nodal DLBCL. Although in part of DLBCL expression of PI9 and loss of MHC-I expression was found, providing a possible immune-escape mechanism in these cases, no correlation with clinical outcome was found.

Bulking agents, antispasmodic and antidepressant medication for the treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common health problem, often presenting in primary care as well as in internal medicine and gastroenterology outpatient clinics. Therapeutic options are dominated by drug therapies but there is uncertainty about their effectiveness. OBJECTIVES: The primary objective of this review was to evaluate the efficacy of bulking agents, antispasmodic and antidepressant medication for the treatment of IBS. SEARCH STRATEGY: A computer assisted search of MEDLINE, EMBASE, PsychInfo and the Cochrane Library was performed for the years 1966-2001; local and national databases were searched in 10 European countries. SELECTION CRITERIA: Randomised trials comparing bulking agents, antispasmodic or antidepressant medications with a placebo, in IBS patients over 12 years of age. Only studies published as a full paper were included. No language criterion was applied. DATA COLLECTION AND ANALYSIS: The search identified 687 studies, 66 of which fulfilled all eligibility criteria. After removal of cross-over studies that did not report separately on the first phase, data from 40 studies remained for analysis. Relative risk (RR), risk difference (RD) and standardized mean difference (SMD) along with 95% confidence intervals were calculated for all subgroups. The number needed to treat (NNT) was also calculated where appropriate. MAIN RESULTS: Forty-one study reports from 40 studies, comprising 78 comparisons, were analysed. These included 11 reports on bulking agents, 6 on antidepressants, and 24 on spasmolytics.BULKING AGENTS: Three studies comprising 159 patients reported a dichotomous outcome for relief of abdominal pain. The pooled RR using a random effects model was 1.22 (95% CI 0.86 - 1.73). Three studies comprising 128 patients reported a continuous outcome for relief of abdominal pain. Using the random effects model, the SMD was 0.68 (95% CI -0.86 - 2.33). Nine studies comprising 482 patients reported a dichotomous outcome for global assessment of improvement. The pooled RR was 1.09 (95% CI 0.78 - 1.50). Five studies comprising 253 patients reported a dichotomous outcome for improvement of symptom score. The pooled RR using a random effects model was 0.93 (95% CI 0.56 - 1.54). Two studies comprising 70 patients reported a continuous outcome for improvement of symptom score; the SMD using a fixed effects model was -0.44 (95% CI -1.20 - 0.31). SPASMOLYTIC AGENTS: Eleven studies comprising 1260 patients reported a dichotomous outcome for relief of abdominal pain. The pooled RR using a random effects model was 1.34 (95% CI 1.13 - 1.59; RD=0.17, 95% CI 0.06 -0.28; NNT=6, 95% CI 4 - 15). Seven studies comprising 467 patients reported a continuous outcome for relief of abdominal pain. Using a fixed effects model the pooled SMD was -0.65 (95% CI -0.94 to -0.35). Sixteen studies comprising 1236 patients reported a dichotomous outcome for global assessment of improvement. The pooled RR using a random effects model was 1.42 (95% CI 1.17 - 1.72; RD=0.20, 95% CI 0.09 -0.30; NNT=5, 95% CI 3 - 11). One study comprising 34 patients reported a dichotomous variable for improvement of symptom score. The RR was 1.33 (95% CI 0.96 - 1.85). Three studies reported a continuous outcome for improvement of symptom score; two studies comprising 66 patients could be pooled. Using a fixed effects model, the SMD was -0.37 (95% CI -0.85 - 0.12). ANTIDEPRESSANTS: Two studies comprising 81 patients reported a dichotomous outcome for relief of abdominal pain. Using the random effects model, the pooled RR was 0.83 (95% CI 0.33 - 2.12). Two studies comprising 101 patients reported a continuous outcome for relief of abdominal pain. The SMD using a random effects model was -0.53 (95% CI -2.29 - 1.23). Four studies comprising 241 patients reported a dichotomous variable for global assessment of improvement. The pooled RR was 1.16 (95% CI 0.78 - 1.73). AUTHORS' CONCLUSIONS: The evidence for efficacy of drug therapies for IBS is weak. Although there is evidence of benefit for antispasmodic drugs for abdominal pain and global assessment of symptoms; it is unclear whether anti-spasmodic subgroups are individually effective. There is no clear evidence of benefit for antidepressants or bulking agents. The physician should be aware that global assessment is a construct containing various dimensions. For each individual, these will have a different weighting and treatment should be aimed at the most debilitating symptom. Stool problems are by definition part of the IBS symptom complex. Bulking agents may improve constipation and can be used empirically, but should be evaluated at an early stage for individual benefit. Future research should pay attention to study methodology and the use of valid outcome measures.