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OBJECTIVE: In the Netherlands, out-of-hours General Practice Cooperatives (GPCs) increasingly collaborate with Emergency Departments (EDs) to form an Emergency Care Access Point (ECAP). ECAPs aim to decrease the number of low-urgent ED attendances, of which many compromise minor traumatic injuries. In this study, we evaluated the impact of ECAP implementation on the incidence of minor traumatic injuries in the ED.METHODS: We evaluated a total of 2772 ED patients who presented with a minor traumatic injury (categorized into traumatic wounds and isolated extremity injuries) 1 year before and 1 year after ECAP implementation. We compared patient characteristics, throughput, diagnosis, treatment and follow-up before and after ECAP implementation.RESULTS: ECAP implementation was associated with a reduction in ED volume for minor traumatic injuries: -12.4% for isolated extremity injuries (1249 vs. 1094) and -74.6% for traumatic wounds (342 vs. 87). Multivariable logistic regression analysis controlling for patient characteristics showed that ECAP implementation was associated with higher rates of substantial injuries in the ED (OR 1.20, 95% CI = 1.01-1.43), and more patients requiring outpatient follow-up.CONCLUSION: Implementation of an ECAP was associated with a reduction of ED utilization by patients with minor traumatic injuries, traumatic wounds in particular. This healthcare intervention may therefore help to reduce ED utilization for low-urgent complaints.

Background Redundant use of diagnostic tests in primary care has shown to be a contributor to rising Dutch healthcare costs. A price display in the test ordering system of the electronic health records (EHRs) could potentially be a low-cost and easy to implement intervention to a decrease in test ordering rate in the primary care setting by creating more cost-awareness among general practitioners (GPs). The aim of this study was to assess the effect of a price display for diagnostic laboratory tests in the EHR on laboratory test ordering behavior of GPs in the Westelijke Mijnstreek region in the Netherlands. Methods A pre-post intervention study among 154 GPs working in 57 general practices was conducted from September 2019, until March 2020, in the Netherlands. The intervention consisted of displaying the costs of 22 laboratory tests at the time of ordering. The primary outcome was the mean test ordering rate per 1.000 patients per month, per general practice. Results Test ordering rates were on average rising prior to the intervention. The total mean monthly test order volume showed a non-statistically significant interruption in this rising trend after the intervention, with the mean monthly test ordering rate levelling out from 322.4 to 322.2 (P = 0.86). A subgroup analysis for solely individually priced tests showed a statistically significant decrease in mean monthly test ordering rate after implementation of the price display for the sum of all tests from 67.2 to 63.3 (P = 0.01), as well as for some of these tests individually (i.e. thrombocytes, ALAT, TSH, folic acid). Leucocytes, ESR, vitamin B12, anti-CCP and NT-proBNP also showed a decrease, albeit not statistically significant (P > 0.05). Conclusions Our study suggests that a price display intervention is a simple tool that can alter physicians order behavior and constrain the expanding use of laboratory tests. Future research might consider alternative study designs and a longer follow-up period. Furthermore, in future studies, the combination with a multitude of interventions, like educational programs and feedback strategies, should be studied, while potentially adverse events caused by reduced testing should also be taken into consideration.

Background For emergency department (ED) patients with suspected infection, a vital sign-based clinical rule is often calculated shortly after the patient arrives. The clinical rule score (normal or abnormal) provides information about diagnosis and/or prognosis. Since vital signs vary over time, the clinical rule scores can change as well. In this prospective multicentre study, we investigate how often the scores of four frequently used clinical rules change during the ED stay of patients with suspected infection. Methods Adult (≥ 18 years) patients with suspected infection were prospectively included in three Dutch EDs between March 2016 and December 2019. Vital signs were measured in 30-min intervals and the quick Sequential Organ Failure Assessment (qSOFA) score, the Systemic Inflammatory Response Syndrome (SIRS) criteria, the Modified Early Warning Score and the National Early Warning Score (NEWS) score were calculated. Using the established cut-off points, we analysed how often alterations in clinical rule scores occurred (i.e. switched from normal to abnormal or vice versa). In addition, we investigated which vital signs caused most alterations. Results We included 1433 patients, of whom a clinical rule score changed once or more in 637 (44.5%) patients. In 6.7–17.5% (depending on the clinical rule) of patients with an initial negative clinical rule score, a positive score occurred later during ED stay. In over half (54.3–65.0%) of patients with an initial positive clinical rule score, the score became negative later on. The respiratory rate caused most (51.2%) alterations. Conclusion After ED arrival, alterations in qSOFA, SIRS, MEWS and/or NEWS score are present in almost half of patients with suspected infection. The most contributing vital sign to these alterations was the respiratory rate. One in 6–15 patients displayed an abnormal clinical rule score after a normal initial score. Clinicians should be aware of the frequency of these alterations in clinical rule scores, as clinical rules are widely used for diagnosis and/or prognosis and the optimal moment of assessing them is unknown.

Inleiding Het grote aantal consulten voor kinderen met koorts zorgt op huisartsenposten voor een hoge werkdruk. Wij gingen na hoe vaak koorts en infectieklachten voorkomen bij kinderen op kinderdagverblijven en hoeveel kinderen daarvoor uiteindelijk een huisarts consulteren. Methode Ouders van 1109 kinderen op kinderdagverblijven in Zuid-Limburg is in februari/maart 2016 gevraagd een vragenlijst in te vullen over een periode van vier weken. In de vragenlijst vroegen we naar het aantal keren dat het kind koorts of andere infectieklachten had, of het hiervoor naar de (huis)arts was geweest, of het kind door ziekte afwezig was geweest van het kinderdagverblijf en of de ouders vrij hadden moeten nemen van hun werk. Resultaten Er kwamen 515 vragenlijsten ingevuld retour (49%). Bijna alle kinderen hadden gedurende de vier onderzochte weken minstens een infectieklacht gehad; slechts 2,5% was klachtenvrij gebleven. Van alle kinderen met klachten was 73,2% niet naar een huisarts of huisartsenpost gegaan. Bijna een derde (32,6%) van de kinderen had minstens een dag verzuimd (320 dagen ziekteverzuim). Iets meer dan een kwart van de ouders (146, 28,3%) had vrij moeten nemen van het werk (mediaan twee dagen) en 82 ouders (15,9%) hadden een vervangende oppas moeten regelen (mediaan een dag). Conclusie De ziektelast van koorts en infecties op kinderdagverblijven is hoog, maar desondanks komt driekwart van de zieke kinderen helemaal niet bij de huisarts.

BackgroundGPs decide which patients with fever need referral to the emergency department (ED). Vital signs, clinical rules, and gut feeling can influence this critical management decision.AimTo investigate which vital signs are measured by GPs, and whether referral is associated with vital signs, clinical rules, or gut feeling.Design & settingProspective observational study at two out-of-hours (OOH) GP cooperatives in the Netherlands.MethodDuring two 9-day periods, GPs performed their regular work-up in patients aged ≥18 years with fever (≥38.0°C). Subsequently, researchers measured missing vital signs for completion of the systemic inflammatory response syndrome (SIRS) criteria and the quick Sequential Organ Failure Assessment (qSOFA) score. Associations between the number of referrals, positive SIRS and qSOFA scores, and GPs’ gut feelings were investigated.ResultsGPs measured and recorded all vital signs required for SIRS criteria and qSOFA score calculations in 24 of 108 (22.2%) assessed patients, and referred 45 (41.7%) to the ED. Higher respiratory rates, temperatures, clinical rules, and gut feeling were associated with referral. During 7-day follow-up, nine (14.3%) of 63 patients who were initially not referred were admitted to hospital.ConclusionGPs measured and recorded all vital signs for SIRS criteria and qSOFA score in one-in-five patients with fever, and referred half of 63 patients who were SIRS-positive and almost all of 22 patients who were qSOFA-positive. Some vital signs and gut feeling were associated with referral, but none were consistently present in all patients who were referred. The vast majority of patients who were not initially referred remained at home during follow-up.

ObjectivesUrinary tract infections (UTIs) are the most prevalent cause for women to consult a general practitioner (GP) and are commonly treated with (broad-spectrum) empirical antibiotics, even though 50% of UTIs are self-limiting. In this study, we aim to explore women’s attitudes and experiences regarding UTIs, in order to determine patients’ willingness to accept delayed antibiotic prescriptions.DesignAn internet-based cross-sectional surveySettingWe recruited participants during 2 weeks of March and April in 2020 through several social media platforms.ParticipantsWe obtained 1476 responses, of which 975 were eligible for analysis.ResultsWe asked women about their knowledge, attitudes and practice regarding UTI-related symptoms. Participants ranked ‘confirmation of diagnosis’ (43.8%) as the most important reason to consult a GP with urinary symptoms, followed by ‘pain relief’ (32%), and ‘antibiotic prescription’ (14.3%). For treatment, 71% of participants reported that their GP prescribed immediate antibiotics, while only 3% received a delayed antibiotic prescription and 1% was advised pain medication. Furthermore, 50% of respondents were aware of the possible self-limiting course of UTIs and 70% would be willing to accept delayed antibiotic treatment, even if a certain diagnosis of UTI was established. Willingness to delay was lower in experienced patients compared to inexperienced patients.ConclusionsWomen are quite receptive to delayed antibiotics as an alternative to immediate antibiotics for UTIs or urinary symptoms. GPs should consider discussing delayed antibiotic treatment more often with women presenting with urinary symptoms.

BACKGROUND: In some countries, such as the Netherlands and Norway, point-of-care testing (POCT) is more widely implemented in general practice compared to countries such as England and Australia. To comprehend what is necessary to realize the benefits of POCT, regarding its integration in primary care, it would be beneficial to have an overview of the structure of healthcare operations and the transactions between stakeholders (also referred to as value networks). The aim of this paper is to identify the current value networks in place applying to POCT implementation at general practices in England, Australia, Norway and the Netherlands and to compare these networks in terms of seven previously published factors that support the successful implementation, sustainability and scale-up of innovations. \ud \ud METHODS: The value networks were described based on formal guidelines and standards published by the respective governments, organizational bodies and affiliates. The value network of each country was validated by at least two relevant stakeholders from the respective country. \ud \ud RESULTS: The analysis revealed that the biggest challenge for countries with low POCT uptake was the lack of effective communication between the several organizations involved with POCT as well as the high workload for general practitioners (GPs) aiming to implement POCT. It is observed that countries with a single national authority responsible for POCT have a better uptake as they can govern the task of POCT roll-out and management and reduce the workload for GPs by assisting with set-up, quality control, training and support. \ud \ud CONCLUSION: Setting up a single national authority may be an effective step towards realizing the full benefits of POCT. Although it is possible for day-to-day operations to fall under the responsibility of the GP, this is only feasible if support and guidance are readily available to ensure that the workload associated with POCT is limited and as low as possible.

Background Urinary tract infections (UTIs) are one of the most common infections in primary care. Previous research showed that GPs find it challenging to diagnose UTIs and frequently divert from guidelines leading to unwarranted antibiotic prescriptions and inefficient use of diagnostics such as urinary cultures. We hypothesise that management of UTIs during out-of-hours care may be extra challenging due to a higher workload and logistical issues regarding diagnostic work-up and obtaining results. We therefore aimed to study the workload, diagnostic work-up and treatment of UTIs during out-of-hours primary care. Methods We performed a retrospective observational cohort study in which we analysed a full year (2018) of electronic patient records of two large Dutch GP out-of-hours centres. All adult patients with UTI symptoms were included in this study. Descriptive statistics and multivariate regression were used to analyse diagnostics and subsequent management. Results A total of 5657 patients were included (78.9% female, mean age of 54 years), with an average of eight patients per day that contact a GP out-of-hours centre because of UTI symptoms. Urinary dipsticks were used in 87.5% of all patients visiting the out-of-hours centres with UTI symptoms. Strikingly, urinary cultures were only requested in 10.3% of patients in which urinary culture was indicated. Seventy-four percent of the patients received antibiotics. Seventy-nine percent of the patients with a negative nitrite test still received antibiotics. Remarkably, patients at risk of complications because of a UTI, such as men, received fewer antibiotic prescriptions. Conclusions In total, 74% of the patients received antibiotics. 8 out of 10 patients still received an antibiotic prescription in case of a negative nitrite test, and 9 out of 10 patients with an indication did not receive a urine culture. In conclusion, we found that correctly diagnosing UTIs and prescribing antibiotics for UTIs is a challenge that needs major improvement, especially during out-of-hours GP care.

Inleiding Point-of-care-tests (POCT’s) kunnen huisartsen ondersteunen bij het diagnosticeren en behandelen van patienten met acute cardiopulmonale symptomen. Momenteel is echter nog niet bekend of het gebruik van POCT’s ook echt effect heeft op klinische uitkomsten bij deze patienten. De auteurs gingen na of het gebruik van POCT’s door de huisarts bij patienten met acute cardiopulmonale symptomen leidt tot nauwkeuriger diagnoses en of dit het klinisch handelen beinvloedt. Methoden De auteurs voerden een systematisch literatuuronderzoek uit in vier bibliografische gegevensbestanden. Twee reviewers screenden artikelen die voor februari 2016 zijn gepubliceerd. Zij includeerden alleen onderzoeken die gaan over het effect van POCT-gebruik door de huisarts op de klinisch diagnostische waarde en op de behandeling en verwijzing van patienten met cardiopulmonale symptomen. Resultaten De auteurs vonden negen geschikte artikelen die gegevens beschrijven van zeven onderzoeken naar de klinisch diagnostische waarde van POCT-gebruik bij 2277 eerstelijnspatienten met acute cardiopulmonale symptomen. Vier artikelen bevatten gegevens over het gebruik van D-dimeer-POCT door huisartsen bij longembolie (gegevens van twee onderzoeken); twee onderzoeken over troponine T en een over heart-type fatty acid-binding protein (H-FABP) bij acuut coronair syndroom; een over B-type natriuretic peptide (BNP) bij hartfalen; een over een 3-in-1-POCT (troponine T, BNP, D-dimeer) bij acuut coronair syndroom, hartfalen en/of longembolie. Slechts een onderzoek was gericht op het effect van POCT-gebruik door huisartsen op de tijdsduur tot de behandeling en een had betrekking op de verwijspercentages. Conclusie Er is momenteel beperkt bewijs dat gebruik van POCT’s door huisartsen bij patienten met acute cardiopulmonale symptomen leidt tot nauwkeuriger diagnoses en het klinisch handelen beinvloedt. Enkele onderzoeken hebben veelbelovende resultaten opgeleverd, voornamelijk wanneer artsen een POCT (D-dimeren) combineren met een klinische beslisregel.

PURPOSE Fever is the most common reason for a child to be taken to a physician, yet the level of unwarranted antibiotic prescribing remains high. We aimed to determine the effect on antibiotic prescribing of providing an illness-focused interactive booklet on fever in children to out-of-hours primary care clinicians.\ud \ud METHODS We conducted a cluster-randomized controlled trial in 20 out-of-hours general practice centers in the Netherlands. Children aged younger than 12 years with fever were included. Family physicians at the 10 intervention sites had access to an illness-focused interactive booklet between November 2015 and June 2016. The primary outcome was antibiotic prescribing during the index consultation. Analysis was performed by fitting 2-level random intercept logistic regression models.\ud \ud RESULTS The trial took place among 3,518 family physicians and 25,355 children. The booklet was used in 28.5% of 11,945 consultations in the intervention group. Compared with usual care, access to the booklet did not significantly alter antibiotic prescribing during the index consultation (odds ratio = 0.90; 95% CI, 0.79-1.02; prescription rate, 23.5% vs 25.2%; intracluster correlation coefficient = 0.005). In contrast, use of the booklet significantly reduced antibiotic prescribing (odds ratio = 0.83; 95% CI, 0.74-0.94; prescription rate, 21.9% vs 25.2%; intracluster correlation coefficient = 0.002). Children managed by family physicians with access to the booklet were less likely to receive any drug prescription, and parents in the booklet group showed a reduced intention to consult again for similar illnesses.\ud \ud CONCLUSIONS Benefit of an illness-focused interactive booklet in improving outcomes of childhood fever in out-of-hours primary care was largely restricted to the cases in which family physicians actually used the booklet. Insight into reasons for use and nonuse may inform future interventions of this type.

PURPOSE Both chronic hepatitis C (HCV) and B virus (HBV) infections are generally asymptomatic, and many remain undetected or are diagnosed at a late stage. Studies that evaluate best practice hepatitis testing strategies are needed to better detect this hidden population. METHODS In this prospective cohort study, we aimed to determine the diagnostic yield (test uptake and rate of positive test results) of a combined public health and primary care birth cohort testing strategy in detecting hidden cases of HCV and HBV infections. We invited all patients aged between 40 and 70 years (n = 6,743) registered with 11 family practices serving 2 higher prevalence areas, or hotspots (ie, estimated HCV prevalence of 1%; national estimated prevalence is 0.1–0.4%), in the south of the Netherlands. RESULTS Test uptake was 50.9% (n = 3,434 patients). No active or chronic HCV infection was detected: 0.00% (95% CI, 0.00%–0.11%). Positive test rates were 0.20% (95% CI, 0.08%–0.42%) for anti-HCV (n = 7), 0.26% (95% CI, 0.12%–0.50%) for hepatitis B surface antigen (n = 9), and 4.14% (95% CI, 3.49%–4.86%) for antihepatitis B core (n = 142). CONCLUSIONS This best practice testing strategy was effective in achieving a high test uptake. It completely failed, however, to detect hidden chronic HCV infections and is not recommended for countries with a low prevalence of the disease.

Background: Pertussis testing is most important when transmission to vulnerable groups is likely. Patients with signs and symptoms suggestive of pertussis are prevalent in primary care, yet general practitioners’ (GPs) reasons (not) to test for pertussis are largely unknown. Objectives: To evaluate GP-reported diagnostic practices for pertussis, reasons for (not) testing and intentions towards testing among GPs. Methods: A total of 594 Dutch GPs were invited by email to participate in a survey study including a questionnaire reflecting on their pertussis diagnostic practices, reasons for (not) testing and the intention to test for pertussis in the year of 2013. Intention to test was measured as the likelihood to test for eight clinical vignettes. Results: In total, 122 GPs (21%) completed the online questionnaire. Most GPs reported having diagnosed at least one pertussis case (84%) in the previous year. Of all GPs, 14% did not perform any pertussis tests in the last year. The most reported reason for testing was to confirm the clinical pertussis diagnosis (70%); the most reported reason for not testing was that the diagnostic test result does not influence treatment (70%). Overall, judging from the clinical vignettes, GPs reported being more likely to perform diagnostic testing based on symptoms than based on vulnerable groups at risk. Conclusion: In contrast to national guidelines, our results suggest that GPs report to test for pertussis mainly based on clinical symptoms rather than based on protecting vulnerable groups at risk.

PURPOSE - C-reactive-protein (CRP) is useful for diagnosis of lower respiratory tract infections (RTIs). A large international trial documented that Internet-based training in CRP point-of-care testing, in enhanced communication skills, or both reduced antibiotic prescribing at 3 months, with risk ratios (RRs) of 0.68, 0.53, 0.38, respectively. We report the longer-term impact in this trial. METHODS - A total of 246 general practices in 6 countries were cluster-randomized to usual care, Internet-based training on CRP point-of-care testing, Internet-based training on enhanced communication skills and interactive booklet, or both interventions combined. The main outcome was antibiotic prescribing for RTIs after 12 months. RESULTS - Of 228 practices providing 3-month data, 74% provided 12-month data, with no demonstrable attrition bias. Between 3 months and 12 months, prescribing for RTIs decreased with usual care (from 58% to 51%), but increased with CRP training (from 35% to 43%) and with both interventions combined (from 32% to 45%); at 12 months, the adjusted RRs compared with usual care were 0.75 (95% CI, 0.51-1.00) and 0.70 (95% CI, 0.49-0.93), respectively. Between 3 months and 12 months, the reduction in prescribing with communication training was maintained (41% and 40%, with an RR at 12 months of 0.70 [95% CI, 0.49-0.94]). Although materials were provided for free, clinicians seldom used booklets and rarely used CRP point-of-care testing. Communication training, but not CRP training, remained efficacious for reducing prescribing for lower RTIs (RR = 0.7195% CI, 0.45-0.99, and RR = 0.76; 95% CI, 0.47-1.06, respectively), whereas both remained efficacious for reducing prescribing for upper RTIs (RR = 0.60; 95% CI, 0.37-0.94, and RR = 0.58; 95% CI, 0.36-0.92, respectively). CONCLUSIONS - Internet-based training in enhanced communication skills remains effective in the longer term for reducing antibiotic prescribing. The early improvement seen with CRP training wanes, and this training becomes ineffective for lower RTIs, the only current indication for using CRP testing.

Background While fever is mostly self-limiting, antibiotic prescription rates for febrile children are high. Although every parent who receives a prescription visits a pharmacy, we have limited insight into pharmacy employees' experiences with these parents. Pharmacy employees do however exert an important role in ensuring children receive correct dosages and in advising parents on administration of antibiotics. Objective To describe pharmacists' and pharmacy assistants' experiences with parents contacting a pharmacy for their febrile child, and to identify ways of improving medication management of these children. Setting Community pharmacies in the Netherlands. Method A qualitative study including 24 Dutch pharmacy employees was conducted, performing four focus group discussions among pharmacy employees. Analysis was based on constant comparative technique using open and axial coding. Main outcome measure Pharmacy employees' experiences with parents contacting a pharmacy for their febrile child. Results Three categories were identified: (1) workload and general experience, (2) inconsistent information on antibiotic prescriptions, (3) improving communication and collaboration. Pharmacy employees experienced that dosing errors in antibiotic prescriptions occur frequently and doctors provide inconsistent information on prescriptions. Consequently, they have to contact doctors, resulting in a higher workload for both stakeholders. They believe this can be improved by providing the indication for antibiotics on prescriptions, especially when deviating from standard dosages. Conclusion Pharmacy employees experience a high amount of dosing errors in paediatric antibiotic prescriptions. Providing the indication for antibiotics in febrile children on prescriptions, especially when deviating from standard dosages, can potentially reduce dosage errors and miscommunication between doctors and pharmacy employees.

BackgroundFever is common in preschool children and is often caused by benign self-limiting infections. Parents' lack of knowledge and fever phobia leads to high healthcare consumption.ObjectiveTo systematically review the effect of providing educational interventions about childhood fever and common infections in well-child clinics (WCCs), prior to illness episodes, on parental practices: healthcare-seeking behaviour (frequency of physician consultations, appropriateness of consultations) and medication management.DesignMedline, Embase, CINAHL, PsycINFO, Cochrane Library, Web of Science were searched. We included randomised controlled trials evaluating interventions in WCC settings focusing on educating parents prior to new illness episodes to improve parental practices during episodes of childhood fever and common infections. Data were extracted on study design, sample characteristics, type of intervention, outcome measures and results.ResultsEight studies were eligible for data extraction. Educating parents, in WCCs, prior to new episodes of childhood fever and common infections reduces daytime physician consultations of parents, home visits and telephone consultations, and enhances medication management. However, single and multicomponent interventions vary in effectiveness in reducing the frequency of daytime physician consultations and differ in their potential to reduce the number of home visits and general practitioner out-of-hours contacts. Only multicomponent interventions achieved a reduction in telephone consultations and improved medication management.ConclusionsEducating parents in WCCs prior to episodes of childhood fever and common infections showed potential to improve parental practices in terms of healthcare-seeking behaviour and medication management.

Summary Background In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events. Methods PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901. Findings 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3–8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93–1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group. Interpretation The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months. Funding The French National Cancer Institute.

Background: C-reactive protein point of care tests (CRP-POCTs) for reducing unnecessary antibiotic use without harming patients with acute exacerbations of COPD (AECOPD) in primary care have not been evaluated in randomized trials. Methods: Patients consulting at 86 general practices in England and Wales with AECOPD were randomized to undergo CRP-POCT guided management or usual management without a CRP-POCT. The co-primary outcomes were patient-reported antibiotic consumption for AECOPD within four weeks (superiority), and COPD health status measured by the Clinical COPD Questionnaire (CCQ) at two weeks (non-inferiority). Results: 653 participants were randomized. Antibiotics were consumed by 57.0% CRP-POCT and 77.4% usual care participants (adjusted odds ratio = 0.31, 95% CI: 0.20 to 0.47). Adjusted mean CCQ score difference at two-weeks was -0.19 points lower (better) for CRP-POCT participants (two-sided 90% CI: -0.33 to -0.05). CRP-POCT participants were prescribed 22% fewer antibiotics at initial consultation (47.7% vs 69.7%, AOR = 0.31, 95% CI: 0.21 to 0.45), and 21% fewer antibiotics over four-week follow-up (59.1% vs 79.7%, AOR = 0.30, 95% CI: 0.20 to 0.46). There were no meaningful between-group differences in secondary clinical, microbiological, condition specific quality of life, or service utilization outcomes. Conclusions: Primary care physician use of CRP-POCT guided management of AECOPD in primary care achieves meaningful reductions in patient reported antibiotic consumption and clinician antibiotic prescribing without a detrimental effect on patient-reported specific health status.

Identifying a child with pneumonia in the large group of children with acute respiratory tract infections can be challenging for primary care physicians. Knowledge on the diagnostic value of specific signs and symptoms may guide future decision rules and guidelines for clinicians. We aimed to identify and systematically review available evidence for the diagnostic value of signs, symptoms, and additional tests to diagnose pneumonia in children in an ambulatory setting in developed countries. We conducted a systematic review, searching in the electronic databases of PubMed and Embase. Quality assessment of studies was done using the QUADAS-2 criteria. After data extraction from selected studies, we calculated and summarized test characteristics (sensitivity, specificity, negative and positive predictive values) of all available signs, symptoms, additional laboratory tests, and chest ultrasonography. The original search yielded 4665 records, of which 17 articles were eligible for analysis: 12 studies on signs and symptoms, 4 on additional laboratory tests, and 6 on ultrasonography. All included studies were performed in a secondary care setting. Risk of bias was present in the majority of studies in the domain of patient selection. Prevalence of pneumonia varied from 3.4% to 71.7%. The diagnostic value of the available 27 individual signs and symptoms to identify pneumonia was low. In a low prevalence setting, (4 studies, pneumonia prevalence 10%), additional diagnostic tests such as oxygen saturation, C-reactive protein, and white blood cell count are more promising. Chest ultrasonography showed high diagnostic value in settings with higher prevalence of pneumonia. Single signs and symptoms from medical history and physical examination or individual additional diagnostic tests are insufficient to diagnose pneumonia in ambulant children. Very few diagnostic studies are conducted in settings with low prevalence of pneumonia. Future research in low prevalence settings should focus on the diagnostic value of the combination of clinical features and additional testing possibly using meta-analysis of individual data.

Contains fulltext : 165739.pdf (Publisher’s version ) (Open Access) BACKGROUND: Inappropriate antibiotic use for acute respiratory tract infections is common in primary health care, but distinguishing serious from self-limiting infections is difficult, particularly in low-resource settings. We assessed whether C-reactive protein point-of-care testing can safely reduce antibiotic use in patients with non-severe acute respiratory tract infections in Vietnam. METHOD: We did a multicentre open-label randomised controlled trial in ten primary health-care centres in northern Vietnam. Patients aged 1-65 years with at least one focal and one systemic symptom of acute respiratory tract infection were assigned 1:1 to receive either C-reactive protein point-of-care testing or routine care, following which antibiotic prescribing decisions were made. Patients with severe acute respiratory tract infection were excluded. Enrolled patients were reassessed on day 3, 4, or 5, and on day 14 a structured telephone interview was done blind to the intervention. Randomised assignments were concealed from prescribers and patients but not masked as the test result was used to assist treatment decisions. The primary outcome was antibiotic use within 14 days of follow-up. All analyses were prespecified in the protocol and the statistical analysis plan. All analyses were done on the intention-to-treat population and the analysis of the primary endpoint was repeated in the per-protocol population. This trial is registered under number NCT01918579. FINDINGS: Between March 17, 2014, and July 3, 2015, 2037 patients (1028 children and 1009 adults) were enrolled and randomised. One adult patient withdrew immediately after randomisation. 1017 patients were assigned to receive C-reactive protein point-of-care testing, and 1019 patients were assigned to receive routine care. 115 patients in the C-reactive protein point-of-care group and 72 patients in the routine care group were excluded in the intention-to-treat analysis due to missing primary endpoint. The number of patients who used antibiotics within 14 days was 581 (64%) of 902 patients in the C-reactive protein group versus 738 (78%) of 947 patients in the control group (odds ratio [OR] 0.49, 95% CI 0.40-0.61; p

Depuis plus de dix ans, les therapeutiques ciblees anti-HER2 ont permis une amelioration revolutionnaire du pronostic des cancers du sein HER2 positifs, faisant de ce traitement la colonne vertebrale de la prise en charge. Malgre le benefice, des phenomenes d’echappement apparaissent au cours du traitement et face a ce constat, de nouvelles strategies therapeutiques ont ete developpees et ont prouve leurs efficacites. Cette synthese detaille la prise en charge therapeutique du cancer du sein metastatique HER2 positif, son evolution therapeutique et les etudes cliniques en cours.

Objectives To evaluate and compare Chlamydia trachomatis (CT) diagnostic test practices of different sexually transmitted infection (STI) care providers in 16-29 year olds from one defined geographic Dutch region (280 000 inhabitants). Both number and proportion of positive CT tests (ie, test positivity) were assessed, and factors associated with these outcomes.Methods Data on laboratory testing and diagnosis of urogenital, anorectal and oropharyngeal CT between 2006 and 2010 were retrieved from general practitioners (GPs), gynaecologists, an STI clinic and a population-based chlamydia screening programme. Multivariable regression analyses explored associations between age, sex, test year, socio-economic status (SES) and STI care provider and the outcomes being the number of tests and test positivity.Results Overall, 22 831 tests were performed (1868 positive; 8.2%). Extragenital (ie, anorectal and oropharyngeal) tests accounted for 4% of all tests (7.5% positive) and were almost exclusively (99%) performed by the STI clinic. STI clinics tested most men (37.2% of all tested men), whereas GPs tested most women (29.9% of all tested women). GPs and STI clinics accounted for 73.3% (1326/1808) of urogenital CT diagnoses. In women, the number of tests increased with age, whereas test positivity decreased for all STI care providers. Lower SES was associated with higher test positivity in GP and gynaecology patients.Conclusions STI clinics performed most CT tests in men, whereas GPs performed most CT tests in women. GPs and STI clinics accounted for the majority of positives. Extragenital CT testing is rarely performed outside the STI clinic and needs to be promoted, especially in men who have sex with men.

Background Point-of-care tests (POCT) can assist general practitioners (GPs) in diagnosing and treating patients with acute cardiopulmonary symptoms, but it is currently unknown if POCT impact relevant clinical outcomes in these patients. Objective To assess whether using POCT in primary care patients with acute cardiopulmonary symptoms leads to more accurate diagnosis and impacts clinical management. Methods We performed a systematic review in four bibliographic databases. Articles published before February 2016 were screened by two reviewers. Studies evaluating the effect of GP use of POCT on clinical diagnostic accuracy and/or effect on treatment and referral rate in patients with cardiopulmonary symptoms were included. Results Our search yielded nine papers describing data from seven studies, on the clinical diagnostic accuracy of POCT in a total of 2277 primary care patients with acute cardiopulmonary symptoms. Four papers showed data on GP use of D-dimer POCT in pulmonary embolism (two studies); two studies on Troponin T in acute coronary syndrome; one on heart-type fatty acid-binding protein (H-FABP) in acute coronary syndrome; one on B-type natriuretic peptide (BNP) in heart failure; one on 3-in-1 POCT (Troponin T, BNP, D-dimer) in acute coronary syndrome, heart failure and/or pulmonary embolism. Only one study assessed the effect of GP use of POCT on treatment initiation and one on actual referral rates. Conclusion There is currently limited and inconclusive evidence that actual GP use of POCT in primary care patients with acute cardiopulmonary symptoms leads to more accurate diagnosis and affects clinical management. However, some studies show promising results, especially when a POCT is combined with a clinical decision rule.

Background Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status. Methods/design This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out. Discussion If shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD. Trial registration ISRCTN registry, ID: ISRCTN24346473. Registered on 20 August 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2144-8) contains supplementary material, which is available to authorized users.

Rationale, aims and objectives The diagnostic work-up of patients with shoulder pain in general practice is complex. General practitioners' (GPs) guidelines advise a pragmatic diagnostic work-up in which additional imaging has a limited role. However, diagnostic ultrasounds are increasingly ordered by GPs, which seems to reflect complexity in management of shoulder pain. This study aimed to explore GPs' perspectives on the diagnostic work-up of patients with shoulder pain. Method This study has a qualitative exploratory design with an inductive approach and was carried out in Dutch general practice. The study population consisted of 18 Dutch GPs who were sampled purposefully with a spread in clinical experience and ordering diagnostic ultrasound. Data were gathered by means of semi-structured interviews and analysed following principles of the constant comparative method. Results Three main categories with subcategories emerged that captured the diagnostic work-up of shoulder pain: variety in diagnostic classifications [(non-)specific diagnosis and interdisciplinary differences], establishing strategies for diagnostic work-up (use of existing tools and motives to deviate from existing tools), and strategies dealing with diagnostic uncertainties (accepting diagnostic uncertainties, diagnostic imaging tests, and interdisciplinary consultation and referral). Conclusions Despite the availability of evidence-based shoulder guidelines, GPs experience uncertainties during diagnostic work-up and apply different strategies when dealing with these uncertainties. At some point, GPs as well as patients seem to have a need for a specific diagnosis. Currently, there appears to be little agreement if, or in which phase of shoulder pain, diagnostic ultrasound is useful or indicated.

C-reactive protein (CRP) is an acute-phase protein, which was originally named for its capacity to precipitate the C-polysaccharide of Streptococcus pneumoniae . The acute-phase response comprises the non-specific physiological and biochemical response to most forms of tissue damage, infection and inflammation. It is now a widely used and acknowledged marker to diagnose and monitor infections, especially in secondary care. But it is now also being used increasingly by primary care physicians to identify patients who are unlikely to benefit from an antibiotic. Thus, CRP is potentially a useful tool to enhance antibiotic stewardship. In the current (March) issue of the BJGP , Lemiengre and colleagues performed a cluster-randomised trial in 2227 children with a non-severe acute infection.1 They were randomised to a brief intervention that elicited and attempted to address parent concerns, GP use of a CRP test, both, or usual care. The brief intervention paradoxically increased antibiotic prescribing, while GP use of CRP alone or GP use of CRP plus the brief intervention had no significant effect on prescribing. Hence, this large study performed in general practice indicates that GP use of CRP in children with non-severe acute infections cannot be supported. This is in line with another interesting paper from this group, which suggests that there may be a role for CRP to guide referral in children with infections, but only in those children at risk of serious infections based on a clinical decision rule.2 In this editorial we look at the role of CRP in guiding antibiotic prescribing decisions. Specifically, we identify the patient populations where we currently have evidence that CRP use by GPs improves prescribing decisions, and will discuss whether adding CRP to decision rules can further improve these antibiotic …

Wat moet je als huisarts met twee tegenstrijdige nieuwsberichten op deze website over CRP-bepalingen bij COPD-exacerbaties? Hoe interpreteer je de koppen bij deze nieuwsberichten, geschreven om huisartsen kort en krachtig bij te praten over hun vakgebied? Is de plaats van CRP nu beperkt of toch zinvol om gerichter antibiotica te kunnen voorschrijven?

ObjectivesTo investigate how many general practitioner (GP)-referred venous thromboembolic events (VTEs) are diagnosed during 1 year in one geographical region and to investigate the (urgent) referral pathway of VTE diagnoses, including the role of laboratory D-dimer testing.DesignHistorical cohort study.SettingGP patients of 47 general practices in a demarcated geographical region of 161 503 inhabitants in the Netherlands.ParticipantsWe analysed all 895 primary care patients in whom either the GP determined a D-dimer value or who had a diagnostic work-up for suspected VTE in a non-academic hospital during 2015.Primary and secondary outcome measuresThe primary outcomes of this study were the total number of VTEs per year and the diagnostic pathways—including the role of GP determined D-dimer testing—of patients urgently referred to secondary care for suspected VTE. Additionally, we explored the use of an age-adjusted D-dimer cut-off.ResultsThe annual VTE incidence was 0.9 per 1000 inhabitants. GPs annually ordered 5.1 D-dimer tests per 1000 inhabitants. Of 470 urgently GP-referred patients, 31.3% had a VTE. Of those urgently referred based on clinical assessment only (without D-dimer testing), 73.8% (96/130) had a VTE; based on clinical assessment and laboratory D-dimer testing yielded 15.0% (51/340) VTE. Applying age-adjusted D-dimer cut-offs to all patients aged 50 years or older resulted in a reduction of positive D-dimer results from 97.9% to 79.4%, without missing any VTE.ConclusionsAlthough D-dimer testing contributes to the diagnostic work-up of VTE, GPs have a high detection rate for VTE in patients who they urgently refer to secondary care based on clinical assessment only.

Achtergrond: We onderzochten het langetermijneffect van een eenmalig bezoek aan een huisarts die een CRP-sneltest gebruikte of een communicatietraining had gevolgd over het spreekuurbezoek en antibioticumvoorschriften van volwassen patienten met een luchtweginfectie op de lange termijn. Methoden: We hebben patienten na een factorieel, clustergerandomiseerd interventieonderzoek 3,5 jaar gevolgd. Van 379 patienten (20 huisartspraktijken) die hun huisarts bezochten vanwege acute hoest, hadden we complete data (88% van het originele trial cohort). Primaire uitkomstmaten waren het aantal consulten voor luchtweginfecties per patient per jaar en het percentage antibioticavoorschriften uitgeschreven tijdens deze consulten. Resultaten: Het gemiddelde aantal consulten voor luchtweginfecties was 0,40 per patient per jaar in de CRP-groep in vergelijking met 0,56 per patient per jaar in de groep zonder CRP-sneltest (p = 0,12). Voor de communicatietrainingsgroep en de groep zonder communicatietraining waren dit respectievelijk 0,36 en 0,57 consulten per patient per jaar (p = 0,09). Tijdens follow-up werd in de CRP-groep 30,7% van de luchtweginfecties behandeld met antibiotica in vergelijking met 35,7% in de groep zonder CRP (p = 0,36). Voor de communicatietrainingsgroep in vergelijking met de groep zonder communicatietraining was dit respectievelijk 26,3% en 39,1% (p = 0,02), respectievelijk. Conclusie: Het gebruik van een CRP-sneltest of toepassing van verbeterde communicatieve vaardigheden door huisartsen zorgt er niet voor dat patienten minder vaak of vaker het spreekuur bezoeken voor luchtweginfecties. De CRP-sneltest werd slechts sporadisch ingezet bij dezelfde patient en medicaliseert derhalve niet. Patienten die werden gezien door een huisarts die de communicatietraining had gevolgd, kregen ook in de 3,5 jaar na de trial significant minder antibiotica voor luchtweginfecties.

To explore experiences with and views of general practitioners (GPs) on a physician communication training method in primary care and its applicability and implementation in daily practice, we performed a semi-structured qualitative study of GPs’ experience of training in and implementing a communication skills training program for managing lower respiratory tract infection (LRTI) which included a seminar, simulated patient consultation together with providing and receiving feedback on ones own transcript, and a seminar in a structured approach to the LRTI consultation. Seventeen out of 20 eligible GPs who had participated in the IMPAC3T trial and were allocated to receiving enhanced physician communication training for managing lower respiratory tract infection participated. GPs’ experiences with the physician communication training method and its specific components were positive. The method gave GPs additional tools for managing LRTI consultations and increased their sense of providing evidence-based management. During the study, GPs reported using almost all communication items covered in the training, but some GPs stated that the communication skills diluted over time, and that they continued to use a selected set of the skills. The general communication items were most regularly used. Implementation of the method in daily practice helped GPs to prescribe fewer antibiotics in LRTI with the only perceived disadvantage being time-pressure. This study suggests that GPs felt positive about the physician communication training method for enhanced management of LRTI in primary care. GPs continued to use some of the communication items, of which general communication items were the most common. Furthermore, GPs believed that implementation of the communication skills in daily practice helped them to prescribe fewer antibiotics. The context-rich communication method could have wider application in common conditions in primary care.

Francis NA, Gillespie D, Nuttall J, Hood K, Little P, Verheij T, Coenen S, Cals, JW, Goossens H, Butler CC; GRACE Project Group. Therapietrouw bij antibioticagebruik voor hoestklachten in 13 Europese landen. Huisarts Wet 2013;56(8):384-7. Naast het correct indiceren van antibiotica door huisartsen, moeten patienten deze middelen ook volgens het voorschrift van de behandeld arts gebruiken. Minder of korter innemen dan de arts heeft geadviseerd zou bacteriele resistentie kunnen bevorderen en kan tot gevolg hebben dat patienten restanten bewaren en op een later tijdstip onjuist gaan gebruiken. In het kader van een groot observationeel onderzoek in 13 Europese landen onderzochten we het daadwerkelijke antibioticagebruik, al dan niet op recept verkregen, bij patienten met een lagere luchtweginfectie voor wie de huisarts een antibioticum had voorgeschreven. Van 3398 volwassen patienten met een lagere luchtweginfectie registreerde de huisarts tijdens het eerste bezoek de klinische gegevens en de behandeling. Tevens hielden deze patienten gedurende vier weken een dagboek bij waarin ze onder andere het daadwerkelijke gebruik van antibiotica vastlegden. Twaalfhonderdnegentig patienten kregen een antibioticum tijdens het eerste consult. Van hen hielden 570 (44,2%) zich volledig aan de voorgeschreven antibioticakuur, 532 (41,2%) namen niets van de voorgeschreven kuur en 392 (30,4%) namen zelfs totaal geen antibiotica tijdens de follow-upperiode van 28 dagen. Van de 1226 patienten die tijdens het eerste consult geen antibioticavoorschrift hadden gekregen, nam 12% toch antibiotica op enig moment tijdens de follow-upperiode van 28 dagen. In Nederland kreeg 41% (80/195) van de patienten een antibioticum. Maar liefst 38% (30/80) van de Nederlandse patienten begon helemaal niet aan de kuur. Bij de patienten die wel aan de kuur begonnen was de therapietrouw goed, 78% (39/50) gebruikte de volledige kuur. Op grond van deze gegevens kunnen we concluderen dat als huisartsen antibiotica voorschrijven, ze met patienten goed moeten communiceren over therapietrouw.

Koorts is verhoging van de lichaamstemperatuur boven de 38 °C, vastgesteld door een rectale meting.

Objectives To explore general practitioners’ (GPs’) experiences with and views on the diagnosis and management of patients with cardiorespiratory symptoms during GP out-of-hours care. We also aimed to identify ways of (diagnostic) support during these consultations. Design Qualitative study; face-to-face semistructured interviews. Setting GP out-of-hours care in the Netherlands. Participants 15 GPs in the province of Limburg, the Netherlands. Results Overall, GPs find cardiorespiratory consultations challenging and difficult. Tension and uncertainty as well as defensive behaviour were the key themes that characterised GPs’ experiences. We identified several subthemes underlying the key themes: setting, potentially severe consequences, absence of a pre-existing relationship and little knowledge of the patient9s background, difficulties differentiating between possible causes of symptoms, changed public opinion and patient population, and previous experiences. GPs approach cardiorespiratory consultations differently and their threshold for referring patients and performing diagnostic tests is lower. We identified differing views on the use of additional diagnostic tests at GP out-of-hours services. Conclusions This study sheds further light on how GPs experience cardiorespiratory consultations during out-of-hours care and how this leads to a high number of cardiorespiratory referrals. GPs relate cardiorespiratory consultation during out-of-hours care with tension and uncertainty leading to defensive behaviour, which can be translated into a different approach towards cardiorespiratory consultations and a lower threshold for referring patients and performing diagnostic tests. Opinions on the possible added value of additional diagnostics in reducing the number of referrals should be further investigated, as we identified differing views on the use of additional diagnostic tests at GP out-of-hours services.

Purpose: HER2 targeted therapies have substantially improved outcomes of patients with HER2 positive metastatic breast cancer (MBC). Medical records of patients with HER2 positive MBC achieving long survival were reviewed to describe their clinical characteristics and to assess whether curability is possible. Patients and methods: One thousand and seven hundred patients with MBC were treated between 01/01/2003 and 31/05/2012 in the 5 hospitals from the Franche-Comte region. All 217 patients with HER2 positive MBC region were retrospectively studied. Results: Among this population of HER2 positive MBC, 56 patients (26%) survived longer than 5 years. The characteristics of these long survivors were the following: median age at diagnosis was 55 years old (range, 33–87); 20 patients (35,7%) were metastatic at presentation; 20 patients (35,7%) had received adjuvant chemotherapy; the median disease-free interval was 17 months; brain, liver, lung, bone metastases were observed in 4 (7%), 19 (34%), 13 (23%), 23 (41%) in cases at occurrence of metastatic disease, respectively; tumours were hormonal receptors positive in 39 cases (70%) of these patients. A total of 16 (29%), 7 (12,5%), 7 (12,5%) and 26 (46%) cases had received 1, 2, 3 or more lines of chemotherapy at metastatic setting. The proportion of HER2 targeted treatment was 79%, 61%, 50% in first, second and third line, respectively. All patients received trastuzumab or lapatinib for their disease and 18 patients (32%) were given an anthracycline containing regimen. There were 7 complete response (CR), there were all observed after one line of chemotherapy based on trastuzumab combined with a taxane in all cases. Among these 7 patients, all continued trastuzumab after CR and all RH+ patients received hormonotherapy after CR. Among these 56 patients, 35 (62,5%) were still alive at the date cutoff in 31/05/2012. Conclusion: A significant proportion of patients with HER2 positive MBC were long survivors. Prospective clinical trials in this subset of patients should take into account this high number of patients with favorable outcome to achieve conclusion in term of survival. Can one consider the curabiblity of some MBC patients with HER2 overexpression? Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-22.

Les patientes atteintes d’un cancer du sein metastatique surexprimant HER2 beneficient aujourd’hui d’un traitement standard par trastuzumab associe a un taxane en premiere ligne. En cas de progression sous trastuzumab, le lapatinib en association avec la capecitabine ou la poursuite du traitement par trastuzumab avec la capecitabine a demontre son interet. Dans le but d’ameliorer encore les resultats dans cette population, nombre de nouvelles therapies sont en cours d’evaluation. Des associations combinant le trastuzumab avec d’autres anticorps monoclonaux comme le pertuzumab et le bevacizumab ou avec un cytotoxique comme le TDM1, ou des antimTOR comme l’everolimus qui ciblent d’autres voies de signalisation impliquees dans la proliferation et la survie cellulaires sont prometteuses et vont enrichir bientot notre arsenal therapeutique.

Aim Non-pegylated liposomal doxorubicin (NPLD) has demonstrated equivalent antitumour activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as a single agent or in combination with cyclophosphamide. This phase II trial was performed to evaluate the efficacy and the safety of NPLD and docetaxel combination in patients with metastatic breast cancer previously exposed to adjuvant anthracyclines. Patients and methods Thirty-four patients received NPLD 60mg/m 2 and docetaxel 75mg/m 2 in a 21-day cycle as first-line therapy of metastatic breast cancer. Treatment was planned for six cycles and was continued until progression or toxicity. Results Objective response rate among response-assessable patients was 79% (95% CI (confidence interval), 64–94%) and 27% (95% CI, 11–43%) presented a complete response. Median progression free survival was 11.3months (95% CI, 6.2–13.3months) and median overall survival was 28.2months (95% CI, 16–36.4months). Symptomatic grade 3 cardiotoxicity occurred in 15% of cases and febrile neutropenia in 47% of the patients. Conclusions The combination of NPLD and docetaxel demonstrated high antitumour activity in a population of metastatic breast cancer patients exposed to adjuvant anthracyclines and showed an unexpected and unexplained 15% symptomatic left ventricular systolic dysfunction rate.

Cals JWL, Van Weert HCPM. Sneltests: hoop of hype? Huisarts Wet 2011;54(10):543-7. Sneltests zijn biomedische tests die de huisarts verricht op patientenmateriaal, zoals bloed, urine en feces. Het gebruik van deze veelal nieuwe tests in de huisartsenpraktijk neemt toe. Sneltests vergroten het diagnostisch arsenaal van de huisarts. Maar dragen ze ook altijd bij aan een doelmatige en kwalitatief goede diagnostiek? We presenteren een lijstje met criteria aan de hand waarvan richtlijnmakers, regionale organisaties en individuele huisartsen een nieuwe sneltest in de praktijk kunnen toetsen. Het gaat daarbij niet louter om uitvoeringsen kwaliteitscriteria. De sneltest dient in de juiste populatie voor de juiste indicaties te zijn geevalueerd. En dan moeten we ons ook houden aan die indicaties – verbreding van het indicatiegebied ligt immers steeds op de loer, met een ongewild risico op foutpositieve en foutnegatieve testuitslagen. Bij problemen in de vergoedingensfeer en om kwaliteitscontrole te garanderen kunnen lokale klinischchemische laboratoria mogelijk een rol spelen.

Een uitgesteld antibioticarecept bij luchtweginfecties leidt tot minder antibioticagebruik zonder dat er meer complicaties optreden en resulteert in een gelijke patienttevredenheid. Dat is de conclusie van een Cochrane-review naar het effect van uitgestelde antibioticarecepten bij luchtweginfecties. Alleen geen recept uitschrijven leidt tot nog minder antibioticagebruik.

Rationale, aims and objectives An economic evaluation of general practitioner (GP) use of C-reactive protein (CRP) point of care test, GP communication skills training, and both GP use of CRP and communication skills training on antibiotic use for lower respiratory tract infections (LRTIs) in general practice. Methods Cost-effectiveness analysis with a time horizon of 28 days alongside a factorial, cluster randomized trial in 431 patients with LRTIs recruited by 40 GPs. Interventions: usual care (control group), GP use of CRP point of care test, GP communication skills training, and both CRP use and communication skills training. Main outcome measure: health care costs. Cost-effectiveness, using the primary outcome measure antibiotic prescribing at index consultation, was assessed by incremental cost-effectiveness ratios (ICER). To adjust for skewed data and clustering, we used non-parametric bootstrapping re-sampling to derive percentile intervals for the mean difference in total costs and the mean difference in effectiveness between the groups. Various implementation scenarios according to GP preference were modelled with corresponding net monetary benefit (NMB) curves based on a given willingness-to-pay (l) for a 1% lower antibiotic prescribing rate. Results The total mean cost per patient in the usual care group was €35.96 with antibiotic prescribing of 68%, €37.58 per patient managed by GPs using CRP tests (antibiotic prescribing 39%, ICER €5.79), €25.61 per patient managed by GPs trained in enhanced communication skills (antibiotic prescribing 33%, dominant) and €37.78 per patient managed by GPs using both interventions (antibiotic prescribing 23%, ICER €4.15). The interventions are cost-effective in any combination (yielding NMB at no willingness-topay), taking into account GPs’ preferences where at least 15% of GPs chose to implement the communication skills training. Conclusions The two strategies, both singly and combined, are cost-effective interventions to reduce antibiotic prescribing for LRTI, at no, or low willingness-to-pay. Taking GP preferences into account will optimize investment in strategies to reduce antibiotic prescribing for LRTI.

Cals JW, Hopstaken RM, Butler CC, Hood K, Hanssen SJ, Dinant GJ. Praten en prikken bij lageluchtweginfecties. Training in communicatieve vaardigheden en de CRP-sneltest. Huisarts Wet 2009;52(12):576-83.

ObjectifsLe propos de cet article est d’evaluer les indications, les schemas, les modalites d’administration de la chimiotherapie d’induction ainsi que les facteurs predictifs de reponse au traitement dans les cancers des voies aerodigestives superieures (VADS) localement avances.MethodologieUn panel d’experts compose d’ORL, de chirurgiens cervicofaciaux, d’oncologues, de radiotherapeutes et de biologistes a analyse la litterature afin d’en etablir une synthese et d’emettre certaines recommandations.SyntheseLes resultats des principaux essais de phase III randomises permettent de conclure que le schema TPF (docetaxel, cisplatine, 5-fluoro-uracile) represente une option de choix s’il y a indication de chimiotherapie d’induction, que ce soit chez des patients operables ou inoperables. Etant donne la fragilite potentielle des patients ayant un cancer des VADS, l’administration de ce schema en pratique quotidienne necessite d’appliquer des mesures preventives rigoureuses et une surveillance adaptee au profil de chaque patient. Concernant les facteurs predictifs de reponse au schema TPF, il n’existe pas de facteurs valides a ce jour, mais les essais en cours vont permettre d’ameliorer les connaissances.ConclusionLes progres de la chimiotherapie d’induction ont permis d’ameliorer le pronostic des patients ayant un cancer des VADS localement avance. Le schema TPF est une avancee majeure dans cette indication, et les essais de strategie en cours vont permettre d’affiner les indications de ce schema.

AIMS: To assess the diagnostic value of lipopolysaccharide-binding protein (LBP) and fibrinogen compared to C-reactive protein (CRP) for pneumonia in primary care patients with lower respiratory tract infection (LRTI). METHODS: Receiver operating characteristic curves summarising test accuracies for LBP, fibrinogen and CRP for pneumonia were constructed. The respective areas under the curve (AUCs) were calculated and compared with that of body temperature, an acknowledged clinical sign to differentiate pneumonia from acute bronchitis in primary care. RESULTS: 11 of 95 patients had radiographically confirmed pneumonia (11.7%). The AUC was 0.90 for CRP, 0.92 for LBP and 0.86 for fibrinogen. Body temperature yielded an AUC of 0.63. Differences between the AUCs were not significant for the three blood tests, but highly significant when compared to body temperature (p

Doel: Bepalen of een trainingsprogramma ter bevordering van de communicatieve vaardigheden van huisartsen bij lageluchtweginfecties, resulteert in de verwerving en handhaving van deze vaardigheden zonder de duur van het consult te verlengen. Het programma bestond uit contextgebonden leerervaringen en ‘peer review’ van transcripten van simulatiepatientconsulten in de eigen praktijk.

Cals JWL, Lardinois RJM, Boumans D, Gonzales R, Hopstaken RM, Butler CC, Dinant GJ. Antibiotica en luchtweginfecties. Wat weet de leek? Huisarts Wet 2008;51(4):190-4.

Objective To determine if a communication skills training program for general practitioners involving context-rich learning experiences and ‘peer review’ of consultation transcripts results in communication skills acquisition and maintenance, while preserving time-efficiency in consultations. Methods A pre-test–post-test evaluation of training 20 general practitioners (GPs) in enhanced communication skills. Audio taped consultations with simulated patients in routine practice conducted before, within 2 weeks and again 6 months after communication skills training were analysed and consultation length measured. Transcripts were scored for specific skills to determine differences in short and longer-term competence of GPs for the communication skills. Results There was good evidence that GPs acquired key communication skills after training and that these were maintained over 6 months. Consultations remained within normal consultation length in primary care. Conclusion Specific communication skills for acute bronchitis can be successfully acquired by GPs through context-rich communication training with peer review of transcripts with simulated patients, without making consultation length unfeasible. Practice Implications This approach to skill acquisition is useful for enhancing communication skills competence in general medical practice.

Contexte L’adequation entre la pratique de chimiotherapie et les referentiels de chimiotherapie existants est peu connue en France. L’objectif de cette etude initiee par le regime general de l’Assurance maladie etait de decrire la pratique en chimiotherapie (CT) et la diversite des referentiels, pour quatre localisations tumorales (sein, colorectal, poumon, ORL). La finalite etait de faire des propositions pour permettre une amelioration des pratiques en CT contribuant ainsi au plan cancer lance par le gouvernement.

Background Mixed methods are commonly used in health services research; however, data are not often integrated to explore complementarity of findings. A triangulation protocol is one approach to integrating such data. A retrospective triangulation protocol was carried out on mixed methods data collected as part of a process evaluation of a trial. The multi-country randomised controlled trial found that a web-based training in communication skills (including use of a patient booklet) and the use of a C-reactive protein (CRP) point-of-care test decreased antibiotic prescribing by general practitioners (GPs) for acute cough. The process evaluation investigated GPs’ and patients’ experiences of taking part in the trial. Methods Three analysts independently compared findings across four data sets: qualitative data collected view semi-structured interviews with (1) 62 patients and (2) 66 GPs and quantitative data collected via questionnaires with (3) 2886 patients and (4) 346 GPs. Pairwise comparisons were made between data sets and were categorised as agreement, partial agreement, dissonance or silence. Results Three instances of dissonance occurred in 39 independent findings. GPs and patients reported different views on the use of a CRP test. GPs felt that the test was useful in convincing patients to accept a no-antibiotic decision, but patient data suggested that this was unnecessary if a full explanation was given. Whilst qualitative data indicated all patients were generally satisfied with their consultation, quantitative data indicated highest levels of satisfaction for those receiving a detailed explanation from their GP with a booklet giving advice on self-care. Both qualitative and quantitative data sets indicated higher patient enablement for those in the communication groups who had received a booklet. Conclusions Use of CRP tests does not appear to engage patients or influence illness perceptions and its effect is more centred on changing clinician behaviour. Communication skills and the patient booklet were relevant and useful for all patients and associated with increased patient satisfaction. A triangulation protocol to integrate qualitative and quantitative data can reveal findings that need further interpretation and also highlight areas of dissonance that lead to a deeper insight than separate analyses. Electronic supplementary material The online version of this article (doi:10.1186/s13012-016-0436-0) contains supplementary material, which is available to authorized users.

Background Fever in children is common and mostly caused by benign self-limiting infections. Yet consultation rates in primary care are high, especially during GP out-of-hours care. Therefore, we aimed to explore experiences of parents when having visited GP out-of-hours services with their febrile child. Methods We performed a qualitative study using 20 semi-structured interviews among parents from different backgrounds presenting to GP out-of-hours care with a febrile child