Search

While clinical guidelines are essential for decision-making based on the latest evidence, they are not all-encompassing for any given patient or context. As such, deviating from guideline recommendations is common practice and can be attributed to contextual, ethical, clinical, or scientific factors. In the setting of diagnostic testing deviating from recommended diagnostic work-up may result in both over- and under-testing. In this Clinical Lesson we discuss two scenarios in primary care, one involving high-sensitivity troponin testing in a patient with episodes of chest discomfort, and the other involving CRP testing in a pediatric patient with acute-onset abdominal pain.

Hydrofluorocarbons (HFCs) released from the use of metered-dose inhalers (MDIs) contribute significantly to climate change. Counterintuitively, these HFCs indirectly cause health damage to asthma and COPD patients, as climate change creates more summer smog and pollen in the air. European regulation is urgently needed to ensure that only MDIs with HFCs with a lower global warming potential will be produced in future. Meanwhile, prescribing less MDIs can have a substantial impact on the reduction of greenhouse gases. If a healthcare professional chooses a greener alternative as a maintenance dose of inhalation medication together with twenty patients this saves 1.8 tons of CO2-eq emissions per year. This is as much CO2-eq per year as one person would save per year by replacing his or her petrol car for an electric car.

At several out-of-hours services primary care, a single dose of ondansetron was compared with standard care (oral rehydration solution (ORS)) in young children with gastroenteritis and persistent vomiting. Although vomiting decreased more often in the ondansetron group compared to the control group in the first hours, ondansetron had no effect on ORS use and did not lead to fewer referrals to the hospital. Unfortunately, the outcome measure diarrhoea was missing as a possible adverse effect of ondansetron. Diarrhoea was reported around 2-3 times more often with ondansetron compared to placebo in four of five other studies in children with gastroenteritis and vomiting. It is therefore questionable whether the limited clinical benefit of ondansetron in children with vomiting due to gastroenteritis outweighs the possible (as yet insufficiently investigated) side effect diarrhoea.

Bleeding symptoms occur frequently in the general population, but the possibility of an underlying bleeding disorder is not always recognised. Women with a bleeding disorder are disproportionally affected due to blood loss during menstruation and giving birth. Taking a thorough family history and a history of bleeding are most important in the workup to detect a potential underlying bleeding disorder. In patients with a bleeding disorder, potentially life-threatening complications due to bleeding can be prevented by compiling an individualized treatment plan and timely targeted blood coagulation treatment. If a bleeding disorder is suspected, initial diagnostic testing consists of determining the aPTT, PT, platelet count and von Willebrand factor activity; global tests for disorders of haemostasis, such as the coagulation time and platelet function are not of any added value. It cannot be excluded that a patient in whom test results are normal may still have a platelet function disorder or a rare bleeding disorder. If there is a strong suspicion of a bleeding disorder this should always be discussed with a coagulation specialist.

Background: The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the third update of a review first published in 2007., Objectives: To assess the efficacy and safety of topical, medical, and surgical treatments for ST of the leg in improving local symptoms and decreasing thromboembolic complications., Search Methods: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (March 2017), CENTRAL (2017, Issue 2), and trials registries (March 2017). We handsearched the reference lists of relevant papers and conference proceedings., Selection Criteria: Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included people with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in a superficial vein., Data Collection and Analysis: Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus. We assessed the quality of the evidence using the GRADE approach., Main Results: We identified three additional trials (613 participants), therefore this update considered 33 studies involving 7296 people with ST of the legs. Treatment included fondaparinux; rivaroxaban; low molecular weight heparin (LMWH); unfractionated heparin (UFH); non-steroidal anti-inflammatory drugs (NSAIDs); compression stockings; and topical, intramuscular, or intravenous treatment to surgical interventions such as thrombectomy or ligation. Only a minority of trials compared treatment with placebo rather than an alternative treatment and many studies were small and of poor quality. Pooling of the data was possible for few outcomes, and none were part of a placebo-controlled trial. In one large, placebo-controlled RCT of 3002 participants, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.04 to 0.50; moderate-quality evidence), ST extension (RR 0.08, 95% CI 0.03 to 0.22; moderate-quality evidence), and ST recurrence (RR 0.21, 95% CI 0.08 to 0.54; moderate-quality evidence) relative to placebo. Major bleeding was infrequent in both groups with very wide CIs around risk estimate (RR 0.99, 95% CI 0.06 to 15.86; moderate-quality evidence). In one RCT on 472 high-risk participants with ST, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban 10 mg (RR 0.33, 95% CI 0.03 to 3.18; low-quality evidence). There were no major bleeding events in either group (low-quality evidence). In another placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (prophylactic: RR 0.44, 95% CI 0.26 to 0.74; therapeutic: RR 0.46, 95% CI 0.27 to 0.77) and NSAIDs (RR 0.46, 95% CI 0.27 to 0.78) reduced the extension (low-quality evidence) and recurrence of ST (low-quality evidence) in comparison to placebo, with no significant effects on symptomatic VTE (low-quality evidence) or major bleeding (low-quality evidence). Overall, topical treatments improved local symptoms compared with placebo, but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatments, topical treatments, or surgery did not report VTE, ST progression, adverse events, or treatment adverse effects., Authors' Conclusions: Prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for ST of the legs for most people. The evidence on topical treatment or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE. Further research is needed to assess the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment in people at various risk of recurrence; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

Dr Robert Edgar Hope-Simpson (1908-2003) was a British general practitioner, who has laid the foundation for unravelling the pathogenesis of shingles. At the beginning of the 20th century, both conditions were known to be related, but the precise relationship was unclear. It was assumed that chickenpox could originate after infection by both a person with shingles or someone with chickenpox, but that both diseases were caused by different viruses. Through rigorous observations in his GP practice and during his field work on the island of Yell, Hope-Simpson developed his hypothesis about the - now scientifically accepted - pathogenesis of shingles. Hope-Simpson's work shows how accurate observations can lead to unexpected new insights and hypotheses.

- The 'Traumatic wounds and bite wounds' treatment guideline by the NHG (Dutch College of General Practitioners) has recommendations for treating traumatic wounds, bite wounds and wound infection.- It is important to distinguish between traumatic wounds and bite wounds because treatment of lacerations and cuts differs from treatment of bites.- Clean a wound under a lukewarm water tap; avoid using disinfectants.- Preferably close traumatic wounds within 12 hours, provided that the wounds have been carefully cleaned and that there are no referral indications. The strict limit of 6 hours has been abandoned because the age of the wound does not seem to be related to increased infection risk.- Do not close bite wounds unless there is a low estimated risk of infection, it is considered cosmetically important, closure is possible within 8 hours, provided that the wounds have been carefully cleaned, and there are no referral indications.

Background: The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the second update of a review first published in 2007., Objectives: To assess the efficacy and safety of topical, medical, and surgical treatments in patients presenting with ST of the legs., Search Methods: For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2012) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11). We handsearched the reference lists of relevant papers and conference proceedings., Selection Criteria: Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included participants with a clinical diagnosis of ST of the legs or an objective diagnosis of a thrombus in a superficial vein., Data Collection and Analysis: Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus., Main Results: We identified four additional trials (986 patients), so this update considered 30 studies involving 6507 participants with ST of the legs.Treatment ranged from fondaparinux, low molecular weight heparin (LMWH), unfractionated heparin (UFH), non-steroidal anti-inflammatory agents (NSAIDs), topical treatment, oral treatment, intramuscular treatment, and intravenous treatment to surgery. Only a minority of trials compared treatment with placebo rather than an alternative treatment, none evaluated the same treatment comparisons on the same study outcomes (which precluded meta-analysis), and many of the studies were small and of poor quality. In one large, placebo-controlled RCT of about 3000 patients, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (RR 0.15; 95% CI 0.04 to 0.50), ST extension (RR 0.08; 95% CI 0.03 to 0.22), and ST recurrence (RR 0.21; 95% CI 0.08 to 0.54) with comparable rates of major bleeding (RR 0.99; 95% CI 0.06 to 15.86) relative to placebo. In a further placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (RR 0.40; 95% CI 0.22 to 0.72 and RR 0.42; 95% CI 0.23 to 0.75, respectively) and NSAIDs (RR 0.41; 95% CI 0.23 to 0.75) reduced the extension and recurrence of ST in comparison to placebo, with no significant effects on symptomatic VTE nor major bleeding. Overall, topical treatments improved local symptoms compared with placebo but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatment, topical treatment, or surgery did not report VTE, ST progression, adverse events, or treatment side effects., Authors' Conclusions: Prophylactic dose fondaparinux given for six weeks appears to be a valid therapeutic option for ST of the legs. The evidence on oral treatments, topical treatment, or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE and ST progression. Further research is needed to assess the role of the new oral direct thrombin and activated factor-X inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

Background: The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is an update of a review first published in 2007., Objectives: To assess the efficacy and safety of topical, medical, and surgical treatments in patients presenting with ST of the legs., Search Methods: For this update the Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched 29 November 2011) and CENTRAL (2011, Issue 4). We handsearched reference lists of relevant papers and conference proceedings., Selection Criteria: Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the leg that included participants with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in the superficial vein., Data Collection and Analysis: Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus., Main Results: Twenty-six studies involving 5521 participants with ST of the legs were included in this review. The methodological quality of most of the trials was poor. Treatment ranged from fondaparinux, low molecular weight heparin (LMWH), unfractionated heparin (UFH), non-steroidal anti-inflammatory agents (NSAIDs), topical treatment, oral treatment, intramuscular treatment, and intravenous treatment to surgery. In a placebo-controlled RCT of about 3000 patients, fondaparinux was associated with a significant reduction in symptomatic VTE (RR 0.15; 95% CI 0.04 to 0.50), extension (RR 0.08; 95% CI 0.03 to 0.22), and recurrence of ST (RR 0.21; 95% CI 0.08 to 0.54) with comparable rates of major bleeding (RR 0.99; 95% CI 0.06 to 15.86) relative to placebo. Both prophylactic and therapeutic doses of LMWH (RR 0.40; 95% CI 0.22 to 0.72 and RR 0.42; 95% CI 0.23 to 0.75, respectively) and NSAIDs (RR 0.41; 95% CI 0.23 to 0.75) reduced the extension and recurrence of ST in comparison to placebo, with no significant effects on symptomatic VTE nor major bleeding. Overall, topical treatments improved local symptoms. However, no data were provided on the effects of these treatments on VTE and ST extension. Surgical treatment combined with elastic stockings in ST was associated with a lower VTE rate and ST progression compared with elastic stockings alone., Authors' Conclusions: Prophylactic dose fondaparinux given for six weeks appears to be a valid therapeutic option for ST of the legs. Further research is needed to assess the role of new oral direct thrombin and activated factor-X inhibitors, LMWH, NSAIDs; the optimal doses and duration of treatment; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

Background: Genetic determinants of plasma levels of protein C (PC) are poorly understood. Recently, we identified a locus on chromosome 20 determining high PC levels in a large Dutch pedigree with unexplained thrombophilia. Candidate genes in the LOD-1 support interval included FOXA2, THBD and PROCR., Objectives: To examine these candidate genes and their influence on plasma levels of PC., Patients/methods: Exons, promoter and 3'UTR of the candidate genes were sequenced in 12 family members with normal to high PC levels. Four haplotypes of PROCR, two SNPs in the neighboring gene EDEM2 and critical SNPs encountered during resequencing were genotyped in the family and in a large group of healthy individuals (the Leiden Thrombophilia Study (LETS) controls). Soluble endothelial protein C receptor (sEPCR) and soluble thrombomodulin (sTM) plasma levels were measured in the family., Results: PROCR haplotype 3 (H3) and FOXA2 rs1055080 were associated with PC levels in the family but only PROCR H3 was also associated with plasma levels in the healthy individuals. Carriers of both variants had higher PC levels than carriers of only PROCR H3 in the family but not in healthy individuals, suggesting that a second determinant is present. EDEM2 SNPs were associated with PC levels, but their effect was small. PC and sEPCR levels were associated in both studies. sTM was not associated with variations of THBD or PC levels., Conclusions: Chromosome 20 harbors genetic determinants of PC and sEPCR levels and the analysis of candidate genes suggests that the PROCR locus is responsible., (© 2011 International Society on Thrombosis and Haemostasis.)

Despite knowledge of various inherited risk factors associated with venous thromboembolism (VTE), no definite cause can be found in about 50% of patients. The lack of an intermediate phenotype in VTE impedes the discovery of new familial risk factors. We set out to define an intermediate phenotype for VTE by performing global coagulation analyses in unexplained thrombophilic families. Families were selected through a proband with VTE but without one of the known thrombophilic defects and at least one 1st or two 2nd degree family members with VTE. Clinical data were collected using a standardized questionnaire. Blood samples were collected for overall haemostasis assays (i.e. thrombin generation time [TGT], endogenous thrombin potential [ETP], prothrombin fragment 1+2 [F1+2] and activated protein C-sensitivity ratio [APC-sr] and clot lysis time [CLT]). Data were analysed using logistic regression. Coagulation assays were performed in 353 individuals of whom 41 (12%) had a history of VTE; these belonged to 17 thrombophilic families. Of the tested variables only the ETP was associated with VTE (odds ratio [OR] 1.03 for each % increase, 95% confidence interval [CI] 1.01-1.05). However, the relatively low number of cases does not firmly exclude the other assays as candidate intermediate phenotypes for venous thrombosis. We found that an increased ETP may serve as an intermediate phenotype for VTE and may be used to discover novel inherited risk factors by genetic linkage analysis.

Introduction: The absolute risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) as well as extension and/or recurrence in superficial vein thrombosis (SVT) of the leg is considerable and underestimated. We retrospectively evaluated therapeutic management, thrombophilic risk factors and clinical outcome of SVT., Methods: A database search was performed for consecutive patients with a suspected SVT of the lower extremities referred to our institution between 1 January 1999 and 31 December 2004. The primary outcome measure was pain reduction at follow-up. Secondary outcome measures were progression or recurrence of SVT in the leg and the occurrence of (a)symptomatic DVT or symptomatic PE at follow-up., Results: In 73 patients follow-up information was present (3/76 non-evaluable patients). In 9/32 (28%) of the patients treated with carbasalate calcium, there was progression of SVT as assessed by ultrasonographic evaluation, compared with 3/11 (27%) in the low-molecular-weight heparin (LMWH) group and 3/6 (50%) in the no treatment group. DVT was diagnosed in 5/36 (14%) of the patients treated with carbasalate calcium compared with 1/13 (1%) in the LMWH and 1/3 (33%) in the other treatment groups at follow-up. Furthermore, 34 were tested for thrombophilic defects, 27 of whom had one or more thrombophilic defect., Conclusion: The results of our study show that SVT may be prone to venous thromboembolism and therefore needs to be treated or carefully followed up.

Background and Objectives: The aim of this systematic review was to summarize the evidence from randomized controlled trials (RCT) concerning the efficacy and safety of medical or surgical treatments of superficial vein thrombosis (SVT) for the prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE)., Design and Methods: A systematic search was performed in MEDLINE, EMBASE and the Cochrane (CENTRAL) database to identify all randomized trials that evaluated the effect of surgical or medical treatment in the prevention of venous thromboembolism (VTE) in patients with SVT of the legs., Results: Five studies were included. Pooling of the data was not possible due to the heterogeneity among the studies. Moreover, three studies had major methodological drawbacks limiting the clinical applicability of the results. One of the remaining (pilot) studies showed a non-significant trend in favor of high- compared to low-dose unfractionated heparin for the prevention of VTE. The last remaining study showed a non-significant trend in favor of short-term treatment with low-molecular-weight heparin (LMWH) or a non-steroidal anti-inflammatory drug (NSAID) as compared to placebo shortly after treatment with respect to VTE, but the apparent benefit disappeared after three months of follow-up. Active treatment of SVT reduced the incidences of SVT extension or recurrence., Interpretation and Conclusions: Treatment with a therapeutic or prophylactic dose of LMWH or a NSAID reduces the incidence of SVT extension or recurrence, but not VTE. More RCT are needed before any evidence-based recommendations on the treatment of SVT for the prevention of VTE can be given. With the present lack of solid evidence we would suggest treating patients with at least intermediate doses of LMWH.