The European Rare Disease Network for HHT Frameworks for management of hereditary haemorrhagic telangiectasia in general and speciality care.

Hereditary haemorrhagic telangiectasia (HHT) is a complex, multisystemic vascular dysplasia affecting approximately 85,000 European Citizens. In 2016, eight founding centres operating within 6 countries, set up a working group dedicated to HHT within what became the European Reference Network on Rare Multisystemic Vascular Diseases. By launch, combined experience exceeded 10,000 HHT patients, and Chairs representing 7 separate specialties provided a median of 24 years' experience in HHT. Integrated were expert patients who focused discussions on the patient experience. Following a 2016-2017 survey to capture priorities, and underpinned by more than 40 monthly meetings, and new data acquisitions, VASCERN HHT generated position statements that distinguish expert HHT care from non-expert HHT practice. Leadership was by specialists in the relevant sub-discipline(s), and 100% consensus was required amongst all clinicians before statements were published or disseminated. One major set of outputs targeted all healthcare professionals and their HHT patients, and include the new Orphanet definition; Do's and Don'ts for common situations; Outcome Measures suitable for all consultations; COVID-19; and anticoagulation. The second output set span aspects of vascular pathophysiology where greater understanding will assist organ-specific specialist clinicians to provide more informed care to HHT patients. These cover cerebral vascular malformations and screening; mucocutaneous telangiectasia and differential diagnosis; anti-angiogenic therapies; circulatory interplays between anaemia and arteriovenous malformations; and microbiological strategies to counteract loss of normal pulmonary capillary function. Overall, the integrated outputs, and documented current practices, provide frameworks for approaches that augment the health and safety of HHT patients in diverse health-care settings.

Safety of direct oral anticoagulants in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolism and/or atrial fibrillation. Over decades, tolerance data has been published for almost 200 HHT-affected users of warfarin and heparins, but there are no published data for the newer direct oral anticoagulants (DOACs) in HHT. METHODS: To provide such data, a retrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN), in Denmark, France, Germany, Italy, the Netherlands and the UK. RESULTS: Although HHT Centres had not specifically recommended the use of DOACs, 32 treatment episodes had been initiated by other clinicians in 28 patients reviewed at the Centres, at median age 65 years (range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes). The 32 treatment episodes used Apixaban (n = 15), Rivaroxaban (n = 14), and Dabigatran (n = 3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15 (26.7%) Apixaban episodes and 7/14 (50%) Rivaroxaban episodes. By a 4 point scale of increasing severity, there was a trend for Rivaroxaban to be associated with a greater bleeding risk both including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associations were maintained after adjustment for gender and treatment indication. Extreme hemorrhagic responses, worse than anything experienced previously, with individual nosebleeds lasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in 5/14 (35.7%) Rivaroxaban episodes compared to 3/15 (20%) Apixaban episodes and published rates of ~ 5% for warfarin and heparin. CONCLUSIONS: Currently, conventional heparin and warfarin remain first choice anticoagulants in HHT. If newer anticoagulants are considered, although study numbers are small, at this stage Apixaban appears to be associated with lesser bleeding risk than Rivaroxaban.

Surgical versus non-surgical management of pleural empyema.

BACKGROUND: Pleural empyema is a collection of pus between the lungs and the chest wall. There is debate about treatment options with the advent of both fibrinolytic enzymes to facilitate tube drainage and less invasive video-assisted thoracoscopic surgery (VATS). OBJECTIVES: To determine which was more effective: surgical (using thoracoscopy or thoracotomy) or non-surgical techniques (thoracocentesis, chest tube drainage); and to establish whether there was an optimum time for intervention. SEARCH STRATEGY: In this updated review we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005) MEDLINE (January 2002 to July Week 4, 2005) and EMBASE (January 2001 to 3rd Quarter 2005). Bibliographies, reference lists of identified studies and review articles were handsearched. Personal communication with authors is ongoing. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of surgical techniques versus non-surgical approaches for treatment of pus in the pleural cavity in children and adults but not neonates. Studies of empyema associated with tuberculosis or malignancy were excluded. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using Jadad criteria (Jadad 1996). Authors were contacted for missing information. The primary outcomes were death or resolution of the empyema. Secondary outcomes addressed the length of time chest tubes were required, pain, hospital stay and any complications. MAIN RESULTS: Only one small randomised study was identified. Some methodological quality considerations cast doubt on the validity of the study with regard to patient selection, unclear allocation concealment and outcome assessor blinding and it scored 'B' overall (Jadad score 3). When compared with chest tube drainage combined with streptokinase, video-assisted thoracoscopic surgery (VATS) had a significantly higher primary treatment success and patients spent less time in hospital. Each treatment group suffered one mortality. The latest search revealed no further published randomised studies but communication with authors revealed two ongoing studies comparing conventional chest tube drainage plus antibiotics with and without fibrinolytics with video-assisted thorascopic surgery (VATS). A small unpublished study is awaiting assessment that compared chest tube drainage and antibiotics with thoracoscopy or thoracotomy plus antibiotics. AUTHORS' CONCLUSIONS: It seems that for large, loculated pleural empyemas VATS is superior to chest tube drainage in terms of duration of chest tubes in situ and length of hospital stay. However, there are questions about validity in the one study which met the inclusion criteria and the study has too few participants to draw conclusions. There are risks of complications (associated with all treatments) which may not be apparent with small numbers. Larger studies are needed.

Surgical versus non-surgical management of pleural empyema.

BACKGROUND: Pleural empyema is a collection of pus between the lungs and the chest wall. Approximately 50% of cases complicate pneumonia. There are a variety of treatment options ranging from intravenous antibiotics alone to open thoracotomy and debridement, depending in part on the stage of the empyema and the severity. The condition changes with time, becoming loculated and more difficult to drain. There is much debate about the most appropriate therapy particularly with the advent of new treatments such as fibrinolytic enzymes (e.g. streptokinase, urokinase) and video-assisted thoracoscopic surgery (VATS). OBJECTIVES: To determine which is more effective for the management of empyema: surgical (e.g. thoracoscopy, thoracotomy) or non-surgical techniques (e.g. thoracocentesis, chest tube drainage) and to establish whether there is an optimum time for intervention. SEARCH STRATEGY: The Cochrane Controlled Trials Register and DARE database were searched in addition to the Cochrane Acute Respiratory Infections Group's own register of trials. A specialised topic search with no language restrictions was used to search MEDLINE and EMBASE using Silverplatter. Bibliographies and the reference lists of identified studies and review articles were handsearched. Personal communication with authors and experts in the field is ongoing. SELECTION CRITERIA: Randomised controlled trials (RCTs) of surgical techniques versus non-surgical approaches for treatment of pus in the pleural cavity in children and adults but not neonates. Studies of empyema associated with tuberculosis or malignancy were excluded. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using Jadad criteria as recommended by the ARI group (Jadad 1996). The primary outcomes were death or resolution of the empyema. Secondary outcomes addressed length of time chest tubes were required, pain, hospital stay and any complications. MAIN RESULTS: Only one small randomised study was identified which met the inclusion criteria. It was conducted in a university thoracic surgery department. There were some methodological quality considerations which cast some doubt on validity ( patient selection, unclear allocation concealment and outcome assessor blinding) and it scored 'B' overall (Jadad score 3). The main results of the study were that when compared with chest tube drainage combined with streptokinase, the video-assisted thoracoscopic surgery (VATS) group had a significantly higher primary treatment success and spent less time in hospital. Each group suffered one mortality. REVIEWER'S CONCLUSIONS: It would appear that for large, loculated pleural empyemas VATS is superior to chest tube drainage with streptokinase in terms of duration of chest tubes and hospital stay. However there are questions about validity and the study is also too small to draw conclusions. There are risks of complications (associated with all treatments) which may not apparent with small numbers. VATS is performed under general anaesthetic and one lung ventilation. Fibrinolytics are also associated with side effects. Further larger multicentre studies need to be conducted.

Diagnosis and investigation of bacterial pneumonias.

This overview has been supported by a review of the literature referring to the management of community-acquired pneumonia (in preparation). Difficulties diagnosing bacterial pneumonia include identifying the pathogens and the validation of radiographic signs suggesting bacterial or mycoplasmal infection. The World Health Organisation (WHO) has published guidelines for diagnosis which seem to be as relevant for developed as developing countries. The main diagnostic features are tachypnoea, fever greater than 38.5 degrees C and chest recession without wheeze. Radiographic features lag behind clinical findings and provide little additional help when antibiotic treatment is considered but are crucial in the proper management of complications.

Skin depigmentation associated with intravenous anaesthetic induction agents.

A case of skin depigmentation associated with intravenous anaesthetic induction agents is described. The differential diagnosis is briefly discussed.