Randomized, double-blind, placebo-controlled, crossover trial of oral doxycycline for epistaxis in hereditary hemorrhagic telangiectasia.

BACKGROUND: Vascular malformations in hereditary hemorrhagic telangiectasia (HHT) lead to chronic recurrent bleeding, hemorrhage, stroke, heart failure, and liver disease. There is great interest in identifying novel therapies for epistaxis in HHT given its associated morbidity and impact on quality of life. We aimed to measure the effectiveness of oral doxycycline for the treatment of epistaxis and explore mechanisms of action on angiogenic, inflammatory and pathway markers in HHT using a randomized controlled trial. METHODS: 13 HHT patients with epistaxis were recruited from the Toronto HHT Center at St. Michael's Hospital. Recruitment was stopped early due to COVID-19-related limitations. The study duration was 24 months. Patients were randomly assigned to the treatment-first or placebo-first study arm. We compared the change in weekly epistaxis duration and frequency, biomarkers, blood measurements, and intravenous iron infusion and blood transfusion requirements between treatment and placebo. RESULTS: There was no significant difference in the change in weekly epistaxis duration (p = 0.136) or frequency (p = 0.261) between treatment and placebo. There was no significant difference in the levels of MMP-9, VEGF, ANG-2, IL-6 or ENG with treatment. Hemoglobin levels were significantly higher (p = 0.0499) during treatment. Ferritin levels were not significantly different between treatment and placebo. There was no significant difference in RBC transfusions between treatment periods (p = 0.299). CONCLUSION: Overall, our study did not demonstrate effectiveness of doxycycline as a treatment for epistaxis in patients with HHT, though the study was underpowered. Secondary analyses provided new observations which may help guide future trials in HHT. Trial Registration ClinicalTrials.gov, NCT03397004. Registered 11 January 2018 - Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03397004.

Abdominal tuberculosis: a descriptive case series of the experience in a Canadian tuberculosis clinic.

OBJECTIVE: To describe the experience with abdominal tuberculosis (TB), including potential risk factors, presentation, diagnosis, treatment and clinical course, at one Canadian clinic. DESIGN: This was a retrospective case series of all patients with abdominal TB (excluding the genito-urinary system and abdominal muscle) who received care at the Saint Michael's Hospital TB Clinic (Toronto, ON, Canada) from April 2003 to July 2016. RESULTS: Of 590 active TB cases encountered between April 2003 and July 2016, 24 (4.1%) had abdominal TB. All cases were foreign-born, and over 50% occurred among individuals who were not recent immigrants. Background abdominal illnesses and immunocompromised health status were rarely seen. Lymphadenitis (58.3%) and the peritoneum (41.7%) were the most common forms of abdominal TB, bowel involvement was infrequent and most had concomitant extra-abdominal disease (62.5%). All cases were cured, largely using ⩾9 months of pharmacotherapy. Gastrointestinal intolerance and liver dysfunction were rarely observed side effects of therapy. CONCLUSIONS: Several traditional TB risk factors occurred infrequently among our cases, which highlights the importance of having a low threshold for considering abdominal TB in the appropriate clinical setting. Although abdominal TB often occurred in the context of disseminated disease, cure was achievable, but ⩾9 months of treatment may generally be needed.

Smoking, activity level and exercise test outcomes in a young population sample without cardiopulmonary disease.

AIM: Whether reduced activity level and exercise intolerance precede the clinical diagnosis of cardiopulmonary disorders in smokers is not known. We examined activity level and exercise test outcomes in a young population-based sample without overt cardiopulmonary disease, differentiating by smoking history. METHODS: This was a multiyear cross-sectional study using United States National Health and Nutrition Examination Survey data from 1999-2004. Self-reported activity level and incremental exercise treadmill testing were obtained on survey participants ages 20-49 years, excluding individuals with cardio-pulmonary disease. RESULTS: Three thousand seven hundred and one individuals completed exercise testing. Compared to never smokers, current smokers with >10 pack years reported significantly higher odds of little or no recreation, sport, or physical activity (adjusted OR 1.62; 95% CI 1.12-2.35). Mean perceived exertion ratings (Borg 6-20) at an estimated standardized workload were significantly greater among current smokers (18.3-18.6) compared to never (17.3) and former smokers (17.9) (p<0.05). There were no significant differences in the proportions of individuals across estimated peak oxygen uptake categories among the groups after adjusting for age and sex. Among former smokers, increasing duration of smoking abstinence was associated with significantly lower likelihood of low estimated peak oxygen uptake categorization (p<0.05). CONCLUSIONS: Among young individuals without overt cardiopulmonary disease, current smokers had reduced daily activity and higher perceived exertion ratings. Besides supporting early smoking cessation, these results set the stage for future studies that examine mechanisms of activity restriction in young smokers and the utility of measures of activity restriction in the earlier diagnosis of smoking-related diseases.