Phenotypic amikacin resistance may not indicate poor response to amikacin in Mycobacterium avium complex pulmonary disease.

When using amikacin to treat Mycobacterium avium complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored whether amikacin resistance characterized by phenotypic drug susceptibility testing was associated with clinical outcomes or mutational resistance in a retrospective cohort of patients with MAC-PD. Despite little aminoglycoside exposure, amikacin resistance was common in our MAC-PD patients but was not associated with worse outcomes or rrs gene mutations.

Cardiovascular disease (CVD) in Canadians with haemophilia: Age-Related CVD in Haemophilia Epidemiological Research (ARCHER study).

INTRODUCTION: Improvements in haemophilia care have increased life expectancy in persons with haemophilia (PWH). This ageing population presents clinicians with management challenges as they develop age-related comorbidities such as cardiovascular disease (CVD). AIMS: To assess the epidemiology of CVD risk factors and events in an ageing Canadian haemophilia population. METHODS: A retrospective, multicentre chart review was carried out at five Canadian Hemophilia Treatment Centres. PWH (A and B) ≥35 years old were included and data were extracted on CVD risk factors and events. RESULTS: Data from 294 patients' charts were analysed including 222 (75.5%) patients with haemophilia A and 72 (24.5%) patients with haemophilia B with a median age at end of follow-up of 54 years (range = 36-90). Mean follow-up duration was 5.86 years. Cardiovascular risk factors were common: hypertension 31.3% (n = 90), diabetes mellitus 10.5% (n = 29), smoking 21.8% (n = 61), obesity 27.6% (n = 69), dyslipidaemia 22.4% (n = 65), family history 8.5% (n = 24), antiretroviral therapy 12.2% (n = 36). There were 24 CVD events (8.2% of the population) with a median age at event of 63 years (range = 46-83). Events consisted of coronary artery disease (CAD), 14; cerebrovascular disease, 4; and atrial fibrillation, 7. CAD was treated with coronary artery bypass grafting in three patients and percutaneous coronary intervention in nine patients. CVD events were complicated by six bleeding events (three minor and three major). CONCLUSION: Cardiovascular disease risk factors and events are relatively common in PWH. PWH can be safely treated for CVD events with similar procedures as the non-PWH populations, though specific clotting factor prophylaxis protocols are not well defined.

Treatment decision-making among Canadian youth with severe haemophilia: a qualitative approach.

The first generation of young men using primary prophylaxis is coming of age. Important questions regarding the management of severe haemophilia with prophylaxis persist: Can prophylaxis be stopped? At what age? To what effect? Can the regimen be individualized? The reasons why some individuals discontinue or poorly comply with prophylaxis are not well understood. These issues have been explored using predominantly quantitative research approaches, yielding little insight into treatment decision-making from the perspectives of persons with haemophilia (PWH). Positioning the PWH as a source of expertise about their condition and its management, we undertook a qualitative study: (i) to explore and understand the lived experience of young men with severe haemophilia A or B and (ii) to identify the factors and inter-relationships between factors that affect young men's treatment decision-making. This manuscript reports primarily on the second objective. A modified Straussian, grounded theory methodology was used for data collection (interviews) and preliminary analysis. The study sample, youth aged 15-29, with severe haemophilia A or B, was chosen selectively and recruited through three Canadian Haemophilia Treatment Centres. We found treatment decision-making to be multi-factorial and used the Framework method to analyze the inter-relationships between factors. A typology of four distinct approaches to treatment was identified: lifestyle routine prophylaxis, situational prophylaxis, strict routine prophylaxis and no prophylaxis. Standardized treatment definitions (i.e.: 'primary' and 'secondary', 'prophylaxis') do not adequately describe the ways participants treat. Naming the variation of approaches documented in this study can improve PWH/provider communication, treatment planning and education.

Cardiovascular disease prevalence and relevance in haemophilia: a scoping review.

The prevalence of cardiovascular disease (CVD) risk and events in patients with haemophilia (PWH) is expected to increase as the longevity of this cohort increases due to treatment advances since the 1950s. The aims of this study were to assess publications of CVD and haemophilia for robustness, determine if the increasing longevity of PWH and associated age-related CVD risk factors result in CVD events; assess the need for an extension of the circle of care for ageing PWH due to the shift in comorbidities. A scoping review was conducted, resulting in a final pool of 30 articles which were organized based on publication dates. A matrix was created to illustrate which articles cited articles published prior to its own publication. This led to the identification of the primary articles, receiving the highest number of citations by other publications, which drive the research pertaining to the study of age-related risk factors of CVD in PWH. The scoping review revealed 14 original articles, four of which indicated a protective effect of haemophilia toward CVD. Twelve articles demonstrated a similar prevalence of CVD in PWH compared to the general population while seven articles concluded a difference in the prevalence of CVD in the ageing haemophilia population. The existing literature presented conflicting evidence regarding the possibility of a protective effect of haemophilia against CVD. The scoping review was not able to finalize whether the longevity of PWH and their associated age-related CVD risk factors result in CVD events because the articles assessed reported conflicting results.

Patterns of tertiary prophylaxis in Canadian adults with severe and moderately severe haemophilia B.

From a young age patients with severe and moderately severe FIX deficiency (haemophilia B) can experience spontaneous or traumatic bleeding and joint destruction may result. The use of coagulation factor IX concentrate to prevent anticipated bleeding, as primary or secondary prophylaxis, has become a common and recommended practice in children. The current practice of using tertiary prophylaxis, in the presence of established joint arthropathy, in adults with haemophilia B is not well characterized. This observational study was conducted to gain a better understanding of the recent Canadian experience with tertiary prophylaxis in adults with severe and moderately severe haemophilia B. Data were collected from all eligible adult (≥ 18 years of age) males with baseline FIX:C ≤ 2% from seven Canadian Hemophilia Treatment centres over a 2-year observation period from 2009 to 2011. Thirty-four per cent of the 67 subjects with moderately severe haemophilia B were exposed to prophylaxis with the majority as continuous prophylaxis (≥45 weeks year(-1) ). The severe subgroup (FIX:C < 1%) demonstrated a 52% exposure rate. None had primary prophylaxis exposure in childhood. Eighty-one per cent used once or twice weekly infusion regimens and reported a median annual bleeding rate of five bleeds per year versus four bleeds per year for those using on-demand treatment. Annual median factor utilization for all subjects using prophylaxis was 196,283 U year(-1) compared to 46,361 U year(-1) for on demand. Approximately 50% of adults with severe haemophilia B are using continuous tertiary prophylaxis in Canada, a practice likely to increase which warrants further study.

Daily ciprofloxacin treatment for patients with advanced liver disease awaiting liver transplantation reduces hospitalizations.

BACKGROUND: Progressive deterioration in liver function is a common cause of hepatic decompensation and indication for liver transplantation in patients with advanced liver disease. Previous studies in animal models of acute and chronic liver disease revealed that daily ciprofloxacin improves biochemical parameters of hepatic function. AIMS: The primary objective of this study was to determine whether hepatic function improves in patients with advanced liver disease after 1 month of daily ciprofloxacin therapy. A secondary objective was to determine whether ciprofloxacin treatment for 1 or 3 months results in fewer hospitalizations for decompensated liver disease. METHODS: Forty-four patients with advanced liver disease awaiting liver transplantation received oral ciprofloxacin (250 or 500 mg twice daily) or placebo for 1 (n=22/group) or 3 (n=10 ciprofloxacin, 14 placebo) months. RESULTS: Compared to placebo recipients, ciprofloxacin-treated patients had mild improvements in serum albumin levels (+1.5 versus -3.4%, p=0.026) while bilirubin and international normalized ratios (INR) of prothrombin times remained unchanged. Overall, fewer hospitalizations occurred in ciprofloxacin-treated patients (1/22, 5% versus 7/22, 32%, respectively, p=0.02) during the study period. Treatment was well tolerated and no resistant infections occurred in either cohort. CONCLUSIONS: The results of this study suggest that daily ciprofloxacin may result in fewer hospitalizations for patients with advanced liver diseases awaiting liver transplantation but not by enhancing hepatic function.

Access to thalidomide for the treatment of multiple myeloma in Canada: physician behaviours and ethical implications.

BACKGROUND: Multiple myeloma is an incurable malignancy. Since the late 1990s, its management has changed with the introduction of novel agents. Thalidomide, which is often called a "novel" therapy, has significantly prolonged survival in multiple myeloma and is considered worldwide to be part of standard of care in this disease. However, thalidomide is not approved in Canada, leading to problems with drug access for patients. METHODS: Our study surveyed Canadian hematologists on their thalidomide prescribing practices and difficulties with drug access. We address some of the ethical issues facing patients and their doctors who are unable to obtain or afford the drug, and who therefore resort to alternative means such as illegal importation. RESULTS: Of the 411 Canadian hematologists contacted, 122 completed the survey, 97 reported that they did not treat myeloma, and 192 did not respond. Assuming that all non-responders treat myeloma, our estimated overall response rate from physicians who treat this disease was 39%. Survey participants indicated that, in Canada, access to thalidomide is a major issue for physicians and myeloma patients alike, and that 81% of respondents are dissatisfied or very dissatisfied with the drug access process. Many physicians felt that the special access process for thalidomide is unduly onerous, influences treatment decisions, and invades patient privacy. We found that 20% of physicians were unaware of the legal implications of obtaining thalidomide from other countries and that at least 23% overtly or covertly support patients in obtaining the drug from a non-Health-Canada-approved source. CONCLUSIONS: The current lack of access to thalidomide in Canada is a concerning problem for patients and health care providers dealing with myeloma. Regulatory changes at the federal level (Health Canada) need to be re-examined to promptly resolve this issue.