Jean-Paul Collet

Long-term Risk of CKD in Children Surviving Episodes of Acute Kidney Injury in the Intensive Care Unit: A Prospective Cohort Study

BACKGROUND The development of standardized acute kidney injury (AKI) definitions has allowed for a better understanding of AKI epidemiology, but the long-term renal outcomes of AKI in the pediatric critical care setting have not been well established. This study was designed to: (1) determine the incidence of chronic kidney disease (CKD) in children 1-3 years after an episode of AKI at a tertiary-care pediatric intensive care unit (ICU), (2) identify the proportion of patients at risk of CKD, and (3) compare ICU admission characteristics in those with and without CKD. DESIGN Prospective cohort study. SETTING & PARTICIPANTS Patients admitted to the British Columbia Childrens Hospital pediatric ICU from 2006-2008 with AKI, as defined by AKI Network (AKIN) criteria. Surviving patients, most with short-term recovery from their AKI, were assessed at 1, 2, or 3 years after AKI. PREDICTORS Severity of AKI as defined by AKIN and several ICU admission characteristics, including demographics, diagnosis, severity of illness, and ventilation data. OUTCOMES & MEASUREMENTS CKD was defined as the presence of albuminuria and/or glomerular filtration rate (GFR) < 60 mL/min/1.73 m2. Being at risk of CKD was defined as having a mildly decreased GFR (60-90 mL/min/1.73 m2), hypertension, and/or hyperfiltration (GFR ≥ 150 mL/min/1.73 m2). RESULTS The proportion of patients with AKI stages 1, 2, and 3 were 44 of 126 (35%), 47 of 126 (37%), and 35 of 126 (28%), respectively. The number of patients with CKD 1-3 years after AKI was 13 of 126 (10.3% overall; 2 of 44 [4.5%] with stage 1, 5 of 47 [10.6%] with stage 2, and 6 of 35 [17.1%] with stage 3; P = 0.2). In addition, 59 of 126 (46.8%) patients were identified as being at risk of CKD. LIMITATIONS Several patients identified with AKI were lost to follow-up, with the potential of underestimating the incidence of CKD. CONCLUSIONS In tertiary-care pediatric ICU patients, ∼10% develop CKD 1-3 years after AKI. The burden of CKD in this population may be higher with further follow-up because several patients were identified as being at risk of CKD. Regardless of the severity of AKI, all pediatric ICU patients should be monitored regularly for long-term kidney damage.

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS)

UNLABELLED Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic non-cancer pain. The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among individuals with chronic non-cancer pain. A standardized herbal cannabis product (12.5% tetrahydrocannabinol) was dispensed to eligible individuals for a 1-year period; controls were individuals with chronic pain from the same clinics who were not cannabis users. The primary outcome consisted of serious adverse events and non-serious adverse events. Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver, and endocrine function. Secondary efficacy parameters included pain and other symptoms, mood, and quality of life. Two hundred and fifteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 216 controls (chronic pain but no current cannabis use) from 7 clinics across Canada. The median daily cannabis dose was 2.5 g/d. There was no difference in risk of serious adverse events (adjusted incidence rate ratio = 1.08, 95% confidence interval = .57-2.04) between groups. Medical cannabis users were at increased risk of non-serious adverse events (adjusted incidence rate ratio = 1.73, 95% confidence interval = 1.41-2.13); most were mild to moderate. There were no differences in secondary safety assessments. Quality-controlled herbal cannabis, when used by patients with experience of cannabis use as part of a monitored treatment program over 1 year, appears to have a reasonable safety profile. Longer-term monitoring for functional outcomes is needed. STUDY REGISTRATION The study was registered with www.controlled-trials.com (ISRCTN19449752). PERSPECTIVE This study evaluated the safety of cannabis use by patients with chronic pain over 1 year. The study found that there was a higher rate of adverse events among cannabis users compared with controls but not for serious adverse events at an average dose of 2.5 g herbal cannabis per day.

Use of warfarin and risk of urogenital cancer: a population-based, nested case-control study

BACKGROUND Indirect evidence suggests that prolonged treatment with warfarin might be associated with a decreased incidence of urogenital cancer. We aimed to assess this association in a large population-based study. METHODS Beneficiaries of Saskatchewan Health who were eligible for prescription drug benefits and aged 50 years or over with no history of cancer since 1967 were enrolled into a nested, matched case-control study. 19 412 new cases of urogenital cancer diagnosed between Jan 1, 1981, and Dec 31, 2002, were identified by use of information from the Saskatchewan Cancer Agency registry. For each case, six controls, totalling 116 470, who were matched for age, sex, and time of diagnosis were selected randomly. Conditional logistic regression analysis was used to calculate adjusted incidence rates of urogenital cancer in relation to warfarin use. FINDINGS Compared with men who never used warfarin, men with 4 years of warfarin use had an adjusted incidence rate of 0.80 (95% CI [0.65-0.99]). For warfarin use 76-100% of the time, the adjusted rate ratios were 0.80 (0.66-0.96) during year 2 preceding diagnosis of prostate cancer, 0.76 (0.62-0.94) during year 3, and 0.67 (0.53-0.86) during year 4. No significant association was found between warfarin and risk of other urogenital cancers. INTERPRETATION Our results suggest that warfarin has an antitumour effect that is specific to prostate cancer. Further investigation, with more complete assessment of confounders and that addresses the effect of warfarin on mortality of prostate cancer, is warranted.

The TEAM trial: safety and efficacy of endovascular treatment of unruptured intracranial aneurysms in the prevention of aneurysmal hemorrhages: a randomized comparison with indefinite deferral of treatment in 2002 patients followed for 10 years.

The management of patients with unruptured aneurysms remains controversial. Patients with unruptured aneurysms may suffer intracranial haemorrhage, but the incidence of this event is still debated; endovascular treatment may prevent rupture, but involves immediate risks. Hence, the balance of risks and benefits of endovascular treatment is uncertain. Here, we report the design of the TEAM trial, the first international, randomized, controlled trial comparing conservative management with endovascular treatment. Primary endpoint is mortality and morbidity (modified Rankin Score ≥ 3) from intracranial haemorrhage or treatment. Secondary endpoints include incidence of hemorrhagic events, morbidity related to endovascular coiling, morphological results, overall clinical outcome and quality of life. Statistical tests compare between probabilities at 5- and 10-years of 1/mortality from haemorrhage related to the lesion, excluding per-operative complications; 2/mortality from haemorrhage or from complications of treatment; 3/combined disease or treatment related mortality and morbidity in the absence of other causes of death or disability. The study will be conducted in 60 international centres and will enrol 2,002 patients equally divided between the two groups, a size sufficient to achieve 80% power at a 0.0167 significance to detect differences in 1) disease or treatment-related poor outcomes from 7–9% to 3–5%; 2) overall mortality from 16 to 11%. Duration of the study is 14 years, the first three years being for patient recruitment plus a minimum of 10 years of follow-up. The TEAM trial thus offers a means to reconcile the introduction of a new approach with the necessity to acknowledge uncertainties.Trial registrationCurrent Controlled Trials ISRCTN62758344 http://www.controlled-trials.com

Home-based screening for biliary atresia using infant stool colour cards: A large-scale prospective cohort study and cost-effectiveness analysis

Objective Biliary atresia (BA), a leading cause of paediatric liver failure and liver transplantation, manifests by three weeks of life as jaundice with acholic stools. Poor outcomes due to delayed diagnosis remain a problem worldwide. We evaluated and assessed the cost-effectiveness of methods of introducing a BA Infant Stool Colour Card (ISCC) screening programme in Canada. Setting and Methods A prospective study at BC Women’s Hospital recruited consecutive healthy newborns through six incrementally more intensive screening approaches. Under the baseline “passive” strategy, families received ISCCs at maternity, with instructions to monitor infant stool colour daily and return the ISCC by mail at age 30 days. Additional strategies were: ISCC mailed to family physician; reminder letters or telephone calls to families or physicians. Random telephone surveys of ISCC non-returners assessed total card utilization. Primary outcome was ISCC utilization rate expressed as a composite outcome of the ISCC return rate and non-returned ISCC use. Markov modelling was used to predict incremental costs and life years gained from screening (passive and reminder), compared with no screening, over a 10-year time horizon. Results 6,187 families were enrolled. Card utilization rates in the passive screening strategy were estimated at 60–94%. For a Canadian population, the increase in cost for passive screening, compared with no screening, is

Validation of classification algorithms for childhood diabetes identified from administrative data

213,584 and the gain in life years is 9.7 (

Validation of diabetes case definitions using administrative claims data

22,000 per life-year gained). Conclusions A BA ISCC screening programme targeting families of newborns is feasible in Canada. Passive distribution of ISCC at maternity is potentially effective and highly cost-effective.

Biofeedback for Nonneuropathic Daytime Voiding Disorders in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Vanderloo SE, Johnson JA, Reimer K, McCrea P, Nuernberger K, Krueger H, Aydede SK, Collet J‐P, Amed S. Validation of classification algorithms for childhood diabetes identified from administrative data.

Combining Both Generic and Disease-Specific Properties: Development of the McGill COPD Quality of Life Questionnaire

Diabet. Med. 28, 424–427 (2011)

Association between antibiotic use and risk of prostate cancer

PURPOSE Biofeedback has been used to treat children with symptoms of bladder dysfunction not responding to standard therapy alone. However, evidence of the effectiveness of biofeedback is scarce and is based on small studies. We conducted a systematic review of the literature to assess the effects of biofeedback as adjunctive therapy for symptoms of nonneuropathic voiding disorders in children up to age 18 years. MATERIALS AND METHODS We searched MEDLINE(®), Embase(®) and CENTRAL on the OvidSP(®) platform as well as conference proceedings for randomized trials presented at scientific conventions, symposia and workshops through August 13, 2013. Hand searches and review of reference lists of retrieved articles were also performed. RESULTS Five eligible studies were included in the systematic review, of which 4 (382 participants) were pooled in the meta-analysis based on available outcomes data. The overall proportion of cases with resolved incontinence at month 6 was similar in the biofeedback and control groups (OR 1.37 [95% CI 0.64 to 2.93], RD 0.07 [-0.09, 0.23]). There was also no significant difference in mean maximum urinary flow rate (mean difference 0.50 ml, range -0.56 to 1.55) or likelihood of urinary tract infection (OR 1.30 [95% CI 0.65 to 2.58]). CONCLUSIONS Current evidence does not support the effectiveness of biofeedback in the management of children with nonneuropathic voiding disorders. More high quality, randomized controlled trials are needed to better evaluate the effect of biofeedback.