Tetyana Kendzerska

Obstructive Sleep Apnea and Incident Diabetes. A Historical Cohort Study

RATIONALE Despite emerging evidence that obstructive sleep apnea (OSA) may cause metabolic disturbances independently of other known risk factors, it remains unclear whether OSA is associated with incident diabetes. OBJECTIVES To evaluate whether risk of incident diabetes was related to the severity and physiologic consequences of OSA. METHODS A historical cohort study was conducted using clinical and provincial health administrative data. All adults without previous diabetes referred with suspected OSA who underwent a diagnostic sleep study at St. Michaels Hospital (Toronto, Canada) between 1994 and 2010 were followed through health administrative data until May 2011 to examine the occurrence of diabetes. All OSA-related variables collected from the sleep study were examined as predictors in Cox regression models, controlling for sex, age, body mass index, smoking status, comorbidities, and income. MEASUREMENTS AND MAIN RESULTS Over a median follow-up of 67 months, 1,017 (11.7%) of 8,678 patients developed diabetes, giving a cumulative incidence at 5 years of 9.1% (95% confidence interval, 8.4-9.8%). In fully adjusted models, patients with apnea-hypopnea index (AHI) greater than 30 had a 30% higher hazard of developing diabetes than those with AHI less than 5. Among other OSA-related variables, AHI in rapid eye movement sleep and time spent with oxygen saturation less than 90% were associated with incident diabetes, as were heart rate, neck circumference, and sleep time. CONCLUSIONS Among people with OSA, and controlling for multiple confounders, initial OSA severity and its physiologic consequences predicted subsequent risk for incident diabetes.

Obstructive sleep apnea and the prevalence and incidence of cancer

Background: A link between obstructive sleep apnea and cancer development or progression has been suggested, possibly through chronic hypoxemia, but supporting evidence is limited. We examined the association between the severity of obstructive sleep apnea and prevalent and incident cancer, controlling for known risk factors for cancer development. Methods: We included all adults referred with possible obstructive sleep apnea who underwent a first diagnostic sleep study at a single large academic hospital between 1994 and 2010. We linked patient data with data from Ontario health administrative databases from 1991 to 2013. Cancer diagnosis was derived from the Ontario Cancer Registry. We assessed the cross-sectional association between obstructive sleep apnea and prevalent cancer at the time of the sleep study (baseline) using logistic regression analysis. Cox regression models were used to investigate the association between obstructive sleep apnea and incident cancer among patients free of cancer at baseline. Results: Of 10 149 patients who underwent a sleep study, 520 (5.1%) had a cancer diagnosis at baseline. Over a median follow-up of 7.8 years, 627 (6.5%) of the 9629 patients who were free of cancer at baseline had incident cancer. In multivariable regression models, the severity of sleep apnea was not significantly associated with either prevalent or incident cancer after adjustment for age, sex, body mass index and smoking status at baseline (apnea–hypopnea index > 30 v. < 5: adjusted odds ratio [OR] 0.96, 95% confidence interval [CI] 0.71–1.30, for prevalent cancer, and adjusted hazard ratio [HR] 1.02, 95% CI 0.80–1.31, for incident cancer; sleep time spent with oxygen saturation < 90%, per 10-minute increase: adjusted OR 1.01, 95% CI 1.00–1.03, for prevalent cancer, and adjusted HR 1.00, 95% CI 0.99–1.02, for incident cancer). Interpretation: In a large cohort, the severity of obstructive sleep apnea was not independently associated with either prevalent or incident cancer. Additional studies are needed to elucidate whether there is an independent association with specific types of cancer.

A systematic review of fatigue in patients with traumatic brain injury: The course, predictors and consequences

BACKGROUND Fatigue is common after traumatic brain injury (TBI). Its risk factors, natural history and consequences are uncertain. Best-evidence synthesis was used to address the gaps. METHODS Five databases were searched for relevant peer-reviewed studies. Of the 33 articles appraised, 22 longitudinal studies were selected. Results were reported separately based on their timing of baseline assessment. RESULTS All studies document changes in fatigue frequency and severity with time, irrespective of setting or TBI severity. There is limited evidence for certain clinical and psychosocial variables as predictors of fatigue severity at follow-up. Early fatigue severity predicted persistent post-concussive symptoms and Glasgow outcome score at follow-up. CONCLUSIONS Fatigue is present before and immediately following injury, and can persist long term. The variation in findings supports the idea of fatigue in TBI as a nonhomogeneous entity, with different factors influencing the course of new onset or chronic fatigue. To decrease the heterogeneity, we emphasize the need for agreement on a core set of relevant fatigue predictors, definitions and outcome criteria. PROSPERO registry number: CRD42013004262.

Self-report instruments for assessing sleep dysfunction in an adult traumatic brain injury population: A systematic review

OBJECTIVES To review the number and characteristics of self-reported sleep measures used to evaluate impaired sleep/wakefulness in traumatic brain injury (TBI) populations. METHODS We conducted a comprehensive peer-reviewed literature search of Medline, Embase, PsycINFO, CINAHL, and various bibliographies. Only standardized self-report measures for evaluating sleep dysfunction and its signs were taken into consideration. RESULTS Sixteen self-report measures used in TBI research and clinical practices were identified. Five were generic, five symptom-related, and six were condition-specific measures. The Pittsburgh sleep quality index and Epworth sleepiness scale were partially validated in post-acute TBI. CONCLUSION Although no instrument has been specifically developed for TBI patients, there are scientific benefits to using the existing measures. However, additional research is needed to examine their applicability to the TBI population. The design and introduction of a new instrument able to triage sleep-related complaints between depressive, other medical, and primary sleep disorders-with a section for caregiver reports-might assist in the identification of the etiology of sleep dysfunction in persons with TBI. In choosing or developing a sleep measure, researchers and clinicians must consider the specific domains they want to screen, diagnose, or monitor. Polysomnography is recommended for diagnosing specific sleep disorders that cannot be diagnosed solely using a self-report measure.

Incident Cardiovascular Events and Death in Individuals With Restless Legs Syndrome or Periodic Limb Movements in Sleep: A Systematic Review

Study Objectives To systematically review the current evidence examining restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) as prognostic factors for all-cause mortality and incident cardiovascular events (CVE) in longitudinal studies published in the adult population. Methods All English language studies (from 1947 to 2016) found through Medline and Embase, as well as bibliographies of identified articles, were considered eligible. Quality was evaluated using published guidelines. Results Among 18 cohorts (reported in 13 manuscripts), 15 evaluated the association between RLS and incident CVE and/or all-cause mortality and 3 between PLMS and CVE and mortality. The follow-up periods ranged from 2 to 20 years. A significant relationship between RLS and CVE was reported in four cohorts with a greater risk suggested for severe RLS with longer duration and secondary forms of RLS. Although a significant association between RLS and all-cause mortality was reported in three cohorts, a meta-analysis we conducted of the four studies of highest quality found no association (pooled hazard ratio = 1.09, 95% confidence interval: 0.80-1.78). A positive association between PLMS and CVE and/or mortality was demonstrated in all included studies with a greater risk attributed to PLMS with arousals. Conclusions The available evidence on RLS as a prognostic factor for incident CVE and all-cause mortality was limited and inconclusive; RLS duration, severity, and secondary manifestations may be important in understanding a possible relationship. Although very limited, the current evidence suggests that PLMS may be a prognostic factor for incident CVE and mortality.

Efficacy of oral iron therapy in improving the developmental outcome of pre-school children with non-anaemic iron deficiency: a systematic review.

OBJECTIVE To systematically review the efficacy and safety of oral Fe therapy in pre-school children (1–5 years) with non-anaemic Fe deficiency, determined by children’s developmental and haematological status and the incidence of reported side-effects. DESIGN A random-effects model was used to show mean differences with 95% confidence intervals of developmental and haematological scores between Fe-treated and non-treated groups. SETTING MEDLINE, EMBASE, Cochrane library and bibliographies of identified articles were searched up to September 2011. Randomized and observational studies were assessed by two reviewers independently. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment and completeness of follow-up. SUBJECTS From the titles of 743 articles, full text review was completed on forty-six and two randomized trials of acceptable quality met the inclusion criteria. The two trials included a total of sixty-nine children. RESULTS One study showed a statistically significant difference in the post-treatment Mental Developmental Index score among children who received oral Fe therapy v. no therapy (mean difference56?3, 95% CI 1?5, 11?0, P value not provided). Both studies showed significant improvement in serum ferritin level (mg/l: mean difference551? 1, 95% CI 33?6, 68?6, P,0?01 and mean difference517?1, 95% CI 7?5, 26?6, P value not provided, respectively) in children who received Fe therapy. CONCLUSIONS Evidence is insufficient to recommend oral Fe therapy to children with non-anaemic Fe deficiency. There is urgent need of conducting adequately powered, randomized trials examining the efficacy of oral Fe therapy in pre-school children with non-anaemic Fe deficiency.

Ten-year trends in direct costs of asthma: a population-based study

There is little information on recent trends in the economic burden of asthma. Our objective was to estimate the excess costs of asthma and their trend in British Columbia, Canada, from 2002 to 2011.

The Effect of Patient Neighborhood Income Level on the Purchase of Continuous Positive Airway Pressure Treatment among Patients with Sleep Apnea

RATIONALE The cost of continuous positive airway pressure (CPAP) treatment for patients with low socioeconomic status may be an important barrier to successful treatment of obstructive sleep apnea under a copayment health care system. OBJECTIVES We evaluated an association between patient neighborhood income level and the purchase of a CPAP device under a cost-sharing health care insurance system. METHODS All adults who underwent a first diagnostic sleep study at St. Michaels Hospital (Toronto, ON, Canada) between 2004 and 2010 were included. Severity of obstructive sleep apnea was determined by the apnea-hypopnea index (AHI) and level of daytime sleepiness (by the Epworth Sleepiness Scale). Patient data were linked to provincial health administrative data from 1991 to 2013 to determine the purchase of CPAP equipment, comorbidities, neighborhood income, and rural status at baseline. Neighborhood income was categorized into quintiles, ranked from poorest (Q1) to wealthiest (Q5). Assuming that the majority of participants with severe obstructive sleep apnea (AHI > 30 events/h) and excessive daytime sleepiness (Epworth Sleepiness Scale ≥ 10) would have been strongly recommended CPAP, we evaluated the association between patient neighborhood income and purchase of a CPAP device in this group via multivariable Cox regressions. MEASUREMENTS AND MAIN RESULTS Of the 695 participants with severe obstructive sleep apnea and excessive daytime sleepiness, 400 (58%) purchased a CPAP device. Patients who accepted CPAP were more likely to live in a higher-income neighborhood. Cumulative incidence of CPAP acceptance at 6 months was 43% for individuals in a low-income neighborhood (Q1) and 52% in combined higher-income neighborhoods (Q2-5) (P = 0.05). Controlling for sex and age, living in higher-income neighborhoods was associated with a 27% increased chance of accepting CPAP compared with the lowest-income neighborhood (hazard ratio Q2-5 vs. Q1, 1.27; 95% confidence interval, 0.98-1.64; P = 0.07). CONCLUSIONS Living in an unfavorable neighborhood is not an obstacle to CPAP treatment among symptomatic patients with severe obstructive sleep apnea under a copayment health care system. However, a potential 27% improvement in CPAP acceptance associated with higher neighborhood income is not inconsequential. Also, the overall CPAP acceptance rate was relatively low, suggesting that obstacles other than finances are primarily responsible.

Fatigue in adults with traumatic brain injury: predictors and consequences. A systematic review of longitudinal study protocols

BackgroundDespite strong indications that fatigue is the most common and debilitating symptom after traumatic brain injury, little is known about its frequency, natural history, or relation to other factors. The current protocol outlines a strategy for a systematic review that will identify, assess, and critically appraise studies that assessed predictors for fatigue and the consequences of fatigue on at least two separate time points following traumatic brain injury.Methods/designMEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CINAHL, and PsycINFO will be systematically searched for relevant peer-reviewed studies. Reference lists of eligible papers will also be searched. All English language studies with a longitudinal design that focus on fatigue in adults with primary-impact traumatic brain injury will be included. Studies on fatigue following brain injury due to secondary pathological processes (intracranial complications, edema, ischemia/infarction, and systemic intracranial conditions) will be excluded. Excluded studies, along with the reasons for exclusion will be reported. Two independent reviewers will conduct all levels of screening, data abstraction, and quality appraisal. Randomized control trial data will be treated as a cohort. The quality will be assessed using the criteria defined by Hayden and colleagues. The review will be conducted and reported in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.ConclusionsThe review will summarize the current knowledge in the field with the aim of increasing understanding and guiding future research on the associations between fatigue and clinically important factors, as well as the consequences of fatigue in traumatic brain injury. PROSPERO registry number: CRD42013004262.

History of Asthma in Patients with Chronic Obstructive Pulmonary Disease. A Comparative Study of Economic Burden.

RATIONALE A diagnosis of asthma is considered an independent risk factor for chronic obstructive pulmonary disease (COPD). However, little is known about health service use patterns in patients with COPD who have a history of asthma in comparison with those without such a history, especially regarding comorbid conditions. OBJECTIVES To estimate the excess costs of COPD in patients with a history of asthma (COPD+asthma) versus those with COPD without such a history (COPD-only); to estimate excess costs attributable to inpatient care, outpatient care, medications, and community care; and to estimate excess costs attributable to comorbid conditions. METHODS We used vital statistics, inpatient and outpatient encounters, filled prescription records, and community care data of patients in British Columbia, Canada, from 1997 to 2012 to create propensity score-matched COPD+asthma and COPD-only cohorts. We calculated and compared the excess medical costs (in 2012 Canadian dollars [