Deva Thiruchelvam

Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study.

BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

The effect of tracheostomy timing during critical illness on long-term survival*

Background:Tracheostomy is common in intensive care unit patients, but the appropriate timing is controversial. Objective:To determine whether earlier tracheostomy is associated with greater long-term survival. Design:Retrospective cohort analysis. Setting:Acute care hospitals in Ontario, Canada (n = 114). Patients:All mechanically ventilated intensive care unit patients who received tracheostomy between April 1, 1992 and March 31, 2004, excluding extreme cases (<2 or ≥28 days) and children (<18 yrs). Measurements:For crude analyses, tracheostomy timing was classified as early (≤10 days) vs. late (>10 days) with mortality measured at multiple follow-up intervals. Proportional hazards analyses considered tracheostomy as a time-dependent variable to adjust for measurable confounders and possible survivor treatment bias. We used stratification, propensity score, and instrumental variable analyses to adjust for patient differences. Results:A total of 10,927 patients received tracheostomy during the study, of which one-third (n = 3758) received early and two-thirds late (n = 7169). Patients receiving early tracheostomy had lower unadjusted 90-day (34.8% vs. 36.9%; p = 0.032), 1 yr (46.5% vs. 49.8%; p = 0.001), and study mortality (63.9% vs. 67.2%; p < 0.001) than patients receiving late tracheostomy. Multivariable analyses treating tracheostomy as a time-dependent variable showed that each additional delay of 1 day was associated with increased mortality (hazard ratio 1.008, 95% confidence interval 1.004–1.012), equivalent to an increase in 90-day mortality from 36.2% to 37.6% per week of delay (relative risk increase 3.9%; number needed to treat, 71 patients to save one life per week delay). Limitations:This analysis provides guidance regarding timing but not patient selection for tracheostomy. Conclusions:Physicians performing early tracheostomy should not anticipate a large potential survival benefit. Future research should concentrate on identifying which patients will receive the most benefit.

HER2/neu and Ki-67 expression predict non-invasive recurrence following breast-conserving therapy for ductal carcinoma in situ.

Background:Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer that may progress to invasive cancer. Identification of factors that predict recurrence and distinguish DCIS from invasive recurrence would facilitate treatment recommendations. We examined the prognostic value of nine molecular markers on the risks of local recurrence (DCIS and invasive) among women treated with breast-conserving therapy.Methods:A total of 213 women who were treated with breast-conserving therapy between 1982 and 2000 were included; 141 received breast-conserving surgery alone and 72 cases received radiotherapy. We performed immunohistochemical staining on the DCIS specimen for nine markers: oestrogen receptor, progesterone receptor, Ki-67, p53, p21, cyclinD1, HER2/neu, calgranulin and psoriasin. We performed univariable and multivariable survival analyses to identify markers associated with the recurrence.Results:The rate of recurrence at 10 years was 36% for patients treated with breast-conserving surgery alone and 18% for women who received breast-conserving surgery and radiotherapy. HER2/neu+/Ki-67+ expression was associated with an increased risk of DCIS recurrence, independent of grade and age (HR=3.22; 95% CI: 1.47–7.03; P=0.003). None of the nine markers were predictive of invasive recurrence.Conclusion:Women with a HER2/neu/neu+/Ki67+ DCIS have a higher risk of developing DCIS local recurrence after breast-conserving surgery.

Delirium after elective surgery among elderly patients taking statins

Background: Postoperative delirium after elective surgery is frequent and potentially serious. We sought to determine whether the use of statin medications was associated with a higher risk of postoperative delirium than other medications that do not alter microvascular autoregulation. Methods: We conducted a retrospective cohort analysis of 284 158 consecutive patients in Ontario aged 65 years and older who were admitted for elective surgery. We identified exposure to statins from outpatient pharmacy records before admission. We identified delirium by examining hospital records after surgery. Results: About 7% (n = 19 501) of the patients were taking statins. Overall, 3195 patients experienced postoperative delirium; the rate was significantly higher among patients taking statins (14 per 1000) than among those not taking statins (11 per 1000) (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.15–1.47, p < 0.001). The increased risk of postoperative delirium persisted after we adjusted for multiple demographic, medical and surgical factors (OR 1.28, 95% CI 1.12–1.46) and exceeded the increased risk of delirium associated with prolonging surgery by 30 minutes (OR 1.20, 95% CI 1.19–1.21). The relative risk associated with statin use was somewhat higher among patients who had noncardiac surgery than among those who had cardiac surgery (adjusted OR 1.33, 95% CI 1.16–1.53), and extended to more complicated cases of delirium. We did not observe an increased risk of delirium with 20 other cardiac or noncardiac medications. Interpretation: The use of statins is associated with an increased risk of postoperative delirium among elderly patients undergoing elective surgery.

Intensive care outcomes in bone marrow transplant recipients: a population-based cohort analysis

IntroductionIntensive care unit (ICU) admission for bone marrow transplant recipients immediately following transplantation is an ominous event, yet the survival of these patients with subsequent ICU admissions is unknown. Our objective was to determine the long-term outcome of bone marrow transplant recipients admitted to an ICU during subsequent hospitalizations.MethodsWe conducted a population-based cohort analysis of all adult bone marrow transplant recipients who received subsequent ICU care in Ontario, Canada from 1 January 1992 to 31 March 2002. The primary endpoint was mortality at 1 year.ResultsA total of 2,653 patients received bone marrow transplantation; 504 of which received ICU care during a subsequent hospitalization. Patients receiving any major procedure during their ICU stay had higher 1-year mortality than those patients who received no ICU procedure (87% versus 44%, P < 0.0001). Death rates at 1 year were highest for those receiving mechanical ventilation (87%), pulmonary artery catheterization (91%), or hemodialysis (94%). In combination, the strongest independent predictors of death at 1 year were mechanical ventilation (odds ratio, 7.4; 95% confidence interval, 4.8 to 11.4) and hemodialysis (odds ratio, 8.7; 95% confidence interval, 2.1 to 36.7), yet no combination of procedures uniformly predicted 100% mortality.ConclusionThe prognosis of bone marrow transplant recipients receiving ICU care during subsequent hospitalizations is very poor but should not be considered futile.

Self-harm Emergencies After Bariatric Surgery: A Population-Based Cohort Study

IMPORTANCE Self-harm behaviors, including suicidal ideation and past suicide attempts, are frequent in bariatric surgery candidates. It is unclear, however, whether these behaviors are mitigated or aggravated by surgery. OBJECTIVE To compare the risk of self-harm behaviors before and after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS In this population-based, self-matched, longitudinal cohort analysis, we studied 8815 adults from Ontario, Canada, who underwent bariatric surgery between April 1, 2006, and March 31, 2011. Follow-up for each patient was 3 years prior to surgery and 3 years after surgery. MAIN OUTCOMES AND MEASURES Self-harm emergencies 3 years before and after surgery. RESULTS The cohort included 8815 patients of whom 7176 (81.4%) were women, 7063 (80.1%) were 35 years or older, and 8681 (98.5%) were treated with gastric bypass. A total of 111 patients had 158 self-harm emergencies during follow-up. Overall, self-harm emergencies significantly increased after surgery (3.63 per 1000 patient-years) compared with before surgery (2.33 per 1000 patient-years), equaling a rate ratio (RR) of 1.54 (95% CI, 1.03-2.30; P = .007). Self-harm emergencies after surgery were higher than before surgery among patients older than 35 years (RR, 1.76; 95% CI, 1.05-2.94; P = .03), those with a low-income status (RR, 2.09; 95% CI, 1.20-3.65; P = .01), and those living in rural areas (RR, 6.49; 95% CI, 1.42-29.63; P = .02). The most common self-harm mechanism was an intentional overdose (115 [72.8%]). A total of 147 events (93.0%) occurred in patients diagnosed as having a mental health disorder during the 5 years before the surgery. CONCLUSIONS AND RELEVANCE In this study, the risk of self-harm emergencies increased after bariatric surgery, underscoring the need for screening for suicide risk during follow-up.

Long-term outcomes of hypofractionation versus conventional radiation therapy after breast-conserving surgery for ductal carcinoma in situ of the breast.

PURPOSE Whole-breast radiation therapy (XRT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) may decrease the risk of local recurrence, but the optimal dose regimen remains unclear. Past studies administered 50 Gy in 25 fractions (conventional); however, treatment pattern studies report that hypofractionated (HF) regimens (42.4 Gy in 16 fractions) are frequently used. We report the impact of HF (vs conventional) on the risk of local recurrence after BCS for DCIS. METHODS AND MATERIALS All women with DCIS treated with BCS and XRT in Ontario, Canada from 1994 to 2003 were identified. Treatment and outcomes were assessed through administrative databases and validated by chart review. Survival analyses were performed. To account for systematic differences between women treated with alternate regimens, we used a propensity score adjustment approach. RESULTS We identified 1609 women, of whom 971 (60%) received conventional regimens and 638 (40%) received HF. A total of 489 patients (30%) received a boost dose, of whom 143 (15%) received conventional radiation therapy and 346 (54%) received HF. The median follow-up time was 9.2 years. The median age at diagnosis was 56 years (interquartile range [IQR], 49-65 years). On univariate analyses, the 10-year actuarial local recurrence-free survival was 86% for conventional radiation therapy and 89% for HF (P=.03). On multivariable analyses, age <45 years (hazard ratio [HR] = 2.4; 95% CI: 1.6-3.4; P<.0001), high (HR=2.9; 95% CI: 1.2-7.3; P=.02) or intermediate nuclear grade (HR=2.7; 95% CI: 1.1-6.6; P=.04), and positive resection margins (HR=1.4; 95% CI: 1.0-2.1; P=.05) were associated with an increased risk of local recurrence. HF was not significantly associated with an increased risk of local recurrence compared with conventional radiation therapy on multivariate analysis (HR=0.8; 95% CI: 0.5-1.2; P=.34). CONCLUSIONS The risk of local recurrence among individuals treated with HF regimens after BCS for DCIS was similar to that among individuals treated with conventional radiation therapy.

Risk of suicide after a concussion

Background: Head injuries have been associated with subsequent suicide among military personnel, but outcomes after a concussion in the community are uncertain. We assessed the long-term risk of suicide after concussions occurring on weekends or weekdays in the community. Methods: We performed a longitudinal cohort analysis of adults with diagnosis of a concussion in Ontario, Canada, from Apr. 1, 1992, to Mar. 31, 2012 (a 20-yr period), excluding severe cases that resulted in hospital admission. The primary outcome was the long-term risk of suicide after a weekend or weekday concussion. Results: We identified 235 110 patients with a concussion. Their mean age was 41 years, 52% were men, and most (86%) lived in an urban location. A total of 667 subsequent suicides occurred over a median follow-up of 9.3 years, equivalent to 31 deaths per 100 000 patients annually or 3 times the population norm. Weekend concussions were associated with a one-third further increased risk of suicide compared with weekday concussions (relative risk 1.36, 95% confidence interval 1.14–1.64). The increased risk applied regardless of patients’ demographic characteristics, was independent of past psychiatric conditions, became accentuated with time and exceeded the risk among military personnel. Half of these patients had visited a physician in the last week of life. Interpretation: Adults with a diagnosis of concussion had an increased long-term risk of suicide, particularly after concussions on weekends. Greater attention to the long-term care of patients after a concussion in the community might save lives because deaths from suicide can be prevented.

Impact of Boost Radiation in the Treatment of Ductal Carcinoma In Situ: A Population-Based Analysis

PURPOSE To report the outcomes of a population of women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and radiation and to evaluate the independent effect of boost radiation on the development of local recurrence. METHODS AND MATERIALS All women diagnosed with DCIS and treated with breast-conserving surgery and radiation therapy in Ontario from 1994 to 2003 were identified. Treatments and outcomes were identified through administrative databases and validated by chart review. The impact of boost radiation on the development of local recurrence was determined using survival analyses. RESULTS We identified 1895 cases of DCIS that were treated by breast-conserving surgery and radiation therapy; 561 patients received boost radiation. The cumulative 10-year rate of local recurrence was 13% for women who received boost radiation and 12% for those who did not (P=.3). The 10-year local recurrence-free survival (LRFS) rate among women who did and who did not receive boost radiation was 88% and 87%, respectively (P=.27), 94% and 93% for invasive LRFS (P=.58), and was 95% and 93% for DCIS LRFS (P=.31). On multivariable analyses, boost radiation was not associated with a lower risk of local recurrence (hazard ratio = 0.82, 95% confidence interval 0.59-1.15) (P=.25). CONCLUSIONS Among a population of women treated with breast-conserving surgery and radiation for DCIS, additional (boost) radiation was not associated with a lower risk of local or invasive recurrence.

Pregnancy and the risk of a traffic crash

Introduction: Pregnancy causes diverse physiologic and lifestyle changes that may contribute to increased driving and driving error. We compared the risk of a serious motor vehicle crash during the second trimester to the baseline risk before pregnancy. Methods: We conducted a population-based self-matched longitudinal cohort analysis of women who gave birth in Ontario between April 1, 2006, and March 31, 2011. We excluded women less than age 18 years, those living outside Ontario, those who lacked a valid health card identifier under universal insurance, and those under the care of a midwife. The primary outcome was a motor vehicle crash resulting in a visit to an emergency department. Results: A total of 507 262 women gave birth during the study period. These women accounted for 6922 motor vehicle crashes as drivers during the 3-year baseline interval (177 per mo) and 757 motor vehicle crashes as drivers during the second trimester (252 per mo), equivalent to a 42% relative increase (95% confidence interval 32%–53%; p < 0.001). The increased risk extended to diverse populations, varied obstetrical cases and different crash characteristics. The increased risk was largest in the early second trimester and compensated for by the third trimester. No similar increase was observed in crashes as passengers or pedestrians, cases of intentional injury or inadvertent falls, or self-reported risky behaviours. Interpretation: Pregnancy is associated with a substantial risk of a serious motor vehicle crash during the second trimester. This risk merits attention for prenatal care.