NSAIDs Linked to Leaks After GI Surgery


Anastomotic leak association found in a statewide cohort study.

Postoperative nonsteroidal anti-inflammatory drug (NSAID) use was associated with anastomotic leak after nonelective colorectal surgery in a population-based surgical database.

The painkillers were associated with a 24% elevated risk for anastomotic leak at the surgical junction after adjustment for other factors (P=0.04), Timo W. Hakkarainen, MD, of the University of Washington Medical Center, Seattle, and colleagues reported online in JAMA Surgery.

The database included 13,082 bariatric or colorectal surgery patients at 47 hospitals participating in Washington’s statewide Surgical Care and Outcomes Assessment Program.

But the association between anastomotic leaks within 90 days of surgery and NSAIDs — used by 24% of the patients — was only significant in the nonelective colorectal surgery group.

In that group, the odds of a leak were 70% higher with NSAID use (rate 12.3% versus 8.3% without NSAID use, P=0.01).

The study considered only post-operative use of the anti-inflammatory drugs, without information on preexisting use for cardiovascular prevention.

As postoperative use of NSAIDs have risen with availability of IV formulations, there have been concerns raised by small studies that NSAIDs impair anastomotic healing in the GI tract, Hakkarainen and colleagues noted.

“The results of this large statewide cohort study show that, among patients undergoing nonelective colorectal resection, postoperative NSAID administration is associated with a significantly increased risk for anastomotic complications. Given that other analgesic regimens are effective and well tolerated, these data may be enough for some surgeons to alter practice patterns,” the study concluded.

Leak was defined by reoperation, rescue stoma, revision of an anastomosis, or percutaneous drainage of an abscess. Results were controlled for age, sex, procedure type (bariatric or colorectal), operative approach, protective ostomy, comorbid conditions, body mass index, a low serum albumin level, and other postoperative analgesic use.

Risk-adjusted 90-day mortality was similar between groups.

Limitations included lack of data on which NSAID was used, at what dose, or how long.

Further study is needed to determine if there’s a dose effect, what the mechanism might be, if it’s limited to certain formulations, and if overall recovery is affected, the group added.

Watch for VTEs Early in TNF Inhibitor Course


Cohort study reports link between bDMARDs and VTE.

There are now more data to ponder as one considers the relation between rheumatoid arthritis (RA) treatment and the risk for venous thromboembolism (VTE) — a cohort study, based on a review of insurance claims, reports a modest link betweenbiological disease-modifying anti-rheumatic drugs (bDMARDs) and VTE.

It also found an increased relative incidence in hospitalization for VTE. The risk is greatest in the first 180 days of treatment.

However, the absolute increase in risk is low, at under 1%.

The investigators identified 29,481 RA patientswho were treated with conventional DMARDs, methotrexate, or bDMARDs for up to a year.

During follow-up, there were 191 VTE events, 31 of them tied to bDMARD use and 29 of those to tumor necrosis factor-alpha inhibitors.

While few of the comparisons were statistically significant, the hazard ratio of VTE for bDMARDs versus conventional DMARDs in the first 180 days was 2.48 (95% confidence interval: 1.14-5.39).

Antithyroid drug use in early pregnancy increased birth defect risk.


The treatment of hyperthyroidism during pregnancy with both methimazole/carbimazole and propylthiouracil was linked to birth defects, but the type of malformations differed, according to recent study findings.

The prevalence of birth defects was greater among children exposed to antithyroid drugsduring early pregnancy (propylthiouracil, 8%; methimazole/carbimazole, 9.1%; methimazole/carbimazole and propylthiouracil, 10.1%; P<.001), according to data. Researchers did not see an increased risk for birth defects in infants born to mothers treated with antithyroid drugs before or after pregnancy (no antithyroid drugs, 5.4%; nonexposed, 5.7%;P<.001).

“It is imperative to treat overt hyperthyroidism in pregnant women, but the use of [antithyroid drugs] in early pregnancy should be limited when possible,” the researchers said. “For the present, it may be optimal to shift women planning pregnancy from [methimazole/carbimazole] to [propylthiouracil] before pregnancy.”

The researchers used the Danish nationwide register-based cohort study, including 817,093 children live-born from 1996 to 2008 to determine how the use of antithyroid drugs used in early pregnancy increased the prevalence of birth defects.

Patients were assigned to the following groups:

  • Propylthiouracil (n=564);
  • Methimazole/carbimazole (n=1,097);
  • Methimazole/carbimazole and propylthiouracil (n=159);
  • No antithyroid drugs during pregnancy, but taken before or after pregnancy (n=3,543); and
  • Nonexposed females (n=811,730).

Data indicate that mothers who were assigned both methimazole/carbimazole (adjusted OR=1.66; 95% CI 1.35-2.04) and propylthiouracil (OR=1.41; 95% CI, 1.03-1.92) with maternal shift between methimazole/carbimazole and propylthiouracil during early pregnancy (OR=1.82; 95% CI, 1.08-3.07) demonstrated an increased prevalence of birth defects, researchers wrote.

In particular, methimazole/carbimazole and propylthiouracil were associated with urinary system malformation, and propylthiouracil with malformations in the face and neck region.

Moreover, choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies and aplasia cutis were common in methimazole/carbimazole-exposed children (combined, adjusted OR=21.8; 95% CI, 13.4-35.4), according to data.

Further studies are warranted to confirm these results, researchers wrote.

PERSPECTIVE
  • There is concern over whether carbimazole/methimazole or propylthiouracil is the most appropriate antithyroid drug to use when treating hyperthyroidism in pregnant women. Traditionally, propylthiouracil has been preferred, as it was felt to be associated with a lower risk for congenital abnormalities. However, concerns regarding propylthiouracil use have arisen owing to the rare complication of propylthiouracil-induced hepatitis in pregnancy, which can have catastrophic consequences.

    This study is very important, as it substantially adds to our current knowledge of birth defects associated with antithyroid drug exposure for carbimazole/methimazole and propylthiouracil. This study crucially highlighted that both carbimazole/methimazole and propylthiouracil were associated with an increased risk for birth defects. However the birth defects associated with propylthiouracil may be less common and severe than those associated with carbimazole/methimazole. Of particular note was that, in the small number of women who switched from carbimazole/methimazole to propylthiouracil during the first trimester, there was no obvious amelioration in the risk for birth defects. This implies switching to propylthiouracil during the first trimester may be too late to prevent carbimazole/methimazole-associated abnormalities. This would support the argument that in women considering pregnancy, propylthiouracil should be used instead of carbimazole/methimazole, as swapping in the first trimester may be too late. However, further studies are needed.

    The use of robust national registry data provided the very large population required to identify rare but clinically important outcomes and also protected against differential recall of exposure between carbimazole/methimazole and propylthiouracil-treated pregnancies. This is a particular strength as traditional reporting methods may be biased by clinicians’ preconceptions regarding these antithyroid drugs.

    • Peter N. Taylor, MRCP
    • Welsh clinical academic trainee in diabetes and endocrinology
      Thyroid Research Group
      Institute of Molecular and Experimental Medicine
      Cardiff University School of Medicine

Women’s intentions to breastfeed: a population-based cohort study.


Objective

Given that intention to breastfeed is a strong predictor of breastfeeding initiation and duration, the objectives of this study were to estimate the population-based prevalence and the factors associated with the intention to breastfeed.

Design

Retrospective population-based cohort study.

Setting

All hospitals in Ontario, Canada (1 April 2009–31 March 2010).

Population

Women who gave birth to live, term, singletons/twins.

Methods

Patient, healthcare provider, and hospital factors that may be associated with intention to breastfeed were analysed using univariable and multivariable regression.

Main outcome measures

Population-based prevalence of intention to breastfeed and its associated factors.

Results

The study included 92 364 women, of whom 78 806 (85.3%) intended to breastfeed. The odds of intending to breastfeed were higher amongst older women with no health problems and women who were cared for exclusively by midwives (adjusted OR 3.64, 95% CI 3.13–4.23). Being pregnant with twins (adjusted OR 0.73, 95% CI 0.57–0.94), not attending antenatal classes (adjusted OR 0.58, 95% CI 0.54–0.62), having previous term or preterm births (adjusted OR 0.79, 95% CI 0.78–0.81, and adjusted OR 0.87, 95% CI 0.82–0.93, respectively), and delivering in a level–1 hospital (adjusted OR 0.85, 95% CI 0.77–0.93) were associated with a lower intention to breastfeed.

Conclusions

In this population-based study ~85% of women intended to breastfeed their babies. Key factors that are associated with the intention to breastfeed were identified, which can now be targeted for intervention programmes aimed at increasing the prevalence of breastfeeding and improving overall child and maternal health.

Source:BJOG

Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States.


Abstract

Objective To determine whether use of serotonin or non-serotonin reuptake inhibitors near to delivery is associated with postpartum hemorrhage.

Design Cohort study.

Setting 2000-07 nationwide Medicaid data (Medicaid Analytic eXtract).

Population 106 000 pregnant women aged 12-55 with a diagnosis of mood or anxiety disorder. Women were categorized into four mutually exclusive exposure groups according to pharmacy dispensing data: current (delivery date), recent (1-30 days before delivery date), past (1-5 months before delivery date), and no exposure (reference group).

Main outcome measures Risk of postpartum hemorrhage by timing of exposure and by serotonin or non-serotonin reuptake inhibitors, classes of antidepressant, and antidepressant types. Relative risks and 95% confidence intervals adjusted for delivery year, risk factors for postpartum hemorrhage, indicators of severity of mood/anxiety disorder, other indications for antidepressants, and other drugs. High dimensional propensity score (hdPS) methods were used to empirically identify and adjust for additional factors.

Results 12 710 (12%) women had current exposure to serotonin reuptake inhibitor monotherapy, and 1495 (1.4%) women had current exposure to non-serotonin reuptake inhibitor monotherapy. The risk of postpartum hemorrhage was 2.8% among women with mood/anxiety disorders but no exposure to antidepressants, 4.0% in the current users of serotonin reuptake inhibitors, 3.8% in the current users of non-serotonin reuptake inhibitors, 3.2% in the recent users of serotonin reuptake inhibitors, 3.1% in the recent users of non-serotonin reuptake inhibitors, 2.5% in the past users of serotonin reuptake inhibitors, and 3.4% in the past users of non-serotonin reuptake inhibitors. Compared with no exposure, women with current exposure to serotonin reuptake inhibitors had a 1.47-fold increased risk of postpartum hemorrhage (95% confidence interval 1.33 to 1.62) and women with current non-serotonin reuptake inhibitor exposure had a 1.39-fold increased risk (1.07 to 1.81). Results were similar with hdPS adjustment. Women with current exposure to serotonin reuptake inhibitors had an adjusted excess risk of 1.26% (0.90% to 1.62%), with a number needed to harm of 80, and for women with current exposure to non-serotonin reuptake inhibitors the excess risk was 1.03% (0.07% to 1.99%), with a number needed to harm of 97. For exposure to serotonin reuptake inhibitors the relative risk was 1.19 (1.03 to 1.38) for recent exposure and 0.93 (0.82 to 1.06) for past exposure; for non-serotonin reuptake inhibitors the figures were 1.17 (0.80 to 1.70) and 1.26 (1.00 to 1.59), respectively. Current exposure to selective serotonin reuptake inhibitor monotherapy was also associated with postpartum hemorrhage (1.42, 1.27 to 1.57), as was current serotonin norepinephrine (noradrenaline) reuptake inhibitor (1.90, 1.37 to 2.63) and tricyclic monotherapy (1.77, 0.90 to 3.47). All types of selective serotonin reuptake inhibitors available for analysis and venlafaxine, a serotonin norepinephrine reuptake inhibitor, were significantly associated with postpartum hemorrhage.

Conclusions Exposure to serotonin and non-serotonin reuptake inhibitors, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclics, close to the time of delivery was associated with a 1.4 to 1.9-fold increased risk for postpartum hemorrhage. While potential confounding by unmeasured factors cannot be ruled out, these findings suggest that patients treated with antidepressants during late pregnancy are more likely to experience postpartum hemorrhage.

Source: BMJ

 

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE).


Background

Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations.

Methods

This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses.

Findings

The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03—1·45] per 10 μg/m3). For PM2·5 the HR was 1·18 (0·96—1·46) per 5 μg/m3. The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10—2·08) and 1·55 (1·05—2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99—1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95—1·07] per 20 μg/m3) or traffic intensity on the nearest street (HR 1·00 [0·97—1·04] per 5000 vehicles per day).

Interpretation

Particulate matter air pollution contributes to lung cancer incidence in Europe.

Source: Lancet

 

Perceived job insecurity as a risk factor for incident coronary heart disease: systematic review and meta-analysis.


Abstract

Objective To determine the association between self reported job insecurity and incident coronary heart disease.

Design A meta-analysis combining individual level data from a collaborative consortium and published studies identified by a systematic review.

Data sources We obtained individual level data from 13 cohort studies participating in the Individual-Participant-Data Meta-analysis in Working Populations Consortium. Four published prospective cohort studies were identified by searches of Medline (to August 2012) and Embase databases (to October 2012), supplemented by manual searches.

Review methods Prospective cohort studies that reported risk estimates for clinically verified incident coronary heart disease by the level of self reported job insecurity. Two independent reviewers extracted published data. Summary estimates of association were obtained using random effects models.

Results The literature search yielded four cohort studies. Together with 13 cohort studies with individual participant data, the meta-analysis comprised up to 174 438 participants with a mean follow-up of 9.7 years and 1892 incident cases of coronary heart disease. Age adjusted relative risk of high versus low job insecurity was 1.32 (95% confidence interval 1.09 to 1.59). The relative risk of job insecurity adjusted for sociodemographic and risk factors was 1.19 (1.00 to 1.42). There was no evidence of significant differences in this association by sex, age (<50 v ≥50 years), national unemployment rate, welfare regime, or job insecurity measure.

Conclusions The modest association between perceived job insecurity and incident coronary heart disease is partly attributable to poorer socioeconomic circumstances and less favourable risk factor profiles among people with job insecurity.

Source: BMJ

Invasive Management of ACS: The Kidneys Are All Right.


Despite early increases in acute kidney injury, invasive treatment is associated with better long-term outcomes than conservative management.
Invasive treatment options for acute coronary syndromes (ACS) might be underused in patients at high risk for renal disease because of concerns about contrast-induced renal failure and other complications. However, comparative data on renal outcomes in patients managed invasively versus conservatively are lacking. Therefore, investigators conducted a cohort study involving 10,516 patients presenting with non-ST-segment-elevation ACS in Alberta, Canada, 41% of whom received early invasive management (coronary catheterization within 2 days after hospital admission). Stratification according to baseline estimated glomerular filtration rate and propensity-score matching resulted in a cohort of 6768 participants.

Compared with conservative management, early invasive therapy was associated with an increased risk for acute renal injury (10.3% vs. 8.7%, P=0.019), but treatments did not differ in risk for dialysis (0.4% vs. 0.3%, P=0.670) during the index hospitalization. During a median follow-up of 2.5 years, the risk for progression to end-stage renal disease did not differ between the two groups (0.3 vs. 0.4 events per 100 person-years, P=0.712). Moreover, early invasive treatment was associated with reduced long-term mortality (2.4 vs. 3.4 events per 100 person-years; P<0.001). The relative reduction in mortality risk was consistent across all strata of baseline renal function.

COMMENT

Although early invasive treatment of acute coronary syndromes increased the risk for acute renal injury compared with conservative management, it did not affect risk for dialysis or progression to end-stage renal disease. The improvements in long-term survival at all levels of baseline renal function suggest that invasive therapy should not be withheld for fear of renal complications.

Source: NEJM

Unhealthy behaviours and disability in older adults: Three-City Dijon cohort study.


Abstract

Objectives To examine the individual and combined associations of unhealthy behaviours (low/intermediate physical activity, consuming fruit and vegetables less than once a day, current smoking/short term ex-smoking, never/former/heavy alcohol drinking), assessed at start of follow-up, with hazard of disability among older French adults and to assess the role of potential mediators, assessed repeatedly, of these associations.

Design Population based cohort study.

Setting Dijon centre of Three-City study.

Participants 3982 (2410 (60.5%) women) French community dwellers aged 65 or over included during 1999-2001; participants were disability-free at baseline when health behaviours were assessed.

Main outcome measure Hierarchical indicator of disability (no, light, moderate, severe) combining data from three disability scales (mobility, instrumental activities of daily living, basic activities of daily living) assessed five times between 2001 and 2012.

Results During the 12 year follow-up, 1236 participants (861 (69.7%) women) developed moderate or severe disability. Interval censored survival analyses (adjusted for age, sex, marital status, and education) showed low/intermediate physical activity (hazard ratio 1.72, 95% confidence interval 1.48 to 2.00), consuming fruit and vegetables less than once a day (1.24, 1.10 to 1.41), and current smoking/short term ex-smoking (1.26, 1.05 to 1.50) to be independently associated with an increased hazard of disability, whereas no robust association with alcohol consumption was found. The hazard of disability increased progressively with the number of unhealthy behaviours independently associated with disability (P<0.001); participants with three unhealthy behaviours had a 2.53 (1.86 to 3.43)-fold increased hazard of disability compared with those with none. Reverse causation bias was verified by excluding participants who developed disability in the first four years of follow-up; these analyses on 890 disability events yielded results similar to those in the main analysis. 30.5% of the association between the unhealthy behaviours score and disability was explained by body mass index, cognitive function, depressive symptoms, trauma, chronic conditions, and cardiovascular disease and its risk factors; the main contributors were chronic conditions and, to a lesser extent, depressive symptoms, trauma, and body mass index.

Conclusions An unhealthy lifestyle is associated with greater hazard of incident disability, and the hazard increases progressively with the number of unhealthy behaviours. Chronic conditions, depressive symptoms, trauma, and body mass index partially explained this association.

Source: BMJ

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE).


Background

Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations.

Methods

This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses.

Findings

The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03—1·45] per 10 μg/m3). For PM2·5 the HR was 1·18 (0·96—1·46) per 5 μg/m3. The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10—2·08) and 1·55 (1·05—2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99—1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95—1·07] per 20 μg/m3) or traffic intensity on the nearest street (HR 1·00 [0·97—1·04] per 5000 vehicles per day).

Interpretation

Particulate matter air pollution contributes to lung cancer incidence in Europe.

Source: Lancet