Ruth Croxford

Which Patients Are Most Likely to Benefit From Total Joint Arthroplasty

OBJECTIVE To evaluate patient predictors of good outcome following total joint arthroplasty (TJA). METHODS A population cohort with hip/knee arthritis (osteoarthritis [OA] or inflammatory arthritis) ages ≥55 years was recruited between 1996 and 1998 (baseline) and assessed annually for demographics, troublesome joints, health status, and overall hip/knee arthritis severity using the Western Ontario and McMaster Universities OA Index (WOMAC). Survey data were linked with administrative databases to identify primary TJAs. Good outcome was defined as an improvement in WOMAC summary score greater than or equal to the minimal important difference (MID; 0.5 SD of the mean change). Logistic regression and Akaikes information criterion were used to determine the optimal number of predictors and the best model of that size. Log Poisson regression was used to determine the relative risk (RR) for a good outcome. RESULTS Primary TJA was performed in 202 patients (mean age 71.0 years; 79.7% female; 82.7% with >1 troublesome hip/knee; 65.8% knee replacements). Mean improvement in WOMAC summary score was 10.2 points (SD 18.05; MID 9 points). Of these patients, 53.5% experienced a good outcome. Four predictors were optimal. The best 4-variable model included pre-TJA WOMAC, comorbidity, number of troublesome hips/knees, and arthritis type (C statistic 0.80). The probability of a good outcome was greater with worse (higher) pre-TJA WOMAC summary scores (adjusted RR 1.32 per 10-point increase; P < 0.0001), fewer troublesome hips/knees (adjusted RR 0.82 per joint; P = 0.002), OA (adjusted RR for rheumatoid arthritis versus OA 0.33; P = 0.009), and fewer comorbidities (adjusted RR per condition 0.88; P = 0.01). CONCLUSION In an OA cohort with a high prevalence of multiple troublesome joints and comorbidity, only half achieved a good TJA outcome, defined as improved pain and disability. A more comprehensive assessment of the benefits and risks of TJA is warranted.

Cardiovascular Safety of Inhaled Long-Acting Bronchodilators in Individuals With Chronic Obstructive Pulmonary Disease

IMPORTANCE Chronic obstructive pulmonary disease (COPD) is a common and deadly disease. Long-acting inhaled β-agonists and anticholinergics, first-line medications for COPD, have been associated with increased risk of cardiovascular outcomes. When choosing between the medications, patients and physicians would benefit from knowing which has the least risk. OBJECTIVE To assess the association of these classes of medications with the risk of hospitalizations and emergency department visits for cardiovascular events. DESIGN We conducted a nested case-control analysis of a retrospective cohort study. We compared the risk of events between patients newly prescribed inhaled long-acting β-agonists and anticholinergics, after matching and adjusting for prognostic factors. SETTING Health care databases from Ontario, the largest province of Canada, with a multicultural population of approximately 13 million. PARTICIPANTS All individuals 66 years or older meeting a validated case definition of COPD, based on health administrative data, and treated for COPD from September 1, 2003, through March 31, 2009. EXPOSURE New use of an inhaled long-acting β-agonist or long-acting anticholinergic. MAIN OUTCOME AND MEASURES An emergency department visit or a hospitalization for a cardiovascular event. RESULTS Of 191 005 eligible patients, 53 532 (28.0%) had a hospitalization or an emergency department visit for a cardiovascular event. Newly prescribed long-acting inhaled β-agonists and anticholinergics were associated with a higher risk of an event compared with nonuse of those medications (respective adjusted odds ratios, 1.31 [95% CI, 1.12-1.52; P < .001] and 1.14 [1.01-1.28; P = .03]). We found no significant difference in events between the 2 medications (adjusted odds ratio of long-acting inhaled β-agonists compared with anticholinergics, 1.15 [95% CI, 0.95-1.38; P = .16]). CONCLUSIONS AND RELEVANCE Among older individuals with COPD, new use of long-acting β-agonists and anticholinergics is associated with similar increased risks of cardiovascular events. Close monitoring of COPD patients requiring long-acting bronchodilators is needed regardless of drug class.

Effect of Maternal and Postweaning Folic Acid Supplementation on Mammary Tumor Risk in the Offspring

Intrauterine and early life exposure to folic acid has significantly increased in North America owing to folic acid fortification, widespread supplemental use, and periconceptional supplementation. We investigated the effects of maternal and postweaning folic acid supplementation on mammary tumor risk in the offspring. Female rats were placed on a control or folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, female pups from each maternal diet group were randomized to the control or supplemented diet and mammary tumors were induced with 7,12 dimethylbenz[a]anthracene at puberty. At necropsy, mammary tumor parameters, genomic DNA methylation, and DNA methyltransferase activity were determined in the offspring. Both maternal and postweaning folic acid supplementation significantly increased the risk of mammary adenocarcinomas in the offspring (OR = 2.1, 95% CI 1.2-3.8, P = 0.008 and OR = 1.9, 95% CI 1.1-3.3, P = 0.03, respectively). Maternal folic acid supplementation also significantly accelerated the rate of mammary adenocarcinoma appearance (P = 0.002) and increased the multiplicity of mammary adenocarcinomas (P = 0.008) in the offspring. Maternal, but not postweaning, folic acid supplementation significantly reduced global DNA methylation (P = 0.03), whereas postweaning, but not maternal, folic acid supplementation significantly decreased DNA methyltransferase activity (P = 0.05) in nonneoplastic mammary glands of the offspring. Our findings suggest that a high intrauterine and postweaning dietary exposure to folic acid may increase the risk of mammary tumors in the offspring. Further, they suggest that this tumor-promoting effect may be mediated in part by altered DNA methylation and DNMT activity.

THE ROLE OF ADJUVANT ADENOIDECTOMY AND TONSILLECTOMY IN THE OUTCOME OF THE INSERTION OF TYMPANOSTOMY TUBES

BACKGROUND Otitis media is the most common medical problem in young children. The usual surgical treatment is myringotomy with insertion of tympanostomy tubes. There is debate about the usefulness of concomitant adenoidectomy or adenotonsillectomy. We examined the effects of these adjuvant procedures on the rates of reinsertion of tympanostomy tubes and rehospitalization for conditions related to otitis media. METHODS Using hospital discharge records for the period 1995 through 1997, we examined the results of surgery for all 37,316 children (defined as persons 19 years of age or younger) in Ontario, Canada, who received tympanostomy tubes as their first surgical treatment for otitis media. We determined the time to the first readmission for conditions related to otitis media and the time to the first reinsertion of tympanostomy tubes. RESULTS As compared with treatment involving the insertion of tympanostomy tubes alone, adjuvant adenoidectomy was associated with a reduction in the likelihood of reinsertion of tympanostomy tubes (relative risk, 0.5; 95 percent confidence interval, 0.5 to 0.6; P<0.001) and the likelihood of readmission for conditions related to otitis media (relative risk, 0.5; 95 percent confidence interval, 0.5 to 0.6; P<0.001). The risk of these outcomes was further reduced if an adjuvant adenotonsillectomy was performed. The effect was age-related. Children as young as one year appeared to benefit from adjuvant adenotonsillectomy; the benefit of an adjuvant adenoidectomy was apparent in two-year-olds and was greatest for children three years of age or older. CONCLUSIONS Performing an adenoidectomy at the time of the initial insertion of tympanostomy tubes substantially reduces the likelihood of additional hospitalizations and operations related to otitis media among children two years of age or older.

A systematic review of medical practice variation in OECD countries

BACKGROUND Major variations in medical practice have been documented internationally. Variations raise questions about the quality, equity, and efficiency of resource allocation and use, and have important implications for health care and health policy. OBJECTIVE To perform a systematic review of the peer-reviewed literature on medical practice variations in OECD countries. METHODS We searched MEDLINE to find publications on medical practice variations in OECD countries published between 2000 and 2011. We present an overview of the characteristics of published studies as well as the magnitude of variations for select high impact conditions. RESULTS A total of 836 studies were included. Consistent with the gray literature, there were large variations across regions, hospitals and physician practices for almost every condition and procedure studied. Many studies focused on high-impact conditions, but very few looked at the causes or outcomes of medical practice variations. CONCLUSION While there were an overwhelming number of publications on medical practice variations the coverage was broad and not often based on a theoretical construct. Future studies should focus on conditions and procedures that are clinically important, policy relevant, resource intensive, and have high levels of public awareness. Further study of the causes and consequences of variations is important.

A population-based nested case-control study of the costs of hip and knee replacement surgery.

Background:Studies of total joint arthroplasty (TJA) have not evaluated the costs and outcomes in the context of expected arthritis worsening. Objectives:Using a cost-consequence approach, to examine changes in direct health care costs and arthritis severity after TJA for hip/knee arthritis compared with contemporaneous changes in matched controls. Research Design:Case control study nested in a population-based prospective cohort. Subjects:In a population cohort with disabling hip/knee osteoarthritis followed from 1996 to 2003, primary TJA recipients were matched with cohort nonrecipients on age, sex, region of residence, comorbidity, and inflammatory arthritis diagnosis. Measures:Pre- and postoperative total and arthritis-attributable direct health care costs, arthritis severity, and general health status were compared for cases and matched controls. Results:Of 2109 participants with no prebaseline TJA, 185 cases received a single elective TJA during the follow-up period; of these, 183 cases and controls were successfully matched. Mean age was 71 years, 77.6% were female, 35.5% had ≥2 comorbidities, and 81.5% had ≥2 joints affected. At baseline, controls had less pain and disability and lower total and arthritis-attributable health care costs than cases. After surgery, although overall health care utilization was unchanged, cases experienced significant decreases in arthritis-attributable costs (mean decrease

All-Cause Mortality and Serious Cardiovascular Events in People with Hip and Knee Osteoarthritis: A Population Based Cohort Study

278 including prescription drugs) and pain and disability (P < 0.0001 for all). Over the same time period, controls experienced a significant increase in total health care costs (mean increase

Effect of maternal and postweaning folic acid supplementation on colorectal cancer risk in the offspring

1978 including prescription drugs, P = 0.04) and no change or worsening of their arthritis status. Conclusion:Compared with matched controls, arthroplasty is associated with significant reductions in pain, disability, and arthritis-attributable direct costs.

Increased Risk of Complications Following Total Joint Arthroplasty in Patients With Rheumatoid Arthritis

Background Because individuals with osteoarthritis (OA) avoid physical activities that exacerbate symptoms, potentially increasing risk for cardiovascular disease (CVD) and death, we assessed the relationship between OA disability and these outcomes. Methods In a population cohort aged 55+ years with at least moderately severe symptomatic hip and/or knee OA, OA disability (Western Ontario McMaster Universities (WOMAC) OA scores; Health Assessment Questionnaire (HAQ) walking score; use of walking aids) and other covariates were assessed by questionnaire. Survey data were linked to health administrative data to determine the relationship between baseline OA symptom severity to all-cause mortality and occurrence of a composite CVD outcome (acute myocardial infarction, coronary revascularization, heart failure, stroke or transient ischemic attack) over a median follow-up of 13.2 and 9.2 years, respectively. Results Of 2156 participants, 1,236 (57.3%) died and 822 (38.1%) experienced a CVD outcome during follow-up. Higher (worse) baseline WOMAC function scores and walking disability were independently associated with a higher all-cause mortality (adjusted hazard ratio, aHR, per 10-point increase in WOMAC function score 1.04, 95% confidence interval, CI 1.01–1.07, p = 0.004; aHR per unit increase in HAQ walking score 1.30, 95% CI 1.22–1.39, p<0.001; and aHR for those using versus not using a walking aid 1.51, 95% CI 1.34–1.70, p<0.001). In survival analysis, censoring on death, risk of our composite CVD outcome was also significantly and independently associated with greater baseline walking disability ((aHR for use of a walking aid  = 1.27, 95% CI 1.10–1.47, p = 0.001; aHR per unit increase in HAQ walking score  = 1.17, 95% CI 1.08–1.27, p<0.001). Conclusions Among individuals with hip and/or knee OA, severity of OA disability was associated with a significant increase in all-cause mortality and serious CVD events after controlling for multiple confounders. Research is needed to elucidate modifiable mechanisms.

Combination Long-Acting β-Agonists and Inhaled Corticosteroids Compared With Long-Acting β-Agonists Alone in Older Adults With Chronic Obstructive Pulmonary Disease

Background Intrauterine and early life exposure to folic acid has significantly increased in North America owing to folic acid fortification, widespread supplemental use and periconceptional folic acid supplementation. The effect of maternal and postweaning folic acid supplementation on colorectal cancer risk in the offspring was investigated. Methods Female rats were placed on a control or supplemental (2.5× the control) diet prior to mating and during pregnancy and lactation. At weaning, male pups from each maternal diet group were randomised to the control or supplemental diet (n=55 per each of the four maternal/pup diet groups) for 31 weeks and colorectal cancer was induced by azoxymethane at 5 weeks of age. At necropsy, colorectal cancer parameters as well as colorectal epithelial proliferation, apoptosis and global DNA methylation were determined in the offspring. Results Maternal, but not postweaning, folic acid supplementation significantly reduced the odds of colorectal adenocarcinoma by 64% in the offspring (OR 0.36; 95% CI 0.18 to 0.71; p=0.003). Pups from the dams fed the control diet that were given postweaning folic acid supplementation had significantly higher tumour multiplicity and burden than other groups (p<0.05). Maternal and postweaning folic acid supplementation interacted in a manner that decreased rectal epithelial proliferation (p<0.05). Both maternal and postweaning folic acid supplementation significantly decreased DNA damage in the rectum (p<0.05). Maternal folic acid supplementation significantly increased (p=0.007), whereas postweaning supplementation significantly decreased (p<0.001), colorectal global DNA methylation. Conclusions The data suggest for the first time that maternal folic acid supplementation at the level equivalent to the average postfortification total folate intake in North America and to that recommended to women at reproductive age protects against the development of colorectal cancer in the offspring. This protective effect may be mediated in part by increased global DNA methylation and decreased epithelial proliferation and DNA damage in the colorectum.