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BACKGROUND: Despite expert recommendations for use, limited evidence identifies effectiveness of mechanical insufflation-exsufflation (MI-E) in addressing respiratory morbidity and resultant health care utilization and costs for individuals with neuromuscular disorders. We examined the impact of provision of publicly funded MI-E devices on health care utilization, health care costs, and survival trajectory. METHODS: This is a retrospective pre/post cohort study linking data on prospectively recruited participants using MI-E to health administrative databases to quantify outcomes. RESULTS: We linked data from 106 participants (8 age < 15 y) and determined annualized health care use pre/post device. We found no difference in emergency department (ED) visit or hospital admission rates. Following MI-E approval, participants required fewer hospital days (median [interquartile range] [IQR]) 0 [0-9] vs 0 [0-4], P = .03). Rates of physician specialist visits also decreased (median IQR 7 [4-11] vs 4 [2-7], P < .001). Conversely, rates of home care nursing and homemaking/personal support visits increased. Following MI-E, total costs were lower for 59.4%, not different for 13.2%, and higher for 27.4%. Physician billing costs decreased whereas home care costs increased. Regression modeling identified pre-MI-E costs were the most important predictor of costs after approval. At 12 months, 23 (21.7%) participants had died. Risk of death was higher for those using more medical devices (hazard ratio 1.12, [95% CI 1.02-1.22]) in the home. CONCLUSIONS: Provision of publicly funded MI-E devices did not influence rates of ED visits or hospital admission but did shift health care utilization and costs from the acute care to community sector. Although increased community costs negated cost savings from physician billings, evidence suggests costs savings from reduced hospital days and fewer specialist visits. Risk of death was highest in individuals requiring multiple medical technologies. [ABSTRACT FROM AUTHOR]

Vitamin B6 is important in fetal development, but little is known of the vitamin B6 status of pregnant women and newborns in North America and potential modifying factors. This prospective study determined maternal and cord plasma concentrations of pyridoxal 5′ phosphate (PLP; an indicator of vitamin B6 status) in a convenience sample of 368 Canadian pregnant women and their newborns. The association of maternal intake of vitamin B6 and fetal genetic variants with cord plasma PLP and homocysteine concentrations was also examined. Dietary and supplemental intakes of vitamin B6 were assessed in early and mid to late pregnancy. PLP concentrations were measured in maternal plasma in early pregnancy and at delivery, and in cord plasma. Six fetal variants of the MTHFR and CβS genes were assessed for their association with cord plasma PLP and homocysteine concentrations. Geometric mean (95% CI) PLP concentrations were 107 (98, 116) nmol/L in early pregnancy and 58 (53, 62) nmol/L at delivery, respectively, and 296 (275, 319) nmol/L in cord blood ( p < .0001). During early pregnancy and at delivery, 3.6% and 5.5% of women had plasma PLP concentrations <20 nmol/L, respectively. Ninety eight percent of the women with supplemental B6 intake of at least the recommended dietary allowance had PLP concentrations >20 nmol/L. Fetal genetic variants were not associated with cord PLP and homocysteine concentrations. Vitamin B6 deficiency is uncommon in a cohort of Canadian pregnant women due largely to prevalent vitamin B6 supplement use. [ABSTRACT FROM AUTHOR]

Folic acid (FA) fortification and widespread supplemental use have significantly increased folate status in North America. Furthermore, >50% of colorectal cancer patients use FA supplement. The increased folate status may interfere with cancer chemotherapy. We investigated the effect of FA supplementation on chemosensitivity of human colon cancer cells to 5-fluorouracil (5-FU) using a xenograft model. Mice harboring human HCT116 colon cancer xenografts were randomized to receive the control, or 4× or 12.5× supplemental levels of FA. Within each diet group, mice were randomized to receive 5-FU+leucovorin or saline and xenograft growth and characteristics were determined. The expression of genes involved in folate metabolism and cancer treatment was determined. FA supplementation and 5-FU significantly interacted to influence xenograft growth (P< 0.007). At the control level, 5-FU significantly inhibited the growth of the xenografts (P< 0.0001). However, at the 4× supplemental level, 5-FU-treated xenografts grew faster than untreated xenografts (P= 0.048) while at the 12.5× supplemental level, 5-FU exhibited no effect. Cell proliferation, degree of necrosis, and expression of the selected genes did not significantly differ by the supplemental levels of FA. Our data suggest that FA supplementation may be detrimental to 5-FU chemotherapy of colon cancer and pose public health concern. [ABSTRACT FROM PUBLISHER]

Background: Mandatory fortification, prevalent supplement use, and public health guidelines recommending periconceptional supplementation have increased folic acid intakes in North American pregnant women. However, the effects of increased folic acid intakes during pregnancy on maternal and cord blood folate concentrations have not been well established. Objectives: In this prospective study, we determined maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA) in a cohort of pregnant Canadian women and their newborns and examined the effect of maternal intakes of folate and folic acid and fetal genetic variants in folate metabolism on folate status. Design: Folate and folic acid intakes of 368 Canadian pregnant women were assessed in early (0-16 wk) and late (23-37 wk) pregnancy. Blood concentrations of folate and UMFAwere measured with the use of immunoassays and liquid chromatography-mass spectrometry, respectively, in maternal samples in early pregnancy (12-16 wk), at delivery (28-42 wk), and in cord blood. Four fetal genetic variants of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were assessed for their association with cord blood concentrations of folate and UMFA. Results: Geometric mean (95% CI) maternal red blood cell (RBC) folate concentrations were 2417 nmol/L (2362, 2472 nmol/L ) and 2793 nmol/L (2721, 2867 nmol/L ) in early pregnancy and at delivery, respectively. The mean (95% CI) cord RBC folate concentration was 2689 nmol/L (2614, 2765 nmol/L). UMFA was detectable in .90% of maternal and cord plasma samples. Although 3 fetal MTHFR and DHFR genetic variants had no effect, the fetal MTHFR 677TT genotype was associated with significantly lower cord serum (P = 0.03) and higher cord RBC (P = 0.02) folate concentrations than those of the wild type. Conclusions: Notwithstanding differences in assays, maternal and cord RBC folate and plasma UMFA concentrations were higher than previously reported values. Functional ramifications of high folate and UMFA concentrations in maternal and fetal circulation warrant additional investigation because an excess folate status may affect long-term health outcomes of the offspring. This study was registered at www.clinicaltrials.gov as NCT02244684. [ABSTRACT FROM AUTHOR]

Objective Therapeutic intraarticular injections are used in the management of hip osteoarthritis (OA). Some studies suggest that their use increases the risk of infection and subsequent revision surgery after primary total hip arthroplasty (THA), while others do not. We undertook this study to clarify the relationship between prior intraarticular injection and the risk of complication in a subsequent primary THA. Methods In a cohort of patients with hip OA who underwent a primary elective THA between 2002 and 2009, we identified those who received ≥1 intraarticular injection performed by a radiologist in the 5 years preceding their THA. Multivariable Cox proportional hazards models were used to determine the relationship between receipt of a presurgical injection (no injection, 1-5 years prior to THA, or <1 year prior to THA) and the occurrence of postsurgical joint infection and revision THA in the following 2 years, while controlling for confounders. Results Of 37,881 eligible THA recipients, 2,468 (6.5%) received an intraarticular injection performed by a radiologist within 5 years of their THA (1,691 at <1 year, 777 at 1-5 years). Controlling for age, sex, comorbidity, frailty, income, and provider volume, those who had an injection in the year preceding surgery were at increased risk of infection (adjusted hazard ratio [HR] 1.37, P = 0.03) and revision THA (adjusted HR 1.53, P = 0.03) within 2 years of the primary THA, relative to patients who did not. The association between prior injection and revision arthroplasty was attenuated and became nonsignificant (adjusted HR 1.41, P = 0.13) after occurrence of postoperative infection was controlled for in the regression model. No effect was found for injection 1-5 years prior to surgery. Conclusion Intraarticular injection in the year preceding THA independently predicted increased risk of infection leading to early revision surgery. Further studies are warranted to elucidate explanations for these findings. [ABSTRACT FROM AUTHOR]

Objective To determine the relationship between surgeon experience with, and complications following, total joint arthroplasty (TJA) in patients with rheumatoid arthritis (RA). Methods Using administrative data, we assembled a cohort of patients with RA who had undergone at least 1 elective primary hip or knee replacement procedure between 2002 and 2009. Cox proportional hazards, censored on death and accounting for clustering of patients within surgeons, were used to determine the relationship between overall and 'RA-specific' surgeon TJA volume and the occurrence of a composite 'complication' outcome (revision, infection, dislocation, or periprosthetic fracture within 2 years of the initial TJA), controlling for potential confounders (patient age, sex, comorbidity, and disease severity). Results We identified 4,762 patients with RA who were eligible for TJAs (1,515 total hip arthroplasties and 3,247 total knee arthroplasties). Among these patients, 152 (3.2%) experienced a surgical complication within 2 years of the procedure. After controlling for patient and hospital factors, greater surgeon TJA volume in patients with RA (RA TJA), but not overall TJA volume (all TJA), was associated with a reduced risk of complications (for surgeon RA TJA volume per 10 cases, adjusted hazard ratio [HR] 0.81, 95% confidence interval [95% CI] 0.71-0.93, P = 0.002; for surgeon all TJA volume, adjusted HR 0.98, 95% CI 0.97-1.00, P = 0.09). Conclusion In a cohort of patients with RA who underwent hip or knee TJA, increased surgeon experience performing TJA in patients with RA, irrespective of their overall TJA experience and hospital factors, was associated with a decreased risk of surgical complications. These findings have potential implications for surgeon training and the referral practices of rheumatologists. [ABSTRACT FROM AUTHOR]

Objective Most of the evidence regarding complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA) are based on patients with osteoarthritis (OA); less is known about outcomes in rheumatoid arthritis (RA). Using a validated algorithm for identifying patients with RA, we undertook this study to compare the rates of complications among THA and TKA recipients between those with RA and those without RA. Methods In patients who underwent a first primary elective THA or TKA between 2002 and 2009, those with RA were identified using a validated algorithm: a hospitalization with a diagnosis code for RA or 3 physician billing claims with a diagnosis code for RA, with at least 1 claim by a specialist (rheumatologist, orthopedic surgeon, or internist) in a 2-year period. Recipients with diagnostic codes suggesting an inflammatory arthritis, but not meeting RA criteria, were classified as having inflammatory arthritis. All remaining patients were deemed to have OA. Cox proportional hazards models, censored on death, were used to determine the relationship between the type of arthritis and the occurrence of specific complications, adjusting for potential confounders (age, sex, comorbidity, and provider volume). Results We identified 43,997 eligible THA recipients (3% with RA) and 71,793 eligible TKA recipients (4% with RA). Total joint arthroplasty recipients with RA had higher age and sex-standardized rates of dislocation following THA (2.45%, compared with 1.21% for recipients with OA) and higher age and sex-standardized rates of infection following TKA (1.26%, compared with 0.84% for recipients with OA). Controlling for potential confounders, recipients with RA remained at increased risk of dislocation within 2 years of THA (adjusted hazard ratio [HR] 1.91, P = 0.001) and remained at increased risk of infection within 2 years of TKA (adjusted HR 1.47, P = 0.03) relative to recipients with OA. Conclusion Patients with RA are at higher risk of dislocation following THA and are at higher risk of infection following TKA relative to those with OA. Further research is warranted to elucidate explanations for these findings, including the roles of medication profile, implant choice, postoperative antibiotic protocol, and method of rehabilitation following joint replacement. [ABSTRACT FROM AUTHOR]

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 Akaike's 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. [ABSTRACT FROM AUTHOR]