Age, period, and cohort effects in adult lifetime asthma prevalence in California: an application of hierarchical age-period-cohort analysis.

PURPOSE: Using 27 years of survey data, the contributions of age, period, and cohort effects on the increase in adult lifetime asthma prevalence in California were examined. METHODS: Lifetime asthma diagnosis for adults was assessed in 1984-1992 and 1995-2011 through the California Behavioral Risk Factor Surveillance System, an annual, cross-sectional, population-based survey (n = 144,100). Using date of survey and date of birth, we classified 18,305 adult respondents with lifetime asthma into 7 age groups, 6 periods, and 17 cohorts. Using hierarchical, cross-classified random effects models, birth cohort, period, and age patterns in adult lifetime asthma prevalence were analyzed. RESULTS: After adjusting for sex, ethnicity, education, and smoking, age effects peak in young adulthood, flatten from 40 to 60 years old, and then decrease in older adulthood. A significant positive trend in asthma prevalence was observed in the two earliest survey periods (1984-1993; P value < .0001). Survey period trends appear to flatten beginning in 2004. Although the overall birth cohort effect was statistically significant, the magnitude of the effect for each birth cohort category was small (P value = .0005). CONCLUSIONS: We observed that strong age and period effects have been driving the increase in lifetime asthma prevalence in California over the past 3 decades.

Near-Roadway Air Pollution and Coronary Heart Disease: Burden of Disease and Potential Impact of a Greenhouse Gas Reduction Strategy in Southern California.

BACKGROUND: Several studies have estimated the burden of coronary heart disease (CHD) mortality from ambient regional particulate matter ≤ 2.5 µm (PM2.5). The burden of near-roadway air pollution (NRAP) generally has not been examined, despite evidence of a causal link with CHD. OBJECTIVE: We investigated the CHD burden from NRAP and compared it with the PM2.5 burden in the California South Coast Air Basin for 2008 and under a compact urban growth greenhouse gas reduction scenario for 2035. METHODS: We estimated the population attributable fraction and number of CHD events attributable to residential traffic density, proximity to a major road, elemental carbon (EC), and PM2.5 compared with the expected disease burden if the population were exposed to background levels of air pollution. RESULTS: In 2008, an estimated 1,300 CHD deaths (6.8% of the total) were attributable to traffic density, 430 deaths (2.4%) to residential proximity to a major road, and 690 (3.7%) to EC. There were 1,900 deaths (10.4%) attributable to PM2.5. Although reduced exposures in 2035 should result in smaller fractions of CHD attributable to traffic density, EC, and PM2.5, the numbers of estimated deaths attributable to each of these exposures are anticipated to increase to 2,500, 900, and 2,900, respectively, due to population aging. A similar pattern of increasing NRAP-attributable CHD hospitalizations was estimated to occur between 2008 and 2035. CONCLUSION: These results suggest that a large burden of preventable CHD mortality is attributable to NRAP and is likely to increase even with decreasing exposure by 2035 due to vulnerability of an aging population. Greenhouse gas reduction strategies developed to mitigate climate change offer unexploited opportunities for air pollution health co-benefits.

Using acupuncture for acute pain in hospitalized children.

OBJECTIVE: Clinical study to determine the acceptability and feasibility of acupuncture for acute postoperative pain control in hospitalized children. DESIGN: Nonrandomized clinical trial. SETTING: A single, tertiary referral pediatric intensive care unit. PATIENTS: A total of 20 patients aged 7 months to 18 years. Eleven of the patients had posterior spinal fusion surgery and the remaining nine patients had other surgical diagnoses. INTERVENTIONS: Two 10- to 15-minute sessions of acupuncture 24-48 hours apart. OUTCOME MEASURES AND RESULTS: The treatment was highly accepted (27 patients were approached and 4 patients refused; of the 23 patients enrolled, 20 patients completed the study). Acupuncture was well tolerated by patients without adverse events related to treatment. In follow-up interviews, 70% of both parents and patients believed acupuncture helped the child's pain. Eighty-five percent of the parents said they would pay out of pocket for acupuncture if not covered by insurance. The pain scores, vital signs, and narcotic usage were recorded before and several times after acupuncture. In posterior spinal fusion patients, the mean pain scores (0-10) immediately before and 4 and 24 hours after acupuncture were: 3.7, 1.7, and 3.1, respectively, after the first acupuncture session and 3.7, 2.2, and 3.1, respectively, after the second session. In the other surgical cohort, the mean pain scores immediately before and 4 and 24 hours after the first session of acupuncture were 2.5, 0.3, and 1.6, respectively. CONCLUSIONS: Our results support that acupuncture is highly accepted and feasible in critically ill, postoperative pediatric patients with acute pain. Our findings suggest that acupuncture may be a potentially useful adjunctive tool for acute pediatric postoperative pain management. A randomized, controlled clinical trial is warranted to confirm these findings.

Disparity in the management of iron overload between patients with sickle cell disease and thalassemia who received transfusions.

BACKGROUND: Transfusion therapy is frequently used to prevent morbidity in sickle cell disease (SCD), and subsequent iron overload is common. The objective of this study was to evaluate the current standard of care in monitoring iron overload and related complications in patients with SCD compared to thalassemia (Thal). STUDY DESIGN AND METHODS: A cross-sectional study was conducted at 31 hematology clinics in the United States, Canada, or the United Kingdom. Patients who received transfusions with a mean serum ferritin level of least 2000 ng per mL were eligible. A total of 199 patients with SCD (113 female; 24.9 +/- 13.2 years) and 142 with Thal (66 female; 25.8 +/- 8.1 years) were recruited, and data were collected between 2001 and 2003 by interview and medical record review. RESULTS: Although both groups were recruited on the basis of significant iron overload, the likelihood of performing a liver biopsy for routine iron monitoring was significantly higher (odds ratio [OR], 3.4; 95% confidence interval [CI], 2.2-5.3) in Thal than SCD. Thal patients were also more likely to be screened for iron-related organ injury including an echocardiograph for cardiomyopathy (OR, 2.6; p < 0.001; 95% CI, 1.6-4.2), alanine aminotransferase for liver function (OR, 8.3; CI, 1.05-64.4), and thyroid-stimulating hormone for hypothyroidism (OR, 12.3; CI, 7.0-21.5). For adult SCD patients, those maintained on simple transfusion with a serum ferritin level of greater than 2500 ng per mL were the least likely to have a liver biopsy (p < 0.03). CONCLUSIONS: These data highlight the unsystematic monitoring of iron and related organ injury in SCD. Until the relationship between iron and related comorbidities is better understood, routine monitoring of iron overload in SCD patients who receive transfusions should be considered a standard part of clinical care.

Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia.

Transfusional iron overload leads to gonadal failure and low bone mass in patients with thalassemia (Thal). However, gonadal failure is rarely reported in transfused patients with sickle cell disease (SCD) and the literature regarding fracture prevalence in SCD is limited. The objective of this study was to assess self-reported fracture prevalence and its relationship to endocrinopathy in transfused Thal or SCD subjects and compare to non-transfused subjects with SCD (NonTxSCD). Eligibility was based on age> or =12 years and liver iron concentration> or =10 mg/g dry wt or serum ferritin> or =2000 ng/mL (Thal or TxSCD) or for NonTxSCD, ferritin<500 ng/mL. Data were collected by patient interview and chart review at 31 clinical centers in the U.S., Canada and the U.K. 152 subjects with Thal (52% Male; 25.6+/-0.7 years), 203 subjects with TxSCD (44% Male, 24.7+/-0.9 years: Mean+/-SE), and 65 NonTxSCD (50% Male, 22.2+/-1.3 years) were enrolled. Overall, male subjects with Thal were more likely to have sustained a fracture in their lifetime (51%) compared to TxSCD (28%) or NonTxSCD (32%) (p=0.005). There was no difference in fracture prevalence among women (Thal: 26%, TxSCD 17%, NonTxSCD: 16%). Fracture was most frequently reported in the upper extremities (53.3% of all fractures) while spine and pelvic fractures were relatively common for such a young cohort: 10.6%. Though overall fracture prevalence was not distinctly different from published healthy cohorts, fewer fractures occurred during the adolescent years. In multivariate analysis, the significant predictors of fracture prevalence were Thal diagnosis (Odds Ratio: 2.3; 1.2-4.6; 95%CI), male gender (OR: 2.6; 1.5-4.5), hypothyroidism (OR: 3.3; 1.1-9.8) and age (OR: 1.1; 1.03-1.08). These data suggest that despite similar iron burden, transfused patients with Thal are at greater risk for fracture than subjects with SCD. Male subjects with Thal and hypothyroidism are at particular risk for fracture, in contrast, transfused subjects with SCD had no greater risk of fracture compared to non-transfused SCD. Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture.

Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload.

A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx-SCD, n = 199), and 64 non-Tx-SCD subjects to describe the frequency of iron-related morbidity and mortality. Subjects recruited from 31 centers in the US, Canada or the UK were similar with respect to age (overall: 25 +/- 11 years, mean +/- SD) and gender (52% female). We found that Tx-SCD subjects were hospitalized more frequently compared with Thal or non-Tx-SCD (P < 0.001). Among those hospitalized, Tx-SCD adult subjects were more likely to be unemployed compared with Thal (RR = 1.6, 95% CI 1.0-2.5) or non-Tx-SCD (RR = 3.1, 95% CI 1.3-7.3). There was a positive relationship between the severity of iron overload, assessed by serum ferritin, and the frequency of hospitalizations (r= 0.20; P = 0.009). Twenty-three deaths were reported (6 Thal, 17 Tx-SCD) in 23.5 +/- 10 months of follow-up. Within the Tx-SCD group, those who died began transfusion (25.3 vs. 12.4 years, P < 0.001) and chelation therapy later (26.8 vs. 14.2 years, P = 0.01) compared with those who survived. The unadjusted death rate in Thal was lower (2.2/100 person years) compared with that in Tx-SCD (7.0/100 person years; RR = 0.38: 95% CI 0.12-0.99). However, no difference was observed when age at death was considered. Despite improvements in therapy, death rate in this contemporary sample of transfused adult subjects with Thal or SCD is 3 times greater than the general US population. Long term follow-up of this unique cohort of subjects will be helpful in further defining the relationship of chronic, heavy iron overload to morbidity and mortality.

Physical therapy alone compared with core decompression and physical therapy for femoral head osteonecrosis in sickle cell disease. Results of a multicenter study at a mean of three years after treatment.

BACKGROUND: Osteonecrosis of the femoral head is a common complication in patients with sickle cell disease, and collapse of the femoral head occurs in 90% of patients within five years after the diagnosis of the osteonecrosis. However, the efficacy of hip core decompression to prevent the progression of osteonecrosis in these patients is still controversial. METHODS: In a prospective multicenter study, we evaluated the safety of hip core decompression and compared the results of decompression and physical therapy with those of physical therapy alone for the treatment of osteonecrosis of the femoral head in patients with sickle cell disease. Forty-six patients (forty-six hips) with sickle cell disease and Steinberg Stage-I, II, or III osteonecrosis of the femoral head were randomized to one of two treatment arms: (1) hip core decompression followed by a physical therapy program or (2) a physical therapy program alone. Eight patients withdrew from the study, leaving thirty-eight who participated. RESULTS: Seventeen patients (seventeen hips) underwent decompression combined with physical therapy, and no intraoperative or immediate postoperative complications occurred. Twenty-one patients (twenty-one hips) were treated with physical therapy alone. After a mean of three years, the hip survival rate was 82% in the group treated with decompression and physical therapy and 86% in the group treated with physical therapy alone. According to a modification of the Harris hip score, the mean clinical improvement was 18.1 points for the patients treated with hip core decompression and physical therapy compared with 15.7 points for those treated with physical therapy alone. With the numbers studied, the differences were not significant. CONCLUSIONS: In this randomized prospective study, physical therapy alone appeared to be as effective as hip core decompression followed by physical therapy in improving hip function and postponing the need for additional surgical intervention at a mean of three years after treatment.

Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease.

Iron-overload associated endocrinopathy is the most frequently reported complication of chronic transfusion therapy in patients with thalassaemia (Thal). This study compared iron-overloaded subjects with Thal (n = 142; 54%M; age 25.8 +/- 8.1 years) and transfused sickle-cell disease (Tx-SCD; n = 199; 43%M, 24.9 +/- 13.2 years) to non-transfused SCD subjects (non-Tx-SCD; n = 64, 50%M, 25.3 +/- 11.3 years), to explore whether the underlying haemoglobinopathy influences the development of endocrinopathy. Subjects were recruited from 31 centres in the USA, Canada and the UK. Subjects with Thal had more evidence of diabetes (13% vs. 2%, P < 0.001), hypogonadism (40% vs. 4%, P < 0.001), hypothyroidism (10% vs. 2%, P = <0.001) and growth failure (33% vs. 7%, P < 0.001), versus Tx-SCD. Fifty-six per cent of Thal had more than one endocrinopathy compared with only 13% of Tx-SCD (P < 0.001). In contrast, Tx-SCD was not different from non-Tx-SCD. Multivariate analysis indicated that endocrinopathy was more likely in Thal than SCD [Odds Ratio (OR) = 9.4, P < 0.001], with duration of chronic transfusion a significant predictor (OR = 1.4 per 10 years of transfusion, P = 0.04). Despite iron overload, endocrinopathy was not increased in Tx-SCD versus non-Tx-SCD, suggesting that the underlying disease may modulate iron-related endocrine injury. However, because transfusion duration remained a significant predictor of endocrinopathy, these data should be confirmed in SCD subjects that have been chronically transfused for longer periods of time.