Summary 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.

A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx-SCD, n 5 199), and 64 non-Tx-SCD subjects to describe the frequency of ironrelated 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 5 1.6, 95% CI 1.0-2.5) or nonTx-SCD (RR 5 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 5 0.20; P 5 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 5 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 5 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. Am. J. Hematol. 82:255-265, 2007. V V C 2006 Wiley-Liss, Inc. Contract

BackgroundThe frequency and intensity of wildfires is anticipated to increase as climate change creates longer, warmer, and drier seasons. Particulate matter (PM) from wildfire smoke has been linked to adverse respiratory and possibly cardiovascular outcomes. Children, older adults, and persons with underlying respiratory and cardiovascular conditions are thought to be particularly vulnerable. This study examines the healthcare utilization of Medi-Cal recipients during the fall 2007 San Diego wildfires, which exposed millions of persons to wildfire smoke.Methods and findingsRespiratory and cardiovascular International Classification of Diseases (ICD)-9 codes were identified from Medi-Cal fee-for-service claims for emergency department presentations, inpatient hospitalizations, and outpatient visits. For a respiratory index and a cardiovascular index of key diagnoses and individual diagnoses, we calculated rate ratios (RRs) for the study population and different age groups for 3 consecutive 5-day exposure periods (P1 [October 22–26], P2 [October 27–31], and P3 [November 1–5]) versus pre-fire comparison periods matched on day of week (5-day periods starting 3, 4, 5, 6, 8, and 9 weeks before each exposed period). We used a bidirectional symmetric case-crossover design to examine emergency department presentations with any respiratory diagnosis and asthma specifically, with exposure based on modeled wildfire-derived fine inhalable particles that are 2.5 micrometers and smaller (PM2.5). We used conditional logistic regression to estimate odds ratios (ORs), adjusting for temperature and relative humidity, to assess same-day and moving averages. We also evaluated the United States Environmental Protection Agency (EPA)’s Air Quality Index (AQI) with this conditional logistic regression method. We identified 21,353 inpatient hospitalizations, 25,922 emergency department presentations, and 297,698 outpatient visits between August 16 and December 15, 2007. During P1, total emergency department presentations were no different than the reference periods (1,071 versus 1,062.2; RR 1.01; 95% confidence interval [CI] 0.95–1.08), those for respiratory diagnoses increased by 34% (288 versus 215.3; RR 1.34; 95% CI 1.18–1.52), and those for asthma increased by 112% (58 versus 27.3; RR 2.12; 95% CI 1.57–2.86). Some visit types continued to be elevated in later time frames, e.g., a 72% increase in outpatient visits for acute bronchitis in P2. Among children aged 0–4, emergency department presentations for respiratory diagnoses increased by 70% in P1, and very young children (0–1) experienced a 243% increase for asthma diagnoses. Associated with a 10 μg/m3 increase in PM2.5 (72-hour moving average), we found 1.08 (95% CI 1.04–1.13) times greater odds of an emergency department presentation for asthma. The AQI level “unhealthy for sensitive groups” was associated with significantly elevated odds of an emergency department presentation for respiratory conditions the day following exposure, compared to the AQI level “good” (OR 1.73; 95% CI...

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.

Objective There are data suggesting that blood product transfusions increase the risk of developing acute lung injury (ALI) in adults, and may be associated with increased mortality in adults with ALI. A possible association between transfusions and adverse outcomes of pediatric patients with ALI has not been studied previously. We tested the hypothesis that blood product transfusions to pediatric patients with ALI within the first 72 hours of the diagnosis would be associated with increased mortality and prolonged mechanical ventilation. Design An epidemiologic database of pediatric ALI prospectively gathered from July 1996 to May 2000 was analyzed. Setting Children were enrolled from both a tertiary referral hospital and a major community children's hospital. Patients Three hundred fifteen patients who met the 1994 American European Consensus Committee definition of ALI between the ages of 36 weeks corrected gestational age and 18 years. Main Outcome Measure Mortality in the pediatric intensive care unit. Results Multivariate analyses indicated that the transfusion of fresh-frozen plasma (FFP) was associated with increased mortality, independent of the severity of hypoxemia (Pao2/Fio2), presence of multiple organ system failure or disseminated intravascular coagulation (odds ratio = 1.08, 95% confidence interval = 1.00–1.17, p = 0.04). FFP transfusion was analyzed as a continuous variable, so that for each milliliter of FFP transfused per kilogram patient body weight per day, the odds of death increased by 1.08. There was a trend toward an association of the transfusion of FFP with a fewer number of days of unassisted ventilation (regression coefficient = −0.21, 95% confidence interval = −0.42–0.01, p = 0.06). Conclusions The transfusion of FFP is associated with an increased risk of mortality in children with ALI. The association between FFP and mortality in children with ALI should be investigated further.

Solid fuels are a major source of indoor air pollution, but in less developed countries the short-term health effects of indoor air pollution are poorly understood. The authors conducted a large cross-sectional study of rural Chinese households to determine associations between individual health status and domestic cooking as a source of indoor air pollution. The study included measures of health status as well as measures of indoor air-pollution sources, such as solid cooking fuels and cooking stoves. Compared with other fuel types, coal was associated with a lower health status, including negative impacts on exhaled carbon monoxide level, forced vital capacity, lifetime prevalence of chronic obstructive pulmonary disease and asthma, and health care utilization. Decreasing household coal use, increasing use of improved stove technology, and increasing kitchen ventilation may decrease the short-term health effects of indoor air pollution.

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 ≥12 years and liver iron concentration ≥ 10 mg/g dry wt or serum ferritin ≥ 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 yrs), 203 subjects with TxSCD (44% Male, 24.7 ±0.9 years: Mean ± SE), and 65 NonTxSCD (50% Male, 22.2 ±1.3 yrs) 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.

Early injury to the systemic and pulmonary endothelium, as measured by plasma vWF-Ag levels, is associated with an increased risk of death and prolonged mechanical ventilation in pediatric patients with ALI.