Hypobaric type oxygenators - physics and physiology.

Brain injury is still a serious complication after cardiac surgery. Gaseous microemboli (GME) are known to contribute to both short and longer-term brain injury after cardiac surgery. Hypobaric and novel dual-chamber oxygenators use the physical behaviors and properties of gases to reduce GME. The aim of this review was to present the basic physics of the gases, the mechanism in which the hypobaric and dual-chamber oxygenators reduce GME, their technical performance, the preclinical studies, and future directions. The gas laws are reviewed as an aid to understanding the mechanisms of action of oxygenators. Hypobaric-type oxygenators employ a high oxygen, no nitrogen environment creating a steep concentration gradient of nitrogen out of the blood and into the oxygenator, reducing the risk of GMEs forming. Adequately powered clinical studies have never been carried out with a hypobaric or dual-chamber oxygenator. These are required before such technology can be recommended for widespread clinical use.

Caffeine ingestion stimulates plasma carnitine clearance in humans.

Increasing skeletal muscle carnitine content can manipulate fuel metabolism and improve exercise performance. Intravenous insulin infusion during hypercarnitinemia increases plasma carnitine clearance and Na+ -dependent muscle carnitine accretion, likely via stimulating Na+ /K+ ATPase pump activity. We hypothesized that the ingestion of high-dose caffeine, also known to stimulate Na+ /K+ ATPase activity, would stimulate plasma carnitine clearance during hypercarnitinemia in humans. In a randomized placebo-controlled study, six healthy young adults (aged 24 ± 5 years, height 175 ± 8 cm, and weight 70 ± 13 kg) underwent three 5-h laboratory visits involving the primed continuous intravenous infusion of l-carnitine (CARN and CARN + CAFF) or saline (CAFF) in parallel with ingestion of caffeine (CARN + CAFF and CAFF) or placebo (CARN) at 0, 2, 3, and 4 h. Regular blood samples were collected to determine concentrations of blood Na+ and K+ , and plasma carnitine and caffeine, concentrations. Caffeine ingestion (i.e., CAFF and CARN + CAFF conditions) and l-carnitine infusion (i.e., CARN and CARN + CAFF) elevated steady-state plasma caffeine (to ~7 µg·mL-1 ) and carnitine (to ~400 µmol·L-1 ) concentrations, respectively, throughout the 5 h infusions. Plasma carnitine concentration was ~15% lower in CARN + CAFF compared with CARN during the final 90 min of the infusion (at 210 min, 356 ± 96 vs. 412 ± 94 µmol·L-1 ; p = 0.0080: at 240 min, 350 ± 91 vs. 406 ± 102 µmol·L-1 ; p = 0.0079: and at 300 min, 357 ± 91 vs. 413 ± 110 µmol·L-1 ; p = 0.0073, respectively). Blood Na+ concentrations were greater in CAFF and CARN + CAFF compared with CARN. Ingestion of high-dose caffeine stimulates plasma carnitine clearance during hypercarnitinemia, likely via increased Na+ /K+ ATPase activity. Carnitine co-ingestion with caffeine may represent a novel muscle carnitine loading strategy in humans, and therefore manipulate skeletal muscle fuel metabolism and improve exercise performance.

A mycoprotein-based high-protein vegan diet supports equivalent daily myofibrillar protein synthesis rates compared with an isonitrogenous omnivorous diet in older adults: a randomised controlled trial.

Animal-derived dietary protein ingestion and physical activity stimulate myofibrillar protein synthesis rates in older adults. We determined whether a non-animal-derived diet can support daily myofibrillar protein synthesis rates to the same extent as an omnivorous diet. Nineteen healthy older adults (aged 66 (sem 1) years; BMI 24 (sem 1) kg/m2; twelve males, seven females) participated in a randomised, parallel-group, controlled trial during which they consumed a 3-d isoenergetic high-protein (1·8 g/kg body mass per d) diet, where the protein was provided from predominantly (71 %) animal (OMNI; n 9; six males, three females) or exclusively vegan (VEG; n 10; six males, four females; mycoprotein providing 57 % of daily protein intake) sources. During the dietary control period, participants conducted a daily bout of unilateral resistance-type leg extension exercise. Before the dietary control period, participants ingested 400 ml of deuterated water, with 50-ml doses consumed daily thereafter. Saliva samples were collected throughout to determine body water 2H enrichments, and muscle samples were collected from rested and exercised muscle to determine daily myofibrillar protein synthesis rates. Deuterated water dosing resulted in body water 2H enrichments of approximately 0·78 (sem 0·03) %. Daily myofibrillar protein synthesis rates were 13 (sem 8) (P = 0·169) and 12 (sem 4) % (P = 0·016) greater in the exercised compared with rested leg (1·59 (sem 0·12) v. 1·77 (sem 0·12) and 1·76 (sem 0·14) v. 1·93 (sem 0·12) %/d) in OMNI and VEG groups, respectively. Daily myofibrillar protein synthesis rates did not differ between OMNI and VEG in either rested or exercised muscle (P > 0·05). Over the course of a 3-d intervention, omnivorous- or vegan-derived dietary protein sources can support equivalent rested and exercised daily myofibrillar protein synthesis rates in healthy older adults consuming a high-protein diet.

The prognostic strength of serum LDH and serum ferritin in children with neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project.

PURPOSE: Age, MYCN status, stage, and histology have been used as neuroblastoma (NB) risk factors for decades. Serum lactate dehydrogenase (LDH) and serum ferritin are reproducible, easily obtained, and prognostic, though never used in risk stratification, except one German trial. We analyzed the prognostic strength of LDH and ferritin, overall, within high-risk NB, and by era, using the International Neuroblastoma Risk Group Data Commons. PATIENTS AND METHODS: Children with NB (1990-2016) were categorized into LDH (n = 8867) and ferritin (n = 8575) risk groups using EFS. Cox models compared the prognostic strength of LDH and ferritin to age, MYCN status, and INSS stage. RESULTS: Higher LDH conferred worse EFS, overall (5-year EFS) (100-899 IU/L: 76 ± 0.6%; 0-99 or 900-1399 IU/L: 60 ± 1.2%; ≥1400 IU/L: 36 ± 1.2%; P < .0001), and in high-risk NB post-2009 (3-year EFS) (117-381 IU/L: 67 ± 8.9%; 382-1334 IU/L: 58 ± 4.4%; 0-116 or ≥1335 IU/L: 46 ± 3.9%; P = .003). Higher ferritin conferred worse EFS, overall (5-year EFS) (1-29 ng/mL: 87 ± 0.9%; 0 or 30-89 ng/mL: 74 ± 0.8%; ≥90 ng/mL: 48 ± 0.9%; P < .0001), and in high-risk NB post-2009 (3-year EFS) (1-53 ng/mL: 71 ± 9.3%; 0 or 54-354 ng/mL: 55 ± 4.7%; ≥355 ng/mL: 34 ± 6.1%; P = .0008). In multivariable analyses adjusting for age, MYCN, and stage, LDH and ferritin maintained independent prognostic ability (P < .0001; adjusted HRs (95% CI): 1.7 (1.5-1.9), 2.3 (2.0-2.7), respectively). CONCLUSIONS: LDH and ferritin are strongly prognostic in NB, overall and within high-risk NB patients treated post-2009 with modern therapy. LDH and ferritin show promise for (a) identifying ultra-high-risk; (b) refining risk stratification; and (c) clinical utility in low-/middle-income countries. Routine collection of LDH and ferritin should be reinitiated for evolving NB risk stratification.

Long-term analysis of children with metastatic neuroblastoma treated in the ENSG5 randomised clinical trial.

BACKGROUND: The European Neuroblastoma Study Group 5 (ENSG5) trial showed that time-intensive "rapid" induction chemotherapy (COJEC) was superior to "standard" 3-weekly chemotherapy for children with high-risk metastatic neuroblastoma. Long-term outcomes of the ENSG5 trial were analysed. PROCEDURE: Patients with metastatic neuroblastoma aged ≥12 months were randomly assigned to "standard" or "rapid" induction, receiving the same chemotherapy drugs and doses. Event-free survival (EFS) and overall survival (OS) were analysed and prognostic factors evaluated. Amongst patients surviving >5 years, a population of children with persistent metastatic disease after the end of treatment was identified and described. RESULTS: Ten-year EFS was 18.2% (95% confidence interval: 12.2-25.2) for the "standard" arm and 26.8% (19.5-34.7) for the "rapid" arm (hazard ratio [HR] 0.85, P = 0.28). Ten-year OS for the "standard" arm was 19.7% (13.4-26.8) and 28.3% (20.8-36.2) for the "rapid arm" (HR 0.83, P = 0.19). There was a trend for worse EFS and OS for patients having MYCN amplification (HR 1.37 and 1.40, respectively) and those with partial and mixed response to induction (HR 1.69 and 1.75 for EFS and 1.66 and 2.00 for OS, respectively). Among 69 patients who survived >5 years, six had persistent metastatic disease after the end of treatment. CONCLUSION: The benefit of the "rapid" induction regimen seems to be maintained in the long term, although the small number of survivors could justify the lack of statistical significance. MYCN amplification and poor metastatic response to induction could be associated with worse outcomes. A small group of patients with persistent metastatic disease that survived long term has been described.

A single day of bed rest, irrespective of energy balance, does not affect skeletal muscle gene expression or insulin sensitivity.

NEW FINDINGS: What is the central question of this study? What are the initial metabolic and molecular events that underpin bed rest-induced skeletal muscle deconditioning, and what is the contribution of energy balance? What is the main finding and its importance? A single day of bed rest, irrespective of energy balance, did not lead to overt changes in skeletal muscle gene expression or insulin sensitivity. More than 1 day of physical inactivity is required to observe the insulin resistance and robust skeletal muscle transcriptional responses associated with bed rest and consequent alterations in energy balance. ABSTRACT: The initial metabolic and molecular events that underpin disuse-induced skeletal muscle deconditioning, and the contribution of energy balance, remain to be investigated. Ten young, healthy men (age 25 ± 1 years; body mass index 25.3 ± 0.8 kg·m-2 ) underwent three 24 h laboratory-based experimental periods in a randomized, crossover manner: (i) controlled habitual physical activity with an energy-balanced diet (CON); (ii) strict bed rest with a diet to maintain energy balance (BR-B); and (iii) strict bed rest with a diet identical to CON, consequently resulting in positive energy balance. Continuous glucose monitoring was performed throughout each visit, with vastus lateralis muscle biopsies and an oral glucose tolerance test performed before and after. In parallel with muscle samples collected from a previous 7 day bed rest study, biopsies were used to examine the expression of genes associated with the regulation of muscle mass and insulin sensitivity. A single day of bed rest, irrespective of energy balance, did not lead to overt changes in whole-body substrate oxidation, indices of insulin sensitivity [i.e. homeostatic model assessment of insulin resistance, BR-B from 2.7 ± 1.7 to 3.1 ± 1.5 (P > 0.05) and Matsuda index, BR-B from 5.9 ± 3.3 to 5.2 ± 2.9 (P > 0.05)] or 24 h glycaemic control/variability compared with CON. Seven days of bed rest led to ∼30-55% lower expression of genes involved in insulin signalling, lipid storage/oxidation and muscle protein breakdown, whereas no such changes were observed after 1 day of bed rest. In conclusion, more than a single day of physical inactivity is required to observe the insulin resistance and robust skeletal muscle transcriptional responses associated with bed rest and consequent alterations in energy balance.

Influence of Ethnicity, Age, and Time on Sex Disparities in Long-Term Cause-Specific Mortality After Acute Myocardial Infarction.

BACKGROUND: We examined the influence of sex, ethnicity, and time on competing cardiovascular and noncardiovascular causes of death following acute myocardial infarction in a multiethnic Asian cohort. METHODS AND RESULTS: For 12 years, we followed a prospective nationwide cohort of 15 151 patients (aged 22-101 years, median age 63 years; 72.3% male; 66.7% Chinese, 19.8% Malay, 13.5% Indian) who were hospitalized for acute myocardial infarction between 2000 and 2005. There were 6463 deaths (4534 cardiovascular, 1929 noncardiovascular). Compared with men, women had a higher risk of cardiovascular death (age-adjusted hazard ratio [HR] 1.3, 95% CI 1.2-1.4) but a similar risk of noncardiovascular death (HR 0.9, 95% CI 0.8-1.0). Sex differences in cardiovascular death varied by ethnicity, age, and time. Compared with Chinese women, Malay women had the greatest increased hazard of cardiovascular death (HR 1.4, 95% CI 1.2-1.6) and a marked imbalance in death due to heart failure or cardiomyopathy (HR 3.4 [95% CI 1.9-6.0] versus HR 1.5 [95% CI 0.6-3.6] for Indian women). Compared with same-age Malay men, Malay women aged 22 to 49 years had a 2.5-fold (95% CI 1.6-3.8) increased hazard of cardiovascular death. Sex disparities in cardiovascular death tapered over time, least among Chinese patients and most among Indian patients; the HR comparing cardiovascular death of Indian women and men decreased from 1.9 (95% CI 1.5-2.4) at 30 days to 0.9 (95% CI 0.5-1.6) at 10 years. CONCLUSION: Age, ethnicity, and time strongly influence the association between sex and specific cardiovascular causes of mortality, suggesting that health care policy to reduce sex disparities in acute myocardial infarction outcomes must consider the complex interplay of these 3 major modifying factors.

The role of fracture reduction and plate position in the aetiology of flexor pollicis longus tendon rupture after volar plate fixation of distal radius fractures.

BACKGROUND: Flexor pollicis longus (FPL) rupture has been described as complication following volar plating for distal radius fractures. It has been hypothesised that this is due to plate prominence. The aim of the study was to investigate the relationship between sub-optimal plate position and fracture reduction on plate prominence. METHODS: Plate prominence was measured in two experimental models. In the first, the effect of plate position was investigated using 18 fresh frozen cadavers with prominence being measured using a micrometer. In the second study, the effect of fracture reduction on plate prominence was investigated using similar methodology with simulated mal-reductions on dry bone models. RESULTS: The results of the first study showed a significant increase in lift-off for three plates (DVR, Synthes Universal and Acu-Loc), if the plates were moved distally or proximally from the anatomical position. Similar increases in prominence were also seen with rotational mal-positions. The results of the second study showed a statistically significant effect on plate prominence for even a 5° mal-reduction (p = 0.001) with worsening lift-off with increasing mal-reduction. These changes are significantly different from baseline and also significantly different to the lift-off recorded with mal-reductions 5° better and worse. Mal-reductions also necessitate more proximal placement of the plate to avoid screw penetration of the articular surface, and each 5° increment is significantly different from baseline. CONCLUSIONS: The results show a statistically and clinically significant effect of both plate position and fracture reduction on plate prominence and support the theory that both contribute to the aetiology of post-operative FPL rupture.

On developing a pragmatic strategy for clinical trials: A case study of hepatocellular carcinoma.

Randomised controlled trials (RCTs) with sufficiently high statistical power are not always feasible for patients when the administration of the treatment is burdensome. Nevertheless, useful information concerning the relative effectiveness of the Test and Standard therapies, may be gleaned from under powered trials, non-randomised comparative studies and/or clinician's beliefs: the latter possibly additionally providing some suggestion of the strength of evidence required in order to adopt the Test therapy into clinical practice. In such circumstances, a Bayesian synthesis may be useful in quantifying the evidence of treatment effectiveness. In this article, we aim to present a Bayesian approach for synthesizing the cumulative evidence of the use of adjuvant hepatic intra-arterial iodine-131-lipiodol (I131L) following curative resection in hepatocellular carcinoma (HCC) patients. We constructed a posterior distribution using the information from two small RCTs, three non-randomised comparative studies, three single arm studies and the views of investigators on the use of I131L. This distribution enables calculation of the probability that the Test therapy is more effective than the Standard by a pre-stipulated amount. If this is very high, then for example, one may conclude the Test may replace the Standard therapy. If it is not, then the Standard would be retained for clinical use. Despite a strong early indication of the effectiveness of I131L, the evolving evidence over a 10-year period became more sceptical of its value. Although highly recommended, difficulties of implementing a Bayesian approach in this context are highlighted.

Impact of the joint association between sex, age and diabetes on long-term mortality after acute myocardial infarction.

BACKGROUND: The role of sex, and its joint effect with age and diabetes mellitus, on mortality subsequent to surviving an acute myocardial infarction (AMI) beyond 30 days are unclear. The high prevalence of diabetes mellitus in an ethnically diverse Asian population motivates this study. METHODS: The study population comprised of a nationwide cohort of Asian patients with AMI, hospitalized between 2000 to 2005, who survived the first 30 days post-admission and were followed prospectively until death or 12 years. RESULTS: Among the 13,389 survivors, there were fewer women (25.5%) who were older than men (median 70 vs. 58 years) and a larger proportion had diabetes mellitus at admission (51.4% vs. 31.4%). During follow-up 4,707 deaths (women 13.2%; men 22.0%) occurred, with women experiencing higher mortality than men with an averaged hazard ratio (HR): 2.08; 95% confidence interval : 1.96-2.20. However the actual adverse outcome, although always greater, reduced over time with an estimated HR: 2.23 (2.04-2.45) at 30 days to HR: 1.75; (1.47-2.09) 12 years later. The difference in mortality also declined with increasing age: HR 1.80 (1.52-2.13) for those aged 22-59, 1.26 (1.11-1.42) for 60-69, 1.06 (0.96-1.17) and 0.96 (0.85-1.09) for those 70-79 and 80-101 years. Significant two-factor interactions were observed between sex, age and diabetes (P < 0.001). Diabetic women <60 years of age had greater mortality than diabetic men of the same age (adjusted HR: 1.44; 1.14-1.84; P = 0.003), while diabetic women and men ≥60 years of age had a less pronounced mortality difference (adjusted HR: 1.12; 0.99-1.26). CONCLUSIONS: One in two women hospitalized for AMI in this Asian cohort had diabetes and the sex disparity in post-MI mortality was most pronounced among these who were <60 years of age. This underscores the need for better secondary prevention in this high-risk group.

Sample size calculations for the design of cluster randomized trials: A summary of methodology.

Cluster randomized trial designs are growing in popularity in, for example, cardiovascular medicine research and other clinical areas and parallel statistical developments concerned with the design and analysis of these trials have been stimulated. Nevertheless, reviews suggest that design issues associated with cluster randomized trials are often poorly appreciated and there remain inadequacies in, for example, describing how the trial size is determined and the associated results are presented. In this paper, our aim is to provide pragmatic guidance for researchers on the methods of calculating sample sizes. We focus attention on designs with the primary purpose of comparing two interventions with respect to continuous, binary, ordered categorical, incidence rate and time-to-event outcome variables. Issues of aggregate and non-aggregate cluster trials, adjustment for variation in cluster size and the effect size are detailed. The problem of establishing the anticipated magnitude of between- and within-cluster variation to enable planning values of the intra-cluster correlation coefficient and the coefficient of variation are also described. Illustrative examples of calculations of trial sizes for each endpoint type are included.

Long-term follow-up of children with high-risk neuroblastoma: the ENSG5 trial experience.

BACKGROUND: Therapy for high-risk neuroblastoma is intensive and multimodal, and significant long-term adverse effects have been described. The aim of this study was to identify the nature and severity of late complications of metastatic neuroblastoma survivors included in the ENSG5 clinical trial. PROCEDURE: The trial protocol included induction chemotherapy (randomized "Standard" OPEC/OJEC vs. "Rapid" COJEC), surgery of primary tumor and high-dose melphalan with stem cell rescue. Two hundred and sixty-two children were randomized, 69 survived >5 years, and 57 were analyzed. Data were obtained from the ENSG5 trial database and verified with questionnaires sent to participating centers. RESULTS: Median follow-up was 12.9 (6.9-16.5) years. No differences were found in late toxicities between treatment arms. Twenty-eight children (49.1%) developed hearing loss. Nine patients (15.8%) developed glomerular filtration rate <80 ml/min/1.73 m(2), but no cases of chronic renal failure were documented. Endocrine complications (28.1% of children) included mainly hypogonadism and delayed growth. Four children developed second malignancies, three of them 5 years after diagnosis: one osteosarcoma, one carcinoma of the parotid gland and one ependymoma. There were no hematological malignancies or deaths in remission. CONCLUSIONS: This study analyzed a wide cohort of high-risk neuroblastoma survivors from a multi-institutional randomized trial and established the profile of long-term toxicity within the setting of an international clinical trial.

A safe and flexible cardiopulmonary bypass technique for complex aortic surgery without the requirement for deep hypothermic circulatory arrest.

This article describes an adaptable technique of full-body perfusion during complex aortic surgery, which was performed on six consecutive patients, at a nasopharyngeal temperature of 28-34 degrees C for a mean duration of 5 hours. A modified perfusion system was used to provide upper and lower body perfusion through axillary and femoral artery cannulation. The option of selective antegrade cerebral perfusion was also available if required. A simple custom-made circuit and application of additional monitoring such as cerebral oximetry makes this technique a safe and flexible method of providing continuous whole-body perfusion at moderate hypothermia and above. We found that these patients all had no major coagulopathies after the procedure and demonstrated no observable neurological, renal, or gastrointestinal dysfunction on recovery.

An international strategy to determine the role of high dose therapy in recurrent Wilms' tumour.

PURPOSE: To review event-free (EFS) and overall survival (OS) from publications describing outcome for children with relapsed Wilms' tumour. Comparisons are made between those receiving myeloablative high dose chemotherapy with autologous stem-cell rescue (HDT) and those not (NoHDT). MATERIALS AND METHODS: Relevant information was extracted from individual patient or summary data and 3-year EFS and OS rates established. These rates were combined in a weighted manner to derive hazard ratios (HRs). RESULTS: Nineteen publications were identified (5 HDT, 6 NoHDT, 8 both). Pooling all studies suggested an advantage to HDT with a hazard ratio (HR) for EFS of 0.87 (95% confidence interval (CI) 0.67-1.12) and 0.94 (0.71-1.24) for OS. A stratified analysis confined to studies that provided individual patient data on both HDT and NoHDT gave HRs of 0.83 (0.56-1.24) and 0.92 (0.59-1.41). Further, analyses of risk groups, defined by treatment and/or histology prior to first relapse, suggested a HR for EFS of 0.90 (95% CI 0.62-1.31) for those of high and 0.50 (CI 0.31-0.82) for the very high risk patients. CONCLUSION: The evidence suggests, although there are many caveats since the information summarised here is not from randomised trials, a great deal of uncertainty concerning the role of HDT in patients following relapse after treatment for their Wilms' tumour. For each risk group we propose a randomised trial comparing a standard with a more intensive therapy with specific choice of regimen tailored to the risk group (and co-operative groups) concerned. A synthesis of updated evidence from studies in this overview together with any emerging studies and future trial information will form the basis for future evidence-based clinical decision-making.

Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study).

BACKGROUND: Gail and others developed a model (GAIL) using age-at-menarche, age-at-birth of first live child, number of previous benign breast biopsy examinations, and number of first-degree-relatives with breast cancer as well as baseline age-specific breast cancer risks for predicting the 5-year risk of invasive breast cancer for Caucasian women. However, the validity of the model for projecting risk in South-East Asian women is uncertain. We evaluated GAIL and attempted to improve its performance for Singapore women of Chinese, Malay and Indian origins. METHODS: Data from the Singapore Breast Screening Programme (SBSP) are used. Motivated by lower breast cancer incidence in many Asian countries, we utilised race-specific invasive breast cancer and other cause mortality rates for Singapore women to produce GAIL-SBSP. By using risk factor information from a nested case-control study within SBSP, alternative models incorporating fewer then additional risk factors were determined. Their accuracy was assessed by comparing the expected cases (E) with the observed (O) by the ratio (E/O) and 95% confidence interval (CI) and the respective concordance statistics estimated. RESULTS: From 28,883 women, GAIL-SBSP predicted 241.83 cases during the 5-year follow-up while 241 were reported (E/O=1.00, CI=0.88 to 1.14). Except for women who had two or more first-degree-relatives with breast cancer, satisfactory prediction was present in almost all risk categories. This agreement was reflected in Chinese and Malay, but not in Indian women. We also found that a simplified model (S-GAIL-SBSP) including only age-at-menarche, age-at-birth of first live child and number of first-degree-relatives performed similarly with associated concordance statistics of 0.5997. Taking account of body mass index and parity did not improve the calibration of S-GAIL-SBSP. CONCLUSIONS: GAIL can be refined by using national race-specific invasive breast cancer rates and mortality rates for causes other than breast cancer. A revised model containing only three variables (S-GAIL-SBSP) provides a simpler approach for projecting absolute risk of invasive breast cancer in South-East Asia women. Nevertheless its role in counseling the individual women regarding their risk of breast cancer remains problematical and needs to be validated in independent data.

Comparing statistical models to predict dengue fever notifications.

Dengue fever (DF) is a serious public health problem in many parts of the world, and, in the absence of a vaccine, disease surveillance and mosquito vector eradication are important in controlling the spread of the disease. DF is primarily transmitted by the female Aedes aegypti mosquito. We compared two statistical models that can be used in the surveillance and forecast of notifiable infectious diseases, namely, the Autoregressive Integrated Moving Average (ARIMA) model and the Knorr-Held two-component (K-H) model. The Mean Absolute Percentage Error (MAPE) was used to compare models. We developed the models using used data on DF notifications in Singapore from January 2001 till December 2006 and then validated the models with data from January 2007 till June 2008. The K-H model resulted in a slightly lower MAPE value of 17.21 as compared to the ARIMA model. We conclude that the models' performances are similar, but we found that the K-H model was relatively more difficult to fit in terms of the specification of the prior parameters and the relatively longer time taken to run the models.

Racial and geographic factors in the incidence of Legg-Calvé-Perthes' disease: a systematic review.

Legg-Calvé-Perthes' disease (Perthes' disease) is a childhood osteonecrosis of the hip for which the disease determinants are poorly understood. In this review, the authors identify studies of Perthes' disease incidence published up to December 2010 and make denominator populations comparable in order to allow meaningful between-study evaluation. Incidence rates and confidence intervals were determined, and, where appropriate, denominator populations were obtained from national statistical offices. Poisson regression was used to determine the influence of race and geography. The review included 21 studies that described 27 populations in 16 countries, with 124 million person-years of observation. The annual incidence among children under age 15 years ranged from 0.2 per 100,000 to 19.1 per 100,000. Race was a key determinant, with East Asians being least affected and whites most affected, though data were insufficient to consider incidence among blacks (for South Asians vs. East Asians, incidence rate ratio = 2.9, 95% confidence interval (CI): 2.4, 3.5; for whites vs. East Asians, incidence rate ratio = 8.8, 95% CI: 8.2, 9.6). Latitude was a strong predictor of disease, even after adjustment for race. Each 10° increase in latitude was associated with an incidence increase of 1.44 (95% CI: 1.30, 1.58) times. While much of the international variation appears to be a function of race, latitude demonstrates a strong association. This observation may offer new epidemiologic insights into the determinants of Perthes' disease.