Dating of Pregnancy in First versus Second Trimester in Relation to Post-Term Birth Rate: A Cohort Study

Objectives

To evaluate in a national standardised setting whether the performance of ultrasound dating during the first rather than the second trimester of pregnancy had consequences regarding the definition of pre- and post-term birth rates.

Methods

A cohort study of 8,551 singleton pregnancies with spontaneous delivery was performed from 2006 to 2012 at Copenhagen University Hospital, Holbæk, Denmark. We determined the duration of pregnancy calculated by last menstrual period, crown rump length (CRL), biparietal diameter (1^st trimester), BPD (2^nd trimester), and head circumference and compared mean and median durations, the mean differences, the systematic discrepancies, and the percentages of pre-term and post-term pregnancies in relation to each method. The primary outcomes were post-term and pre-term birth rates defined by different dating methods.

Results

The change from use of second to first trimester measurements for dating was associated with a significant increase in the rate of post-term deliveries from 2.1–2.9% and a significant decrease in the rate of pre-term deliveries from 5.4–4.6% caused by systematic discrepancies. Thereby 25.1% would pass 41 weeks when GA is defined by CRL and 17.3% when BPD (2^nd trimester) is used. Calibration for these discrepancies resulted in a lower post-term birth rate, from 3.1–1.4%, when first compared to second trimester dating was used.

Conclusions

Systematic discrepancies were identified when biometric formulas were used to determine duration of pregnancy. This should be corrected in clinical practice to avoid an overestimation of post-term birth and unnecessary inductions when first trimester formulas are used.     

Lower Inter-Partum Interval and Unhealthy Life-Style Factors Are Inversely Associated with n-3 Essential Fatty Acids Changes during Pregnancy: A Prospective Cohort with Brazilian Women

Objective

To analyze serum fatty acids concentrations during healthy pregnancy and evaluate whether socioeconomic, demographic, obstetric, nutritional, anthropometric and lifestyle factors are associated with their longitudinal changes.

Study design

A prospective cohort of 225 pregnant women was followed in the 5^th–13^th, 20^th–26^th and 30^th–36^th weeks of gestation. Serum samples were collected in each trimester of pregnancy and analyzed to determine the fatty acids composition using a high-throughput robotic direct methylation method coupled with fast gas-liquid chromatography. The independent variables comprised the subjects’ socioeconomic and demographic status, obstetric history, early pregnancy body mass index (BMI), dietary and lifestyle parameters. Analyses were performed using linear mixed-effects models.

Results

The overall absolute concentrations of fatty acids increased from the 1^st to the 2^nd trimester and slightly increased from the 2^nd to the 3^rd trimester. Early pregnancy BMI, inter-partum interval and weekly fish intake were the factors associated with changes in eicosapentaenoic + docosahexaenoic acids (EPA+DHA) and total n-3 polyunsaturated fatty acids (PUFAs). Early pregnancy BMI, age and monthly per-capita income were inversely associated with the changes in the n-6/n-3 ratio. Alcohol consumption was positively associated with the n-6/n-3 ratio.

Conclusion

Early pregnancy BMI was positively associated with EPA+DHA and total n-3 PUFAs, while presenting a reduced weekly fish intake and a lower inter-partum interval were associated with lower levels of n-3 PUFAs. A lower per-capita family income and a drinking habit were factors that were positively associated with a higher n-6/n-3 ratio.     

Risk Factors and Post-Resection Independent Predictive Score for the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma

Background

Independent risk factors associated with hepatitis B (HBV)-related hepatocellular carcinoma (HCC) after resection remains unknown. An accurate risk score for HCC recurrence is lacking.

Methods

We prospectively followed up 200 patients who underwent liver resection for HBV-related HCC for at least 2 years. Demographic, biochemical, tumor, virological and anti-viral treatment factors were analyzed to identify independent risk factors associated with recurrence after resection and a risk score for HCC recurrence formulated.

Results

Two hundred patients (80% male) who underwent liver resection for HBV-related HCC were recruited. The median time of recurrence was 184 weeks (IQR 52–207 weeks) for the entire cohort and 100 patients (50%) developed HCC recurrence. Stepwise Cox regression analysis identified that one-month post resection HBV DNA >20,000 IU/mL (p = 0.019; relative risk (RR) 1.67; 95% confidence interval (C.I.): 1.09–2.57), the presence of lymphovascular permeation (p<0.001; RR 2.69; 95% C.I.: 1.75–4.12), microsatellite lesions (p<0.001; RR 2.86; 95% C.I.: 1.82–4.51), and AFP >100ng/mL before resection (p = 0.021; RR 1.63; 95% C.I.: 1.08–2.47) were independently associated with HCC recurrence. Antiviral treatment before resection (p = 0.024; RR 0.1; 95% C.I.: 0.01–0.74) was independently associated with reduced risk of HCC recurrence. A post-resection independent predictive score (PRIPS) was derived and validated with sensitivity of 75.3% and 60.6% and specificity of 55.7% and 79.2%, to predict the 1- and 3-year risks for the HCC recurrence respectively with the hazard ratio of 2.71 (95% C.I.: 2.12–3.48; p<0.001). The AUC for the 1- and 3-year prediction were 0.675 (95% C.I.: 0.6–0.78) and 0.746 (95% C.I.: 0.69–0.82) respectively.

Conclusion

Several tumor, virological and biochemical factors were associated with a higher cumulative risk of HCC recurrence after resection. PRIPS was derived for more accurate risk assessment. Regardless of the HBV DNA level, antiviral treatment should be given to patients before resection to reduce the risk of recurrence.     

Association of Gestational Age at Birth with Reasons for Subsequent Hospitalisation: 18 Years of Follow-Up in a Western Australian Population Study

Background

Preterm infants are at a higher risk of hospitalisation following discharge from the hospital after birth. The reasons for rehospitalisation and the association with gestational age are not well understood.

Methods

This was a retrospective birth cohort study of all live, singleton infants born in Western Australia between 1^st January 1980 and 31^st December 2010, followed to 18 years of age. Risks of rehospitalisation following birth discharge by principal diagnoses were compared for gestational age categories (<32, 32–33, 34–36, 37–38 weeks) and term births (39–41weeks). Causes of hospitalisations at various gestational age categories were identified using ICD-based discharge diagnostic codes.

Results

Risk of rehospitalisation was inversely correlated with gestational age. Growth-related concerns were the main causes for rehospitalisation in the neonatal period (<1 month of age) for all gestational ages. Infection was the most common reason for hospitalisation from 29 days to 1 year of age, and up to 5 years of age. Injury-related hospitalisations increased in prevalence from 5 years to 18 years of age. Risk of rehospitalisation was higher for all preterm infants for most causes.

Conclusions

The highest risks of rehospitalisation were for infection related causes for most GA categories. Compared with full term born infants, those born at shorter GA remain vulnerable to subsequent hospitalisation for a variety of causes up until 18 years of age.     

Dialysis-Requiring Acute Kidney Injury in Denmark 2000-2012: Time Trends of Incidence and Prevalence of Risk Factors—A Nationwide Study

Introduction

Dialysis-requiring acute kidney injury is a severe illness associated with poor prognosis. However, information pertaining to incidence rates and prevalence of risk factors remains limited in spite of increasing focus. We evaluate time trends of incidence rates and changing patterns in prevalence of comorbidities, concurrent medication, and other risk factors in nationwide retrospective cohort study.

Materials and Methods

All patients with dialysis-requiring acute kidney injury were identified between January 1^st 2000 and December 31^st 2012. By cross-referencing data from national administrative registries, the association of changing patterns in dialysis treatment, comorbidity, concurrent medication and demographics with incidence of dialysis-requiring acute kidney injury was evaluated.

Results

A total of 18,561 adult patients with dialysis-requiring AKI were identified between 2000 and 2012. Crude incidence rate of dialysis-requiring AKI increased from 143 per million (95% confidence interval, 137–144) in 2000 to 366 per million (357–375) in 2006, and remained stable hereafter. Notably, incidence of continuous veno-venous hemodialysis (CRRT) and use of acute renal replacement therapy in elderly >75 years increased substantially from 23 per million (20–26) and 328 per million (300–355) in 2000, to 213 per million (206–220) and 1124 per million (1076–1172) in 2012, respectively. Simultaneously, patient characteristics and demographics shifted towards increased age and comorbidity.

Conclusions

Although growth in crude incidence rate of dialysis-requiring AKI stabilized in 2006, continuous growth in use of CRRT, and acute renal replacement therapy of elderly patients >75 years, was observed. Our results indicate an underlying shift in clinical paradigm, as opposed to unadulterated growth in incidence of dialysis-requiring AKI.     

Blood Lead Levels in Children Aged 0–6 Years Old in Hunan Province,China from 2009–2013

Objectives

The aim of this study is to describe blood lead levels (BLLs) and the prevalence of elevated blood lead levels (EBLLs) in children aged 0–6 years old and to analyze the BLL trend in children from 2009 to 2013 in China.

Methods

A total of 124,376 children aged 0–6 years old were recruited for this study from January 1^st 2009 to December 31^st 2013. Their blood lead levels were analyzed using atomic absorption spectrometry.

Results

The median BLL was 64.3 μg/L (IQR: 49.6–81.0), and the range was 4.3–799.0 μg/L. Blood lead levels were significantly higher in boys (66.0 μg/L) than in girls (61.9 μg/L) (P<0.001). The overall prevalence of BLLs≥100 μg/L was 10.54% in children aged 0–6 years in Hunan Province. Between 2009 and 2013, the prevalence of EBLLs (≥100 μg/L) decreased from 18.31% to 4.26% in children aged 0–6 years and increased with age. The prevalence of EBLLs has dramatically decreased in two stages (2009–2010 and 2012–2013), with a slight fluctuation in 2010 and 2011.

Conclusions

Both BLLs and the prevalence of EBLLs in children aged 0–6 years old declined substantially from 2009 to 2013 in Hunan Province; however, both remain at unacceptably high levels compared to developed countries. Comprehensive strategies are required to further reduce blood lead levels in children.     

Consent for Brain Tissue Donation after Intracerebral Haemorrhage: A Community-Based Study

Background

Spontaneous intracerebral haemorrhage is a devastating form of stroke and its incidence increases with age. Obtaining brain tissue following intracerebral haemorrhage helps to understand its cause. Given declining autopsy rates worldwide, the feasibility of establishing an autopsy-based collection and its generalisability are uncertain.

Methods

We used multiple overlapping sources of case ascertainment to identify every adult diagnosed with intracerebral haemorrhage between 1^st June 2010-31^st May 2012, whilst resident in the Lothian region of Scotland. We sought consent from patients with intracerebral haemorrhage (or their nearest relative if the patient lacked mental capacity) to conduct a research autopsy.

Results

Of 295 adults with acute intracerebral haemorrhage, 110 (37%) could not be approached to consider donation. Of 185 adults/relatives approached, 91 (49%) consented to research autopsy. There were no differences in baseline demographic variables or markers of intracerebral haemorrhage severity between consenters and non-consenters. Adults who died and became donors (n = 46) differed from the rest of the cohort (n = 249) by being older (median age 80, IQR 76–86 vs. 75, IQR 65–83, p = 0.002) and having larger haemorrhages (median volume 23ml, IQR 13–50 vs. 13ml, IQR 4–40; p = 0.002).

Conclusions

Nearly half of those approached consent to brain tissue donation after acute intracerebral haemorrhage. The characteristics of adults who gave consent were comparable to those in an entire community, although those who donate early are older and have larger haemorrhage volumes.     

Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a,Randomized, Double-Blind,Placebo-Controlled Research in Japanese Patients

Objective

Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS.

Design

A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.

Methods

The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7). The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1^st endpoint) and upon completion or discontinuation of the study (2^nd endpoint) of the dosing.

Results

Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1^st and 2^nd endpoint analysis. In the 1^st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%), eating and drinking (P = 2.2%), ALSFRS-R total (P = 17.6%), grip strength (P = 19.8%) compared to the placebo group. In the 2^nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%), ALSAQ40-communication (P = 11.9%), eating and drinking (P = 13.6%), and neck forward-bent test (P = 15.4%) of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.

Conclusions

BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.

Trial Registration

UMIN Clinical Trials UMIN000008527     

Insulin Resistance Change and Antiretroviral Therapy Exposure in HIV-Infected and Uninfected Rwandan Women: A Longitudinal Analysis

Background

We longitudinally assessed predictors of insulin resistance (IR) change among HIV-uninfected and HIV-infected (ART-initiators and ART-non-initiators) Rwandan women.

Methodology

HIV-infected (HIV+) and uninfected (HIV-) women provided demographic and clinical measures: age, body mass index (BMI) in Kg/(height in meters)², Fat-Mass (FMI) and Fat-Free-Mass (FFMI) index, fasting serum glucose and insulin. Homeostasis Model Assessment (HOMA) was calculated to estimate IR change over time in log₁₀ transformed HOMA measured at study enrollment or prior to ART initiation in 3 groups: HIV- (n = 194), HIV+ ART-non-initiators (n=95) and HIV+ ART-initiators (n=371). ANCOVA linear regression models of change in log₁₀-HOMA were fit with all models included the first log₁₀ HOMA as a predictor.

Results

Mean±SD log₁₀-HOMA was -0.18±0.39 at the 1^st and -0.21±0.41 at the 2^nd measure, with mean change of 0.03±0.44. In the final model (all women) BMI at 1^st HOMA measure (0.014; 95% CI=0.006-0.021 per kg/m²; p<0.001) and change in BMI from 1^st to 2^nd measure (0.024; 95% CI=0.013-0.035 per kg/m²; p<0.001) predicted HOMA change. When restricted to subjects with FMI measures, FMI at 1^st HOMA measure (0.020; 95% CI=0.010-0.030 per kg/m²; p<0.001) and change in FMI from 1^st to 2^nd measure (0.032; 95% CI=0.020-0.043 per kg/m²; p<0.0001) predicted change in HOMA. While ART use did not predict change in log₁₀-HOMA, untreated HIV+ women had a significant decline in IR over time. Use or duration of AZT, d4T and EFV was not associated with HOMA change in HIV+ women.

Conclusions

Baseline BMI and change in BMI, and in particular fat mass and change in fat mass predicted insulin resistance change over ~3 years in HIV-infected and uninfected Rwandan women. Exposure to specific ART (d4T, AZT, EFV) did not predict insulin resistance change in ART-treated HIV-infected Rwandan women.     

Risk of Developing Depressive Disorders following Hepatocellular Carcinoma: A Nationwide Population-Based Study

Background & Aims

To evaluate the risk of depressive disorders among patients with Hepatocellular Carcinoma (HCC) using the National Health Insurance Research Database (NHIRD) in Taiwan.

Methods

We conducted a retrospective study of a newly diagnosed HCC cohort of 55,973 participants who were selected from the NHIRD. Patients were observed for a maximum of 6 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in HCC patients.

Results

Of the total 55,973 HCC patients, 1,041 patients (1.86%) were diagnosed with depressive disorders during a mean (SD) follow-up period of 1.1 (1.2) years. The Cox multivariate proportional hazards analysis showed that age of 40–59 (HR 1.376, 95% CI 1.049–1.805, p = 0.021), age of 60–79 (HR 1.341, 95% CI 1.025–1.753, p = 0.032), women (HR 1.474 95% CI 1.301–1.669, p < 0.001), metastasis (HR 1.916, 95% CI 1.243–2.953, p = 0.003), and HCV (HR 1.445, 95% CI 1.231–1.697, p < 0.001) were independent risk factors for developing depressive disorders.

Conclusions

Our study indicated a subsequent risk of depressive disorders in patients with HCC, and the risk increased for those with female gender, aged 40 to 59, aged 60 to 79, with metastasis, or with HCV. Psychological evaluation and support are two critical issues in these HCC patients with the risk factors.     

Presence of a Physician Safety Champion Is Associated with a Reduction in Urinary Catheter Utilization in the Pediatric Intensive Care Unit

Background

Safety champions are effective in a variety of safety initiatives; however, there are no reports of their role in hospital-acquired infections prevention.

Objective

We aimed to describe the association of the presence of a physician safety champion with our urinary catheter device utilization ratios (DUR) in the Pediatric Intensive Care Unit (PICU).

Methods

Our PICU has incidence rates of catheter-associated urinary tract infections (CAUTI) and urinary catheter DUR above the 90^th percentile. Using a quasi-experimental design, we compared our DUR when the PICU team was exposed and unexposed (champion’s maternity leaves) to a physician safety champion. Hospital acquired infection (HAI) surveillance of all PICU admissions between April 1^st 2009 and June 29^th 2013 was done prospectively. To ensure stable acuity of the patient population over time, we used the central venous catheter (CVC) DUR as a control.

Results

The urinary catheter DUR was 0.44 (95% confidence interval [CI] 0.42–0.45) during the unexposed period versus 0.39 (95%CI 0.38–0.40) during the exposed period, for an absolute difference of 0.05 (95%CI 0.03–0.06; p<0.0001). The overall CVC DUR increased from 0.57 (95%CI 0.55–0.58) during the unexposed period to 0.63 (95%CI 0.61–0.64) during the exposed period, an absolute increase of 0.06 (95%CI 0.04–0.08; p<0.0001). Comparing the exposed and unexposed periods, adjusting for time trend, we observed a 17% decrease in the urinary catheter DUR when the safety champion was present (odds ratio [OR] 0.83; 95%CI 0.77–0.90). The rate of catheter-associated urinary tract infections did not change.

Conclusions

The presence of a unit-based safety champion can have a positive impact on urinary catheter DUR in a PICU.     

Factors Associated with Low-Level Viraemia and Virological Failure: Results from the Austrian HIV Cohort Study

Background

In human immunodeficiency virus treatment adequate virological suppression is warranted, nevertheless for some patients it remains a challenge. We investigated factors associated with low-level viraemia (LLV) and virological failure (VF) under combined antiretroviral therapy (cART).

Materials and Methods

We analysed patients receiving standard regimens between 1^st July 2012 and 1^st July 2013 with at least one viral load (VL) measurement below the quantification limit (BLQ) in their treatment history. After a minimum of 6 months of unmodified cART, the next single VL measurement within 6 months was analysed. VF was defined as HIV RNA levels ≥200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLQ were identified by logistic regression models.

Results

Of 2276 participants, 1972 (86.6%) were BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher risk for LLV and VF was shown in patients with cART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from centres using the Abbott compared to the Roche assay to measure VL. A higher risk for LLV but not for VF was found in patients with a higher VL before cART [for >99.999 copies/mL: aOR (95% CI): 4.19 (2.07–8.49); for 10.000–99.999 copies/mL: aOR (95% CI): 2.52 (1.23–5.19)] and shorter cART duration [for <9 months: aOR (95% CI): 2.59 (1.38–4.86)]. A higher risk for VF but not for LLV was found in younger patients [for <30 years: aOR (95% CI): 2.76 (1.03–7.35); for 30–50 years: aOR (95% CI): 2.70 (1.26–5.79)], people originating from high prevalence countries [aOR (95% CI): 2.20 (1.09–4.42)] and in male injecting drug users [aOR (95% CI): 2.72 (1.38–5.34)].

Conclusions

For both VF and LLV, factors associated with adherence play a prominent role. Furthermore, performance characteristics of the diagnostic assay used for VL quantification should also be taken into consideration.     

Patient-Related Risk Factors for Periprosthetic Joint Infection after Total Joint Arthroplasty: A Systematic Review and Meta-Analysis

Background

Periprosthetic joint infections (PJIs) are dreaded complications of total joint arthroplasties. The risk of developing PJIs is likely to be influenced by several patient factors such as sociodemographic characteristics, body mass index (BMI), and medical and surgical histories. However, the nature and magnitude of the long-term longitudinal associations between these patient-related factors and risk of developing PJIs are uncertain.

Objective

To conduct a systematic review and meta-analysis to assess the associations between several patient-related factors and PJI.

Data Sources

MEDLINE, EMBASE, Web of Science, Cochrane Library, and reference lists of relevant studies from inception to September 2015.

Study Selection

Longitudinal studies with at least one-year of follow-up for PJIs after total joint arthroplasty.

Data Extraction and Synthesis

Two investigators extracted data on study characteristics, methods, and outcomes. A consensus was reached with involvement of a third. The relative risk (RR) with 95% confidence intervals was used as the summary measure of association across studies. Study-specific RRs with 95% confidence intervals were meta-analysed using random effect models and were grouped by study-level characteristics.

Results

Sixty-six observational (23 prospective cohort and 43 retrospective cohort or case-control) studies with data on 512,508 participants were included. Comparing males to females and smokers to non-smokers, the pooled RRs for PJI were 1.36 (1.18–1.57) and 1.83 (1.24–2.70) respectively. There was no evidence of any significant associations of PJI with age and high alcohol intake. Comparing BMI ≥ 30 versus < 30 kg/m²; ≥ 35 versus < 35 kg/m²; and ≥ 40 versus < 40 kg/m²; the pooled RRs were 1.60 (1.29–1.99); 1.53 (1.22–1.92); and 3.68 (2.25–6.01) respectively. Histories of diabetes, rheumatoid arthritis, depression, steroid use, and previous joint surgery were also associated with increased risk of PJI. The results remained similar when grouped by relevant study level characteristics.

Conclusions

Several potentially modifiable patient-related factors are associated with the risk of developing PJIs. Identifying patients with these risk factors who are due to have arthroplasty surgery and modulating these risk factors might be essential in reducing the incidence of PJI. Further research is however warranted to assess the potential clinical utility of these risk factors as risk assessment tools for PJI.

Systematic Review Registration

PROSPERO 2015: CRD42015023485     

Organisational Factors Induce Prolonged Emergency Department Length of Stay in Elderly Patients – A Retrospective Cohort Study

Study objective

To assess the association of patient and organisational factors with emergency department length of stay (ED-LOS) in elderly ED patients (226565 years old) and in younger patients (<65 years old).

Methods

A retrospective cohort study of internal medicine patients visiting the emergency department between September 1^st 2010 and August 31^st 2011 was performed. All emergency department visits by internal medicine patients 226565 years old and a random sample of internal medicine patients <65 years old were included. Organisational factors were defined as non-medical factors. ED-LOS is defined as the time between ED arrival and ED discharge or admission. Prolonged ED-LOS is defined as ≥75^th percentile of ED-LOS in the study population, which was 208 minutes.

Results

Data on 1782 emergency department visits by elderly patients and 597 emergency department visits by younger patients were analysed. Prolonged ED-LOS in elderly patients was associated with three organisational factors: >1 consultation during the emergency department visit (odds ratio (OR) 3.2, 95% confidence interval (CI) 2.3–4.3), a higher number of diagnostic tests (OR 1.2, 95% CI 1.16–1.33) and evaluation by a medical student or non-trainee resident compared with a medical specialist (OR 4.2, 95% CI 2.0–8.8 and OR 2.3, 95% CI 1.4–3.9). In younger patients, prolonged ED-LOS was associated with >1 consultation (OR 2.6, 95% CI 1.4–4.6). Factors associated with shorter ED-LOS were arrival during nights or weekends as well as a high urgency level in elderly patients and self-referral in younger patients.

Conclusion

Organisational factors, such as a higher number of consultations and tests in the emergency department and a lower seniority of the physician, were the main aspects associated with prolonged ED-LOS in elderly patients. Optimisation of the organisation and coordination of emergency care is important to accommodate the needs of the continuously growing number of elderly patients in a better way.     

A Prognostic Score for Patients with Intermediate-Stage Hepatocellular Carcinoma Treated with Transarterial Chemoembolization

Background

Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE.

Methods

Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; n = 187) and two affiliated hospitals (validation cohort; n = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child–Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions.

Results

The number of lesions and the Child–Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0–7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child–Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0–2 points, 3 points, 4 points, 5 points, and 6–7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; p < 0.0001). These results were confirmed in the external validation cohort (p < 0.0001).

Conclusions

The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.     

The Efficacy of Continued Sorafenib Treatment after Radiologic Confirmation of Progressive Disease in Patients with Advanced Hepatocellular Carcinoma

Background

Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC.

Methods

We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled.

Results

Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107–0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047–0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355–5.691), and post-PD sorafenib administration (0.279, 0.150–0.510).

Conclusion

Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients.     

Surgery or Consultation: A Population-Based Cohort Study of Use of Orthopaedic Surgeon Services

Background

This population-based cohort study has the objective to understand the sociodemographic characteristics and health conditions of patients who do not receive surgery within 18 months following an ambulatory visit to an orthopaedic surgeon.

Methods

Administrative healthcare databases in Ontario, Canada were linked to identify all patients making an initial ambulatory visit to orthopaedic surgeons between October 1^st, 2004 and September 30^th, 2005. Logistic regression was used to examine predictors of not receiving surgery within 18 months.

Results

Of the 477,945 patients in the cohort 49% visited orthopaedic surgeons for injury, and 24% for arthritis. Overall, 79.3% did not receive surgery within 18 months of the initial visit, which varied somewhat by diagnosis at first visit (84.5% for injury and 73.0% for arthritis) with highest proportions in the 0–24 and 25–44 age groups. The distribution by income quintile of patients visiting was skewed towards higher incomes. Regression analysis for each diagnostic group showed that younger patients were significantly more likely to be non-surgical than those aged 65+ years (age 0–24: OR 3.45 95%CI 3.33–3.57; age 25–44: OR 1.30 95%CI 1.27–1.33). The odds of not getting surgery were significantly higher for women than men for injury and other conditions; the opposite was true for arthritis and bone conditions.

Conclusion

A substantial proportion of referrals were for expert diagnosis or advice on management and treatment. The findings also suggest socioeconomic inequalities in access to orthopaedic care. Further research is needed to investigate whether the high caseload of non-surgical cases affects waiting times to see a surgeon. This paper contributes to the development of evidence-based strategies to streamline access to surgery, and to develop models of care for non-surgical patients to optimize the use of scarce orthopaedic surgeon resources and to enhance the management of musculoskeletal disorders across the care continuum.     

Evolutionary Changes of Hepatitis B Virus Pre-S Mutations Prior to Development of Hepatocellular Carcinoma

Background and Aims

Deletions/mutations in the hepatitis B virus (HBV) pre-S region have been associated with hepatocellular carcinoma (HCC). We aimed to study the evolutionary changes of pre-S mutations prior to HCC development.

Methods

We studied the HBV pre-S sequences at 1 to 10 years preceding diagnosis of HCC in 74 patients with HBV-related HCC (HCC group). 148 chronic hepatitis B patients matched for sex and age in 2:1 ratio, who had been followed up for at least 3 years without HCC (HCC-free group) were recruited as controls. 56 and 47 patients of HCC and HCC-free groups respectively had serially stored sera for longitudinally examination at 1–3 years, 4–6 years, 7–9 years and ≥10 years prior to the recruitment of the study.

Results

Compared to the HCC-free group, higher frequencies of pre-S deletions and point mutations (at 11 codons) were observed in the HCC group (p<0.05). Multiple logistic regression analysis showed that pre-S deletions, point mutations at codon 51 and 167 were independent factors associated with HCC. Longitudinal observation showed that pre-S deletions and most of the 11 HCC-associated pre-S point mutations existed at least 10 years before HCC development, and were more prevalent preceding HCC development in patients from HCC groups than HCC-free group. The number of HCC-associated pre-S point mutations increased over time preceding HCC development, and correlated positively with the time to HCC diagnosis (r = 0.220, p = 0.005).

Conclusions

High prevalence and cumulative evolution of pre-S mutations preceding HCC development suggested a possible carcinogenic role of pre-S mutations and their potential application in HCC risk prediction.     

Six-Minute Walk Test in Renal Failure Patients: Representative Results,Performance Analysis and Perceived Dyspnea Predictors

Objectives

Six-minute walk test in dialysis population hasn’t been consistently evaluated for the isolated impact of renal failure and other predictive factors. We measured six-minute walk distance in patients representative for low level of comorbidity and searched for potentially modifiable predictive factors of performance and dyspnea.

Methods

This was a cross-sectional study with hemodialysis patients (N = 90) and control subjects (N = 140). Main outcome measures: six-minute walk test distance and dyspnea severity using the 10-item Borg scale.

Results

Median distance decreased from 600m below the 6^th decade to 420m in the 8^th decade of age. Dialysis dependence predicted 101.5m shorter distance in the adjusted model that explained 70% of variability in results. Adjusted for significant covariates of age, height and spontaneous gait speed, fat mass (but not lean body mass) and serum total iron binding capacity were significantly associated with distance (95% CI for B coefficients -4.6 to –1.4 m/kg and 0.1 to 5 m/μmol/l, respectively). Serum total iron binding capacity as an explanatory variable was superior to C-reactive protein and albumin. Dialysis dependence, odds ratio (OR) 2.97 (1.11–7.94), spontaneous gait speed, OR 0.08 (0.02–0.41), rate-pressure product, OR 1.15 (1.08–1.23) and hemoglobin, OR 0.95 (0.92–0.98) predicted dyspnea in the adjusted model.

Conclusions

Renal failure without the confounding effect of comorbidity is a significant negative predictor of performance at six-minute walk test and perceived level of dyspnea. Body fat mass and serum total iron binding capacity are the main potentially modifiable predictors of performance, total iron binding capacity being superior to C-reactive protein and albumin. Although hemoglobin is not associated with test performance, it negatively predicts perceived shortness of breath.