Comparing Bleeding Risk Assessment Focused on Modifiable Risk Factors Only Versus Validated Bleeding Risk Scores in Atrial Fibrillation

Background

There is uncertainty whether a focus on modifiable bleeding risk factors offers better prediction of major bleeding than other existing bleeding risk scores.

The HAS-BLED,ATRIA, and ORBIT Bleeding Scores in Atrial Fibrillation Patients Using Non-Vitamin K Antagonist Oral Anticoagulants

Background

Various bleeding risk scores have been proposed to assess the risk of bleeding in patients with atrial fibrillation taking oral anticoagulants. Limited data are available with these scores, in users of non-vitamin K antagonist oral anticoagulants.

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE‐LY trial

Background

Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives

To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE‐LY trial.

Methods

HAS‐BLED, ORBIT, ATRIA and HEMORR₂HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results

There were 1182 (6.5%) major bleeding events during a median follow‐up of 2.0 years. For all the four schemes, high‐risk subgroups had higher risk of major bleeding (all P  < 0.001). The ORBIT score showed the best discrimination with c‐indices of 0.66, 0.66 and 0.62, respectively, for major, life‐threatening and intracranial bleeding, which were significantly better than for the HAS‐BLED score (difference in c‐indices: 0.050, 0.053 and 0.048, respectively, all P  < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P  = 0.0019), ATRIA (P  < 0.001) and HEMORR₂HAGES (P  < 0.001) scores. HAS‐BLED score showed a nonsignificant trend for interaction (P  = 0.0607).

Conclusions

Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

     

Diagnostic accuracy of EUS and CT of vascular invasion in pancreatic cancer: a systematic review

Objective

The objective of this study was to summarize the accuracy of preoperative vascular invasion with endoscopic ultrasound (EUS) and computed tomography (CT) test performance in pancreatic cancer with meta-analysis

Method

Two reviewers searched MEDLINE database to identify relevant studies. The reference lists of the trials were manually searched. Included studies used surgical and/or histological findings as the “gold standard,” and provided sufficient data to construct a diagnostic 2 × 2 table. A statistical program of Meta-Disc was used to calculate the pooled sensitivity, specificity, positive LR, negative LR, DOR, and the SROC curve. Publication bias was assessed by Deeks’ asymmetry test. Sensitivity analysis and subgroup analysis were calculated to down the heterogeneity. Meta-regression was calculated to evaluate potential sources of heterogeneity

Result

A total of 30 studies with 1,554 patients were included for the analysis, nine of these studies compared EUS with CT to assess the diagnostic efficiency The pooled sensitivity of EUS and CT was 72 % (95 % CI 67–77 %) and 63 % (95 % CI 58–67 %), and the pooled specificity of EUS and CT was 89 % (95 % CI 86–92 %) and 92 % (95 % CI 90–94 %), respectively. The positive LR of EUS and CT was 5.14 (95 % CI 3.14–8.40) and 6.21 (95 % CI 3.96–9.71), and the negative LR was 0.36 (95 % CI 0.25–0.52) and 0.41 (95 % CI 0.31–0.55), respectively. The AUCs of EUS and CT were 0.9037 and 0.8948. The subgroup analysis of nine studies performed both EUS and CT showed CT scan with a lower sensitivity of 48 % (95 % CI 0.40–0.56), when compared to EUS of 69 % (95 % CI 0.61–0.77). The overall AUCs of CT scan appear to be lower (AUCs = 0.8589), compared with EUS (AUCs = 0.9379)

Conclusion

EUS performed better than CT in differentiating vascular invasion preoperative on pancreatic cancer. EUS could provide other additional information when compared with CT.     

Stereotactic body radiotherapy with flattening filter-free beams for prostate cancer: assessment of patient-reported quality of life

Purpose

Stereotactic body radiotherapy (SBRT) is an emerging treatment approach reported as safe and effective strategy for low- and intermediate-risk prostate cancer patients. End point of the current study is to appraise the patient-reported quality of life according to the expanded prostate cancer index composite (EPIC) questionnaire.

Methods

In the framework of a prospective mono-institutional phase II trial, EPIC questionnaire was dispensed (up to 1 year after treatment) to a cohort of 46 patients of 72 treated with 5 fractions of 7 Gy each to the prostate. SBRT was delivered with RapidArc VMAT with 10 MV flattening filter-free photon beams.

Results

Median follow-up of patients was 14.5 months (range: 6–23). Acute rectal toxicity was mild (only 23/72 cases with G1–2 and no G3–4) as well as urinary (50/72 G1–2 and no G3–4). At the moment, four cases of G1 late rectal toxicity and 22 cases of G1 urinary (1 of G2) were reported. Urinary, rectal, sexual, and hormonal scores resulted stable over time: 1 year scores resulted, respectively, in ?0.3, +2.8, ?1.7, and ?2.8 % variations with respect to baseline. No significant differences were observed also when data were stratified according to functional and bother sub-scales.

Conclusions

Stereotactic body radiotherapy (SBRT) treatment of prostate with RapidArc and high-intensity photon beams resulted to be well tolerated by patients with mild toxicity profiles and good patient-reported quality of life perception for the first year after treatment. Longer follow-up in the trial cohort is in progress.     

Post-operative outcomes in adult obstructive sleep apnea patients undergoing non-upper airway surgery: a systematic review and meta-analysis

Background:

With the current obesity epidemic, obstructive sleep apnea (OSA) has become increasingly common. Several studies have reported on the risk of post-operative complications in OSA patients undergoing non-upper airway surgeries. The objective of our study was to systematically review the medical literature reporting the incidence of post-operative complications in patients with OSA.

Methods:

We conducted a systematic review using the Cochrane Collaboration Methodology. We searched Medline via Ovid, Pubmed, Embase, and Evidence-Based Medicine Reviews databases from 1950 to 2012. We rated the quality of evidence for each outcome using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Meta-analysis was done using Review Manager Version 5.0.20.

Results:

Our search resulted in 18 eligible studies. OSA was found to be associated with a significantly increased incidence of post-operative hypoxemia (odds ratio [OR]?=?3.06; 95 % confidence interval [CI] 2.35–3.97), respiratory complications (OR?=?2.77, 95 % CI 1.73–4.43), cardiac complications (OR?=?1.76 95 % CI 1.16–2.67), neurological complications (OR?=?2.65, 95 % CI 1.43–4.92), and unplanned intensive care unit (ICU) transfer (OR?=?2.97, 95 % CI 1.90–4.64). Re-intubation (OR?=?1.37, 95 % CI 0.65–2.91) was not significantly increased in patients with OSA. The association between OSA and post-operative outcomes remained unchanged with sub-group analysis including only studies that used polysomnography (PSG) for diagnosis.

Conclusions:

OSA patients are at increased risk of post-operative complications from non-upper airway surgeries. Early diagnosis and treatment of OSA might decrease post-operative complications in these patients. There is a need for further studies to assess the benefit of peri-operative treatment of OSA on post-operative outcomes.     

Evaluation of the temperament and character properties of patients with ankylosing spondylitis

Purpose

The aim of this study was to evaluate temperament and character of ankylosing spondylitis (AS) patients and to examine the association between these specific temperament and character properties and clinical variables.

Patients and methods

This study involved 73 AS patients. Temperament properties of patients were evaluated using Cloninger’s Temperament and Character Inventory (TCI). Association between clinical variables and specific temperament features were evaluated using correlation and regression analyses.

Results

Forty eight (65.8?%) of the study participants were men and the mean age was 42?±?11.4 years. There was slight negative correlations between self directedness (S) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores (p?=?0.01, r?=???0.30), and between the Visual Analog Scale (VAS) and reward dependence (RD) scores (p?=?0.03, r?=???0.26). Regression analysis showed that correlations between BASDAI and S, and between VAS and RD scores were statistically significant.

Conclusion

Our study showed that the dimensions temperament and character are related to disease activation, and disease course is more severe in patients who have low scores in these TCI dimensions. Therefore, we suggest that evaluating temperament and character properties of AS patients will help clinicians to predict treatment compliance and motivation of patients during disease course.     

Association of epicardial fat thickness with TIMI risk score in NSTEMI/USAP patients

Background

The association of epicardial adipose tissue (EAT) with coronary artery disease has been shown in previous studies. Furthermore, the relationship between EAT and acute coronary syndrome was studied recently. Herein, we investigated the relationship between EAT thickness and the thrombolysis in myocardial infarction (TIMI) risk score for non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris (USAP).

Patients and methods

The study included 144 patients with NSTEMI/USAP. The study population was divided into two subgroups according to TIMI risk scores as group I (≤?4, n?=?86) and group II (>?4, n?=?58). Stepwise multivariable logistic regression analysis was used to assess the independent association of clinical parameters with TIMI risk score.

Results

EAT thickness was higher in group II than in group I (8.2?±?2.1 vs. 6.2?±?2.2, p?Conclusion In conclusion, EAT thickness is independently associated with TIMI risk score and may be an emerging risk factor for adverse events in NSTEMI/USAP patients.     

The prognostic significance of the prognostic nutritional index in cancer: a systematic review and meta-analysis

Purpose

The prognostic nutritional index (PNI) is a simple and effective parameter, initially created to evaluate preoperative nutritional conditions and surgical risk. It has been recently been found to be associated with short- and long-term outcomes of various malignancies. We performed a meta-analysis to determine the predictive significance of PNI in cancer, as a mean to assist in determining the optimal surgery timing and in improving the survival of cancer patients.

Methods

Data were retrieved from PubMed and ISI Web of Science to identify eligible studies. Odds ratios (ORs) and hazard ratios (HRs) were extracted and pooled to explore the relationships of PNI with patient survival and clinicopathological features.

Results

Fourteen studies with a total of 3,414 participants met the inclusion criteria. Low PNI was associated with poor overall survival (pooled OR 1.80, 95 % confidence interval [CI] 1.59–2.04) and the presence of post-operative complications (pooled OR 2.45, 95 % CI 1.31–4.58) in cancer patients, but not with cancer-specific survival (CSS) (pooled HR 1.81, 95 % CI 0.94–3.49). PNI was also found to be associated with invasion depth (pooled OR 5.07, 95 % CI 2.34–10.96) and lymph node metastasis (pooled OR 3.70, 95 % CI 2.32–5.92) in gastric cancer, whereas TNM stage was the only clinicopathological feature associated with PNI in colorectal carcinoma (pooled OR 1.81, 95 % CI 1.24–2.64).

Conclusions

PNI might be an effective predictive indicator for the prognosis of cancer, especially digestive system carcinomas. Further studies are required to verify the significance of PNI in clinical practice.     

A phase II study of radiofrequency ablation therapy for thoracic malignancies with evaluation by FDG-PET

Purpose

Computed tomography (CT)-guided radiofrequency ablation (RFA) is safe and effective for patients with unresectable primary, recurrent, or metastatic thoracic malignancies. Several studies have shown the benefit of employing 18-fluoro-deoxyglucose positron-emission tomography (FDG-PET) to follow thoracic malignancies treated with RFA. In this prospective study, we show the safety and therapeutic efficacy of RFA and the utility of FDG-PET as tool for early detection of local recurrence.

Methods

Twenty patients were enrolled in this study, and 24 lesions were ablated. Seven lesions were primary lung cancer, and 17 lesions were recurrent tumors or metastases from extrathoracic sites. Tumor size was in the range of 0.4–3.3 cm in diameter (mean: 1.5 cm). CT and FDG-PET scans were scheduled 7–14 days and 3–6 months after RFA treatment.

Results

There were 17 adverse events (70.8 %) in 24 ablations included 13 pneumothoraces, two cases of chest pain, and two episodes of fever. With a median follow-up of 35.9 months (range 1–62 months), the overall 2-year survival rate was 84.2 %. Local recurrence occurred at four sites (2-year local control rate was 74.3 %). The FDG-PET results 7–14 days after RFA did not predict recurrence, whereas positive findings 3–6 months after RFA significantly correlated with local recurrence (p = 0.0016).

Conclusions

We confirmed the effectiveness of RFA for unresectable primary and secondary thoracic malignancies. FDG-PET analysis 3–6 months after ablation is a useful tool to assess local control.     

Assessing health-state utility values in patients with metastatic colorectal cancer: a utility study in the United Kingdom and the Netherlands

Purpose

This study aimed to elicit EuroQol Quality of Life 5-Dimensions (EQ-5D) utility values from patients with second-line metastatic colorectal cancer (mCRC) pre- and post-progression.

Methods

A cross-sectional study was conducted in five hospitals in the Netherlands and the UK. Patients with mCRC were eligible if prescribed a second or subsequent line of therapy or best supportive care (BSC), received prior oxaliplatin in first-line therapy, and had Eastern Cooperative Oncology Group (ECOG) performance status scores of 0–2 at second-line initiation. Patients completed the EuroQol Quality of Life 5-Dimensions 3-levels (EQ-5D-3L) questionnaire and were categorized as pre- or post-progression. Chart data including patient demographics, clinical history, prior/current treatments and serious adverse events (SAEs) were collected. Mean utilities were estimated; uni- and multivariate analyses were conducted.

Results

Seventy-five patients were enrolled; 42 were pre-progression defined as second line or third line following an AE on second line and 33 were post-progression defined as third or subsequent therapy lines or BSC. Patient/disease characteristics and number of SAEs were similar between cohorts. Mean utility scores were 0.741 (SD?=?0.230) and 0.731 (SD?=?0.292) for pre- and post-progression cohorts, respectively. Compared to pre-progression, more patients reported increased anxiety/depression (36 vs. 12 %) and fewer problems with daily activities (64 vs. 38 %) post-progression. More patients pre-progression were on active treatment at enrolment (83 vs. 42 %) compared to post-progression.

Conclusions

This is the first real-world study to collect utilities for patients with second-line mCRC pre- and post-disease progression. Utility values were similar pre- and post-progression. To further explore the effect of radiological progression on utilities, longitudinal research is required that includes patients in palliative care centres.     

Sleep studies in children on long-term non-invasive respiratory support

Purpose

The aim of this study was to assess the impact of changes in respiratory support (RS) settings recommended after a titration polysomnography (PSG), in terms of daytime symptoms and quality of life.

Methods

A retrospective chart review of all RS (CPAP and bi-level ventilation) titration studies was carried out at our tertiary paediatric sleep laboratory in the past 5 years. All patients with at least two studies in the past 5 years were included in the analysis. Parents completed the obstructive sleep apnoea (OSA)-18 and Paediatric Daytime Sleepiness Scale (PDSS) questionnaires on the night of each PSG. Results are presented as means (SD).

Results

A total of 42 patients (25 on CPAP and 17 on bi-level ventilation, age 11 (6)?years) had 71 pairs of titration studies (41 CPAP and 30 bi-level). Changes in RS settings were recommended in 27 of 41 (65 %) CPAP studies and 11 of 30 (36 %) bi-level studies. Overall, changes were fully implemented by the treating physician in 55 % of cases. There was an improvement in total OSA-18 score between studies in 48 % of the paired CPAP studies and 65 % of bi-level studies. OSA-18 scores improved in 47 % of the studies where any recommended change had been implemented versus 0 % of those where none of the recommended changes had been made (p?=?0.1).

Conclusions

Titration studies frequently led to recommendations for a change in RS settings in these patients on long-term RS. Symptom scores were more likely to improve if recommendations for change were implemented by the time of the follow-up study.     

Independent effects of circulating glucose,insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

Aims/hypothesis

Cardiac steatosis and myocardial insulin resistance elevate the risk of cardiac complications in obesity and diabetes. We aimed to disentangle the effects of circulating glucose, insulin and NEFA on myocardial triacylglycerol (TG) content and myocardial glucose uptake.

Methods

Twenty-two pigs were stratified according to four protocols: low NEFA?+?low insulin (nicotinic acid), high NEFA?+?low insulin (fasting) and high insulin?+?low NEFA?±?high glucose (hyperinsulinaemia–hyperglycaemia or hyperinsulinaemia–euglycaemia). Positron emission tomography, [U-¹³C]palmitate enrichment techniques and tissue biopsies were used to assess myocardial metabolism. Heart rate and rate–pressure product (RPP) were monitored.

Results

Myocardial glucose extraction was increased by NEFA suppression and was similar in the hyperinsulinaemia–hypergylcaemia, hyperinsulinaemia–euglycaemia and nicotinic acid groups. Hyperglycaemia enhanced myocardial glucose uptake due to a mass action. Myocardial TG content was greatest in the fasting group, whereas hyperinsulinaemia had a mild effect. Heart rate and RPP increased in hyperinsulinaemia–euglycaemia, in which cardiac glycogen content was reduced. Heart rate correlated with myocardial TG and glycogen content.

Conclusions/interpretation

Elevated NEFA levels represent a powerful, self-sufficient promoter of cardiac TG accumulation and are a downregulator of myocardial glucose uptake, indicating that the focus of treatment should be to ‘normalise’ adipose tissue function to lower the risk of cardiac TG accumulation and myocardial insulin resistance. The observation that hyperinsulinaemia and nicotinic acid led to myocardial fuel deprivation provides a potential explanation for the cardiovascular outcomes reported in recent intensive glucose-lowering and NEFA-lowering clinical trials.     

Tamoxifen as a therapeutic agent in acromegaly

Objective

Administration of high doses of estrogens to patients with acromegaly has been shown to improve symptomatology of acromegaly and glucose tolerance more than 50 years ago. Selective estrogen receptor modulators (SERMs) mimic the effects of estrogen in bone, liver and the cardiovascular system, but function as an anti-estrogen in endometrial and breast tissue. In this study, we evaluated hormonal effects of a SERM, tamoxifen, in active acromegalic patients with particular emphasis on its use in males.

Design

We studied 15 men and 2 post-menopausal women with biochemically-active acromegaly despite the fact that other modalities were ineffective in normalizing their insulin-like growth factor-1 (IGF-1) levels. All patients were treated with tamoxifen 20–40 mg daily for 2–11 months (median of 4 months).

Methods

IGF-1 and growth hormone (GH) levels were assessed immediately before the beginning of treatment and at 2–4 monthly intervals thereafter. Baseline and treatment levels of total and bioavailable testosterone were measured in men.

Results

Tamoxifen did not affect basal GH secretion, but it decreased circulating IGF-I in 14 patients (82 %) by an average of 90 ± 4 mcg/L, (p = 0.005), and normalized plasma IGF-I in 8 patients (47 %). Total and bioavailable testosterone levels increased in all evaluable men (n = 8). Tamoxifen was well tolerated.

Conclusion

Tamoxifen might be useful in the treatment of patients with biochemically-mild active acromegaly, but longer term studies are warranted.     

The HAS‐BLED Score for Predicting Major Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: A Systematic Review and Meta‐analysis

Our objective was to compare the diagnostic accuracy between the HAS‐BLED score and any of HEMORR₂HAGES, ATRIA, CHADS₂, or CHA₂DS₂‐VASc scores in anticoagulated patients with atrial fibrillation. We systematically searched the Cochrane Library, MEDLINE, PubMed, and Embase databases for relevant studies. Data were extracted and analyzed according to predefined clinical endpoints. Eleven studies were identified. Discrimination analysis demonstrates that HAS‐BLED has no significant C‐statistic differences for bleeding risk prediction compared with ATRIA or HEMORR₂HAGES, but it has significant differences compared with CHADS₂ or CHA₂DS₂‐VASc. The significant positive net reclassification improvement and integrated discrimination improvement values also show that HAS‐BLED is superior to that of any of HEMORR₂HAGES, ATRIA, CHADS₂, or CHA₂DS₂‐VASc scores. According to calibration analysis of HAS‐BLED, it overpredicts the risk of bleeding in the low (risk ratio [RR]: 1.16, 95% confidence interval [CI]: 0.63‐2.13, P = 0.64) risk stratification but underpredicts that in the moderate (RR: 0.66, 95% CI: 0.51‐0.86, P = 0.002) and high (RR: 0.88, 95% CI: 0.70‐1.10, P = 0.27) risk stratifications. The HAS‐BLED score not only performs better than the HEMORR₂HAGES and ATRIA bleeding scores, but it also is superior to the CHADS₂ and CHA₂DS₂‐VASc stroke scores for bleeding prediction. The HAS‐BLED score should be the optimal choice to assess major bleeding risk in clinical practice.     

Evaluation of four comorbidity indices and Charlson comorbidity index adjustment for colorectal cancer patients

Introduction

Cancer survival is related not only to primary malignancy but also to concomitant nonmalignant diseases. The aim of this study was to investigate the prognostic capacity of four comorbidity indices [the Charlson comorbidity index (CCI), the Elixhauser method, the National Institute on Aging (NIA) and National Cancer Institute (NCI) comorbidity index, and the Adult Comorbidity Evaluation-27 (ACE-27)] for both cancer-related and all-cause mortality among colorectal cancer patients. A modified version of the CCI adapted for colorectal cancer patients was also built.

Methods

The study population comprised 468 cases of colorectal cancer diagnosed between 1 January 2000 and 31 December 2010 at a community hospital. Data were prospectively collected and abstracted from patients’ clinical records. Kaplan-Meier method and multivariate logistic regression models were performed for survival and risk of death analysis.

Results

Only moderate or severe renal disease [hazard ratio (HR) 2.71, 95 % confidence interval (CI) 1.11–6.63] and AIDS (HR 3.27, 95 % CI 1.23–8.68) were independently associated with cancer-specific mortality, with a population attributable risk of 5.18 and 4.36 %, respectively. For each index, the highest comorbidity burden was significantly associated with poorer overall survival (NIA/NCI: HR 2.14, 95 % CI 1.14–4.01; Elixhauser: HR 1.98, 95 % CI 1.09–1.42; ACE-27: HR 1.78, 95 % CI 1.07–1.23; CCI: HR 1.68, 95 % CI 1.05–1.42) and cancer-specific survival. The modified version of the CCI resulted in a higher predictive power compared with other indices studied (cancer-specific mortality HR?=?2.37, 95 % CI 1.37–4.08).

Conclusions

The comorbidity assessment tools provided better prognostic prevision of prospective outcome of colorectal cancer patients than single comorbid conditions.     

Effectiveness of enzyme replacement therapy in adults with late-onset Pompe disease: results from the NCS-LSD cohort study

Objectives

To determine the effectiveness of enzyme replacement therapy (ERT) for adults with late-onset Pompe disease.

Design

A longitudinal cohort study including prospective and retrospective clinical outcome data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data.

Participants

Consenting adults (N?=?62) with a diagnosis of late-onset Pompe disease who attended a specialist treatment centre in England. This cohort represented 83 % of all patients in the UK with a confirmed diagnosis of this rare condition. At study entry, all but three patients were receiving ERT (range of treatment duration, 0 to 3.1 years).

Outcome measures

Percent predicted forced vital capacity (%FVC); ventilation dependency; mobility; 6 min walk test (6MWT); muscle strength and body mass index (BMI).

Results

An association was found between time on ERT and significant increases in the distance walked in the 6MWT (p?p?Conclusions These data provide some further evidence of the effectiveness of ERT in adults with late-onset Pompe disease.

Synopsis

The results of this longitudinal cohort study of 62 adults with late-onset Pompe disease, provide further evidence on the effectiveness of ERT in this rare condition.     

Factors influencing the response of psychological symptoms to continuous positive airway pressure therapy

Purpose

To examine whether in obstructive sleep apnea (OSA) patients the degree of sleepiness, slow-wave sleep (SWS) loss, and hypoxia influence the response of psychological symptoms to continuous positive airway pressure (CPAP) therapy.

Methods

A prospectively planned cohort was assessed. Participants underwent full overnight polysomnography. All answered the Symptom Checklist-90-Revised (SCL-90) and the Epworth sleepiness scale (ESS). Only cases with an apnea-hypopnea index ≤60 events/h were 24 invited to participate. In an interview by telephone, after a follow-up period between 2 months and 1 year, patients informed whether they were in treatment with CPAP or remained voluntarily untreated. Subjects who accepted to participate answered for the second time the SCL-90 and the ESS. The baseline variables of interest were: (a) score of the ESS, (b) duration of SWS, and (c) time with arterial oxygen saturation below 90 %. The outcomes were the change in SCL-90 scores in all dimensions and indices of the questionnaire.

Results

A number of 73 patients, mostly men, were included. In uncontrolled analyses, CPAP-treated patients showed significant improvement at follow-up in 10 of the 13 SCL-90 scores. Comparing with the control group, only six scores were improved. Baseline sleepiness was the best predictor of SCL-90 improvement after CPAP treatment in the univariate analyses, and the only significant predictor of improvement in a multivariate regression model.

Conclusions

Sleepiness may supersede other factors that influence psychological improvement in CPAP-treated patients with severe OSA.     

Cholangiocarcinoma and High-Grade Dysplasia in Young Patients with Primary Sclerosing Cholangitis

Introduction

Cholangiocarcinoma (CCA) is very often an adulthood disease with primary sclerosing cholangitis (PSC) as one of the risk factors. It is rarely seen in the pediatric population, and when it is diagnosed before adulthood, it can be associated with PSC as well as HIV infection, biliary atresia, radiation therapy, and choledochal cyst. Although there have been some case reports of pediatric CCA, cases of childhood CCA associated with PSC are still relatively rare.

Aim

To describe the clinical and pathologic features of CCA in pediatric patients with previously diagnosed PSC.

Methods

Retrospective study

Results

Four patients with PSC (age range 15–18, mean 17 years) were included in this study. All patients underwent ERCP for diagnosis. Tissue samples obtained included routine cytology and FISH. ERCP was used to target sites for tissue acquisition in all patients. 3/4 of patients have inflammatory bowel disease (two Crohn’s disease and one ulcerative colitis). Alkaline phosphatase was elevated in 3/4 patients, aspartate aminotransferase/alanine aminotransferase were elevated in 2/4 patients, and total bilirubin/direct bilirubin were elevated in 2/4 patients. 4/4 patients had positive FISH studies, and 3/4 patients had brush cytology concerning for CCA. 2/4 patients received chemotherapy, one patient underwent orthotopic liver transplant, and one patient underwent Whipple procedure. Two patients died soon after being diagnosed.

Conclusions

Young patients with PSC can develop CCA. This finding has implications for both screening and surveillance for cancer in pediatric patients with PSC.     

Serum ferritin,diabetes, diabetes control,and insulin resistance

Aims

The present study aims to investigate the association between serum ferritin and diabetes, diabetes control, and insulin resistance (IR) and examine whether gender is a modifier for these associations in a community-based sample.

Methods

A cross-sectional survey of 8,235 participants was conducted in 2009. Serum ferritin, glucose, hemoglobin A1c (HbA1c), insulin, inflammatory markers, and lipid markers were measured. IR was estimated with a Homeostasis Model Assessment (HOMA-IR) equation. Multiple logistic and linear regression models were applied to evaluate these associations.

Results

The numbers of diabetic patients and non-diabetic participants in the present study were 644 (7.8 %) and 7,591 (92.2 %). After adjusting for multiple confounders, the odds ratios (ORs) and 95 % confidence intervals (CIs) for diabetes were 1.48 (1.31–1.69) in men and 1.43 (1.24–1.65) in women for one-unit increase in log-transformed serum ferritin levels. Likewise, ORs (95 % CIs) for poor diabetes control (HbA1c ≥7.5 %) were 1.58 (1.21–2.05) and 1.37 (1.07–1.77) in men and women, respectively. As for HOMA-IR, the respective betas (P value) for one-unit increase in log-transformed serum ferritin were 0.07 (P < 0.0001) and 0.06 (P < 0.0001) in men and women.

Conclusions

In conclusion, elevated serum ferritin levels were associated with higher risks of diabetes, higher levels of HbA1c, and HOMA-IR independent of several confounders.