A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber with reduced kidney function.

Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m2. Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 µm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2% of 33,222 and 11.3% of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95-1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted.

The East-West late lumen loss study: Comparison of angiographic late lumen loss between Eastern and Western drug-eluting stent study cohorts.

BACKGROUND: Regulatory decisions approving new coronary drug-eluting stent (DES) require mechanistic observations of angiographic late lumen loss (LLL). Patient safety and device approval times could be enhanced if angiographic follow-up data were found to be generalizable across jurisdictions and geographies. The objectives were to assess the comparability of in-segment LLL in Eastern and Western DES populations using the world's largest compilation of follow-up quantitative coronary angiography data. METHODS: Data from 4 manufacturers involving 29 DES clinical trials in Eastern and Western hemispheres were compiled. "East" and "West" cohorts were defined by trial location. Independent core laboratories quantified in-segment LLL for all studies. East and West were compared before and after adjustment for clinical and anatomic covariates known to correlate with LLL via conditioning on propensity score quintiles. An international panel of experts and regulators prospectively established a clinically meaningful difference between East and West mean in-segment LLL of ±0.40 mm. RESULTS: The data set comprised 2,047 East and 4,456 West patients. Unadjusted mean ± SD for West and East in-segment LLL (mm) was 0.25 ± 0.46 and 0.12 ± 0.42, respectively (difference 0.13 mm; 95% CI 0.11-0.16). Propensity score-adjusted in-segment LLL East and West least squares means were 0.11 and 0.26 mm, respectively (difference 0.15 mm; 95% CI 0.13-0.18). CONCLUSIONS: In the world's largest compilation of DES protocol 8- to 13-month angiographic follow-up data, clinically meaningful comparability of in-segment LLL by independent core laboratory quantitative coronary angiography in East and West cohorts was demonstrated in both unadjusted and adjusted comparisons. These findings suggest that DES LLL, once characterized, could be generalized across regulatory jurisdictions over the course of global registration efforts.

A Clinical Scoring System to Predict the Clinical Sequelae of Computed Tomography Diagnosed Intussusception.

INTRODUCTION: Intussusception in adults is increasingly diagnosed on cross-sectional imaging with a lack of clear recommendations on management. The presence of an underlying lead point is a key to guiding management as its absence can predict spontaneous resolution. We studied adult patients with computed tomography (CT) diagnosed intussusception formulate a clinical scoring system to predict the risk of an underlying lead point. METHODOLOGY: We performed a retrospective review of all adult patients who underwent CT scans of the abdomen and pelvis in our institution between 2001 and 2014. Independent associations of an underlying lead point were derived following multivariable analysis, from which a clinical scoring system was developed. RESULTS: We studied 140 patients. In multivariable analysis, six factors were found to be independently associated with the presence of an underlying lead point, namely gender, abdominal pain, CT evidence of colonic involvement, CT evidence of a lead point, distal diameter ≥27 mm and minimum wall thickness ≥3 mm. A nine-point clinical scoring system was developed, with a cutoff score of four or higher yielding a sensitivity and specificity of 0.75 and 0.81, respectively. CONCLUSION: Our clinical scoring system provides a quantitative tool to predict the likelihood of an underlying lead point in CT-diagnosed intussusception in adults to help guide management.

Greater rheumatoid arthritis joint improvement with more subjects achieving response across improvement categories using novel versus existing ultrasound methods.

We compared the change in joint inflammation and the proportion of subjects achieving threshold levels of improvement using the existing methods employing ultrasonography on pre-determined joint sites versus novel methods. These novel methods select the most affected joints based on (i) ultrasonography-the Individualized-Ultrasound (IUS) method, or (ii) ultrasonography and clinical joint assessment-the individualized-Composite-Ultrasound (ICUS) method. Mean 3-month change in total inflammation score (ΔTIS) and 95% CI was computed for each method on 24 RA subjects initiated or escalated on treatment. Individual improvement in TIS per subject, calculated as the 3-month ΔTIS divided by the maximum possible TIS score expressed as a percentage, was used to obtain the proportion of subjects achieving response across improvement categories. Mean 3-month ΔTIS was significantly greater (p values ranging from 0.0003 to 0.0026) for novel versus existing methods using 12- and 7-joint approaches. Using 12-joint approach, percentages of subjects in improvement categories ≥5%, ≥10%, ≥15% and ≥20% were, respectively, 50, 37.5, 12.5 and 8.3% for IUS; 58.3, 37.5, 12.5 and 8.3% for ICUS; and 16.7, 0, 0 and 0% for the existing method. Using 7-joint approach, the respective category percentages were 62.5, 37.5, 25 and 12.5% for IUS; 62.5, 41.7, 16.7 and 8.3% for ICUS; and 12.5, 4.2, 4.2 and 0% for the existing method. Novel ultrasound methods are more likely to detect improvement in joint inflammation, with more subjects achieving response across improvement categories, thereby representing a substantial advantage over the existing methods. However, this requires confirmation in larger RA cohorts.

Effect of a spiritual care training program for staff on patient outcomes.

OBJECTIVE: Physicians and nurses do not assess spirituality routinely, even though spiritual care is a vital part of palliative care for patients with an advanced serious illness. The aim of our study was to determine whether a training program for healthcare professionals on spirituality and the taking of a spiritual history would result in improved patient quality of life (QoL) and spiritual well-being. METHOD: This was a cluster-controlled trial of a spiritual care training program for palliative care doctors and nurses. Three of seven clinical teams (clusters) received the intervention, while the other four served as controls. Included patients were newly referred to the palliative care service, had an estimated survival of more than one month, and were aware of their diagnosis and prognosis. The primary outcome measure was the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) patient-reported questionnaire, which patients completed at two timepoints. Total FACIT-Sp score includes the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, which measures overall quality of life, as well as a spiritual well-being score. RESULTS: Some 144 patients completed the FACIT-Sp at both timepoints-74 in the control group and 70 in the intervention group. The change in overall quality of life, measured by change in FACT-G scores, was 3.89 points (95% confidence interval [CI 95%] = -0.42 to 8.19, p = 0.076) higher in the intervention group than in the control group. The difference between the intervention and control groups in terms of change in spiritual well-being was 0.32 (CI 95% = -2.23 to 2.88, p = 0.804). SIGNIFICANCE OF RESULTS: A brief spiritual care training program can possibly help bring about enhanced improvement of global patient QoL, but the effect on patients' spiritual well-being was not as evident in our participants. Further study with larger sample sizes is needed to allow for more definite conclusions to be drawn.

Trends and predictors of asthma costs: results from a 10-year longitudinal study.

Research on asthma costs often focuses on estimating average asthma costs. Trends in asthma costs and patterns of medication use, especially for those who have been followed up and under treatment, have received much less attention. This study's objective was to document asthma costs over time for asthma patients who are enrolled in an asthma care programme in Singapore and to identify its predictors, using a 10-year longitudinal dataset.The study population comprised different cohorts of 939 asthma patients entering the programme at different times during 2004-2013. Average asthma costs were estimated and the trends over time examined graphically, within and across patient cohorts. Regression analyses were conducted to examine cost predictors, with a focus on the relationship between risk factors at programme enrolment and subsequent asthma costs.The results indicate that 10-year average annual asthma cost was GBP 341 per patient. The main drivers of costs were asthma medications and consultation fees. Use of combined inhaled corticosteroid/long-acting ß-agonist medications increased over time, but this was accompanied by declines in controller drug use, doctor visits and total asthma drug costs. Obesity, smoking and asthma severity were the main predictors of subsequent asthma costs, especially for females.

Rationale and design of the East-West late lumen loss study: Comparison of late lumen loss between Eastern and Western drug-eluting stent study cohorts.

BACKGROUND: The contemporary evaluation of novel drug-eluting stents (DES) includes mechanistic observations that characterize postdeployment stent behavior. Quantification of late lumen loss due to neointimal hyperplasia 8-13 months after stent implantation, via quantitative coronary angiography (QCA), constitutes such an observation and is required by most regulatory authorities. Late lumen loss, as determined by QCA, has been validated as a surrogate for clinical endpoints such as target vessel revascularization. The mechanistic response to DES has not been directly compared across predominantly Asian or Western populations, whereas understanding their comparability across geographic populations could enhance global DES evaluation. OBJECTIVE: The East-West late lumen loss study is designed to demonstrate whether the residual differences in late lumen loss, as assessed by QCA, is different between Eastern and Western DES recipients from studies with protocol angiography at 8-13 months of follow-up. METHODS: Data from independent core laboratories that have characterized angiographic late lumen loss in DES clinical trials with protocol follow-up angiography will be compiled and dichotomized into Eastern and Western populations. A prospectively developed propensity score model incorporating clinical and anatomic variables affecting late lumen loss will be used to adjust comparisons of QCA measurements. CONCLUSION: Documentation of whether there are clinically meaningful differences in mechanistic response to DES implantation across genetically unique geographies could facilitate both the quality and efficiency of global device evaluation requiring invasive follow-up for novel stent designs.

A novel cardiovascular risk stratification model incorporating ECG and heart rate variability for patients presenting to the emergency department with chest pain.

BACKGROUND: Risk stratification models can be employed at the emergency department (ED) to evaluate patient prognosis and guide choice of treatment. We derived and validated a new cardiovascular risk stratification model comprising vital signs, heart rate variability (HRV) parameters, and demographic and electrocardiogram (ECG) variables. METHODS: We conducted a single-center, observational cohort study of patients presenting to the ED with chest pain. All patients above 21 years of age and in sinus rhythm were eligible. ECGs were collected and evaluated for 12-lead ECG abnormalities. Routine monitoring ECG data were processed to obtain HRV parameters. Vital signs and demographic data were obtained from electronic medical records. Thirty-day major adverse cardiac events (MACE) were the primary endpoint, including death, acute myocardial infarction, and revascularization. Candidate variables were identified using univariate analysis; the model for the final risk score was derived by multivariable logistic regression. We compared the performance of the new model with that of the thrombolysis in myocardial infarct (TIMI) score using receiver operating characteristic (ROC) analysis. RESULTS: In total, 763 patients were included in this study; 254 (33 %) met the primary endpoint, the mean age was 60 (σ = 13) years, and the majority was male (65 %). Nineteen candidate predictors were entered into the multivariable model for backward variable elimination. The final model contained 10 clinical variables, including age, gender, heart rate, three HRV parameters (average R-to-R interval (RR), triangular interpolation of normal-to-normal (NN) intervals, and high-frequency power), and four 12-lead ECG variables (ST elevation, ST depression, Q wave, and QT prolongation). Our proposed model outperformed the TIMI score for prediction of MACE (area under the ROC curve 0.780 versus 0.653). At the cutoff score of 9 (range 0-37), our model had sensitivity of 0.709 (95 % CI 0.653, 0.765), specificity of 0.674 (95 % CI 0.633, 0.715), positive predictive value of 0.520 (95 % CI 0.468, 0.573), and negative predictive value of 0.823 (95 % CI 0.786, 0.859). CONCLUSIONS: A non-invasive and objective ECG- and HRV-based risk stratification tool performed well against the TIMI score, but future research warrants use of an external validation cohort.

Retinal microvascular calibre and risk of diabetes mellitus: a systematic review and participant-level meta-analysis.

AIMS/HYPOTHESIS: The calibre of the retinal vessels has been linked to diabetes mellitus but studies have not shown consistent results. We conducted a participant-level meta-analysis to evaluate the association between retinal arteriolar and venular calibre and diabetes. METHODS: We performed a systematic review on MEDLINE and EMBASE for articles published up to December 2014. We identified five population-based prospective cohort studies that provided individual-level data on 18,771 diabetes-free participants. We used discrete time proportional hazards models to estimate pooled HRs of diabetes associated with 1 SD (20 µm) change in retinal vascular calibre. RESULTS: We identified 2,581 incident cases of diabetes over a median follow-up period of 10 years (interquartile interval of 3.4-15.8 years). After adjustment for demographic, lifestyle and clinical factors, retinal venular calibre was significantly associated with incident diabetes (pooled HR 1.09 [95% CI 1.02, 1.15] per SD increase in venular calibre). This association persisted in analyses excluding individuals with <5 years of follow-up (1.07 [1.0, 1.12]) or those with impaired fasting glucose at baseline (1.10 [1.03, 1.17]); in subgroup analyses, the association was stronger in men than in women but was consistent across subgroups of race/ethnicity, smoking status, hypertension and BMI categories. Retinal arteriolar calibre was not associated with diabetes (0.95 [0.86, 1.06] per SD decrease in arteriolar calibre). CONCLUSIONS/INTERPRETATION: Wider retinal venules but not narrower retinal arterioles were associated with a modestly increased risk for diabetes. Knowledge of pathological mechanisms underlying wider retinal venule may provide further insights concerning microvascular alterations in diabetes.

Validation of the MSKCC Gastrointestinal Stromal Tumor Nomogram and Comparison with Other Prognostication Systems: Single-Institution Experience with 289 Patients.

PURPOSE: To validate the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic nomogram in a single-institution cohort of patients with gastrointestinal stromal tumors (GISTs), and to compare its predictive accuracy against other established risk classification systems, including the National Institutes of Health (NIH), Armed Forces Institute of Pathology (AFIP), and Joensuu criteria. METHODS: We retrospectively reviewed 289 patients who underwent surgical resection for primary localized GISTs without adjuvant imatinib therapy and compared the actuarial recurrence-free survival (RFS) with the predicted RFS. RESULTS: Tumors >5 cm in size, with high mitotic index, and which had ruptured were significantly associated with recurrent disease. The 2-year RFS was 77.2 % [95 % confidence interval (CI) 71.6-81.8], and the 5-year RFS was 67.9 % (95 % CI 61.7-73.4). The concordance probability of the nomogram of 2-year RFS was 0.71 (SE 0.02), and 5-year RFS was 0.71 (SE 0.19). The 2-year and 5-year MSKCC nomogram probability calculations and the AFIP criteria gave a better estimation of RFS compared to the NIH (p < 0.001) and Joensuu (p < 0.001) criteria. There was no significant difference between the predictive accuracy of the nomogram compared to the AFIP criteria. CONCLUSIONS: The MSKCC nomogram slightly underestimated the probability of RFS after surgical resection of GISTs. It was associated with a significantly better predictive accuracy compared to the NIH and Joensuu. This study suggests that there is a wider than expected prognostic divergence between gastric GISTs versus GISTs arising from the small intestine.

GnRH antagonist pre-treatment: one centre's experience for IVF-ICSI cycle scheduling.

Scheduling gonadotrophin-releasing hormone antagonist (GnRH-ant) cycles for IVF intracytoplasmic sperm injection in patients is a challenge because of unpredictable ovum retrieval procedures on weekends, when less manpower is available. Recently, the use of GnRH-ant pre-treatment to delay an IVF and intracytoplasmic sperm injection (ICSI) cycle showed no negative effect on clinical pregnancy rates. An age-matched, case-control study was conducted to evaluate the effectiveness of such pre-treatment for scheduling purposes. Patients (n = 140) undergoing their first ovarian stimulation for IVF-ICSI were included. Patients starting their stimulation on Tuesdays or Wednesdays were most likely to have their ovum retrieval procedure on Saturdays. Seventy patients received a 3-day course of GnRH-ant before starting stimulation, and were compared with 70 age-matched controls not receiving pre-treatment. The main outcomes were the proportion of ovum retrieval procedures occurring on Saturdays, clinical pregnancy rate and live birth rates. A five-fold reduction in the number of ovum retrievals occurred on Saturdays compared with controls (7.1% versus 34.3%; OR 0.15; 95% CI 0.05 to 0.42; P < 0.001), with no significant differences in clinical pregnancy rate (40.9% versus 37.5%) and live birth rate (27.3% versus 31.3%). GnRH-ant pre-treatment is an effective tool for scheduling of GnRH-ant cycles.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Obstructing Colorectal Cancer Treated by Endoscopic Stenting as a Bridge to Surgery.

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) has been reported to predict adverse survival outcomes among patients with colorectal cancer (CRC). This study evaluates the prognostic value of NLR among patients with obstructing CRC who successfully underwent stenting before curative surgery. METHODS: We retrospectively reviewed patients who underwent stenting before surgery. Patient demographics, tumor characteristics, perioperative outcomes, recurrence-free survival (RFS), and overall survival (OS) were analyzed. NLR was calculated from the differential white blood cell counts at least 4 days after successful stenting, before elective surgery. Optimal cutoff to dichotomize NLR was obtained by maximizing log-rank test statistic with recursive partitioning of KaplanMeier RFS and OS curves. The optimal cutoff for high NLR was ≥ 5 at presentation before stenting, and ≥ 4 after stenting. RESULTS: Fifty-seven patients with localized obstructing CRC underwent successful endoscopic stenting before curative surgery. High NLR was associated with lymphovascular invasion (P = 0.006) and apical lymph node involvement (P = 0.034). Major perioperative complication(s) (hazard ratio [HR], 11.34; 95% confidence interval [CI], 2.49 to 51.56; P < 0.01) and high NLR (HR, 3.69; 95% CI, 1.46 to 9.35; P < 0.01) negatively impacted OS on univariate and multivariate analyses. High NLR negatively impacted RFS on univariate analysis (HR, 2.91; 95% CI, 1.29 to 6.60; P = 0.01). CONCLUSION: NLR of ≥ 4 after stenting is an independent prognostic factor among patients with obstructing localized CRC who are successfully decompressed by endoscopic stenting before curative surgery.

Age and diabetes mellitus associated with worse outcomes after percutaneous coronary intervention in a multi-ethnic Asian dialysis patient population.

INTRODUCTION: There is limited literature on clinical outcomes following percutaneous coronary intervention (PCI) in Asian dialysis patients. We evaluated the angiographic characteristics and clinical outcomes of dialysis patients treated with PCI in an Asian society. METHODS: A retrospective analysis was performed of 274 dialysis patients who underwent PCI in a tertiary care institution from January 2007 to December 2012. Data on clinical and angiographic characteristics was collected. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiac death, acute myocardial infarction (AMI) and stroke at two years. RESULTS: 274 patients (65.0% male, median age 62.0 years) with 336 lesions (81.8% Type B2) were treated. 431 stents (35.0% drug-eluting stents) with a mean diameter of 2.96 mm and mean length of 21.30 mm were implanted. The MACE rate was 55.8% (n = 153) at two years, from death (36.5%) and AMI (35.0%). In multivariable analysis, age and diabetes mellitus were significant predictors of both mortality (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.05-1.12, p < 0.001; OR 2.65, 95% CI 1.46-4.82, p = 0.001, respectively) and MACE (OR 1.06, 95% CI 1.03-1.08, p < 0.001; OR 1.84, 95% CI 1.07-3.15, p = 0.027, respectively). Left ventricular ejection fraction (LVEF) (OR 0.97, 95% CI 0.95-0.99, p = 0.006) was a significant predictor of mortality but not MACE. CONCLUSION: Asian dialysis patients who underwent PCI had a two-year MACE rate of 55.8% due to death and AMI. Age, LVEF and diabetes mellitus were significant predictors of mortality at two years.

Stenting as a bridge to surgery for obstructed stage IV colorectal cancers - long-term outcomes of a 10-year study.

INTRODUCTION: Successful stenting of an obstructing colorectal tumor can avert upfront emergency surgery in malnourished obstructed patients with metastatic disease and poor physiological condition. This study aims to evaluate the outcomes of stenting followed by primary colorectal tumor resection among patients with obstructed stage IV colorectal cancer at presentation, over a 10-year period. METHODS: From 2007 to 2016, a cohort comprising 25 consecutive patients were retrospectively reviewed from a prospectively collected database. The durability of palliation of bowel obstruction, oncological outcomes and factors influencing overall survival were analyzed. RESULTS: No re-interventions were required for bowel obstruction during the study period. The overall perioperative morbidity rate was 16%, with no postoperative 90-day mortality. Laparoscopic resection rate was 52% and stoma formation rate was 8%. The median overall survival was 24 months for the entire cohort, and the 1-, 3- and 5-year survival rates were 80%, 35% and 23.33% respectively. More than one site of distant metastases, peritoneal involvement, and elevated carcinoembryonic antigen levels were significantly associated with poorer survival outcomes. Patients with peritoneal-only metastasis had worse outcomes, with a median survival of 7 months and no patients surviving beyond 18 months. CONCLUSION: Stenting followed by resection of the primary obstructing colorectal cancer provides durable palliation among patients with stage IV disease, with low perioperative morbidity and stoma formation rates. Superior survival was observed among patients with single-site, non-peritoneal distant metastases.

The Characteristics of Patients Associated With High Caregiver Burden in Parkinson's Disease in Singapore.

Introduction: Given the complex multitude of Parkinson's disease (PD) symptoms, caregiving for PD patients can be highly demanding. Our study was aimed to investigate the characteristics of PD patients related to different levels of caregiver burden. Methods: This cross-sectional study recruited 104 idiopathic PD patient-caregiver pairs. Patients were evaluated on motor, non-motor symptoms, and quality of life (QoL). Caregiver burden was quantified using Zarit Burden Inventory and subsequently stratified into 3 subgroups. Statistical analysis was performed to identify differences in the no-or little, mild-moderate, and high caregiver burden subgroups. Results: The mean disease duration was significantly longer in the high caregiver burden group compared to no-or little group (9.63 vs. 5.17 years; p-value 0.003). The mean levodopa equivalent daily dose (LEDD) and mean total UPDRS Part IV scores (UPDRS4) were significantly higher in the high caregiver burden group compared to no-or little group (p-value 0.011 and 0.004, respectively). The high caregiver burden group had significantly higher median QoL scores (PDQ-39) for PD patients for domain 2 (ADL, p-value 0.005), domain 4 (stigma, p-value 0.005), and domain 6 (cognition, p-value 0.002) compared to no-or little group. Conclusion: Greater caregiver burden was observed in PD patients with more prolonged disease duration, higher LEDD to control motor symptoms as well as greater levodopa related motor complications. Further studies on potential interventions to mitigate or delay levodopa related motor complications may reduce caregiver burden. Marked worsening in patient's QoL, specifically ADL, stigma and cognition in the high compared to no-or little caregiver burden group suggests the possible utility of monitoring these factors for early identification of increasing caregiver stress and burden.

Complications and Pain in Obstructive Sleep Apnoea - Comparing Single and Multilevel Surgery.

INTRODUCTION: This study aimed to investigate differences in the complication rate and postoperative pain score between single and multilevel surgery performed on patients with obstructive sleep apnoea. MATERIALS AND METHODS: A retrospective analysis was performed on patients with obstructive sleep apnoea who underwent surgery in a tertiary referral centre over 3 years. Patients who underwent single-level nasal, palatal or tongue surgery were compared with patients who underwent concurrent multilevel surgery of 2 or 3 levels. Complications and the postoperative Visual Analogue Scale pain score were recorded and the outcomes between single and multilevel groups were compared. RESULTS: The overall complication rate for patients was 12.6%, 6.7% if only patients requiring intervention were considered. The adjusted odds ratio (OR) for complication rate for patients undergoing multilevel surgery and single-level surgery was 2.76. It was statistically significant (P=0.053) after adjusting for confounders. There was more pain in patients who underwent multilevel surgery than in the single-level surgery group. CONCLUSION: Concurrent multilevel surgery is a feasible option in patients with multilevel obstruction, especially if they are undergoing palate and tongue surgery, nose and palate surgery or nose and tongue surgery. There may be more complications, though it is not statistically significant. Further studies are required to investigate the differences between single-level nasal surgery and 3-level multilevel surgery. More patients undergoing multilevel surgery than single-level surgery experienced pain. Multilevel surgery patients should have their analgesia reviewed regularly and titrated accordingly.

Novel joint selection methods can reduce sample size for rheumatoid arthritis clinical trials with ultrasound endpoints.

OBJECTIVES: To determine whether novel methods of selecting joints through (i) ultrasonography (individualized-ultrasound [IUS] method), or (ii) ultrasonography and clinical examination (individualized-composite-ultrasound [ICUS] method) translate into smaller rheumatoid arthritis (RA) clinical trial sample sizes when compared to existing methods utilizing predetermined joint sites for ultrasonography. METHODS: Cohen's effect size (ES) was estimated (ES^) and a 95% CI (ES^L, ES^U) calculated on a mean change in 3-month total inflammatory score for each method. Corresponding 95% CIs [nL(ES^U), nU(ES^L)] were obtained on a post hoc sample size reflecting the uncertainty in ES^. Sample size calculations were based on a one-sample t-test as the patient numbers needed to provide 80% power at α = 0.05 to reject a null hypothesis H0 : ES = 0 versus alternative hypotheses H1 : ES = ES^, ES = ES^L and ES = ES^U. We aimed to provide point and interval estimates on projected sample sizes for future studies reflecting the uncertainty in our study ES^S. RESULTS: Twenty-four treated RA patients were followed up for 3 months. Utilizing the 12-joint approach and existing methods, the post hoc sample size (95% CI) was 22 (10-245). Corresponding sample sizes using ICUS and IUS were 11 (7-40) and 11 (6-38), respectively. Utilizing a seven-joint approach, the corresponding sample sizes using ICUS and IUS methods were nine (6-24) and 11 (6-35), respectively. CONCLUSIONS: Our pilot study suggests that sample size for RA clinical trials with ultrasound endpoints may be reduced using the novel methods, providing justification for larger studies to confirm these observations.

Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma: A critical appraisal of the evidence.

AIM: To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas (HCC). METHODS: A systematic review of the published literature was performed using the PubMed database from 1st January 1999 to 31st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC. The primary end point was to determine the overall survival (OS) and disease free survival (DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve (i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC (defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC. RESULTS: We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to (1) BCLC stage B or C HCC, (2) Size of HCC and (3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7% (range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0% (range 0.0-42.0). The collective median 5-year OS of both stages was 27.9% (0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR (95%CI) = 1.00 (0.76-1.31)] and mortality [RR (95%CI) = 1.15 (0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%. CONCLUSION: Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.

Beyond HbA1c: Comparing Glycemic Variability and Glycemic Indices in Predicting Hypoglycemia in Type 1 and Type 2 Diabetes.

BACKGROUND: Hypoglycemia is the major impediment to therapy intensification in diabetes. Although higher individualized HbA1c targets are perceived to reduce the risk of hypoglycemia in those at risk of hypoglycemia, HbA1c itself is a poor predictor of hypoglycemia. We assessed the use of glycemic variability (GV) and glycemic indices as independent predictors of hypoglycemia. METHODS: A retrospective observational study of 60 type 1 and 100 type 2 diabetes subjects. All underwent professional continuous glucose monitoring (CGM) for 3-6 days and recorded self-monitored blood glucose (SMBG). Indices were calculated from both CGM and SMBG. Statistical analyses included regression and area under receiver operator curve (AUC) analyses. RESULTS: Hypoglycemia frequency (53.3% vs. 24%, P < 0.05) and %CV (40.1% ± 10% vs. 29.4% ± 7.8%, P < 0.001) were significantly higher in type 1 diabetes compared with type 2 diabetes. HbA1c was, at best, a weak predictor of hypoglycemia. %CVCGM, Low Blood Glucose Index (LBGI)CGM, Glycemic Risk Assessment Diabetes Equation (GRADE)HypoglycemiaCGM, and Hypoglycemia IndexCGM predicted hypoglycemia well. %CVCGM and %CVSMBG consistently remained a robust discriminator of hypoglycemia in type 1 diabetes (AUC 0.88). In type 2 diabetes, a combination of HbA1c and %CVSMBG or LBGISMBG could help discriminate hypoglycemia. CONCLUSION: Assessment of glycemia should go beyond HbA1c and incorporate measures of GV and glycemic indices. %CVSMBG in type 1 diabetes and LBGISMBG or a combination of HbA1c and %CVSMBG in type 2 diabetes discriminated hypoglycemia well. In defining hypoglycemia risk using GV and glycemic indices, diabetes subtypes and data source (CGM vs. SMBG) must be considered.

Surgical management decreases disease recurrence risk in recurrent pyogenic cholangitis.

BACKGROUND: Recurrent pyogenic cholangitis (RPC) has a high risk of disease recurrence. We present our experience with RPC and examine the factors associated with disease recurrence. METHODS: We performed a retrospective review of all patients with RPC treated at two tertiary institutions between January 1990 and December 2013. Patients with liver atrophy and/or abscess were categorized as being associated with parenchymal disease (PD). RESULTS: We studied 157 patients with a median age of 59.0 (interquartile range (IQR): 47.0-70.0) years and a median follow-up duration of 71.0 (IQR: 26.0-109.0) months. There were 64 (40.8%) and 93 (59.2%) patients with and without associated PD, respectively. Disease recurrence rate was 43.9% in our overall cohort through the course of follow-up. Surgical treatment was an independent prognostic factor for decreased disease recurrence risk (hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.18-0.87, P = 0.021). Stratified analysis revealed that liver resection was prognostic for lower risk of disease recurrence among patients with PD (HR 0.38, 95% CI 0.15-0.94, P = 0.036), while biliary bypass was prognostic for lower risk of disease recurrence among patients without PD (HR 0.30, 95% CI 0.15-0.61, P = 0.001). The overall post-operative complication rate among surgically treated patients was 31.1%, and the presence of bilobar stones was found to be independently associated with higher odds of post-operative complications (odds ratio 3.51, 95% CI 1.26-9.81, P = 0.017). CONCLUSION: Surgical treatment is associated with decreased recurrence risk in RPC, but with significant post-operative morbidity. Where surgery is deemed appropriate, patients with and without PD are likely to benefit from liver resection and biliary bypass, respectively.