Evaluation of lorcaserin on progression of prediabetes to type 2 diabetes and reversion to euglycemia

Objectives: Lorcaserin is a selective 5-HT_2C (5-hydroxytryptamine 2C) receptor agonist indicated for weight management. Here, we assess the impact of lorcaserin on progression from prediabetes to type 2 diabetes (T2D) and on reversion from prediabetes to euglycemia.

Methods: This is a post hoc analysis of pooled data from two Phase 3 studies, BLOOM and BLOSSOM (N = 6136), evaluating the impact of lorcaserin on weight and glycemic parameters over 52 weeks in the subpopulation of obese/overweight subjects with prediabetes, alternately defined by fasting plasma glucose (FPG) 100–125 mg/dl or glycated hemoglobin (HbA1c) 5.7–6.4% at baseline.

Results: At Week 52, in the subpopulation with prediabetes, nearly twice as many lorcaserin-treated subjects achieved ≥5% weight loss versus placebo (HbA1c: 55.6% vs. 27.5%, p < 0.001; FPG: 52.8% vs. 28.8%, p < 0.001), and a significantly lower percentage of lorcaserin-treated subjects progressed to T2D versus placebo based on HbA1c (lorcaserin 3.2%, placebo 5.0%, p = 0.032) but not FPG (lorcaserin 1.6%, placebo 2.6%, p = 0.227). A significantly greater proportion of lorcaserin-treated subjects versus placebo also reverted to euglycemia based on both HbA1c (lorcaserin 40%, placebo 29.5%, p < 0.001) and FPG (lorcaserin 52.4%, placebo 46.5%, p = 0.047).

Conclusion: In subjects with prediabetes, lorcaserin may contribute to weight loss and improve glycemic parameters, and thus may help with preventing progression to T2D and promoting reversion to euglycemia.

Clinical trial registration: www.clinicaltrials.gov identifiers are NCT00395135 (BLOOM) and NCT00603902 (BLOSSOM)     

Ethnic differences in the prevalence of peripheral arterial disease: a systematic review and meta-analysis

Background: Previous studies have demonstrated higher rates of peripheral arterial disease (PAD) in blacks and lower in Asians compared to whites. The aim of this study is to undertake a comprehensive review of literature on ethnic differences in the epidemiology of PAD.

Methods: A systemic review and meta-analysis included studies reporting PAD prevalence in general or diabetic populations, and comparing PAD prevalence in ethnic groups.

Results: Mean prevalence of PAD in general population for whites, blacks and Asians was 3.5%, 6.7% and 3.7% respectively. Meta-analysis demonstrated higher prevalence of PAD in blacks (p < 0.001) and lower amongst Asians (p < 0.001), compared to whites. In diabetic population, the mean prevalence of PAD for whites, blacks, east Asians and south Asians was 17%, 25.3%, 13.5% and 7.6% respectively. In diabetic population, south Asians had a lower PAD prevalence (p < 0.001) compared to whites; there was no significant difference between blacks and whites. Overall females have higher PAD rates, in general (3.8% vs 3.2%; p < 0.001) and in diabetic population (13.7% vs 10%; p < 0.001).

Conclusion: Blacks are vulnerable to PAD, in contrast to Asians who have lower prevalence of PAD when compared to whites. Further research is needed in order to identify the factors that generate this difference.     

Interferon-based treatment is superior to nucleos(t)ide analog in reducing HBV-related hepatocellular carcinoma for chronic hepatitis B patients at high risk

Background: The effect of nucleos(t)ide analogs (NAs) versus interferon (IFN) on the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) is controversial. We assessed whether antiviral strategy affected HCC development in CHB patients at different HCC risks.

Methods: 1112 CHB patients with antiviral therapy were included in this retrospective study. Patients treated with NAs only were classified into NAs group (n = 682) while those received IFN treatment with or without NAs were defined as IFN group (n = 430). Propensity score matching (PSM) was applied to minimize baseline differences.

Results: Totally, 31 patients developed HCC during follow-up (median 5.41 years). The cumulative HCC incidence at 10 years was significantly lower in the IFN group than NAs group (2.7% vs 8.0%, p < 0.001). Similar results were obtained in the PSM-cohort. Patients with IFN-based treatment were less likely to develop HCC than those with NAs (Hazard ratio = 0.15; 95% CI 0.04–0.66; p = 0.012). Subgroup analyses demonstrated that this superiority of IFN in reducing HCC development was obvious in patients at high- but not low-risk of HCC.

Conclusions: Reduction of HCC development was more significant in CHB patients at higher HCC risk with IFN-based therapy than NAs treatment.     

Adenosine triphosphate/adenosine guided pulmonary vein isolation does not improve the outcomes of ablation: a meta-analysis of randomized controlled trials

Background: Successful pulmonary vein isolation (PVI) is the most reliable predictor of success after ablation in patients with atrial fibrillation (AF). Adenosine triphosphate (ATP) unmasks the dormant conduction and can be used to improve the effectiveness of PVI. The impact of ATP guided PVI on clinical outcomes is discordant in various randomized controlled trials (RCTs).

Objectives: To delineate the incremental benefit of ATP during PVI in patients with AF through a meta-analysis.

Methods and results: Database searches through January 2017 identified 5 RCTs (enrolling 2839 patients) comparing ATP guided PVI versus standard PVI (non-ATP). Four trials exclusively studied paroxysmal AF while one trial included both paroxysmal and non-paroxysmal AF patients. Baseline characteristics, dose of adenosine and ablation strategies were clearly identified among all the trials. The risk ratio (RR) for AF episodes lasting >30 s after 3-month blanking period was calculated with random effects meta-analysis and showed no difference at a median follow up of 12 months [RR: 1.02, 95 % Confidence interval (CI): 0.85 to 1.25; p = 0.82]. Similarly, the number of repeat ablation was similar in both groups [RR: 1.02, 95 % CI: 0.63, 1.56; p = 0.98].

Conclusions: ATP guided PVI does not decrease the recurrence of AF or the need for repeat ablation at 12 months.     

A comparison of high frequency chest wall oscillation and intrapulmonary percussive ventilation for airway clearance in pediatric patients with tracheostomy

Objectives: The aim of this study was to compare two modes of airway clearance, the intrapulmonary percussive ventilation system (IPV) to high frequency chest wall oscillation system (HFCWO) in medically complex pediatric patients with tracheostomy requiring long term care.

Methods: This was a single center, retrospective study comparing the number of respiratory illnesses, lower respiratory tract infections (LRTI), utilization of bronchodilator and systemic steroids, and respiratory illnesses requiring acute care hospitalizations. A total of 8 tracheostomy dependent patients between the ages of 1–22 years were included for a 2-year study period. Each patient was used as their own control. During the period studied, the only variable in the medical regimen was the modality used for airway clearance. A Poisson regression model and generalized estimating equations were used to compare pre and post rates and to account for the correlation of count data from the same individual. Additionally, the paired differences (post—pre) for each event count were computed to provide the median and range of reductions in event rates while using intrapulmonary percussive ventilation system device. The non-parametric wilcoxon signed-rank test employed to determine whether the results from the Poisson model were consistently observed regardless of method of analysis.

Results: The total number of respiratory illnesses were reduced from 32 per year on HFCWO therapy to 15 per year on IPV system therapy (p < 0.001). The total number of LRTI requiring antibiotic use were decreased from 15 per year to 6 per year (p = 0.01), use of bronchodilator treatments were reduced from 53 to 21 (p < 0.001) and utilization of systemic steroids were reduced from 12 to 4 on IPV (p = 0.003). Numbers of hospitalizations to acute care facilities were reduced from 8 to 3 hospitalizations during the period of IPV use for airway clearance (p = 0.003).

Conclusion: This study suggests that airway clearance by IPV therapy could be more effective and beneficial in providing airway clearance in specific subsets of the medically complex pediatric population.     

Safety of oral direct acting antiviral regimens for chronic hepatitis C in real life conditions

Objectives: Direct acting antivirals (DAA) are extremely effective to treat chronic hepatitis C. The aim of this study was to evaluate, by using objective variables, the safety of DAA combinations under clinical practice conditions.

Methods: A retrospective study was carried out in mono-infected patients with chronic hepatitis C treated with DAA between January and December 2015 in our centre. Discontinuations, treatment modifications, deaths and laboratory parameters were studied (liver function tests, hemoglobin, creatinine and lipid profile at baseline, weeks 4, 8 and post 12). Temporal variation of laboratory parameters was analyzed by t-test for paired data, and comparison between groups was made by t-test for independent samples and ANOVA.

Results: 227 patients were included (40.5% cirrhotic). Sustained virological response (SVR) was achieved in 97.3% of patients. In only one case was the antiviral medication suspended due to toxicity, and there were no voluntary treatment discontinuations. The use of ribavirin (RBV) was associated with mild transient hyperbilirubinemia (41.2%) and anemia (32.6%, with RBV dose reduction in 7.9% of cases). There was an elevation in total cholesterol and LDL-cholesterol (LDL-C) during and after treatment: mean increase of 23 mg/dL (0.59 mmol/L) and 22 mg/dL (0.57 mmol/L), respectively in post 12 (p < .0001). An increment of 20% of patients with cholesterol levels over optimal figures was observed after DAA completion.

Conclusion: DAA have an optimum safety profile in real life conditions, with infrequent discontinuation and minor laboratory alterations.     

The effect of intravenous insulin,apheresis and oral lipid-lowering agents on non-fasting hypertriglyceridemia and associated pancreatitis

Objectives: There is evidence that increasing severity of hypertriglyceridemia increases the risk of acute pancreatitis. There is a debate about superiority of treatment methods and previous works have specifically called for direct comparison between IV insulin and apheresis techniques. Identify patient characteristics predictive of lipid-lowering therapy selection in a large community hospital for treatment of hypertriglyceridemia; evaluate for a concentration-dependent relationship between hypertriglyceridemia severity and risk of acute pancreatitis; assess for differences in clinical outcomes between patients treated with IV insulin versus apheresis.

Methods: Single center, retrospective cohort study including patients with hypertriglyceridemia between January 2007 and December 2016. Main measures included frequency of pancreatitis, choice of lipid-lowering therapy, and clinical comparisons of diet, oral lipid-lowering agents, IV insulin, and apheresis.

Results: Initial serum triglyceride level and disease acuity was higher among patients in insulin and apheresis groups. Neither triglyceride level, Charlson comorbidity index, age, BISAP score, nor initial CRP predicted use of IV insulin versus apheresis. Prevalence of pancreatitis increased with higher triglyceride level, reaching 48% with triglycerides >2000 md/dL (p < 0.001). There was a significant decrease in serum triglycerides at each time interval (p < 0.05) in patients treated with IV insulin and apheresis, but no difference in clearance rate between the two. Length of stay did not differ between IV insulin and apheresis.

Conclusion: The presence of pancreatitis, hyperglycemia, and hypertriglyceridemia severity influenced selection of therapies like IV insulin and apheresis. We found no superiority of either IV insulin or apheresis in the treatment of severe hypertriglyceridemia among patients hospitalized for pancreatitis.     

Serum vitamin D levels correlate to coronary artery disease severity: a retrospective chart analysis

Background: The pro-atherosclerotic nature of vitamin D deficiency has been shown to increase cardiovascular events. We further emphasized and evaluated the severity of coronary artery disease (CAD) with varying levels of vitamin D in relation to age, gender, ethnicity and baseline confounders.

Methods: A retrospective, single-center study of 9,399 patients admitted between 2005 and 2014 for chest pain who underwent coronary angiography. Patients without a vitamin D level, measured as 25-dihydroxyvitamin D (25[OH]D) were excluded from our study. 25(OH)D deficiency and insufficiency were defined by having serum concentration levels of less than 20 ng/ml and 20 to 29.9 ng/ml, respectively, while normal levels were defined as greater than or equal to 30 ng/ml. We assessed levels of 25(OH)D and extent of coronary disease with coronary angiography as obstructive CAD (left main stenosis of ≥50% or any stenosis of ≥70%), non-obstructive CAD (≥1 stenosis ≥20% but no stenosis ≥70%) and normal coronaries (no stenosis >20%).

Results: Among 9,399 patients, 1,311 qualified, of which 308 patients (23%) had normal 25(OH)D levels, 552 patients (42%) had 25(OH)D deficiency and 451 patients (35%) had 25(OH)D insufficiency. In an analysis of the extent of coronary disease, we identified 20% of patients having normal coronaries, 55% having obstructive CAD and 25% having non-obstructive CAD. Baseline clinical risk factors and co-morbidities did not differ between the groups.

Patients with normal 25(OH)D levels were found to have normal coronaries compared to patients with 25(OH)D deficiency or insufficiency (OR: 7, 95% CI: 5.2 – 9.5, p < 0.0001). Comparing patients with normal 25(OH)D levels, patients with 25(OH)D deficiency or insufficiency (<29 ng/ml), 62% were found to have obstructive CAD (n = 624, OR: 2.9, 95% CI: 2.3-3.7, p < 0.0001) and 25% had non-obstructive CAD (n = 249, OR: 1.5, 95% CI: 1.1-2, p = 0.02).

Conclusion: Normal coronaries and CAD were shown to correlate with normal and low levels of 25(OH)D, respectively. There is an inverse relationship between the percentage of coronary artery occlusion and serum 25(OH)D concentrations. Vitamin D may provide benefits in risk stratification of patients with CAD and serve as a possible risk factor.     

Usefulness of cardiometabolic index for the estimation of ischemic stroke risk among general population in rural China

Objectives: Cardiometabolic index (CMI) has been recognized as a novel and practical marker for the assessment of cardiometabolic risk as it is independently related to diabetes and atherosclerotic progression. This study tested the hypothesis that CMI represents a risk of ischemic stroke in a general population of rural China.

Methods: From July 2012 to August 2013, we examined data from a large cross-sectional study of 11,345 participants (mean age 53.8 years; 60.8% females) who underwent biochemical determinations and anthropometric measurements in rural areas of northeast China. Ischemic stroke was documented as a history of cerebrovascular events and verified by medical record review.

Results: The prevalence of ischemic stroke was given to 3.1% of females and 3.2% of males. The cardio-metabolic profile was notably more adverse in ischemic stroke groups, irrespective of gender. A dose-response manner was detected for the prevalence of ischemic stroke, exhibiting a significant increase from the lowest to the highest quartiles of CMI (1.2% to 6.4% in females, P for trend<0.001; 2.3% to 4.3% in males, P for trend = 0.017). In multivariable analysis, for every 1 SD increment in CMI, the probability of ischemic stroke increased by 18% in females and 14% in males, respectively. The odds ratios for ischemic stroke comparing the top versus bottom quartiles of CMI were 2.047 (95%CI: 1.168–3.587) for females and 1.722 (95%CI: 1.019–2.910) for males. According to the area under receiver operating characteristic (AUC), the discrimination power of CMI in predicting ischemic stroke was relatively higher for females (AUC: 0.685) than males (AUC: 0.573).

Conclusion: The strong and independent association of CMI with ischemic stroke in females, in comparison with the much lesser degree in males, provides further insight to better stratify by sex in investigations of ischemic stroke and solidly corroborates the potential role of ischemic stroke prevention targeted at CMI.     

Predictive validity of the ACC/AHA pooled cohort equations in predicting residual-specific mortality in a national prospective cohort study of adults in the United States

Objective: The predictive validity of the Pooled Cohort risk (PCR) equations for residual-specific mortality (deaths not resulting from the 9 leading causes of death) among a national sample of U.S. adults has not previously been evaluated, which was the purpose of this study.

Methods: Data from the 1999–2010 National Health and Nutrition Examination Survey were used, with participants followed up through 31 December 2011 to ascertain mortality status. The analyzed sample included 11,171 cardiovascular disease-free adults (40–79 years of age). The 10-year risk of a first atherosclerotic cardiovascular disease (ASCVD) event was determined from the PCR equations.

Results: For the entire sample, 849,202 person-months occurred with an incidence rate of 0.29 (95% CI: 0.25–0.33) residual-specific deaths per 1,000 person-months. The unweighted median follow-up duration was 72 months. For all analyses, ASCVD risk score (via the PCR equations) was significantly associated with residual-specific mortality. In a fully adjusted model including moderate-to-vigorous physical activity (MVPA), obesity, age (yrs; continuous measure), gender (male/female) and race-ethnicity (Mexican American, non-Hispanic white, non-Hispanic black and other) as covariates, those with an ASCVD ≥ 20 (vs. < 20) had a 91% increased hazard of residual-specific death during the follow-up period (HR = 1.91; 95% CI: 1.10–3.31). Expressed as probability, there was a 66% chance that those with ASCVD ≥ 20 (vs. < 20) would have a residual specific-death during the follow-up period.

Conclusion: The 10-year predicted risk of a first ASCVD event via the PCR equations was directly associated with residual-specific mortality among those free of cardiovascular disease (CVD) at baseline, providing evidence of predictive validity of the PCR equations among this national sample of U.S. adults.     

A randomized,double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design

Objectives: The objective of this paper was to evaluate the efficacy, duration of effect, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: Adults with ADHD Rating Scale, Version IV (ADHD-RS-IV) scores ≥24 were randomized to SHP465 MAS (50 or 75 mg), placebo, or 25 mg MAS IR in a double-blind, three-period, crossover study using a simulated adult workplace environment. On the final day of each 7-day treatment period, efficacy was assessed for 16 h postdose. Primary efficacy analyses for Permanent Product Measure of Performance (PERMP) total score averaged across all postdose assessments and each postdose time point were conducted in the intent-to-treat population using a mixed linear model. Secondary end-points included PERMP problems attempted and answered correctly and ADHD-RS-IV scores based on clinician ratings of counselor observations using the Time Segment Rating System and participant self-report. Tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.

Results: Least squares mean (95% CI) treatment differences (combined 50/75 mg SHP465 MAS–placebo) significantly favored SHP465 MAS over placebo for PERMP total score averaged across all postdose assessments (18.38 [11.28, 25.47]; P < .0001) and at each postdose assessment (all P < .02). Nominal superiority of MAS IR over placebo for PERMP total score averaged across all postdose assessments was observed (nominal P = .0001); treatment differences between SHP465 MAS and MAS IR were not significant (nominal P = .2443). The two most frequently reported TEAEs associated with SHP465 MAS were insomnia (36.5%) and anorexia (21.2%). Mean increases in pulse and blood pressure with SHP465 MAS exceeded those of placebo.

Conclusions: SHP465 MAS (combined 50/75 mg) significantly improved PERMP total score versus placebo, with superiority observed from 2 to 16 h postdose. The tolerability profile of SHP465 MAS was similar to previous reports of SHP465 MAS in adults with ADHD.

Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT00928148 identifier is NCT00928148.     

Clinical features,long-term clinical outcomes,and prognostic factors of tuberculous meningitis in West China: a multivariate analysis of 154 adults

Background: Tuberculosis is prevalent in China, which is the second greatest contributor to the global tuberculosis burden. Tuberculosis meningitis (TBM) is the most severe disease form but few reports describe long-term clinical outcomes and prognostic factors. Thus, we studied these features in Chinese TBM patients.

Methods: A retrospective follow-up study was used to collect clinical features and outcomes of adult TB meningitis at the First Affiliated Hospital of Chongqing Medical University from June 2012 to August 2015. Univariate analysis and multivariate analysis were used to identify predictive factors associated with outcomes at discharge and follow-up.

Results: TBM patients (N = 154) were a median age of 41 years (range: 16–82 years). Median time to follow-up was 26.4 months (range: 9.3–46.5 months) and 31% had poor outcomes at follow-up and limb weakness (p = 0.016), lower GCS scores (p < 0.001), cranial-nerve palsy (p = 0.024), and hydrocephalus (p = 0.009) were closely associated with these poor outcomes. Furthermore, a high neutrophil to lymphocytes ratio, high D-dimer, a low albumin to globulin ratio and slow background of EEG associated with poor outcomes as well.

Conclusions: Mortality and disability associated with TBM are high in China. Limb weakness, GCS scores, cranial-nerve palsy and hydrocephalus were independent predictors of poor outcomes, and AGR, NLR, D-dimer, and EEG abnormalities may be prognostic factors of TBM.     

Comorbidities and cardiovascular risk factors in an aged cohort of HIV-infected patients on antiretroviral treatment in a Spanish hospital in 2016

Objectives: The increased survival of HIV-infected individuals has resulted in a premature aging of this population, with the consequent development of premature age-related comorbidities and risk factors. We aimed to describe the prevalence of age-related comorbidities and cardiovascular risk factors in older adults with HIV infection on antiretroviral therapy (ART).

Methods: A retrospective cross-sectional study was undertaken in a cohort of HIV patients aged ≥50 years on ART in September 2016 in Spain. The prevalence of comorbidities (liver cirrhosis, respiratory diseases, cancer, cardiovascular, diabetes, and kidney and bone disorders) and risk factors (smoking, dyslipidemia, and arterial hypertension) was captured.

Results: Among the 339 patients included in the study, any comorbidity was present in 52%, the most common being cirrhosis (19%), chronic lung disease (13%), and diabetes mellitus (11%). Over three quarters (78%) had any risk factor: dyslipidemia (55%) and smoking (44%). A higher prevalence of cardiovascular disease was seen in patients ≥60 years in comparison to those aged 50–59 years (23% vs 8%, p = 0.001). Of all study patients, 44% took more than three drugs in addition to their ART, while 29% received no additional pharmacological interventions.

Conclusions: Comorbidities and risk factors for chronic diseases are very common in HIV-infected patients aged ≥50 years and increase with age, so they should be early considered in the clinical management of these patients. It is important to encourage healthy lifestyles to prevent comorbidities and to control risk factors. Concomitant treatments with ART should be carefully monitored to prevent drug interactions, adverse effects, and patient adherence failures.     

Subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder manual therapy plus exercise intervention in individuals with subacromial impingement syndrome: a prospective,randomized controlled clinical trial pilot study

Objectives: To determine the subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder non-thrust plus exercise in patients with subacromial pathology.

Methods: This was a randomized, single blinded controlled trial pilot study. This trial was registered at ClinicalTrials.gov (NCT01753271) and reported according to Consolidated Standards of Reporting Trials requirements. Patients were randomly assigned to either shoulder treatment plus cervicothoracic spinal thrust/non-thrust or shoulder treatment-only group. Primary outcomes were average pain intensity (Numeric Pain Rating Scale) and physical function (Shoulder Pain and Disability Index) at 2 weeks, 4 weeks, and patient discharge.

Results: 18 patients, mean age 43.1(15.8) years satisfied the eligibility criteria and were analyzed for follow-up data. Both groups showed statistically significant improvements in both pain and function at 2 weeks, 4 weeks, and discharge. The between-group differences for changes in pain or physical function were not significant at any time point.

Discussion: The addition of cervicothoracic spinal thrust/non-thrust to the shoulder treatment-only group did not significantly alter improvement in pain or function in patients with subacromial pathology. Both approaches appeared to provide an equally notable benefit. Both groups improved on all outcomes and met the criteria for clinical relevance for both pain and function.

Level of Evidence: 2b.     

Prevalence of abnormal serum liver enzymes in patients with type 2 diabetes mellitus: a cross-sectional study from China

Objectives: This cross-sectional study aimed to determine the prevalence of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in Chinese type 2 diabetic patients and identify contributing risk factors.

Methods: This cross-sectional study was conducted in rural areas of China, and 1,198 type 2 diabetic patients with complete data were recruited. Elevated ALT and AST levels were defined as >40 U/L. Prevalence of abnormal liver enzymes was analyzed and multivariable analysis was used to identify independent risk factors.

Results: 10.3% and 6.1% diabetic patients had elevated ALT and elevated AST, respectively. The prevalence of elevated liver enzymes was gender-related; it was 13.8% in men and 7.5% in women for elevated ALT, and 7.4% in men and 3.1% in women for elevated AST. High triglyceride was positively associated with both elevated ALT (OR 1.80, 95% CI 1.08–3.01, p = 0.024) and elevated AST (OR 2.24, 95%CI 1.08–4.65, p = 0.031), while taking anti-diabetes medicine was inversely related to both elevated ALT (OR 0.48, 95% CI 0.29–0.80, p = 0.005) and elevated AST (OR 0.37, 95% CI 0.17–0.82, p = 0.014). The risk of elevated ALT in diabetic patients increased with the presence of obesity (OR 2.54, 95% CI 1.07–6.01, p = 0.034), and was lower in women (OR 0.37, 95% CI 0.19–0.72, p = 0.003). Hypertension (OR 4.33, 95% CI 1.41–13.30, p = 0.011), current drinking status (OR 2.90, 95% CI 1.21–6.96, p = 0.017) and national minority (OR 3.26, 95%CI 1.31–8.12, p = 0.011) were risk factors for elevated AST.

Conclusion: A relatively high prevalence of abnormal serum liver enzymes in diabetic patients was demonstrated in China, especially in males. More attention should be paid to preventing liver injuries in diabetic patients.     

Efficacy of methylnaltrexone for the treatment of opiod-induced constipation: a meta-analysis and systematic review

Objective: Constipation is a common adverse effect in patients requiring long-term opioid therapy for pain control. Methylnaltrexone, a quaternary peripheral mu-opioid receptor antagonist, is an effective treatment of opioid induced constipation (OIC) without affecting centrally mediated analgesia. Our objective was to conduct a review and meta-analysis to evaluate the efficacy of methylnaltrexone for treatment of OIC, as well as to provide a clinical discussion regarding newly developed alternatives and provide the current treatment algorithm utilized at our institution.

Methods: We performed a systematic review and meta-analysis of randomized control trials using Cochrane Collaboration Databases and MEDLINE from 2007-present. Literature related to methylnaltrexone, opioids, opioid receptors, opioid antagonists, opioid-induced constipation were reviewed. A meta-analysis was completed with the primary outcome of rescue-free bowel movement (RFBM) within four hours of administration. All pooled analyses were based on random-effects models.

Results: 1239 patients were analyzed; 599 received methylnaltrexone and 640 received placebo. With a 95% CI calculated, the true risk difference is between 0.267 and 0.385, demonstrating a statistically significant difference in RFBM between treatment and placebo groups (p < 0.0001). Both the 0.15 mg/kg, 0.30 mg/kg doses every other day, and 12 mg/day dose were found to have increased risk of RFBM compared to placebo.

Conclusion: Results support the use of methylnaltrexone. Furthermore, the use of methylnaltrexone to induce laxation may decrease use of health care resources, increase work productivity, and improve cost utilization. New treatments have been made available; however, controlled clinical studies are needed to demonstrate long–term efficacy, safety and cost–effectiveness. Possible limitations of this study include the relatively small number of randomized, placebo-controlled trials investigating the efficacy of methylnaltrexone versus placebo. There is also the possibility of publication bias, which may lead to overestimating the efficacy of methylnaltrexone in treating OIC.     

Increased mechanosensivity of the greater occipital nerve in subjects with side-dominant head and neck pain – a diagnostic case-control study

Objectives: To investigate differences in pressure pain thresholds (PPTs) and longitudinal mechanosensitivity of the greater occipital nerve (GON) between patients with side-dominant head and neck pain (SDHNP) and healthy controls. Evaluation of neural sensitivity is not a standard procedure in the physical examination of headache patients but may influence treatment decisions.

Methods: Two blinded investigators evaluated PPTs on two different locations bilaterally over the GON as well as the occipitalis longsitting-slump (OLSS) in subjects with SDHNP (n = 38)) and healthy controls (n = 38).

Results: Pressure pain sensitivity of the GON was lower at the occiput in patients compared to controls (p = 0.001). Differences in pressure sensitivity of the GON at the nucheal line, or between the dominant headache side and the non-dominant side were not found (p > 0.05). The OLSS showed significant higher pain intensity in SDHNP (p < 0.001). In comparison to the non-dominant side, the dominant side was significantly more sensitive (p = 0.004).

Discussion: Palpation of the GON at the occiput and the OLSS may be potentially relevant tests in SDHNP. One explanation for an increased bilateral sensitivity may be sensitization mechanisms. Future research should investigate the efficacy of neurodynamic techniques directed at the GON.

Level of Evidence: 3b.     

Cross-sectional association of exercise,strengthening activities,and cardiorespiratory fitness on generalized anxiety,panic and depressive symptoms

Objective: Limited research has evaluated the individual and combined associations of physical activity (PA), cardiorespiratory fitness (CRF) and muscle strengthening activities (MSA) on generalized anxiety, panic and depressive symptoms. We evaluated this topic in a representative sample of young (20–39 years) adults, with considerations by sex.

Methods: Data from the 1999–2004 National Health and Nutrition Examination Survey (N = 2088) were used. Generalized anxiety, panic and depressive symptoms were assessed via self-report as well as using the Generalized Anxiety Disorder, Panic Disorder, and Depressive Disorders modules of the automated version of the World Health Organization Composite International Diagnostic Interview (CIDI-Auto 2.1). PA and MSA were assessed via validated self-report questionnaires and CRF was determined via a submaximal treadmill-based test. An index variable was created summing the number (range = 0–3) of these parameters for each participant. For example, those meeting PA guidelines, MSA guidelines and having moderate-to-high CRF were classified as having an index score of 3.

Results: MSA was not independently associated with generalized anxiety, panic and depressive symptoms, but those with higher levels of PA and CRF had a reduced odds of these symptoms (ranging from 40 to 46% reduced odds). Compared to those with an index score of 0, those with an index score of 1, 2, and 3, respectively, had a 39%, 54% and 71% reduced odds of having generalized anxiety, panic and depressive symptoms. Results were consistent across both sexes.

Conclusion: PA and CRF, but not MSA, were independently associated with generalized anxiety, panic and depressive symptoms. There was evidence of an additive association between PA, CRF, and MSA on these symptoms.     

Knowledge and attitudes of family doctors,dermatologists, and endocrinologists on sun exposure and vitamin D

Objectives: Vitamin D is an important component of bone metabolism. Skin cells synthesize vitamin D when exposed to the sun. However, prolonged sun exposure damages the skin and increases the risk for skin cancer. The objective is to evaluate and compare the attitudes and recommendations of family doctors, dermatologists, and endocrinologists on exposure to the sun and vitamin D.

Methods: In a cross-sectional study, a questionnaire was completed by personal interview in a study population of 78 family doctors, 21 dermatologists, and 22 endocrinologists.

Results: On a scale of 1–10, the mean score for recommendations to reduce sun exposure was 4.7 for dermatologists, 4.2 for endocrinologists, and 6.4 for family doctors (p < 0.001). Family doctors recommended a mean daily exposure to the sun of 67.4 min compared to 41.4 by dermatologists, and 47.1 by endocrinologists (p = 0.007). Dermatologists and endocrinologists were more likely to recommend protective measures such as hats and long sleeves during sun exposure than family doctors (p < 0.0001). There were no statistically significant differences between male and female doctors for the entire study population.

Conclusions: There is little consensus among these medical practitioners, whether specialists or primary care doctors, concerning sun exposure. Further studies should evaluate the optimal duration and intensity of sun exposure and doctors’ recommendations should be based on the findings.     

Prevalence and reliability of treatment-based classification for subgrouping patients with low back pain

Objectives: To observe the distribution of patients who presented with low back pain (LBP) and to determine the between therapists’ interrater reliability of assessments in a private outpatient setting using treatment-based classification (TBC) subgroups.

Methods: An observational and methodological study was conducted. Four hundred and twenty-nine patients (231 male; 198 female) presenting LBP symptoms and referred to conservative treatment were assessed by 13 physical therapists who conducted a 60-min examination process utilizing TBC subgroups. Interrater reliability analyses from six raters were assessed using Fleiss’ kappa and previously recorded data (n = 30).

Results: In this study, 65.74% of patients were classified in only one subgroup, the most prevalent being stabilization (21.91%), followed by extension (15.38%), traction (11.89%), flexion (10.96%), manipulation (5.13%), and lateral shift (0.47%). Approximately 20.98% of patients were classified in two subgroups, where the most frequent overlaps were flexion + stabilization (7.46%), extension + stabilization (6.06%), flexion + traction (4.20%), extension + manipulation (1.86%), and 13.29% of patients were not classified in any TBC subgroup. Analysis of interrater reliability showed a kappa value of 0.62 and an overall agreement of 66% between raters.

Discussion: LBP is a heterogeneous clinical condition and several classification methods are proposed in the attempt to observe better outcomes for patients. Eighty-five percent of patients assessed were able to be classified when using the TBC assessment and reliability analysis showed a substantial agreement between raters.

Level of Evidence: 2c.