The effects of 2 weeks of interval vs continuous walking training on glycaemic control and whole-body oxidative stress in individuals with type 2 diabetes: a controlled,randomised, crossover trial

Aims/hypothesis

The aim of this study was to evaluate the effects of oxygen consumption-matched short-term interval walking training (IWT) vs continuous walking training (CWT) on glycaemic control, including glycaemic variability, in individuals with type 2 diabetes. We also assessed whether any training-induced improvements in glycaemic control were associated with systemic oxidative stress levels.

Methods

Participants (n?=?14) with type 2 diabetes completed a crossover trial using three interventions (control intervention [CON], CWT and IWT), each lasting 2 weeks. These were performed in a randomised order (computerised generated randomisation) and separated by washout periods of 4 or 8 weeks after CON or training interventions, respectively. Training included ten supervised treadmill sessions, lasting 60 min/session, and was performed at the research facility. CWT was performed at moderate walking speed (75.6%?±?2.5% of walking peak oxygen consumption [\( \overset{.}{V}{\mathrm{O}}_{2\mathrm{peak}} \)]), while IWT was performed as alternating 3 min repetitions at slow (58.9%?±?2.0% \( \overset{.}{V}{\mathrm{O}}_{2\mathrm{peak}} \)) and fast (90.0%?±?3.6% \( \overset{.}{V}{\mathrm{O}}_{2\mathrm{peak}} \)) walking speed. Before and after each intervention, the following was assessed: 24 h continuous glucose monitoring (CGM) and urinary free 8-iso prostaglandin F_2α (8-iso PGF_2α; a marker for oxidative stress), physical fitness and body composition. Neither participants nor assessors were blinded to the interventions.

Results

No intervention-induced changes were seen in physical fitness or body composition. Compared with baseline, IWT reduced mean glucose levels non-significantly (?0.7?±?0.3 mmol/l, p?=?0.08) and significantly reduced maximum glucose levels (?1.8?±?0.5 mmol/l, p?=?0.04) and mean amplitude of glycaemic excursions (MAGE; ?1.7?±?0.4 mmol/l, p?=?0.02), whereas no significant within-group changes were seen with CON or CWT. Although 8-iso PGF_2α was associated with minimum glucose levels at baseline, no change in 8-iso PGF_2α was seen with any intervention, nor were there any associations between changes in 8-iso PGF_2α and changes in glycaemic control (p?>?0.05 for all). No adverse effects were observed with any of the interventions.

Conclusions/interpretation

Short-term IWT, but not CWT, improves CGM-derived measures of glycaemic control independent of changes in physical fitness and body composition in individuals with type 2 diabetes. Systemic oxidative stress levels are unaffected by short-term walking and changes in oxidative stress levels are not associated with changes in glycaemic control.

Trial registration

ClinicalTrials.gov NCT02320526

Funding

The Centre for Physical Activity Research (CFAS) is supported by a grant from TrygFonden. During the study period, the Centre of Inflammation and Metabolism (CIM) was supported by a grant from the Danish National Research Foundation (DNRF55). The study was further supported by grants from Diabetesforeningen, Augustinusfonden and Krista og Viggo Petersens Fond. CIM/CFAS is a member of the Danish Center for Strategic Research in Type 2 Diabetes (DD2; the Danish Council for Strategic Research, grant no. 09-067009 and 09-075724). MR-L was supported by a post-doctoral grant from the Danish Diabetes Academy supported by the Novo Nordisk Foundation.

     

Obstructive sleep apnea does not impair cardiorespiratory responses to progressive exercise performed until exhaustion in hypertensive elderly

Background

Elderly people have a high prevalence to systemic arterial hypertension (SAH) and obstructive sleep apnea (OSA). Both comorbidities are closely associated and inflict damage on cardiorespiratory capacity.

Methods

In order to assess cardiorespiratory responses to the cardiopulmonary exercise test (CPET) among hypertensive elderly with OSA, we enrolled 28 subjects into two different groups: without OSA (No-OSA: apnea/hypopnea index (AHI) < 5 events/h; n = 15) and with OSA (OSA: AHI ≥ 15 events/h; n = 13). All subjects underwent CPET and polysomnographic assessments. After normality and homogeneity evaluations, independent t test and Pearson’s correlation were performed. The significance level employed was p ≤ 0.05.

Results

Hypertensive elderly with OSA presented lower heart rate recovery (HRR) in the second minute (HRR₂) in relation to the No-OSA group. A negative correlation between AHI and ventilation (VE) (r = ?0.63, p = 0.02) was found in polysomnography and CPET data comparisons, and oxygen saturation (O₂S) levels significantly correlated with VE/VCO_2slope (r = 0.66, p = 0.01); in addition, No-OSA group presented a positive correlation between oxygen consumption and O₂S (r = 0.66, p = 0.01), unlike the OSA group.

Conclusions

OSA does not affect the CPET variables in hypertensive elderly, but it attenuates the HRR₂. The association between O₂S during sleep with ventilatory responses probably occurs due to the adaptations in the oxygen transport system unleashed via mechanical respiratory feedback; thus, it has been identified that OSA compromises the oxygen supply in hypertensive elderly.

     

Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender

Background

Clopidogrel is an irreversible antagonist of P2Y₁₂ receptors (P2Y₁₂Rs) used as an antiplatelet drug to reduce risk of thrombosis. P2Y₁₂Rs are expressed in gastrointestinal (GI) tract where they might regulate GI function.

Aim

To evaluate if blockade of P2Y₁₂Rs by clopidogrel is associated with higher incidence of GI symptoms in patients with irritable bowel syndrome (IBS).

Methods

A retrospective analysis of our institutional database was conducted for a 13-year period. IBS patients were identified, and their demographics, GI symptoms and clopidogrel therapy were collected. Logistic regression models were used to characterize symptoms in clopidogrel versus no-clopidogrel IBS-groups, adjusting for Age and Sex differences. An additional study characterized the P2Y₁₂R distribution in human gut.

Results

The search identified 7217 IBS patients (6761 no-clopidogrel/456 clopidogrel). There were a higher proportion of patients with GI symptoms on clopidogrel (68%) compared to controls (60%, p = 0.0011) that were Females (70 vs. 60%, p = 0.0003) not Males (61 vs. 60%; p = 0.8312). In Females, clopidogrel was associated with higher incidence of GI symptoms (Age adjusted; p < 0.0001) for pain, constipation, gastroparesis (p ≤ 0.0001) and psychogenic pain (p = 0.0006). Age or Sex (adjusted models) influenced one or more GI symptoms (i.e., pain, p < 0.0001; constipation, p < 0.0001/p = 0.008; diarrhea, flatulence, p = 0.01). P2Y₁₂R immunoreactivity was abundant in human ENS; glial-to-neuron ratio of P2Y₁₂Rs expressed in Females ? Males.

Conclusions

Irreversible blockade of P2Y₁₂R by clopidogrel is associated with higher incidence of GI symptoms in Female IBS patients, although Age or Sex alone contributes to symptomatology. Prospective studies can determine clinical implications of P2Y₁₂Rs in IBS.

     

Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study

Aims/hypothesis

The hyperglycaemic clamp technique and the frequently sampled IVGTT are unsuitable techniques to assess beta cell function (BCF) in large cohorts. Therefore, the aim of this study was to evaluate the discriminatory ability of simple OGTT-based BCF indices for prediction of prediabetes (meaning impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes.

Methods

Glucose metabolism status was assessed by 2 h 75 g OGTT at baseline (n?=?476, mean age 59.2 years, 38.7% women) and after 7 years of follow-up (n?=?416) in the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study (1999–2009). Baseline plasma glucose, insulin and C-peptide values during OGTTs were used to calculate 21 simple indices of BCF. Disposition indices (BCF index × Matsuda index), to compensate for the prevailing level of insulin resistance, were calculated for the BCF indices with the best discriminatory abilities. The discriminatory ability of the BCF indices was estimated by the area under the receiver operating characteristics curve (ROC AUC) with an outcome of incident prediabetes (n?=?73) or type 2 diabetes (n?=?60 and n?=?18 cases, respectively, in individuals who were non-diabetic or had normal glucose metabolism at baseline).

Results

For incident prediabetes (n?=?73), all ROC AUCs were less than 70%, whereas for incident type 2 diabetes, I₃₀/I₀, CP₃₀/CP₀, ΔI₃₀/ΔG₃₀, ΔCP₃₀/ΔG₃₀ (where I, CP and G are the plasma concentrations of insulin, C-peptide and glucose, respectively, at the times indicated), and corrected insulin response at 30 min had ROC AUCs over 70%. In at-baseline non-diabetic individuals, disposition indices ΔI₃₀/ΔG₃₀, ΔCP₃₀/ΔG₃₀ and corrected insulin response at 30 min had ROC AUCs of over 80% for incident type 2 diabetes. Moreover, these BCF disposition indices had significantly better discriminatory abilities for incident type 2 diabetes than the Matsuda index alone.

Conclusions/interpretation

BCF indices reflecting early-phase insulin secretion have the best ability to discriminate individuals who will develop prediabetes and type 2 diabetes. Of these, ΔCP₃₀/ΔG₃₀, often referred to as the C-peptidogenic index, performed consistently well.

     

Breaking sitting with light activities vs structured exercise: a randomised crossover study demonstrating benefits for glycaemic control and insulin sensitivity in type 2 diabetes

Aims/hypothesis

We aimed to examine the effects of breaking sitting with standing and light-intensity walking vs an energy-matched bout of structured exercise on 24 h glucose levels and insulin resistance in patients with type 2 diabetes.

Methods

In a randomised crossover study, 19 patients with type 2 diabetes (13 men/6 women, 63?±?9 years old) who were not using insulin each followed three regimens under free-living conditions, each lasting 4 days: (1) Sitting: 4415 steps/day with 14 h sitting/day; (2) Exercise: 4823 steps/day with 1.1 h/day of sitting replaced by moderate- to vigorous-intensity cycling (at an intensity of 5.9 metabolic equivalents [METs]); and (3) Sit Less: 17,502 steps/day with 4.7 h/day of sitting replaced by standing and light-intensity walking (an additional 2.5 h and 2.2 h, respectively, compared with the hours spent doing these activities in the Sitting regimen). Blocked randomisation was performed using a block size of six regimen orders using sealed, non-translucent envelopes. Individuals who assessed the outcomes were blinded to group assignment. Meals were standardised during each intervention. Physical activity and glucose levels were assessed for 24 h/day by accelerometry (activPAL) and a glucose monitor (iPro2), respectively. The incremental AUC (iAUC) for 24 h glucose (primary outcome) and insulin resistance (HOMA2-IR) were assessed on days 4 and 5, respectively.

Results

The iAUC for 24 h glucose (mean?±?SEM) was significantly lower during the Sit Less intervention than in Sitting (1263?±?189 min?×?mmol/l vs 1974?±?324 min?×?mmol/l; p?=?0.002), and was similar between Sit Less and Exercise (Exercise: 1383?±?194 min?×?mmol/l; p?=?0.499). Exercise failed to improve HOMA2-IR compared with Sitting (2.06?±?0.28 vs 2.16?±?0.26; p?=?0.177). In contrast, Sit Less (1.89?±?0.26) significantly reduced HOMA2-IR compared with Exercise (p?=?0.015) as well as Sitting (p?=?0.001).

Conclusions/interpretation

Breaking sitting with standing and light-intensity walking effectively improved 24 h glucose levels and improved insulin sensitivity in individuals with type 2 diabetes to a greater extent than structured exercise. Thus, our results suggest that breaking sitting with standing and light-intensity walking may be an alternative to structured exercise to promote glycaemic control in patients type 2 diabetes.

Trial registration:

Clinicaltrials.gov NCT02371239

Funding:

The study was supported by a Kootstra grant from Maastricht University Medical Centre⁺, and the Dutch Heart Foundation. Financial support was also provided by Novo Nordisk BV, and Medtronic and Roche made the equipment available for continuous glucose monitoring

     

Application of objective clinical human reliability analysis (OCHRA) in assessment of technical performance in laparoscopic rectal cancer surgery

Background

Laparoscopic rectal resection is technically challenging, with outcomes dependent upon technical performance. No robust objective assessment tool exists for laparoscopic rectal resection surgery. This study aimed to investigate the application of the objective clinical human reliability analysis (OCHRA) technique for assessing technical performance of laparoscopic rectal surgery and explore the validity and reliability of this technique.

Methods

Laparoscopic rectal cancer resection operations were described in the format of a hierarchical task analysis. Potential technical errors were defined. The OCHRA technique was used to identify technical errors enacted in videos of twenty consecutive laparoscopic rectal cancer resection operations from a single site. The procedural task, spatial location, and circumstances of all identified errors were logged. Clinical validity was assessed through correlation with clinical outcomes; reliability was assessed by test–retest.

Results

A total of 335 execution errors identified, with a median 15 per operation. More errors were observed during pelvic tasks compared with abdominal tasks (p < 0.001). Within the pelvis, more errors were observed during dissection on the right side than the left (p = 0.03). Test–retest confirmed reliability (r = 0.97, p < 0.001). A significant correlation was observed between error frequency and mesorectal specimen quality (r _s = 0.52, p = 0.02) and with blood loss (r _s = 0.609, p = 0.004).

Conclusions

OCHRA offers a valid and reliable method for evaluating technical performance of laparoscopic rectal surgery.

     

Severe Hemoptysis Associated with Bacterial Pulmonary Infection: Clinical Features,Significance of Parenchymal Necrosis,and Outcome

Purpose

Severe hemoptysis (SH) associated with non-tuberculosis bacterial lower respiratory tract infection (LRTI) is poorly described, and the efficacy of the usual decision-making process is unknown. This study aimed at describing the clinical, radiological patterns, mechanism, and microbiological spectrum of SH related to bacterial LRTI, and assessing whether the severity of hemoptysis and the results of usual therapeutic strategy are influenced by the presence of parenchymal necrosis.

Methods

A single-center analysis of patients with SH related to bacterial LRTI from a prospective registry of consecutive patients with SH admitted to the intensive care unit of a tertiary referral center between November 1996 and May 2013.

Results

Of 1504 patients with SH during the study period, 65 (4.3%) had SH related to bacterial LRTI, including non-necrotizing infections (n = 31), necrotizing pneumonia (n = 23), pulmonary abscess (n = 10), and excavated nodule (n = 1). The presence of parenchymal necrosis (n = 34, 52%) was associated with a more abundant bleeding (volume: 200 ml [70–300] vs. 80 ml [30–170]; p = 0.01) and a more frequent need for endovascular procedure (26/34; 76% vs. 9/31; 29%; p < 0.001). Additionally, in case of parenchymal necrosis, the pulmonary artery vasculature was involved in 16 patients (47%), and the failure rate of endovascular treatment was up to 25% despite multiple procedures.

Conclusions

Bacterial LRTI is a rare cause of SH. The presence of parenchymal necrosis is more likely associated with bleeding severity, pulmonary vasculature involvement, and endovascular treatment failure.

     

Influence of <Emphasis Type="Italic">TGFB1</Emphasis>+<Emphasis Type="Italic">869T</Emphasis>>C functional polymorphism in non-small cell lung cancer (NSCLC) risk

Purpose

Lung cancer is the third most common type of cancer in Europe and is the first cause of death by cancer worldwide. Non-small cell lung cancer accounts for 75–85% of all histological types of LC. The transforming growth factor beta 1 is a multifunctional regulatory polypeptide that controls many aspects of cellular function (cellular proliferation, differentiation, migration, apoptosis, immune surveillance). TGFB1+869T>C is a functional polymorphism described in TGFB1 gene and this transition has been associated with higher circulating levels of TGFß1 that may modulate cellular microenvironment and consequently LC development and prognosis.

Methods

We studied TGFB + 869T > C functional polymorphism by allelic discrimination using 7300 real-time polymerase chain reaction system in 305 patients with NSCLC and 380 healthy individuals.

Results

We found an increased risk for C carriers to develop NSCLC, both epidermoid NSCLC and non-epidermoid NSCLC (odds ratio (OR) = 2.03, P < 0.0001, OR = 2.37, P < 0.001 and OR = 1.83, P = 0.001, respectively). TGFB1+869T>C functional polymorphism may influence NSCLC susceptibility with impact in cellular microenvironment.

Conclusions

Our results suggest that individual differences influence the susceptibility to LC and tumoral behavior. This genetic profiling may help define higher risk groups for an individualized chemoprevention strategy and therapy.

     

Anxiety,Depression, and Health-Related QOL in Patients Diagnosed with PAH or CTEPH

Background

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening diseases with a high burden of symptoms. Although depression, anxiety, and reduced health related quality of life (HRQOL) have also been reported, a comparative analysis which explores these traits and their underlying factors was lacking.

Methods

A retrospective analysis of depression, anxiety, and health related QOL was conducted using a Hospital anxiety and depression scale (HADS) as well as the SF-36 HRQOL questionnaire. Results from these tools were compared with haemodynamic and functional parameters in 70 PAH and 23 CTEPH outpatients from a German tertiary care center specializing in pulmonary hypertension.

Results

Although HRQOL was reduced in both cohorts of patients, individuals diagnosed with CTEPH scored lower in nearly all SF-36 parameters. Significance was noted in both “mental health” (p = 0.01) and “mental component summary score” (MCS) (p = 0.02). Depression was also more frequent in patients with CTEPH (56%) than in patients with PAH (30%), (p = 0.03). Overall, depression and anxiety correlated with most SF-36 scales in both PAH and CTEPH. In CTEPH, depression also correlated with the Borg Dyspnea Scale (r = 0.44, p = 0.01). These patients also had significantly lower pCO₂ levels than the PAH cohort reflecting more severe ventilation/perfusion mismatch. All other haemodynamic and functional parameters did not differ across the groups.

Conclusion

While both cohorts of patients suffer from a reduced HRQOL as well as depression and anxiety, decreases in mental health parameters are more pronounced in the CTEPH cohort. This suggests a strong effort to improve early detection, especially in dyspneic patients with classical risk factors for CTEPH and PAH and argues for mental illness interventions alongside routine clinical care provided to patients diagnosed with PAH or CTEPH.

     

Association Between CD4<Superscript>+</Superscript>, Viral Load,and Pulmonary Function in HIV

Purpose

The antiretroviral therapy era has shifted the epidemiology of HIV-associated diseases, increasing the recognition of non-infectious pulmonary complications secondary to HIV. We aimed to determine the association between CD4⁺, viral load, and pulmonary function in individuals with uncontrolled HIV, and determine how changes in these parameters are associated with pulmonary function longitudinally.

Methods

This is a retrospective observational study of individuals with HIV who underwent pulmonary function testing in an urban medical center between August 1997 and November 2015.

Results

Of the 146 participants (mean age 52 ± 10 years), 49% were Hispanic, 56% were men, and 44% were current smokers. CD4⁺ <200 cells/μl was associated with significant diffusion impairment compared to CD4⁺ ≥200 cells/μl (DL_CO 56 vs. 70%, p = <0.01). VL (viral load) ≥75 copies/ml was associated with significant diffusion impairment compared to VL <75 copies/ml (DL_CO 60 vs. 71%, p = <0.01). No difference in FEV1, FEV1/FVC, or TLC was noted between groups. In univariate analysis, CD4⁺ and VL correlated with DL_CO (r = +0.33; p = <0.01; r = ?0.26; p = <0.01) and no correlation was noted with FEV₁, FEV₁/FVC, or TLC. Current smoking and history of AIDS correlated with DL_CO (r = ?0.20; p = 0.03; r = ?0.20; p = 0.04). After adjusting for smoking and other confounders, VL ≥75 copies/ml correlated with a 11.2 (CI 95% [3.03–19.4], p = <0.01) decrease in DL_CO. In Spearman’s Rank correlation, there was a negative correlation between change in VL and change in DL_CO over time (ρ = ?0.47; p = <0.01).

Conclusion

The presence of viremia in individuals with HIV is independently associated with impaired DL_CO. Suppression of VL may allow for recovery in diffusing capacity over time, though the degree to which this occurs requires further investigation.

     

Sphenoid sinus microbiota in pituitary apoplexy: a preliminary study

Purpose

There is a high incidence of abnormal sphenoid sinus changes in patients with pituitary apoplexy (PA). Their pathophysiology is currently unexplored and may reflect an inflammatory or infective process. In this preliminary study, we characterised the microbiota of sphenoid sinus mucosa in patients with PA and compared findings to a control group of surgically treated non-functioning pituitary adenomas (NFPAs).

Methods

In this prospective observational study of patients undergoing trans-sphenoidal surgery for PA or NFPA, sphenoid sinus mucosal specimens were microbiologically profiled through PCR-cloning of the 16S rRNA gene.

Results

Ten patients (five with PA and five with NFPAs) with a mean age of 51 years (range 23–71) were included. Differences in the sphenoid sinus microbiota of the PA and NFPA groups were observed. Four PA patients harboured Enterobacteriaceae (Enterobacter spp., N = 3; Escherichia coli, N = 1). In contrast, patients with NFPAs had a sinus microbiota more representative of health, including Staphylococcus epidermidis (N = 2) or Corynebacterium spp. (N = 2).

Conclusions

PA may be associated with an abnormal sphenoid sinus microbiota that is similar to that seen in patients with sphenoid sinusitis.

     

The impact of prophylactic administration of a neutrophil elastase inhibitor on the postoperative course in older patients undergoing esophagectomy for esophageal cancer: a propensity score-matched analysis

Background

Sivelestat, a selective inhibitor of neutrophil elastase, has been reported to reduce acute lung injury associated with systemic inflammatory response syndrome (SIRS). However, no study has addressed the effect of prophylactic sivelestat administration on the postoperative course following an esophagectomy in older patients.

Methods

In this retrospective study of patients aged >70 years, we performed a propensity score-matched analysis to compare short and long-term outcomes between patients who received early postoperative sivelestat administration (n = 42) and those who did not receive sivelestat (controls; n = 42) after a transthoracic esophagectomy for esophageal cancer (EC).

Results

Patient backgrounds were well balanced between the two groups. The sivelestat group showed significantly shorter SIRS durations compared to the control group (2 vs 5 days, p = 0.001). In addition, postoperative hospital stays were shorter in the sivelestat group than in the control group (26 vs 31 days, p = 0.013). Other factors did not differ between the two groups, including the reoperation rate, ICU stay, duration of mechanical ventilation, and duration of O₂ supply. Postoperatively, the sivelestat group showed significantly lower heart rates than the control group (repeated-measures ANOVA, p = 0.0389) while respiratory rates, the SpO₂ levels, and body temperatures did not significantly differ between the two groups. Finally, long-term survival appeared to be not different between the two groups.

Conclusions

Sivelestat effectively stabilized postoperative vital signs and shortened SIRS durations. Thus, prophylactic sivelestat led to shorter hospital stays among older patients with EC who underwent an esophagectomy.

     

Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats

Background

Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE).

Aim

The aim of this study was to clarify the effect of LDA on chronic RE in rats.

Methods

Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2–0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells.

Results

Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p < 0.05). The grade of severity correlated with the depth of inflammation (r _s = 0.492, p < 0.001).

Conclusions

Maximal dose aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.

     

Long-term efficacy of comprehensive multidisciplinary antibiotic stewardship programs centered on weekly prospective audit and feedback

Objective

To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes.

Design

Before–after study.

Setting

National university hospital with 934 beds.

Intervention

Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration.

Methods

The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of Pseudomonas aeruginosa, the proportion of patients isolated methicillin-resistant Staphylococcus aureus (MRSA) among all patients isolated S. aureus, the incidence of MRSA, and the 30-day mortality attributable to bacteremia.

Results

The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (P = 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (P < 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (P = 0.57 for trend).

Conclusion

The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of P. aeruginosa, and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.

     

Toxin positivity and <Emphasis Type="Italic">tcdB</Emphasis> gene load in broad-spectrum <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection

Purpose

This study aimed to evaluate the clinical significance of toxin positivity and toxin gene load, and the relation between them in the broad spectrum of Clostridium difficile infection (CDI) including colonization, significant diarrhea, and severe disease.

Methods

We included 2671 fecal samples submitted for CDI diagnosis and 180 samples from healthy individuals. The clinical spectrum was categorized as category I (toxigenic C. difficile positive without clinical CDI criteria), category II (mild CDI), and category III (severe CDI). Clinical parameters were compared based on toxin EIA and tcdB C _t values. C _t values of tcdB PCR for predicting toxin EIA positivity were assessed using receiver-operating characteristic (ROC) curves.

Results

The median C _t values of tcdB PCR and toxin positivity were not significantly correlated with clinical spectrum of CDI (27.5, 28.2, and 26.1 for tcdB C _t and 55.0, 56.6, and 60.9% for toxin EIA positivity in category I, II, and III, respectively, P > 0.05). There were significant differences in the tcdB C _t values between toxin EIA-positive and -negative groups (P < 0.001). Optimal cutoff for the tcdB C _t value for estimating toxin EIA positivity was 26.3 with 79.3% sensitivity and 83.6% specificity with good area under the curves (AUC, 0.848).

Conclusions

The C _t values successfully predicted toxin EIA positivity and could be used as a surrogate for toxin EIA positivity in the diagnostic algorithm and routine analysis. Further studies are needed to validate the clinical significance of tcdB PCR C _t value in toxigenic C. difficile colonization and infection.

     

Risk factors and outcomes of acute lower gastrointestinal bleeding in intestinal Behçet’s disease

Background

Intestinal Behçet’s disease (BD) can cause acute lower gastrointestinal bleeding, which is sometimes fatal.

Aim

We aimed to identify the risk factors and outcomes of acute lower gastrointestinal bleeding and factors associated with rebleeding in intestinal BD patients.

Methods

Of the total of 588 intestinal BD patients, we retrospectively reviewed the medical records of 66 (11.2%) patients with acute lower gastrointestinal bleeding and compared them with those of 132 matched patients without bleeding.

Results

The baseline characteristics were comparable between the bleeding group (n = 66) and the non-bleeding group (n = 132). On multivariate analysis, the independent factors significantly associated with lower gastrointestinal bleeding were older age (>52 years) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.058–4.684, p = 0.035) and a nodular ulcer margin (HR 7.1, 95% CI 2.084–24.189, p = 0.002). Rebleeding occurred in 23 patients (34.8%). Female patients (p = 0.044) and those with previous use of corticosteroids or azathioprine (p = 0.034) were more likely to develop rebleeding. On multivariate analysis, only use of steroids or azathioprine was significantly associated with rebleeding (HR 3.2, 95% CI 1.070–9.462, p = 0.037).

Conclusions

Age >52 years and the presence of a nodular margin of the ulcer were found to be related to increased risk of bleeding in patients with intestinal BD. Rebleeding is not uncommon and not effectively prevented with currently available medications. Further studies are warranted to identify effective measures to decrease rebleeding in intestinal BD.

     

Interrupting prolonged sitting in type 2 diabetes: nocturnal persistence of improved glycaemic control

Aims/hypothesis

We aimed to examine the effect of interrupting 7 h prolonged sitting with brief bouts of walking or resistance activities on 22 h glucose homeostasis (including nocturnal-to-following morning hyperglycaemia) in adults with type 2 diabetes.

Methods

This study is an extension of a previously published randomised crossover trial, which included 24 inactive overweight/obese adults with type 2 diabetes (14 men; 62?±?6 years) who completed three 7 h laboratory conditions, separated by 6–14 day washout periods: SIT: (1) prolonged sitting (control); (2) light-intensity walking (LW): sitting plus 3 min bouts of light-intensity walking at 3.2 km/h every 30 min; (3) simple resistance activities (SRA): sitting plus 3 min bouts of simple resistance activities (alternating half-squats, calf raises, brief gluteal contractions and knee raises) every 30 min. In the present study, continuous glucose monitoring was performed for 22 h, encompassing the 7 h laboratory trial, the evening free-living period after leaving the laboratory and sleeping periods. Meals and meal times were standardised across conditions for all participants.

Results

Compared with SIT, both LW and SRA reduced 22 h glucose [SIT: 11.6?±?0.3 mmol/l, LW: 8.9?±?0.3 mmol/l, SRA: 8.7?±?0.3 mmol/l; p?<?0.001] and nocturnal mean glucose concentrations [SIT: 10.6?±?0.4 mmol/l, LW: 8.1?±?0.4 mmol/l, SRA: 8.3?±?0.4 mmol/l; p?<?0.001]. Furthermore, mean glucose concentrations were sustained nocturnally at a lower level until the morning following the intervention for both LW and SRA (waking glucose both ?2.7?±?0.4 mmol/l compared with SIT; p?<?0.001).

Conclusions/interpretation

Interrupting 7 h prolonged sitting time with either LW or SRA reduced 22 h hyperglycaemia. The glycaemic improvements persisted after these laboratory conditions and nocturnally, until waking the following morning. These findings may have implications for adults with relatively well-controlled type 2 diabetes who engage in prolonged periods of sitting, for example, highly desk-bound workers.

Trial registration:

anzctr.org.au ACTRN12613000576729

Funding:

This research was supported by a National Health and Medical Research Council (NHMRC) project grant (no. 1081734) and the Victorian Government Operational Infrastructure Support scheme.

     

Cost-Effectiveness of Primary HPV Testing,Cytology and Co-testing as Cervical Cancer Screening for Women Above Age 30 Years

Background

Cervical cancer screening guidelines for women aged ≥30 years allow for co-testing or primary cytology testing. Our objective was to determine the test characteristics and costs associated with Cytology, HPV and Co-testing screening strategies.

Main Methods

Retrospective cohort study of women undergoing cervical cancer screening with both cytology and HPV (Hybrid Capture 2) testing from 2004 to 2010 in an integrated health system. The electronic health record was used to identify women aged ≥30 years who had co-testing. Unsatisfactory or unavailable test results and incorrectly ordered tests were excluded. The main outcome was biopsy-proven cervical intraepithelial neoplasia grade 3 or higher (CIN3+).

Key Results

The final cohort consisted of 99,549 women. Subjects were mostly white (78.4 %), married (70.7 %), never smokers (61.3 %) and with private insurance (86.1 %). Overall, 5121 (5.1 %) tested positive for HPV and 6115 (6.1 %) had cytology ≥ ASCUS; 1681 had both and underwent colposcopy and 310 (0.3 %) had CIN3+. Sensitivity for CIN3+ was 91.9 % for Primary Cytology, 99.4 % for Co-testing, and 94.8 % for Primary HPV; specificity was 97.3 % for Co-testing and Primary Cytology and 97.9 % for Primary HPV. Over a 3-year screening interval, Primary HPV detected more cases of CIN3+ and was less expensive than Primary Cytology. Co-testing detected 14 more cases of CIN3+ than Primary HPV, but required an additional 100,277 cytology tests and 566 colposcopies at an added cost of $2.38 million, or $170,096 per additional case detected.

Conclusions

Primary HPV was more effective and less expensive than Primary Cytology. Primary HPV screening appears to represent a cost-effective alternative to Co-testing.

     

Statin Use,Diabetes Incidence and Overall Mortality in Normoglycemic and Impaired Fasting Glucose Patients

BACKGROUND

The association between the use of statins and the risk of diabetes and increased mortality within the same population has been a source of controversy, and may underestimate the value of statins for patients at risk.

OBJECTIVE

We aimed to assess whether statin use increases the risk of developing diabetes or affects overall mortality among normoglycemic patients and patients with impaired fasting glucose (IFG).

DESIGN AND PARTICIPANTS

Observational cohort study of 13,508 normoglycemic patients (n?=?4460; 33 % taking statins) and 4563 IFG patients (n?=?1865; 41 % taking statin) among residents of Olmsted County, Minnesota, with clinical data in the Mayo Clinic electronic medical record and at least one outpatient fasting glucose test between 1999 and 2004. Demographics, vital signs, tobacco use, laboratory results, medications and comorbidities were obtained by electronic search for the period 1999–2004. Results were analyzed by Cox proportional hazards models, and the risk of incident diabetes and mortality were analyzed by survival curves using the Kaplan–Meier method.

MAIN MEASURES

The main endpoints were new clinical diagnosis of diabetes mellitus and total mortality.

KEY RESULTS

After a mean of 6 years of follow-up, statin use was found to be associated with an increased risk of incident diabetes in the normoglycemic (HR 1.19; 95 % CI, 1.05 to 1.35; p?=?0.007) and IFG groups (HR 1.24; 95%CI, 1.11 to 1.38; p?=?0.0001). At the same time, overall mortality decreased in both normoglycemic (HR 0.70; 95 % CI, 0.66 to 0.80; p?<?0.0001) and IFG patients (HR 0.77, 95 % CI, 0.64 to 0.91; p?=?0.0029) with statin use.

CONCLUSION

In general, recommendations for statin use should not be affected by concerns over an increased risk of developing diabetes, since the benefit of reduced mortality clearly outweighs this small (19–24 %) risk.