Analyzing the performance of ArcCHECK diode array detector for VMAT plan

Aim

The aim of this study is to evaluate performance of ArcCHECK diode array detector for the volumetric modulated arc therapy (VMAT) patient specific quality assurance (QA). VMAT patient specific QA results were correlated with ion chamber measurement. Dose response of the ArcCHECK detector was studied.

Background

VMAT delivery technique improves the dose distribution. It is complex in nature and requires proper QA before its clinical implementation. ArcCHECK is a novel three dimensional dosimetry system.

Materials and methods

Twelve retrospective VMAT plans were calculated on ArcCHECK phantom. Point dose and dose map were measured simultaneously with ion chamber (IC-15) and ArcCHECK diode array detector, respectively. These measurements were compared with their respective TPS calculated values.

Results

The ion chamber measurements are in good agreement with TPS calculated doses. Mean difference between them is 0.50% with standard deviation of 0.51%. Concordance correlation coefficient (CCC) obtained for ion chamber measurements is 0.9996. These results demonstrate a strong correlation between the absolute dose predicted by our TPS and the measured dose. The CCC between ArcCHECK doses and TPS predictions on the CAX was found to be 0.9978. In gamma analysis of dose map, the mean passing rate was 98.53% for 3% dose difference and 3 mm distance to agreement.

Conclusions

The VMAT patient specific QA with an ion chamber and ArcCHECK phantom are consistent with the TPS calculated dose. Statistically good agreement was observed between ArcCHECK measured and TPS calculated. Hence, it can be used for routine VMAT QA.     

Trajectory log file sensitivity: A critical analysis using DVH and EPID

Aim

The aim of this study was to investigate the sensitivity of the trajectory log file based quality assurance to detect potential errors such as MLC positioning and gantry positioning by comparing it with EPID measurement using the most commonly used criteria of 3%/3?mm.

The Impact of Different Levels of Adaptive Iterative Dose Reduction 3D on Image Quality of 320-Row Coronary CT Angiography: A Clinical Trial

Purpose

The aim of this study was the systematic image quality evaluation of coronary CT angiography (CTA), reconstructed with the 3 different levels of adaptive iterative dose reduction (AIDR 3D) and compared to filtered back projection (FBP) with quantum denoising software (QDS).

Methods

Standard-dose CTA raw data of 30 patients with mean radiation dose of 3.2 ± 2.6 mSv were reconstructed using AIDR 3D mild, standard, strong and compared to FBP/QDS. Objective image quality comparison (signal, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), contour sharpness) was performed using 21 measurement points per patient, including measurements in each coronary artery from proximal to distal.

Results

Objective image quality parameters improved with increasing levels of AIDR 3D. Noise was lowest in AIDR 3D strong (p≤0.001 at 20/21 measurement points; compared with FBP/QDS). Signal and contour sharpness analysis showed no significant difference between the reconstruction algorithms for most measurement points. Best coronary SNR and CNR were achieved with AIDR 3D strong. No loss of SNR or CNR in distal segments was seen with AIDR 3D as compared to FBP.

Conclusions

On standard-dose coronary CTA images, AIDR 3D strong showed higher objective image quality than FBP/QDS without reducing contour sharpness.

Trial Registration

Clinicaltrials.gov NCT00967876     

Sinonasal Microbiome Sampling: A Comparison of Techniques

Background

The role of the sino-nasal microbiome in CRS remains unclear. We hypothesized that the bacteria within mucosal-associated biofilms may be different from the more superficial-lying, free-floating bacteria in the sinuses and that this may impact on the microbiome results obtained. This study investigates whether there is a significant difference in the microbiota of a sinonasal mucosal tissue sample versus a swab sample.

Methods

Cross-sectional study with paired design. Mucosal biopsy and swab samples were obtained intra-operatively from the ethmoid sinuses of 6 patients with CRS. Extracted DNA was sequenced on a Roche-454 sequencer using 16S-rRNA gene targeted primers. Data were analyzed using QIIME 1.8 software package.

Results

At a maximum subsampling depth of 1,100 reads, the mean observed species richness was 33.3 species (30.6 for swab, versus 36 for mucosa; p > 0.05). There was no significant difference in phylogenetic and non-phylogenetic alpha diversity metrics (Faith’s PD_Whole_Tree and Shannon’s index) between the two sampling methods (p > 0.05). The type of sample also had no significant effect on phylogenetic and non-phylogenetic beta diversity metrics (Unifrac and Bray-Curtis; p > 0.05).

Conclusion

We observed no significant difference between the microbiota of mucosal tissue and swab samples. This suggests that less invasive swab samples are representative of the sinonasal mucosa microbiome and can be used for future sinonasal microbiome studies.     

A study on the correlation between plan complexity and gamma index analysis in patient specific quality assurance of volumetric modulated arc therapy

Aim

To evaluate the new Octavius 4D system for patient specific quality assurance and to study the correlation between plan complexity and gamma index analysis in patient specific quality assurance of VMAT using the Octavius 4D system.

Background

McNiven (2010) proposed a study to evaluate the utility of a complexity metric, the Modulation Complexity Score, to evaluate the relationship of the metric with deliverability in IMRT.

Materials and methods

Evaluation of the Octavius 4D system was carried out by gamma evaluation of user defined MLC created patterns and AAPM TG 119 benchmark plans. The relationship between plan complexity expressed as Modulation Complexity Score (MCS) and the gamma index analysis was established by a planar and volumetric gamma analysis of 106 clinically approved VMAT patient plans of different sites.

Results

Average volumetric 3D global gamma evaluation (3 mm/3%) results for the evaluation plans was 97.41% for 6 MV X-rays and 98.30% for 15 MV X-rays. Average MCS values for the head and neck, pelvic and thoracic plans were 0.2224, 0.3615 and 0.1874. Average volumetric 3D global gamma analysis (3 mm/3%) results for the head and neck, pelvic and thoracic VMAT plans were 95.45%, 97.51% and 96.98%, respectively. Out of 90 correlation analyses between the MCS and gamma passing rate, only 3 had the r value greater than 0.5.

Conclusions

The Octavius 4D system is a suitable device for patient specific pretreatment QA. Global and local gamma analysis results showed a weak correlation with the MCS.     

Ideal Cardiovascular Health Metrics Are Associated with Disability Independently of Vascular Conditions

Background

Vascular risk factors may be associated with disability independently of vascular events. We examined whether the American Heart Association’s 7 ideal cardiovascular health (CVH) metrics were independently associated with disability in a nationally representative cohort.

Methods

Adults age ≥20 years from the National Health and Nutrition Examination Survey 2005–2012 were included. Ideal CVH was calculated as a composite of 7 measures, each scored 0–2. Primary predictors were number of ideal CVH metrics and score of CVH metrics. The outcome was a dichotomous score from 20 activities of daily living (ADL) and instrumental ADLs. Unadjusted and adjusted weighted logistic models estimated associations between ideal CVH and disability. The data were analyzed in 2015.

Results

Among 22692 participants, mean age was 46.9 years. Cardiac disease and stroke were present in 6.6% and 2.8%; 90.3% had poor physical activity and 89.9% poor diet. Among 3975 individuals with full CVH data, in fully adjusted models, OR for disability was 0.90 (95% CI 0.83–0.98) per point increase in ideal CVH score, and 0.84 (0.73–0.97) per additional number of ideal CVH metrics.

Conclusions

CVH metrics were strongly and significantly associated with reduced odds of disability independently of vascular and non-vascular conditions. Poorer CVH may cause subclinical vascular disease resulting in disability.     

Head-to-Head Comparison of Two Popular Cortical Thickness Extraction Algorithms: A Cross-Sectional and Longitudinal Study

Background and Purpose

The measurement of cortical shrinkage is a candidate marker of disease progression in Alzheimer’s. This study evaluated the performance of two pipelines: Civet-CLASP (v1.1.9) and Freesurfer (v5.3.0).

Methods

Images from 185 ADNI1 cases (69 elderly controls (CTR), 37 stable MCI (sMCI), 27 progressive MCI (pMCI), and 52 Alzheimer (AD) patients) scanned at baseline, month 12, and month 24 were processed using the two pipelines and two interconnected e-infrastructures: neuGRID (https://neugrid4you.eu) and VIP (http://vip.creatis.insa-lyon.fr). The vertex-by-vertex cross-algorithm comparison was made possible applying the 3D gradient vector flow (GVF) and closest point search (CPS) techniques.

Results

The cortical thickness measured with Freesurfer was systematically lower by one third if compared to Civet’s. Cross-sectionally, Freesurfer’s effect size was significantly different in the posterior division of the temporal fusiform cortex. Both pipelines were weakly or mildly correlated with the Mini Mental State Examination score (MMSE) and the hippocampal volumetry. Civet differed significantly from Freesurfer in large frontal, parietal, temporal and occipital regions (p<0.05). In a discriminant analysis with cortical ROIs having effect size larger than 0.8, both pipelines gave no significant differences in area under the curve (AUC). Longitudinally, effect sizes were not significantly different in any of the 28 ROIs tested. Both pipelines weakly correlated with MMSE decay, showing no significant differences. Freesurfer mildly correlated with hippocampal thinning rate and differed in the supramarginal gyrus, temporal gyrus, and in the lateral occipital cortex compared to Civet (p<0.05). In a discriminant analysis with ROIs having effect size larger than 0.6, both pipelines yielded no significant differences in the AUC.

Conclusions

Civet appears slightly more sensitive to the typical AD atrophic pattern at the MCI stage, but both pipelines can accurately characterize the topography of cortical thinning at the dementia stage.     

Administration of a CXCL12 Analog in Endotoxemia Is Associated with Anti-Inflammatory,Anti-Oxidative and Cytoprotective Effects In Vivo

Background

The chemokine receptor CXCR4 is a multifunctional receptor which is activated by its natural ligand C-X-C motif chemokine 12 (CXCL12). As CXCR4 is part of the lipopolysaccharide sensing complex and CXCL12 analogs are not well characterized in inflammation, we aimed to uncover the systemic effects of a CXCL12 analog in severe systemic inflammation and to evaluate its impact on endotoxin induced organ damages by using a sublethal LPS dose.

Methods

The plasma stable CXCL12 analog CTCE-0214D was synthesized and administered subcutaneously shortly before LPS treatment. After 24 hours, mice were sacrificed and blood was obtained for TNF alpha, IFN gamma and blood glucose evaluation. Oxidative stress in the liver and spleen was assessed and liver biotransformation capacity was determined. Finally, CXCR4, CXCL12 and TLR4 expression patterns in liver, spleen and thymus tissue as well as the presence of different markers for apoptosis and oxidative stress were determined by means of immunohistochemistry.

Results

CTCE-0214D distinctly reduced the LPS mediated effects on TNF alpha, IFN gamma, ALAT and blood glucose levels. It attenuated oxidative stress in the liver and spleen tissue and enhanced liver biotransformation capacity unambiguously. Furthermore, in all three organs investigated, CTCE-0214D diminished the LPS induced expression of CXCR4, CXCL12, TLR4, NF-κB, cleaved caspase-3 and gp91 phox, whereas heme oxygenase 1 expression and activity was induced above average. Additionally, TUNEL staining revealed anti-apoptotic effects of CTCE-0214D.

Conclusions

In summary, CTCE-0214D displayed anti-inflammatory, anti-oxidative and cytoprotective features. It attenuated reactive oxygen species, induced heme oxygenase 1 activity and mitigated apoptosis. Thus, the CXCR4/CXCL12 axis seems to be a promising target in the treatment of acute systemic inflammation, especially when accompanied by a hepatic dysfunction and an excessive production of free radicals.     

Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women’s Health Initiative Memory Study

Context

The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio) have been reported, as have adverse relations with saturated fatty acids and D6D ratio.

Objective

To determine the associations between red blood cell (RBC) fatty acid distributions and incident type 2 diabetes.

Design

Prospective observational cohort study nested in the Women’s Health Initiative Memory Study.

Setting

General population.

Subjects

Postmenopausal women.

Main Outcome Measures

Self-reported incident type 2 diabetes.

Results

There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.81–0.95) per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04–1.25; and HR 1.24, 95% CI 1.14–1.35, respectively). None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids.

Conclusions

Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes.     

Short Meditation Trainings Enhance Non-REM Sleep Low-Frequency Oscillations

Study Objectives

We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity.

Design

High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention.

Setting

Sound-attenuated sleep research room.

Patients or Participants

Twenty-four long-term meditators and twenty-four meditation-naïve controls.

Interventions

Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation.

Measurements and Results

We found an increase in EEG low-frequency oscillatory activities (1–12 Hz, centered around 7–8 Hz) over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25–40 Hz). There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naïve group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience.

Conclusions

This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior parietal and occipital regions showing chronic, long-lasting plastic changes in long-term meditators.     

Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study

Objective

The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease.

Methods

Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition.

Results

Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79).

Conclusions

Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration.

Classification of Evidence

This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest.

Trial Registration

Clinical Trials.gov NCT01815281     

A Multicenter,Open-Label,Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18–40 Year Old Subjects with Diagnosed Atopic Dermatitis

Background

Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.

Objective

This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects.

Methods

Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.

Results

The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.

Limitations

The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.

Conclusion

MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.

Trial Registration

ClinicalTrials.gov NCT00316602     

Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI

Introduction

Right ventricular (RV) function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH). The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI) to derive RV kinetic energy (KE) work density and energy loss in the pulmonary artery (PA) to better characterize RV work in PAH patients.

Methods

4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA.

Results

PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007) as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001) throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction.

Conclusion

This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.     

Re-Infection Outcomes Following One- And Two-Stage Surgical Revision of Infected Knee Prosthesis: A Systematic Review and Meta-Analysis

Background

Periprosthetic joint infection (PJI) is a serious complication of total knee arthroplasty. Two-stage revision is the most widely used technique and considered as the most effective for treating periprosthetic knee infection. The one-stage revision strategy is an emerging alternative option, however, its performance in comparison to the two-stage strategy is unclear. We therefore sought to ask if there was a difference in re-infection rates and other clinical outcomes when comparing the one-stage to the two-stage revision strategy.

Objective

Our first objective was to compare re-infection (new and recurrent infections) rates for one- and two-stage revision surgery for periprosthetic knee infection. Our second objective was to compare between the two revision strategies, clinical outcomes as measured by postoperative Knee Society Knee score, Knee Society Function score, Hospital for Special Surgery knee score, WOMAC score, and range of motion.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE, EMBASE, Web of Science, Cochrane Library, reference lists of relevant studies to August 2015, and correspondence with investigators.

Study selection

Longitudinal (prospective or retrospective cohort) studies conducted in generally unselected patients with periprosthetic knee infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision surgery. No clinical trials comparing both revision strategies were identified.

Review methods

Two independent investigators extracted data and discrepancies were resolved by consensus with a third investigator. Re-infection rates from 10 one-stage studies (423 participants) and 108 two-stage studies (5,129 participants) were meta-analysed using random-effect models after arcsine transformation.

Results

The rate (95% confidence intervals) of re-infection was 7.6% (3.4–13.1) in one-stage studies. The corresponding re-infection rate for two-stage revision was 8.8% (7.2–10.6). In subgroup analyses, re-infection rates remained generally similar for several study-level and clinically relevant characteristics. Postoperative clinical outcomes of knee scores and range of motion were similar for both revision strategies.

Limitations

Potential bias owing to the limited number of one-stage revision studies and inability to explore heterogeneity in greater detail.

Conclusions

Available evidence from aggregate published data suggest the one-stage revision strategy may be as effective as the two-stage revision strategy in treating infected knee prostheses in generally unselected patients. Further investigation is warranted.

Systematic review registration

PROSPERO 2015: CRD42015017327     

Performance of Different Analytical Software Packages in Quantification of DNA Methylation by Pyrosequencing

Background

Pyrosequencing has emerged as an alternative method of nucleic acid sequencing, well suited for many applications which aim to characterize single nucleotide polymorphisms, mutations, microbial types and CpG methylation in the target DNA. The commercially available pyrosequencing systems can harbor two different types of software which allow analysis in AQ or CpG mode, respectively, both widely employed for DNA methylation analysis.

Objective

Aim of the study was to assess the performance for DNA methylation analysis at CpG sites of the two pyrosequencing software which allow analysis in AQ or CpG mode, respectively. Despite CpG mode having been specifically generated for CpG methylation quantification, many investigations on this topic have been carried out with AQ mode. As proof of equivalent performance of the two software for this type of analysis is not available, the focus of this paper was to evaluate if the two modes currently used for CpG methylation assessment by pyrosequencing may give overlapping results.

Methods

We compared the performance of the two software in quantifying DNA methylation in the promoter of selected genes (GSTP1, MGMT, LINE-1) by testing two case series which include DNA from paraffin embedded prostate cancer tissues (PC study, N = 36) and DNA from blood fractions of healthy people (DD study, N = 28), respectively.

Results

We found discrepancy in the two pyrosequencing software-based quality assignment of DNA methylation assays. Compared to the software for analysis in the AQ mode, less permissive criteria are supported by the Pyro Q-CpG software, which enables analysis in CpG mode. CpG mode warns the operators about potential unsatisfactory performance of the assay and ensures a more accurate quantitative evaluation of DNA methylation at CpG sites.

Conclusion

The implementation of CpG mode is strongly advisable in order to improve the reliability of the methylation analysis results achievable by pyrosequencing.     

Cue Recognition and Integration – Eye Tracking Evidence of Processing Differences in Sentence Comprehension in Aphasia

Purpose

We aimed at further elucidating whether aphasic patients’ difficulties in understanding non-canonical sentence structures, such as Passive or Object-Verb-Subject sentences, can be attributed to impaired morphosyntactic cue recognition, and to problems in integrating competing interpretations.

Methods

A sentence-picture matching task with canonical and non-canonical spoken sentences was performed using concurrent eye tracking. Accuracy, reaction time, and eye tracking data (fixations) of 50 healthy subjects and 12 aphasic patients were analysed.

Results

Patients showed increased error rates and reaction times, as well as delayed fixation preferences for target pictures in non-canonical sentences. Patients’ fixation patterns differed from healthy controls and revealed deficits in recognizing and immediately integrating morphosyntactic cues.

Conclusion

Our study corroborates the notion that difficulties in understanding syntactically complex sentences are attributable to a processing deficit encompassing delayed and therefore impaired recognition and integration of cues, as well as increased competition between interpretations.     

Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis: A Systematic Review and Meta-Analysis

Background

The two-stage revision strategy has been claimed as being the “gold standard” for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option; however, its effectiveness in comparison to the two-stage strategy remains uncertain.

Objective

To compare the effectiveness of one- and two-stage revision strategies in treating prosthetic hip infection, using re-infection as an outcome.

Design

Systematic review and meta-analysis.

Data Sources

MEDLINE, EMBASE, Web of Science, Cochrane Library, manual search of bibliographies to March 2015, and email contact with investigators.

Study Selection

Cohort studies (prospective or retrospective) conducted in generally unselected patients with prosthetic hip infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision. No clinical trials were identified.

Review Methods

Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection from 38 one-stage studies (2,536 participants) and 60 two-stage studies (3,288 participants) were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics.

Results

In one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0–10.8). The corresponding re-infection rate after two-stage revision was 7.9% (6.2–9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no strong evidence of publication bias among contributing studies.

Conclusion

Evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision among unselected patients. More detailed analyses under a broader range of circumstances and exploration of other sources of heterogeneity will require collaborative pooling of individual participant data.

Systematic Review Registration

PROSPERO 2015: CRD42015016559     

Use of Oral Bisphosphonates in Primary Prevention of Fractures in Postmenopausal Women: A Population-Based Cohort Study

Oral bisphosphonates are first-line drugs in the treatment of osteoporosis under most guidelines, and have been shown to decrease risk of first fracture only in asymptomatic vertebral fractures and in clinical trial populations that are generally very different from the general population.

Objective

To compare incidence of first osteoporotic fracture in two cohorts of postmenopausal women, one treated with bisphosphonates and the other only with calcium and vitamin D.

Design

Retrospective population cohort study with paired matching based on data from electronic health records.

Setting

Women aged 60 years and older in 2005, from 21 primary care centers in a healthcare region of Spain.

Participants

Two groups of women aged 60 years and older (n = 1208), prescribed either calcium and vitamin D (CalVitD) or bisphosphonates (BIPHOS) with or without calcium and vitamin D, were compared for the end point of first recorded osteoporotic-related fracture, with 5-years follow-up.

Main Outcome Measure

Incidence of first fracture: Vertebral fracture, osteoporosis with pathological fracture, fracture of the upper humeral epiphysis, fracture of the lower radial epiphysis, or femur fracture.

Results

Estimated 10-year risk of fracture was 11.4% (95% confidence interval: 9.6 to 13.2), 11.8% (9.2 to 14.3) in the BIPHOS group and 11.1% (8.6 to 13.6) in the CalVitD group. No significant differences were found between groups in total fractures (Hazard ratio = 0.934 (0.67 to 1.31)) or location (vertebral, femoral, radial or humeral).

Conclusions

In postmenopausal women, bisphosphonates have not been shown to better decrease risk of first fracture compared with calcium and vitamin D therapy alone.     

A Randomized Pilot Trial Comparing Position Emission Tomography (PET)-Guided Dose Escalation Radiotherapy to Conventional Radiotherapy in Chemoradiotherapy Treatment of Locally Advanced Nasopharyngeal Carcinoma

Background

This pilot trial is designed to determine whether PET/CT-guided radiotherapy dose escalation can improve local control while minimizing toxicity for the treatment of locally advanced nasopharyngeal carcinoma.

Methods

67 patients were randomized into the three treatment arms: conventional chemoradiotherapy (group A), CT-guided dose escalation chemoradiotherapy (group B) and PET/CT-guided dose escalation chemoradiotherapy (group C). Radiotherapy was delivered using the simultaneous modulated accelerated radiation therapy (SMART) technique in the dose-escalation treatment arms. Patients received concurrent and adjuvant chemotherapy.

Results

The use of PET/CT significantly changed the treatment volume delineation of the gross tumor volume. 3-year local progression-free (LPF) survival rates of three groups were 83.3%, 90.9% and 100%, respectively. The 3-year regional progression-free survival (RPFS) rates were 95.8%, 95.5% and 100%, respectively. The 3-year disease free survival (DFS) rates were 79.2%, 86.4% and 95.2%, respectively. The 3-year overall survival (OS) rates were 83.3%, 90.9% and 95.2%, respectively. The 3-year disease-free survival (DFS) rates were 79.2%, 86.4% and 95.2%, respectively. No patient had grade 4 late toxicity.

Conclusions

PET/CT-guided dose escalation radiotherapy is well-tolerated and appears to be superior to conventional chemoradiotherapy for locally advanced NPC.

Trial Registration

ClinicalTrials.gov NCT02089204