Laparoscopic versus open gastrectomy for gastric cancer

BACKGROUND: Gastric cancer is the third most common cause of cancer-related mortality in the world. Currently there are two surgical options for potentially curable patients (i.e. people with non-metastatic gastric cancer), laparoscopic and open gastrectomy. However, it is not clear whether one of these options is superior. OBJECTIVES: To assess the benefits and harms of laparoscopic gastrectomy or laparoscopy-assisted gastrectomy versus open gastrectomy for people with gastric cancer. In particular, we planned to investigate the effects by patient groups, such as cancer stage, anaesthetic risk, and body mass index (BMI), and by intervention methods, such as method of anastomosis, type of gastrectomy and laparoscopic or laparoscopically-assisted gastrectomy. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index, ClinicalTrials.gov and the WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) until September 2015. We also screened reference lists from included trials. SELECTION CRITERIA: Two review authors independently selected references for further assessment by going through all titles and abstracts. Further selection was based on review of full text articles for selected references. Data collection and analysis Two review authors independently extracted study data. We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary outcomes, the mean difference (MD) or the standardised mean difference (SMD) with 95% CI for continuous outcomes and the hazard ratio (HR) for time-to-event outcomes. We performed meta-analyses where it was meaningful. MAIN RESULTS: In total, 2794 participants were randomised in 13 trials included in this review. All the trials were at unclear or high risk of bias. One trial (which included 53 participants) did not contribute any data to this review. A total of 213 participants were excluded in the remaining trials after randomisation, leaving a total of 2528 randomised participants for analysis, with 1288 undergoing laparoscopic gastrectomy and 1240 undergoing open gastrectomy. All the participants were suitable for major surgery. There was no difference in the proportion of participants who died within thirty days of treatment between laparoscopic gastrectomy (7/1188: adjusted proportion = 0.6% (based on meta-analysis)) and open gastrectomy (4/1447: 0.3%) (RR 1.60, 95% CI 0.50 to 5.10; risk difference 0.00, 95% CI -0.01 to 0.01; participants = 2335; studies = 11; I2 = 0%; low quality evidence). There were no events in either group for short-term recurrence (participants = 103; studies = 3), proportion requiring blood transfusion (participants = 66; studies = 2), and proportion with positive margins at histopathology (participants = 28; studies = 1). None of the trials reported health-related quality of life, time to return to normal activity or time to return to work. The differences in long-term mortality (HR 0.94, 95% CI 0.70 to 1.25; participants = 195; studies = 3; I2 = 0%; very low quality evidence), serious adverse events within three months (laparoscopic gastrectomy (7/216: adjusted proportion = 3.6%) versus open gastrectomy (13/216: 6%) (RR 0.60, 95% CI 0.27 to 1.34; participants = 432; studies = 8; I2 = 0%; very low quality evidence), long-term recurrence (HR 0.95, 95% CI 0.70 to 1.30; participants = 162; studies = 4; very low quality evidence), adverse events within three months (laparoscopic gastrectomy (204/268: adjusted proportion = 16.1%) versus open gastrectomy (253/1222: 20.7%) (RR 0.78, 95% CI 0.60 to 1.01; participants = 2490; studies = 11; I2 = 38%; very low quality evidence), quantity of perioperative blood transfused (SMD 0.05, 95% CI -0.27 to 0.38; participants = 143; studies = 2; I2 = 0%; very low quality evidence), length of hospital stay (MD -1.82 days, 95% CI -3.72 to 0.07; participants = 319; studies = 6; I2 = 83%; very low quality evidence), and number of lymph nodes harvested (MD -0.63, 95% CI -1.51 to 0.25; participants = 472; studies = 9; I2 = 40%; very low quality evidence) were imprecise. There was no alteration in the interpretation of the results in any of the subgroups. AUTHORS' CONCLUSIONS: Based on low quality evidence, there is no difference in short-term mortality between laparoscopic and open gastrectomy. Based on very low quality evidence, there is no evidence for any differences in short-term or long-term outcomes between laparoscopic and open gastrectomy. However, the data are sparse, and the confidence intervals were wide, suggesting that significant benefits or harms of laparoscopic gastrectomy cannot be ruled out. Several trials are currently being conducted and interim results of these trials have been included in this review. These trials need to perform intention-to-treat analysis to ensure that the results are reliable and report the results according to the CONSORT Statement

Cost-effectiveness of Spa treatment for fibromyalgia: general health improvement is not for free

Objectives: To estimate the cost-effectiveness of an adjuvant treatment course of spa treatment compared with usual care only in patients with fibromyalgia syndrome (FM). - \ud Methods: 134 patients with FM, selected from a rheumatology outpatient department and from members of the Dutch FM patient association were randomly assigned to a 2½ week spa treatment course in Tunisia or to usual care only. Results are expressed as quality-adjusted life years (QALYs) for a 6-month as well as a 12-month time horizon. Utilities were derived form the Short Form 6D (SF-6D) scores and the visual analogue scale (VAS) rating general health. Costs were reported from societal perspective. Mean incremental cost per patient and the incremental cost utility ratio (ICER) were calculated; 95% confidence intervals (CIs) were estimated using double-sided bootstrapping. -\ud Results: The data of 128 (55 spa and 73 controls) of the 134 patients (96%) could be used for analysis. Improvement in general health was found in the spa group until 6 months of follow-up by both the SF-6D (AUC 0.32 vs 0.30, P<0.05) and the VAS (AUC 0.23 vs 0.19, P<0.01). After 1yr no significant between-group differences were found. Mean incremental cost of spa treatment was E1311 per patient (95% CI 369–2439), equalling the cost of the intervention (thalassotherapy including airfare and lodging), or E885 per patient based on a more realistic cost estimate. -\ud Conclusions: The temporary improvement in quality of life due to an adjuvant treatment course of spa therapy for patients with FM is associated with limited incremental costs per patient

Cost-of-illness of rheumatoid arthritis and ankylosing spondylitis

OBJECTIVES:\ud To assess, quantify and summarise the cost of illness of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) from the societal perspective.\ud \ud METHODS:\ud Original studies reporting costs of RA or AS were searched systematically. Both cost-of-illness studies and economic evaluations of therapies were included. Studies were appraised for patient and study characteristics, type of costs and actual costs. Reported costs were aggregated by cost categories and overall mean costs were summarised by cost domain (healthcare, patient and family, and productivity costs).\ud \ud RESULTS:\ud Overall mean costs of RA (€14,906 per year) were above that of AS (€9,374 per year), while the relative distribution of costs over cost domains was approximately similar. For both diseases, productivity costs based on the human cost approach were 3 to 10 times higher than the friction costs and accounted for more than half the total costs of both diseases.\ud \ud CONCLUSIONS:\ud Productivity costs constitute the largest part of the total cost-off-illness of RA and AS reflecting the high burden of the disease on work participation. Although total and direct costs of illness in RA were higher than in AS, the average age of AS patients was 10 years lower and therefore, lifetime costs associated with AS may actually be equal or higher

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field

Systemic sclerosis-associated pulmonary hypertension: why disease-specific composite endpoints are needed

Pulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc). In clinical trials PAH-SSc has been grouped with other forms, including idiopathic PAH. The primary endpoint for most pivotal studies was improvement in exercise capacity. However, composite clinical endpoints that better reflect long-term outcome may be more meaningful. We discuss potential endpoints and consider why the same measures may not be appropriate for both idiopathic PAH and PAH-SSc due to inherent differences in clinical outcome and management strategies of these two forms of PAH. Failure to take this into account may compromise progress in managing PAH in SSc

Correction: Performance of risk prediction scores for cardiovascular mortality in older persons: External validation of the SCORE OP and appraisal

[This corrects the article DOI: 10.1371/journal.pone.0231097.

Impact of Janus Kinase Inhibition with Tofacitinib on Fundamental Processes of Bone Healing

Both inflammatory diseases like rheumatoid arthritis (RA) and anti-inflammatory treatment of RA with glucocorticoids (GCs) or non-steroidal anti-inflammatory drugs (NSAIDs) negatively influence bone metabolism and fracture healing. Janus kinase (JAK) inhibition with tofacitinib has been demonstrated to act as a potent anti-inflammatory therapeutic agent in the treatment of RA, but its impact on the fundamental processes of bone regeneration is currently controversially discussed and at least in part elusive. Therefore, in this study, we aimed to examine the effects of tofacitinib on processes of bone healing focusing on recruitment of human mesenchymal stromal cells (hMSCs) into the inflammatory microenvironment of the fracture gap, chondrogenesis, osteogenesis and osteoclastogenesis. We performed our analyses under conditions of reduced oxygen availability in order to mimic the in vivo situation of the fracture gap most optimal. We demonstrate that tofacitinib dose-dependently promotes the recruitment of hMSCs under hypoxia but inhibits recruitment of hMSCs under normoxia. With regard to the chondrogenic differentiation of hMSCs, we demonstrate that tofacitinib does not inhibit survival at therapeutically relevant doses of 10-100 nM. Moreover, tofacitinib dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast differentiation and activity. We conclude from our data that tofacitinib may influence bone healing by promotion of hMSC recruitment into the hypoxic microenvironment of the fracture gap but does not interfere with the cartilaginous phase of the soft callus phase of fracture healing process. We assume that tofacitinib may promote bone formation and reduce bone resorption, which could in part explain the positive impact of tofacitinib on bone erosions in RA. Thus, we hypothesize that it will be unnecessary to stop this medication in case of fracture and suggest that positive effects on osteoporosis are likely

Multimodal imaging for clinical target volume definition in prone whole-breast irradiation: a single institution experience

Aim: The aim was identification of reference structures for breast clinical target volume (CTV) in prone position, throughout image fusion process. Materials & methods: We analyzed breast glandular tissue distribution in 20 diagnostic MRIs, referring to structures reported in ESTRO guidelines for supine irradiation. The volume containing breast glandular tissue in all cases was defined as MRI prone CTV (MRIpCTV). Then in ten subsequent patients planned for prone irradiation, MRI and computed tomography (CT) simulation was acquired. MRIpCTV was defined followed by our findings and transferred to CT for definitive delineation. Results: MRIpCTV was defined by the caudal edge of clavicular head, 3 mm above inframammary fold, by the medial thoracic artery, by a plane passing through the lateral surface of pectoralis muscles, by the anterior surface of pectoralis muscles and 3 mm from the skin. Deformed CTV was consistent with anatomy on CT; the limits chosen for MRIpCTV fit adequately also for CT. Conclusion: Prone irradiation is an alternative set up for selected cases, so the sample is very small. However, our suggestions could be of aid in defining prone CTV. The good consistency between MRI and CT seems to confirm that MRI may be unnecessary in routine practice

Joyful, Joyful! The Musical Significance of Beethoven\u27s Ninth

Almost everyone is familiar with Beethoven’s Fifth Symphony and the famous four note motif that represents fate knocking at the door. His Third Symphony, or “The Heroic Symphony” that was originally written for Napoleon Bonaparte, enjoyed great success and helped shape the future of classical music. However, Beethoven’s Ninth Symphony which contains the well-known tune “Ode to Joy” most drastically impacted classical music’s future. Beethoven was a master at taking simple ideas and combining them with past musical traditions to create something extravagant and new. This is most evident in his Ninth Symphony. In this work, Beethoven did something that was never done before when he added vocal soloists and a choir into the last movement. This symphony was based on the poem by Friedrich Schiller that emphasized universal brotherhood and unity. To express this, Beethoven added the choir and solo voices, consequently impacting the music of future composers. Beethoven’s Ninth Symphony conclusively bridged the gap between classical and romantic music and set the standard for future composers through his use of the choral finale combined with past musical traditions

Periodicities and Plasma Density Structure of Jupiter’s Dawnside Magnetosphere

The ability to quantify variations in magnetic field topology and density within Jupiter’s magnetosphere is an important step in understanding the overall structure and dynamics. The Juno spacecraft has provided a rich data set in the dawnside magnetosphere. The recent Grid Agnostic MHD for Extended Research Applications (GAMERA) global simulation study by Zhang et al. (2021) showed a highly structured plasmadisc with closed magnetic field lines mapping between the outer dawn-tail flank and the high latitude polar region. To test these model predictions, we examined Juno’s magnetic field data and electron/energetic particle data to categorize portions of orbits 1-15 into one of three regions based on plasma confinement: the flux pileup region, the intermediate region, and the plasmadisc region. For each region we examined periodicities from magnetic field fluctuations and particle density fluctuations on the 1-10 hours time scale. Periodicities on this time scale could relate to internal (e.g. plasmadisc structure) or external processes (e.g. Kelvin-Helmholtz vortices). Similar analysis was performed on the GAMERA simulation with the data split into two regions, an outer (150 \u3e R \u3e 60) region and an inner (R \u3c 60) region. Finally, using published density moments from Huscher et al. (2021) we compared the relative density variations of the Juno moments and the GAMERA simulation to further understand the overall structure and dynamics of the plasmadisc. The agreement between data and simulation supports the existence of such a highly structured plasmadisc